Sepsis

J Thorac Cardiovasc Surg, 1993 Dec, 106(6), 1088 - 91
Management of delayed esophageal perforation with mediastinal sepsis . Esophagectomy or primary repair?
Salo JA, Isolauri JO, Heikkila LJ, Markkula HT, Heikkinen LO, Kivilaakso EO, Mattila SP.
Ninety patients with esophageal perforations were operated on at our institutions between 1970 and 1992 . Thirty-four of them were seen after delayed diagnosis (> 24 hours) with mediastinal sepsis caused by perforation of the thoracic esophagus . There were 18 patients with spontaneous ruptures, 11 with instrumental perforations (including one caused during laparotomy), and 3 perforations caused by foreign bodies . One patient had perforation of an esophageal ulcer into the pericardium and another had perforation of an esophageal diverticulum into the mediastinum . Nineteen patients underwent primary repair of the perforation with cleansing and drainage of the mediastinum and the pleural cavity . The remaining 15 had primary extirpation of the thoracic esophagus, irrigation of the mediastinum with antibiotics, cervical esophagostomy, gastrostomy, and drainage of the mediastinum and pleural cavity . Nineteen of the 34 patients survived (hospital mortality 44%) . Of patients with primary repair, only six survived (in-hospital mortality 68%), whereas only two patients treated with esophagectomy died (in-hospital mortality 13%) . The difference was highly significant (p = 0.001) . The most common cause of death was multiorgan failure resulting from sepsis . Postoperative complications developed in four patients treated with primary repair (two sepsis, one empyema, and one anuria) and in seven patients treated with esophagectomy (two empyema, two sepsis, one pneumonia, one mediastinal abscess, and one brain abscess) . After healing of the mediastinitis, the esophagogastric continuity was reconstructed with colon in 11 patients and stomach in two patients . In the management of delayed esophageal perforation with mediastinal sepsis, esophagectomy is superior to primary repair alone, which often leads to mediastinal leakage, continued sepsis, and death.

Circ Shock, 1993 Dec, 41(4), 213 - 20
Ketoisocaproate infusion improves survival from experimental sepsis by an antioxidant mechanism; Yonekura T et al.; Sepsis was induced in rats by cecal ligation and puncture . A nutrient mixture was infused that also contained either (A) sodium 2-ketoisocaproate (NaKIC) or (B) NaHCO3, at 18.75 mmol kg/day . In group A, 34 of 43 rats (79%) survived, while only 24 of 44 rats (55%) in group B survived (P < 0.02) . In a second experiment, cecal ligation and puncture were performed 1 week after bilateral adrenalectomy or sham adrenalectomy . All adrenalectomized rats died within 2 days of CLP, whether corticosterone replacement level was low, normal, or high . Four of eight sham-adrenalectomized rats receiving NaHCO3 died, but none of seven receiving NaKIC died . Combining both experiments by ANOVA, the effect of KIC on survival in adrenal-intact animals is highly significant (P = 0.002) . In NaKIC-infused rats, blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as blood levels of oxidized glutathione and ratio of oxidized/reduced glutathione were significantly lower . We conclude that KIC infusion improves survival of septic rats by an antioxidant mechanism, probably involving reaction with hydrogen peroxide.

J Appl Physiol, 1993 Dec, 75(6), 2521 - 8
Pulmonary transvascular fluid flux and cardiovascular function in sheep with chronic sepsis; Nakazawa H et al.; We studied the mechanisms responsible for the changes in lung lymph flow (QL) in chronic sepsis induced by the continuous infusion of endotoxin {lipopolysaccharide (LPS), 10 ng.kg-1.min-1} . Sheep (n = 11) were studied in the unanesthetized state 7 days after preparation, and cardiopulmonary variables were measured . In the control group (n = 5) given lactated Ringer solution, no significant changes were observed in any measured variables . In the LPS group (n = 6), QL increased from 11.7 +/- 3.8 to 54.0 +/- 15.0 (SE) ml/h 24 h after LPS infusion had begun . This elevation in QL was associated with little or no change (P > 0.05) in reflection coefficient (0.80 +/- 0.03 to 0.87 +/- 0.05) or pulmonary microvascular pressure (14.3 +/- 0.4 to 16.7 +/- 1.2 mmHg) . The filtration coefficient, however, was significantly elevated (0.018 +/- 0.006 to 0.083 +/- 0.024 ml.min-1.mmHg-1) . In association with changes in QL that occur as a result of LPS administration, there was a significant increase in cardiac index (6.1 +/- 0.5 to 10.2 +/- 0.3 l.min-1.m-2) and a reduction in mean arterial pressure (90.2 +/- 4.4 to 73.7 +/- 7.3 mmHg) and systemic vascular resistance index (1,229 +/- 134 to 583 +/- 62 dyn.s.cm-5.m2), findings similar to those noted in septic humans.

Nutr Hosp, 1993 Dec, 8(9), 567 - 73
{The effect of sepsis on liver protein synthesis}; Planas M et al.; A study was made of the possible influence of sepsis on liver protein synthesis in septic and control rats, fed either parenterally (TPN) or with water and feed available "ad libitum" . Liver protein synthesis was determined using the single massive dose method . In experiment I, the septic and control animals received TPN for twenty-four hours: in experiment II water and food was available to them "ad libitum" . Twenty-four hours after the sepsis occurred, the animals were injected with a massive dose of 14C-labelled leucine, and slaughtered by decapitation . The septic animals with water and feed available "ad libitum" were fasted voluntarily without any intake . This group of fasted septic animals was the only one which lost weight . Liver protein synthesis increased in septic animals in comparison with the control animals, whether receiving TPN (112.2 +/- 8/78.5 +/- 13) or with "ad libitum" nutrition (97.2 +/- 15/60.8 +/- 8) . The increased liver protein synthesis in the septic animals was modified (although with reduced significance) by parenteral nutrition (112.2 +/- 8/97.2 +/- 15) . Our results suggest that sepsis increases liver protein synthesis, and that this protein synthesis may be enhanced by parenteral nutrition.

Curr Opin Biotechnol, 1993 Dec, 4(6), 714 - 21
Targets for sepsis therapies: tumor necrosis factor versus interleukin-1; Russell DA et al.; Clinical testing of therapies for sepsis that target tumor necrosis factor and interleukin-1 is currently in progress . It is now clear from early clinical results that patients display a heterogeneous response to anti-cytokine therapies that may be related to the stage or severity of disease . Experimental results show that either cytokine may contribute to the metabolic derangements that lead to organ dysfunction in severe sepsis . They also provide a physiological basis for understanding the benefits of anti-cytokine therapy in the most severely ill patients.

Blood, 1993 Nov 15, 82(10), 3170 - 6
The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients; Fingerle G et al.; Staining with CD14 and CD16 monoclonal antibodies will identify two monocyte subpopulations in human blood: a major population of regular monocytes, which strongly expresses the CD14 antigen (CD14++), and a minor population with weak expression of CD14 and expression of the CD16 antigen (CD14+/CD16+ cells) . As shown herein, the latter cells account for 45 +/- 22 cells/microL and 9% +/- 5% of the monocytes in healthy control donors (n = 35) . In septicemia patients, the CD14+/CD16+ cells can become a major population, with more than 50% of all monocytes in 3 of 18 patients and with more than 500 cells in 4 of 18 cases . There was no correlation of CD14+/CD16+ cells to any clinical parameter except for CD14+/CD16+ percentage and body temperature (P = .013) . The CD14++ regular monocytes showed a substantial decrease in CD14 antigen density in 9 of 11 patients . Three-color immunofluorescence shows that the CD14+/CD16+ monocytes in septicemia patients when compared with the CD14++ monocytes exhibit a higher level of class II antigen and a lower level of CD11b and CD33 antigens, consistent with a more mature nature of the CD14+/CD16+ cells . Levels of interleukin-6 (IL-6) were increased in septicemia patients; 3 of 5 patients with high numbers of CD14+/CD16+ cells (> 200/microL) had high levels of IL-6 (> 250/U/mL) . These data suggest that septicemia may lead to substantial changes in blood monocyte composition and this may be related to elevated levels of cytokines such as IL-6.

JPEN J Parenter Enteral Nutr, 1993 Nov-Dec, 17(6), 507 - 12
The role of the imino transporter protein in sepsis-impaired intestinal proline absorption; Gardiner K et al.; Recently, sepsis has been shown to impair intestinal amino acid absorption in addition to gut metabolic and barrier functions . We investigated intestinal proline absorption in a rabbit model of sepsis . Twelve hours after intraperitoneal injection of lipopolysaccharide, proline uptake by everted jejunal sacs prepared from septic animals (480.4 +/- 67.4 nmol per sac per hour) was significantly reduced compared with controls (846.8 +/- 73.5 nmol per sac per hour) (p < .001 by t test) . We next investigated whether reduced expression of transporter proteins contributed to the impaired intestinal proline uptake during sepsis . The proline (imino) carrier of rabbit jejunum is covalently bound by fluorescein isothiocyanate (FITC) and/or phenylisothiocyanate with irreversible inhibition of proline uptake . This binding and inhibition is prevented by sodium chloride and L-proline . Single-cell suspensions of rabbit enterocytes were prepared 12 hours after intraperitoneal injection of lipopolysaccharide/saline or saline alone . Enterocytes were incubated for 30 minutes in tris(hydroxymethyl)aminomethane/ethylenediaminetetraacetate (Tris/EDTA) buffer; buffer with 1 mM phenylisothiocyanate; or buffer with 10 mM proline, 100 mM sodium chloride, and 1 mM phenylisothiocyanate . After incubation with 10 microM FITC in Tris/EDTA buffer for 15 minutes, the percent positivity and fluorescent intensity of FITC binding to enterocytes were determined by using flow cytometry . Sepsis significantly reduced the percentage of enterocytes binding FITC and the fluorescent intensity of FITC binding of proline/sodium chloride-pretreated or untreated cells . This suggests that sepsis depresses the expression of imino transporters by rabbit enterocytes, which may explain the reduced intestinal proline absorption.

Crit Care Med, 1993 Nov, 21(11), 1770 - 6
Free radicals and antioxidants in sepsis; Goode HF et al.; OBJECTIVES: The clinical condition of sepsis is caused by the release of numerous mediators from many cells . The purpose of this review is to describe the results of studies in which the role of free radicals and/or the potential therapeutic value of antioxidants are assessed . DATA SOURCES: The studies described in this review come from a variety of sources, including Med-Line CD-ROM computerized database, Index Medicus, and references identified from the bibliographies of pertinent articles and books . Reports were confined to English language articles from 1966 to 1992 . STUDY SELECTION: All retrieved references in which free-radical activity was assessed or antioxidants were measured or administered in sepsis or endotoxemia were included . This selection process encompassed clinical, animal and in vitro cell culture work . DATA EXTRACTION: Cited literature was found in reputable peer-reviewed clinical or basic science journals . DATA SYNTHESIS: Any contradictions in the results of studies are discussed . CONCLUSIONS: There is evidence that free radicals play an important role in the pathogenesis of sepsis . Antioxidant therapy has the potential to protect against such injury . It is suggested that combination therapy, which augments the endogenous antioxidant defenses, is likely to be the best approach.

Aust N Z J Surg, 1993 Nov, 63(11), 888 - 93
Laparostomy: a technique for the management of severe abdominal sepsis; Pick AW et al.; The mortality from acute suppurative peritonitis may approach 70%, survivors often undergoing multiple operations and requiring protracted intensive medical support . Attempts to improve prognosis fail when they rely on the diagnosis of persistent or recurrent collections . The results of laparostomy in conjunction with continuous peritoneal irrigation (CPI), which aims to primarily eradicate and subsequently prevent the recurrence of sepsis are reported . Two deaths occurred in this series of seven patients, only one attributed to persistent sepsis . Overall, the mortality of 28% compares favourably with similar patient series and suggests that laparostomy with CPI deserves consideration in the management of selected patients with severely contaminated abdominal cavities.

Cytokine, 1993 Nov, 5(6), 578 - 82
Overall interleukin-6 production exceeds 7 mg/day in multiple myeloma complicated by sepsis; Lu ZY et al.; We previously reported that injection of anti-IL-6 monoclonal antibody (mAb) in a patient with multiple myeloma (MM) induced the circulation of high amounts of IL-6 in the form of IL-6/anti-IL-6 monomeric complexes . This made it possible to estimate overall daily IL-6 production in patients in vivo, which had not been achieved in animals or humans before . In this study, estimations are given for a patient with MM who developed Escherichia coli sepsis during anti-IL-6 mAb . During the first 12 days, the overall IL-6 production was estimated at 1.5 to 2.0 micrograms/day . On day 13, serum IL-6 concentration, in the form of IL-6/anti-IL-6 complexes, increased 1000-fold and was 1.7 x 10(6) pg/ml, in relation with the development of E . coli sepsis . Overall IL-6 production was estimated to be greater than 7 mg/day, i.e . 3500 times higher than before sepsis . Serum IL-6 levels in the form of monomeric immune complexes remained very high for 20 days after sepsis indicating the persistence of very high overall IL-6 production (100 to 3500-fold greater than pre-sepsis production) . This study demonstrates a considerable and persistent potential for IL-6 production in this patient during and after sepsis.

J Pediatr Gastroenterol Nutr, 1993 Nov, 17(4), 392 - 6
Do umbilical vein catheterization and sepsis lead to portal vein thrombosis? A prospective, clinical, and sonographic evaluation; Yadav S et al.; Extrahepatic portal vein obstruction (EHPVO) affects 20-30% of all patients with portal hypertension in India . The etiopathogenesis of this disease is unknown . In retrospective studies, umbilical vein cannulation and sepsis have been alleged to cause portal thrombosis . This prospective study was undertaken to detect clinically and by serial sonography whether thrombosis and consequent obstruction of the splenoportal venous system develops after umbilical vein catheterization and sepsis . Forty-seven children who had undergone exchange transfusion for hyperbilirubinemia, belonging to two different age groups, were studied . Twenty-two new-borns (Group A) were studied within 4 weeks of birth and later at 3-month intervals until the age of 12 months and subsequently at 24 months . Another group of 25 children (Group B), 1- to 5-year-olds who had earlier undergone exchange transfusion and 15 healthy newborns (Group C) were also screened . In Group A, seven (29%) neonates had septicemia, and in five, the splenic vein could not be initially visualized . The splenic vein was not seen in five of the 15 newborns in Group A who had no umbilical sepsis . Twenty-one of the 22 neonates in Group A were followed-up, and the splenic vein was well visualized and found patent on subsequent ultrasound in all of them . In Group B, four (16%) children had umbilical sepsis . None of these or the other Group B children showed any thrombosis or obstruction of the splenoportal system . The portal vein and its branches and the splenic vein were visualized in all healthy (Group C) neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

New Horiz, 1993 Nov, 1(4), 538 - 49
Postinjury multiple organ failure: role of extrathoracic injury and sepsis in adult respiratory distress syndrome; Moore FA et al.; Adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF) occur as a result of an unbridled systemic inflammatory response (i.e., severe systemic inflammatory response syndrome {SIRS}) . Early epidemiologic studies concluded that infection with systemic sepsis was the common pathway for the development of ARDS and eventual MOF . As a consequence, research investigation from 1977 to 1987 focused on later clinical events (e.g., immunosuppression, persistent hypercatabolism, and bacterial translocation) . Now, it is believed that an initial massive traumatic insult can create severe SIRS independent of infection (one-hit model) . Alternatively, a less severe traumatic insult can create an inflammatory environment (i.e., primes the host) such that a later, otherwise innocuous, secondary inflammatory insult precipitates severe SIRS (two-hit model) . As a result of these newer inflammatory models, research interest over the last 5 yrs has shifted to investigating earlier clinical events (e.g., unrecognized flow-dependent oxygen consumption, ischemia/reperfusion, and priming/activation of the inflammatory response) . The traditional infection models of ARDS and MOF are applicable to current research and patient care efforts . However, the inflammatory models emphasize the pivotal role of the initial traumatic insult . Moreover, while ARDS occurs earlier than other types of overt organ failure, it is now believed that simultaneous organ injury is occurring, presumably via similar inflammatory mechanisms.

Ann Intern Med, 1993 Oct 15, 119(8), 771 - 8
Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome; Casey LC et al.; OBJECTIVE: To determine whether plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and lipopolysaccharide are detectable in patients when they first present with the sepsis syndrome and to determine whether levels correlate with patient survival . DESIGN: Prospective study comparing patients with the sepsis syndrome, critically ill patients without sepsis, and normal healthy volunteers . SETTING: Tertiary care hospital affiliated with a medical school . PATIENTS: The study included 97 consecutive patients on a medical service who met the criteria for the sepsis syndrome; 20 critically ill patients without sepsis who were in the medical intensive care unit; and 20 healthy volunteers who served as comparison groups . MEASUREMENTS: Plasma tumor necrosis factor-alpha, IL-1 beta, interleukin-6, and endotoxin (lipopolysaccharide) levels were measured when a patient was first identified as having the sepsis syndrome . Survival was defined as being alive 30 days after the sepsis syndrome was diagnosed . RESULTS: Fifty-four percent of patients with the sepsis syndrome had detectable levels of TNF-alpha (median, 26 pg/mL; range, nondetectable to 1000 pg/mL); 37% had detectable levels of IL-1 (median, 20 pg/mL; range, nondetectable to 2850 pg/mL); 80% had detectable levels of IL-6 (median, 415 pg/mL; range, nondetectable to 2380 pg/mL); and 89% had detectable levels of lipopolysaccharide (median, 2.6; range, nondetectable to 12.5 endotoxin units {EU}/mL) . In all cases levels were higher than those in critically ill patients without sepsis and normal healthy controls (P < 0.001 for all comparisons) . Plasma levels of TNF-alpha, IL-1 beta, IL-6, and lipopolysaccharide were detectable in patients regardless of culture status . The IL-6 level was 69% (95% CI, 30% to 108%) higher in patients who died compared with those who survived . The scores for the individual levels of TNF-alpha, IL-1 beta, IL-6, and lipopolysaccharide were summed to arrive at a total lipopolysaccharide-cytokine score, and mortality increased with lipopolysaccharide-cytokine score (P < 0.001) . CONCLUSIONS: Patients with the sepsis syndrome have detectable levels of circulating TNF-alpha, IL-1, IL-6, and lipopolysaccharide independent of culture-documented infection . Lipopolysaccharide and cytokines may play a pathogenic role in sepsis, and the combination of several elevated factors may be important in determining patient survival.

Chest, 1993 Oct, 104(4), 1296 - 7
Sepsis syndrome and death after bronchoalveolar lavage; de Fijter JW et al.; Bronchoalveolar lavage is widely used in the management of patients with interstitial lung diseases and is considered a safe procedure . We describe a patient who died with a picture consistent with acute pulmonary edema and septic shock following bronchoalveolar lavage . This potential complication has not been previously reported.

J Infect Dis, 1993 Oct, 168(4), 955 - 60
Release of soluble receptors for tumor necrosis factor in clinical sepsis and experimental endotoxemia; van der Poll T et al.; To assess the role of tumor necrosis factor (TNF) in the appearance of soluble TNF receptors (sTNFRs), 20 consecutive patients with a clinical diagnosis of sepsis were studied as were 7 chimpanzees after administration of endotoxin (4 ng/kg) with or without pentoxifylline . The patients had markedly elevated serum levels of sTNFR-p55 and sTNFR-p75 compared with healthy controls (P < .0001 for both receptors) . The levels of both soluble receptors correlated with simultaneously measured immunoreactive TNF concentrations (p55: r = .63, P < .01; p75: r = .69, P < .001) . In the chimpanzees, endotoxin induced subsequent rises in the serum concentrations of TNF and sTNFRs . Although pentoxifylline reduced the TNF response to intravenous endotoxin to 20% (P < .05), the appearance of sTNFRs was only moderately inhibited (sTNFR-p55 to 79% on average, P < .05; sTNFR-p75 to 77%, P = .12) . These results indicate that TNF either does not play an important role in the appearance of sTNFRs in systemic infection or that a small amount of TNF remaining in the circulation after some bacterial challenges is sufficient to preserve the secretion of its soluble receptors.

Clin Investig, 1993 Oct, 71(10), 791 - 4
Instant therapy of acquired agranulocytosis and sepsis by recombinant granulocyte-macrophage colony-stimulating factor in a polytrauma patient; Gross-Weege W et al.; Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to an intensive-care patient with polytrauma in a life-threatening situation with acquired agranulocytosis and sepsis . Mature granulocytes reappeared in the blood 2 days after initiation of rhGM-CSF therapy; granulocyte precursors peaked at 43% after 5 days . Bone marrow examination performed 7 days after the beginning of rhGM-CSF therapy revealed complete regeneration of granulopoiesis . The functional analysis of these blood leukocytes in vitro showed regular production of reactive oxygen radicals . Clinically, the patient recovered without any serious side effects due to the rhGM-CSF therapy . These results suggest that rhGM-CSF accelerates granulocyte recovery from acquired agranulocytosis with the presence of their functional activity.

Eur J Surg, 1993 Oct, 159(10), 535 - 9
Effect of sepsis-related cytokines on lipid synthesis by isolated human hepatocytes; Arias-Diaz J et al.; OBJECTIVE: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) and other sepsis related cytokines on the synthesis of several lipid fractions by human hepatocytes . DESIGN: Laboratory study . SETTING: University departments of surgery and biochemistry . MATERIAL: Livers from eight donors of other organs . MAIN OUTCOME MEASURES: Effect of TNF-alpha, interleukin-1 (IL-1), and interleukin-6 (IL-6) on the synthesis of triacylglycerol and phospholipids by freshly isolated human hepatocytes . RESULTS: All three cytokines, particularly TNF-alpha, inhibited the incorporation of D-glucose uniformly labelled with 14C (D-(U-14C) glucose) into phosphatidylcholine . The incorporation of D-(U-14C) glucose into triacylglycerol and free fatty acids was significantly stimulated by TNF-alpha and IL-1, but not by IL-6 . When palmitate uniformly labelled with 14C was used as the radiolabelled precursor, TNF-alpha stimulated the synthesis of both triacylglycerol and phosphatidylcholine, neither of which was affected by IL-1 or IL-6 . CONCLUSION: Changes that are induced by cytokines in lipid synthesis by hepatocytes can contribute to the impairment of lipid metabolism seen in septic patients . TNF-alpha seemed to have more effect than the other two cytokines.

Circ Shock, 1993 Oct, 41(2), 82 - 7
Effect of subcutaneous Escherichia coli-induced hypermetabolic sepsis on hepatic gluconeogenesis and its hormonal responsiveness in the rat; Deaciuc IV et al.; In hypermetabolic sepsis, gluconeogenesis is markedly elevated during fasting, and is manifested as an increased rate of glucose appearance (Ra) . The likely causes of such a change are alterations in 1) concentration of systemic hormones, 2) concentration of glucose precursors, especially lactate, 3) activity of the key enzymes of the pathway, and 4) hormone receptors and/or transmembrane signalling mechanisms, involved in the hormonal regulation of the pathway . In this study, we investigated the importance of the latter two factors in the increase of gluconeogenesis during hypermetabolic sepsis . Rats were rendered septic by repeated subcutaneous administration of live Escherichia coli . The livers were perfused in vitro in a nonrecirculating mode to measure the rate of gluconeogenesis from saturating concentrations of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM), and the response of gluconeogenesis to vasopressin (VP, 0.1 and 1.0 nM), glucagon (Glc, 0.1 and 1.0 nM), and prostaglandin (PG) F2 alpha (5 microM) . The rate of gluconeogenesis without precursor supply was approximately 20-30 mumoles/100 g b w/hr during the first 4-6 min of perfusion, followed by a continuous decline to very low levels . Infusion of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM) increased glucose output, and maintained it at approximately 100-110 and approximately 130-140 mumoles/100 g b w/hr, respectively . VP, Glc, and PGF2 alpha stimulated the rate of gluconeogenesis in a dose-dependent manner (VP and Glc) . No differences were observed between control and septic rats using these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Circ Shock, 1993 Oct, 41(2), 77 - 81
Evidence of increased nitric oxide production in patients with the sepsis syndrome; Evans T et al.; To investigate whether the hypotension of septic shock is due to an excess production of nitric oxide (NO), we have determined the serum levels of nitrate and nitrite (NO3/NO2), the stable end-products of NO, in 12 patients with the sepsis syndrome and marked hypotension . Compared to a mean NO3/NO2 level of 36.4 microM in controls (n = 7), the group of septic patients had a significantly elevated mean NO3/NO2 level of 124 microM (P < 0.01, Wilcoxon two-sample test) . A lesser elevation was also seen in a group of postoperative patients (mean level 87.3 microM, n = 7), which was significantly elevated compared to controls (P < 0.01, Wilcoxon two-sample test), but was not significantly lower than the septic group (0.1 > P > 0.05, Wilcoxon two-sample test) . These data suggest that NO may be responsible, at least in part, for the hypotension of septic shock.

Am J Physiol, 1993 Oct, 265(4 Pt 1), E660 - 6
Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis; Breuille D et al.; Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver . Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past . However, the identity of the active agent in alterations of protein metabolism is still controversial . To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline . Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats . Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection . The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis . Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

Burns, 1993 Oct, 19(5), 434 - 6
Experience with polymicrobial sepsis in a regional burn unit; Still JM Jr et al.; A 2-year review of 795 patients admitted to a regional burn unit was carried out to determine the incidence of polymicrobial sepsis . Of 38 bacteraemic patients, 21 (55 per cent) had polymicrobial sepsis in 1990 . Of 38 cases in 1991, 12 patients (31.6 per cent) had polymicrobic infections . Of 36 deaths in 1990, 13 were attributed to sepsis, 12 of 29 (31.6 per cent) in 1991 . Of the patients who died in 1990, eight (21 per cent) were polymicrobic septic deaths and six (15.8 per cent) in 1991 . The problem has been reported in immunocompromised patients, especially those with terminal malignancies, but has rarely been noted in burn patients . Recognition of the seriousness of the problem and the aggressive antibiotic therapy appropriate to the organisms in question is advised.

Turk J Pediatr, 1993 Oct-Dec, 35(4), 277 - 81
The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants; Erdem G et al.; The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospective randomized study . All infants received antibiotic therapy and fresh plasma and/or whole blood transfusions . Twenty randomly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days . Although the mortality rate in preterm infants whose gestational ages were 31-34 weeks in the immunotherapy group was slightly lower than in the control group, the general mortality rate from sepsis in the control group (9/24) and in the immunotherapy group (6/20) showed no statistically significant difference (37.5% vs 30.0%, p < 0.05).

Nippon Kyobu Geka Gakkai Zasshi, 1993 Sep, 41(9), 1573 - 7
{Case report of MRSA sepsis required two valve replacement twice a year--trying case with hyperthermal extracorporeal circulation}; Hori T et al.; We report a case in conjunction with MRSA sepsis, who needed re-mitral valve replacement (re-MVR) and re-tricuspid valve imposition (re-TVI), and who was successfully treated with a number of antibiotics in conjunction with hyperthermal extracorporeal circulation . Initially, we performed MVR and tricuspid valve superimposition on a 62-year-old woman lationing under the MRSA sepsis condition to control against heart failure . However, she developed a fever following the first operation, and MRSA was detected from her blood cultivation . She thus underwent treatment employing many kinds of antibiotics . A thickened C.E . valve at the tricuspid valve cardiac echogram suggested PVE, we performed a second operation of re-MVR and re-TVI about a year after the first operation . We used a tangl of antibiotics during the operation, adding Vancomycin into the extracorporeal circulation, and utilized hyperthermal extracorporeal circulation . This patient's postoperative course was uneventful, with no recurrence arising at 23 months after the second operation.

Circ Shock, 1993 Sep, 41(1), 19 - 25
Externalization and internalization of (Na+ + K+)-ATPase in rat heart during different phases of sepsis; Tang C et al.; Changes in the distribution of (Na+ + K+)-ATPase in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied . Sepsis was induced by cecal ligation and puncture (CLP) . The alpha-subunit of (Na+ + K+)-ATPase was photoaffinity labeled with {alpha-32P}8-N3ATP . The results show that septic rat heart exhibits hyperdynamic (hypermetabolic) phase during early (9 hr post-CLP), followed by hypodynamic (hypometabolic) phase during late (18 hr post-CLP) sepsis . Marker enzyme and beta-adrenergic receptor assays depict that the light vesicle fraction is the intracellular site of surface receptor . The incorporation of the photolabel into the alpha-subunit (M(r) = 98,000) of the (Na+ + K+)-ATPase in sarcolemmal fraction was increased by 60% (P < 0.01) during early sepsis, but was decreased by 63% (P < 0.01) during late sepsis . In contrast, the binding of 98,000-M(r) peptide in light vesicles was decreased by 40% (P < 0.01) in early sepsis, but was increased by 102% (P < 0.01) during late sepsis . The ouabain-sensitive (Na+ + K+)-ATPase activity was increased by 31% (P < 0.05) during the early sepsis, but was decreased by 32% (P < 0.01) during late sepsis in the sarcolemmal fraction; while in the light vesicle fraction, the (Na+ + K+)-ATPase activity was decreased by 21% (P < 0.01) during early sepsis, but was increased by 47% (P < 0.01) during the late phase of sepsis . The yield of membrane proteins for each specific fraction remained unchanged for control, early sepsis, and late sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Crit Care Med, 1993 Sep, 21(9), 1312 - 8
Effects of blood transfusion on oxygen transport variables in severe sepsis; Lorente JA et al.; OBJECTIVE: To investigate whether increasing oxygen delivery (DO2) by increasing hematocrit results in increases in oxygen uptake (VO2) in septic patients with an abnormal DO2/VO2 relationship . DESIGN: Prospective, randomized, interventional crossover study . SETTING: Tertiary care hospital . PATIENTS: A consecutive sample of 16 patients admitted to the intensive care unit, who were diagnosed as having severe sepsis by defined criteria and who had a hemoglobin concentration of < 10 g/dL . INTERVENTIONS: Patients received, in random order, an infusion of dobutamine (10 micrograms/kg/min) and a blood transfusion (800 mL of packed red blood cells in 90 mins) . Hemodynamic and oxygen transport variables were determined before and after each treatment, allowing at least 20 mins during the infusion of dobutamine to achieve the steady state . MEASUREMENTS AND MAIN RESULTS: Changes in DO2 and VO2 induced by each intervention were measured . Dobutamine significantly increased DO2 (48.5 +/- 6.9%; p = .0001) and VO2 (21.7 +/- 3.3%; p = .0001) . Blood transfusion increased DO2 (21.4 +/- 4.3%; p = .005) but VO2 did not change significantly (2.2 +/- 4.1%) . Correlation coefficients for the percent changes of DO2 and VO2 (r2 = .67, p = .001 for dobutamine; and r2 = 21, p = .07 for blood transfusion) were significantly different for each treatment (p = .0001) . CONCLUSIONS: In patients with an abnormal DO2-dependent VO2, as shown by increases in VO2 brought about by an infusion of dobutamine, blood transfusion does not significantly increase VO2, despite significant changes in DO2 . The VO2, in some critically ill patients, depends more on blood flow than on global DO2.

Crit Care Med, 1993 Sep, 21(9), 1287 - 95
L-arginine pathway in the sepsis syndrome; Lorente JA et al.; OBJECTIVE: To investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome . DESIGN: Prospective, intervention study . SETTING: Tertiary care hospital . PATIENTS: Fifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by defined criteria . INTERVENTIONS: Eight patients received N omega-nitro-L-arginine (20 mg/kg, iv bolus) followed by L-arginine (200 mg/kg, iv bolus) . Seven patients received L-arginine alone (200 mg/kg) . MEASUREMENTS AND MAIN RESULTS: In the first group, hemodynamic and oxygen transport variables were recorded at baseline, during 45 mins after the injection of N omega-nitro-L-arginine, and during 45 mins after the administration of L-arginine . In the second group, hemodynamic parameters were recorded at baseline and during 15 mins after the administration of L-arginine . Data are mean +/- SEM . The administration of N omega-nitro-L-arginine was followed by hypertension (mean blood pressure increased from 89 +/- 8 to a maximum of 140 +/- 12 mm Hg) accompanied by a decrease in cardiac index (from 3.51 +/- 0.39 to a minimum of 2.65 +/- 0.21 L/min/m2) and an increase in right atrial and pulmonary artery occlusion pressure . Systemic vascular resistance index increased from 1871.1 +/- 302.3 to 3825.6 +/- 244.4 dyne.sec/cm5.m2, and pulmonary vascular resistance increased from 533.2 +/- 125.8 to 816.0 +/- 117.3 dyne.sec/cm5.m2 . These changes induced by N omega-nitro-L-arginine were reversed by the administration of L-arginine . The administration of L-arginine to another group of patients caused transient hypotension (from 103 +/- 6 to 81 +/- 10 mm Hg) and an increase in cardiac index (from 3.57 +/- 0.15 to 4.74 +/- 0.54 L/min/m2) . Both systemic and pulmonary vascular resistance indices decreased (from 1987.6 +/- 163.9 to 1251.4 +/- 231.5 dyne.sec/cm5.m2, and from 486.1 +/- 65.2 to 380.5 +/- 70.3 dyne.sec/cm5.m2) . Parallel to the increase in oxygen transport due to the increase in cardiac output, oxygen consumption index increased significantly 1 min after L-arginine (from 127.0 +/- 19.0 to 182.5 +/- 37.3 mL/min/m2) . All mentioned changes were statistically significant (p < .05) . CONCLUSIONS: A continuous basal release of nitric oxide plays a role in the regulation of systemic and pulmonary vascular tone in patients with sepsis syndrome . L-arginine has systemic and pulmonary vasodilatory actions.

Prof Nurse, 1993 Sep, 8(12), 775 - 9
Simply a case of good practice . Avoiding catheter-related sepsis in total parenteral nutrition; Roberts PH; Catheter-related sepsis is a well-known complication associated with the administration of total parenteral nutrition . A strict aseptic approach, supplemented with a knowledge of how the infection occurs, will do much to avoid this problem.

J Pediatr Surg, 1993 Sep, 28(9), 1144 - 6
Pentoxifylline improves resting membrane potential in sepsis; Refsum SE et al.; The resting membrane potential (RMP) of skeletal muscle cells was investigated in a hyperdynamic animal model of sepsis . Reduced membrane potential is known to parallel the clinical course of sepsis and hemorrhagic shock in animal models . Pentoxifylline (PTF), a dimethyl xanthine derivative of the theophylline family, may improve the metabolic effects of sepsis . A cecal ligation and puncture (CL&P) sepsis model in Wistar rats was used in which RMP was measured with differing administration regimes of PTF . The RMP decreased less rapidly in our study when PTF was administered after CL&P and this effect was most noticeable after 18 hours . Administration of PTF before CL&P had little effect on membrane potential fall-off . These results suggest a potential role for PTF in the management of sepsis.

Vopr Med Khim, 1993 Sep-Oct, 39(5), 19 - 21
{Fatty acid composition and functional status of erythrocyte membranes in patients with sepsis}; Soboleva MK et al.; Distinct alterations in fatty acid composition and in the functional state of erythrocyte membranes were detected in 58 patients with sepsis; these alterations were phase-dependent and correlated highly with clinical picture . Considerable increase in content of saturated and monounsaturated fatty acids and a decrease in concentration of lipoproteins were found in erythrocyte membranes under inauspicious conditions of sepsis development . In these patients activities of superoxide dismutase and glucose-6-phosphate dehydrogenase were decreased, while content of SH-groups was lowered and lipid peroxidation was inhibited . The alterations observed in fatty acid composition of erythrocyte membranes and a decrease in metabolic activity of red blood cells may be responsible for hemolysis in patients with sepsis.

Cardiovasc Intervent Radiol, 1993 Sep-Oct, 16(5), 328 - 31
Abdominal wall cellulitis and sepsis secondary to percutaneous cecostomy; Maginot TJ et al.; We report 1 case of abdominal wall cellulitis and sepsis which developed following percutaneous placement of a Cope catheter for cecal decompression in a patient with Ogilvie's syndrome . This case highlights that further laboratory investigation and clinical evaluation are needed to determine the safest and most efficacious technique of percutaneous drainage.

An Esp Pediatr, 1993 Sep, 39(3), 223 - 6
{Elastase-alpha 1-antiprotease in neonatal sepsis}; Iriondo Sanz M et al.; Elastase-alpha 1-proteinase inhibitor complex (E-alpha 1-PI) was evaluated in 682 blood samples from 516 newborn infants . They were divided into three groups: control (group 1; n = 99), non-infectious (group 2; n = 338) and infectious (group 3; n = 82) . The plasma values of E-alpha 1-PI complex (median; minimum-maximum, in microgram/L) were 180; 46-296 in group 1, 337; 40-2524 in group 2 and 954.5; 183-8160 in group 3 . Significant differences were found between the groups (p < 0.001) . E-alpha 1-PI complex in blood showed a sensitivity of 75%, specificity of 81.9%, positive predictive value of 30.6% and negative predictive value of 96.8% for the diagnosis of neonatal infection.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1993 Sep, 9(5), 372 - 5, 398
{Influence of burn shock on the prognosis of burn wound sepsis in mice}; Dong HL; The influence of burn shock on the prognosis of burn wound sepsis was investigated in mice . Mice with full-thickness burn of 13% TBSA was injected subcutaneously under the burned area immediately after burning with 0.2ml P . aeruginosa (1 x 10(3)CFU/ml) or 0.2 ml K . pneumoniae (5 x 10(3)CFU/ml) . The survival rate in P . aeruginosa burn wound sepsis was 49% in resuscitation group (n = 53) on 7 postburn day and 17% in non-resuscitation group (n = 24) (P < 0.01) . The mean survival time in dead mice of resuscitation group (n = 27) was 4.2 +/- 1.7 days and 2.5 +/- 0.6 days in that of non-resuscitation group (n = 20) (p < 0.01) . The survival rate in K . pneumoniae burn wound sepsis was 69% in resuscitation group (n = 26) on 7 postburn day and 15% in non-resuscitation group (n = 13) (P < 0.01) . The mean survival time in dead mice of resuscitation group (n = 8) was 5 +/- 1.35 days and 2.1 +/- 0.3 days in that of non-resuscitation group (n = 11) (p < 0.01) . These results indicated that burn shock might increase the mortality of burn wound sepsis and resuscitation could improve the prognosis of burn wound sepsis.

JAMA, 1993 Aug 25, 270(8), 975 - 9
Pathogenesis of disseminated intravascular coagulation in sepsis; Levi M et al.; OBJECTIVE--To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention . DATA SOURCES--Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis . STUDY SELECTION--Studies selected for detailed review were those reporting specifics about the mechanism of activation of coagulation and fibrinolysis in experimental human and animal models of sepsis . Data extraction guidelines for assessing data quality included validity of the model, quality of the laboratory assessment of activation of coagulation and fibrinolysis, and methodological considerations, such as the presence of control experiments and statistical analysis . DATA SYNTHESIS--After the presence of endotoxin in the circulation, significant coagulation activation can be detected . This activation is preceded by an increase in the serum levels of various cytokines, such as tumor necrosis factor and interleukins . Inhibition of the increase in tumor necrosis factor results in inhibition of coagulation activation . Measurement of molecular markers for the activation of coagulation proteins at various levels indicates that the activation of coagulation is mediated by the tissue factor-dependent pathway, which is further confirmed by experiments in which the inhibition of the tissue factor-dependent pathway resulted in complete inhibition of coagulation activation . The activation of coagulation seems to be amplified by impaired function of the protein C-protein S inhibitory pathway . An imbalance between coagulation and fibrinolysis, ultimately leading to plasminogen activator inhibitor type 1-mediated inhibition of fibrinolysis, may further promote the procoagulant state . CONCLUSION--The increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in sepsis may have therapeutic implications; however, their efficacy needs to be assessed in appropriate clinical trials.

Br J Hosp Med, 1993 Aug 18-31, 50(4), 204 - 5
Decision making in surgery: acute anorectal sepsis; Thomas P; Acute perineal inflammation is a common surgical emergency, presenting in most cases with an abscess arising from infection within the many tissue planes in this area . Simple drainage of such an abscess leads to immediate symptomatic relief but this should be accompanied by diagnostic manoeuvres that allow any underlying fistulae to be found and eradicated.

Lancet, 1993 Aug 14, 342(8868), 402 - 3
Rapid diagnosis of central venous catheter sepsis; Rushforth JA et al.; Signs of infection with a central venous access device in situ raise the possibility of catheter sepsis . We evaluated three tests for diagnosis of infection in infants with suspected catheter sepsis . The acridine orange leucocyte cytospin (AOLC) test was 87% sensitive and 94% specific in the diagnosis of catheter-related sepsis defined by quantitative blood culture . The C-reactive protein and nitroblue tetrazolium tests were not as useful . Using the AOLC results, available in an hour, we now remove fewer catheters on suspicion of sepsis alone.

Am J Physiol, 1993 Aug, 265(2 Pt 2), R385 - 91
Biphasic intracellular redistribution of alpha 1-adrenergic receptors in rat liver during sepsis; Hwang TL et al.; Changes in the distribution of alpha 1-adrenergic receptors in two subcellular fractions, the plasma membrane and the light vesicle, of rat liver during sepsis were studied using {3H}prazosin binding and photoaffinity labeling with {125I}arylazidoprazosin in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Sepsis was induced by cecal ligation and puncture (CLP) . Septic rats exhibit two metabolically distinct phases: an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis) . {3H}prazosin binding studies show that during early sepsis, the maximal binding capacity (Bmax) was increased by 35% in plasma membranes but was decreased by 28% in light vesicles; while during late sepsis, the Bmax was decreased by 30% in plasma membranes but was increased by 33% in light vesicles . The photoaffinity labeling studies revealed two major binding peptides with M(r) of 77,000 and 68,000 Da and one minor binding protein with M(r) of 39,000 Da . The total binding for the three labeled peptides during early sepsis was increased by 26% in plasma membranes but was decreased by 33% in light vesicles, while during late sepsis the total binding was decreased by 19% in plasma membranes but was increased by 35% in light vesicles . These data indicate that alpha 1-adrenergic receptors in the rat liver were externalized from light vesicles to plasma membranes during the hyperglycemic phase while they were internalized from surface membranes to intracellular sites during the hypoglycemic phase of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Nippon Geka Gakkai Zasshi, 1993 Aug, 94(8), 775 - 80
{Treatment of sepsis by extracorporeal elimination of endotoxin using fiber-immobilized polymyxin B}; Aoki H et al.; To remove endotoxin directly from the blood, an affinity adsorbent (PMX) has been developed . PMX is composed of a ligand of polymyxin B and a carrier of polystyrene fibers . We treated 16 patients, suffering from septic shock or multiple organ failure by PMX-F hemoperfusion . The pretreatment level of endotoxin decreased significantly from 80pg/ml to 21pg/ml on average 2 hours after the hemoperfusion . The hyperdynamic status in the cardiac index and the decreased systemic vascular resistance, which are characteristic to endotoxin shock, were normalized after the treatment . In septic shock patients with systolic pressure under 10mmHg, the systolic pressure increased significantly from pretreatment level . Nine of the sixteen patients remained alive for two weeks after the therapy, and seven out of the nine patients discharged alive . Hemoperfusion with PMX is likely to become an effective treatment for sepsis and septic shock.

Circ Shock, 1993 Aug, 40(4), 303 - 10
Effect of sepsis on brain energy metabolism in normoxic and hypoxic rats; Hotchkiss RS et al.; Neurological abnormalities including agitation, confusion, disorientation, lethargy, and obtundation are early characteristic findings in patients with sepsis . The etiology of the changes in mental status that occur during severe infection is unknown . We investigated the effects of sepsis on intermediary metabolism and bioenergetics in the brain during normoxia and moderate hypoxia (8% inspired O2 concentration) in rats 36-42 hr following cecal ligation and perforation . The rats were anesthetized with halothane, and brains frozen using the funnel-freezing technique . Perchloric acid extracts of brains were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy . There was no impairment in bioenergetics or intermediary metabolism in septic brain, and sepsis did not compromise the ability of the brain to maintain high-energy phosphates during hypoxia . Hypoxia did cause the brain lactate-to-pyruvate ratio to increase equivalently in both septic and control rats from approximately 9:1 to 20:1 (P < 0.001) . We conclude that the neurologic changes which are characteristic of sepsis are unlikely to be due to alterations in cellular energy stores or intermediately metabolism . In addition, there is no evidence that sepsis results in brain cellular hypoxia.

Circ Shock, 1993 Aug, 40(4), 295 - 302
Sepsis-induced alterations in phosphoenolpyruvate carboxykinase expression: the role of insulin and glucagon; Deutschman CS et al.; Sepsis is associated with a decrease in the intrinsic gluconeogenic capacity of hepatocytes . The mechanism underlying this depression is unknown . This study sought to investigate whether decreased expression of phosphoenolpyruvate carboxykinase (PEPCK), a rate limiting enzyme in hepatic gluconeogenesis, might contribute to the decreased gluconeogenesis in sepsis . Therefore, we determined the effects of sepsis on the steady-state level of PEPCK mRNA and on PEPCK activity . Further, levels of insulin and glucagon, which modulate PEPCK expression under normal conditions, were also measured . Rats were subjected to either cecal ligation and puncture, or sham operation . Twenty-four hr later, the steady-state level of PEPCK mRNA was determined by Northern Blot hybridization analysis, and PEPCK activity was measured by 14C incorporation into phosphoenolpyruvate . Insulin and glucagon levels were determined by radioimmunoassay, and the insulin/glucagon ratio calculated . The steady-state levels of PEPCK mRNA were significantly decreased in septic animals relative to sham-operated animals . The specific activity of PEPCK in sham-operated animals was 1.67 +/- 0.25 U/mg protein, compared to 0.93 +/- 0.18 U/mg protein in septic animals (P < 0.05) . The insulin/glucagon ratio was lower in septic animals than in sham-operated controls . To investigate the specific effect of the insulin-glucagon ratios observed in septic and sham operated rats on hepatocytes under non-septic conditions, cultures of primary rat hepatocytes were used . These cells were incubated with levels of insulin and glucagon equivalent to those found following cecal ligation and puncture or sham operation . Hormonal conditions designed to mimic sepsis were associated with an increase in PEPCK expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Physiol, 1993 Aug, 265(2 Pt 1), E284 - 8
Plasma NE concentrations do not accurately reflect sympathetic nervous system activity in human sepsis; Leinhardt DJ et al.; Plasma norepinephrine concentrations ({NE}) when raised in patients with sepsis are thought to indicate increased activity of the sympathetic nervous system (SNS) . However, increased SNS activity may occur without a concomitant rise in plasma {NE} . Measurement of NE kinetics (clearance and spillover) is a more accurate and direct assessment of SNS activity . In the present study plasma {NE} and NE kinetics were measured in six patients with intra-abdominal sepsis (septic) using tritiated NE infused to achieve a plateau plasma concentration . The measurements were repeated in the same patients after they had recovered (nonseptic) . NE clearance and spillover were both significantly higher (P < 0.05) in the septic compared with the nonseptic state . However, there was no statistically significant difference in plasma {NE} between the two conditions . Plasma {NE} indicates no alteration in SNS activity during the septic state, whereas NE kinetics indicate increased activity of the SNS during sepsis . The results suggest that plasma {NE} is a poor indicator of SNS activity during septic illness.

Surgery, 1993 Aug, 114(2), 352 - 8; discussion 358-9
Pentoxifylline restores cardiac output and tissue perfusion after trauma-hemorrhage and decreases susceptibility to sepsis; Wang P et al.; BACKGROUND . Although pentoxifylline produces various beneficial effects in a preheparinized model of hemorrhagic shock, it was unknown whether this agent restores the depressed cardiac output (CO) and tissue perfusion in a nonheparinized model of trauma-hemorrhage and resuscitation and, if so, whether it decreases the susceptibility to sepsis after hemorrhage . METHODS . After laparotomy (i.e., induction of trauma), rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate . The animals were then resuscitated with Ringer's lactate, four times the volume of shed blood . Pentoxifylline (50 mg/kg body weight) or normal saline solution was infused intravenously more than 95 minutes during and after resuscitation . At 1.5 and 4 hours after resuscitation, CO, tissue perfusion, and plasma liver enzyme levels were determined . Sepsis was induced by cecal ligation and puncture at 20 hours after hemorrhage, and the necrotic cecum was excised 10 hours thereafter . RESULTS . CO and tissue perfusion in the liver, kidney, spleen, and small intestine decreased significantly after hemorrhage and resuscitation . Pentoxifylline treatment, however, restored the depressed CO and tissue perfusion . The elevated liver enzyme levels were also significantly reduced by pentoxifylline treatment . Moreover, pentoxifylline prevented the increased mortality of posthemorrhaged rats subjected to sepsis . CONCLUSIONS . Because pentoxifylline restored the depressed CO and tissue perfusion and decreased the susceptibility to sepsis, this agent appears to be a useful adjunct to crystalloid resuscitation after trauma and hemorrhage, even in the absence of blood resuscitation.

Crit Care Med, 1993 Aug, 21(8), 1192 - 9
Changes in myocardial blood flow rates during hyperdynamic sepsis with induced changes in arterial perfusing pressures and metabolic need; Raper RF et al.; OBJECTIVE: To determine whether hyperdynamic sepsis is associated with dysregulation in the control of myocardial blood flow rates unrelated to hypotension or the use of anesthetic agents . DESIGN: Prospective, nonrandomized, controlled trial . SETTING: Experimental laboratory . SUBJECTS: Fifteen mature male sheep (34 to 61 kg) . INTERVENTIONS: Data were recorded in study subjects before and after the induction of sepsis following cecal ligation and perforation . Data were then recorded during: a) an infusion of prostaglandin E1 (PGE1), which decreased mean arterial perfusing pressure; and b) an infusion of zymosan-activated plasma, which increased mean pulmonary arterial pressures . MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow rates were measured by the radiolabeled microsphere technique and cardiac index was measured by the thermodilution technique . Cardiac index (change delta) postcecal ligation and perforation minus baseline (+2.3 +/- 1.0 L/min/m2; p < .01) was increased in the septic study . Blood flow rate to the left ventricle was simultaneously increased, and was not further affected when the PGE1 infusion decreased the mean arterial perfusing pressures (-19 +/- 4%) . During the infusion of zymosan-activated plasma, mean pulmonary arterial pressures increased (50 +/- 30%) and right ventricular blood flow was increased (zymosan minus postcecal ligation and perforation study: delta 17.8 +/- 50 mL/100 g/min; p < .01) . CONCLUSIONS: In this model of hyperdynamic sepsis, increases in blood flow to both the left and right ventricles were positively coupled to changes in respective ventricular work . From the interventional PGE1 and zymosan-activated plasma infusion studies, we found no evidence to support previous suggestions that the regulation of myocardial blood flow rates according to changes in perfusing pressure and/or metabolic oxygen need is significantly altered during hyperdynamic sepsis.

Behring Inst Mitt, 1993 Aug, (92), 218 - 28
Endothelial and leukocyte activation in experimental polytrauma and sepsis; Redl H et al.; Vascular endothelial-PMN interactions are critical reactions in the development of organ failure . Both cell types are activated by LPS and proinflammatory cytokines in sepsis . Reactions that are collectively referred to as endothelial activation include expression of procoagulant activity and increased adhesiveness of the endothelium for leukocytes . Some parameters, which are related to endothelial activation are significantly changed during sepsis and altered by anti-TNF therapy (e.g . PAI-1, thrombomodulin), while others (e.g . sELAM) are increased by sepsis but not influenced by anti-TNF therapy . Leukocyte activation (accompanied by elastase release) leads to rearrangement of the CD11/CD18 structures and thereby increased adherence.

Surgery, 1993 Aug, 114(2), 243 - 50; discussion 250-1
Mechanisms of cytokine cascade activation in patients with sepsis: normal cytokine transcription despite reduced CD14 receptor expression; Ertel W et al.; BACKGROUND . Lipopolysaccharide causes activation of monocytes/macrophages with excessive secretion of cytokines resulting in hypotension and shock in patients with sepsis . Lipopolysaccharide may induce these responses by interacting with lipopolysaccharide-binding protein and then binding to the cell surface protein CD14 or by acting directly with CD11-CD18 on monocytes/macrophages . The role of CD14 and CD11-CD18 in the activation of macrophages with enhanced cytokine transcription in patients with septic shock remains to be determined . METHODS . To study this, heparinized blood was obtained from 16 patients with septic shock on days 0, 1, 3, 5, 7, and 10 and compared with 20 control patients . The expression of CD14 and CD11b on monocytes in whole blood was measured by direct immunofluorescence and flow cytometry . Moreover, whole blood was stimulated with lipopolysaccharide (1 microgram/ml) for 0, 1, 2, 4, 8, and 24 hours, and messenger RNA expression for tumor necrosis factor-alpha, interleukin-beta (IL-1 beta), and IL-6 was determined on isolated peripheral blood mononuclear cells with Northern blot analysis . RESULTS . Both CD14 expression and receptor density on monocytes from whole blood were markedly suppressed (-63% on day 3; p < 0.05) in the septic group compared with controls . Although CD11b expression was also decreased (-24% on day 1; p < 0.05), receptor density on monocytes was slightly increased in the septic group in comparison with the control group . Kinetics and intensity of messenger RNA expression for tumor necrosis factor-alpha, IL-1 beta, and IL-6 were similar in both groups . CONCLUSIONS . These data indicate that in patients with septic shock, lipopolysaccharide-mediated signaling and cytokine transcription are unchanged despite a significant reduction of CD14 expression and density on monocytes . Thus, lipopolysaccharide-induced activation of monocytes from patients with sepsis may occur through direct binding of lipopolysaccharide to the CD11-CD18 complex or other lipopolysaccharide receptors, whereas binding of the lipopolysaccharide-lipopolysaccharide-binding protein complex to the CD14 receptor may not play a pivotal role in sepsis.

South Med J, 1993 Jul, 86(7), 832 - 6
Myeloperoxidase deficiency and severe sepsis; Grossl NA et al.; We have described a 45-year-old obese white man found to have myeloperoxidase (MPO) deficiency of the granulocytic and monocytic series . Pancreatic necrosis due to bacterial infection developed as a complication of acute pancreatitis . Subsequently, he died of sepsis . MPO staining of terminal antemortem blood smears and postmortem bone marrow aspirates showed absence of MPO in cells of the myelocytic and monocytic series . Family members' neutrophils and monocytes stained positive for MPO . MPO deficiency associated with severe sepsis is rarely reported . This case serves as a review of the association between hereditary and acquired MPO deficiency and severe infection.

Cell Mol Biol (Noisy-le-grand), 1993 Jul, 39(5), 537 - 42
The effects of endotoxin administration on blood amino acid concentrations: similarities with sepsis; Garcia-Martinez C et al.; Following an acute endotoxin (LPS) administration (1 mg/kg body weight) to rats, there was a decrease in the blood concentration of most gluconeogenic amino acids, alanine, glycine, serine, threonine and proline . While the administration of the endotoxin induced no changes in the concentrations of aromatic amino acids, it decreased the concentration of both branched-chain amino acids (leucine, isoleucine and valine) and basic amino acids (lysine, arginine, histidine and ornithine) . On a global basis, the endotoxin significantly decreased the total blood amino acid concentration 2 hrs . after the administration, the effect lasting as long as 8 hrs . after endotoxin treatment . This decrease was mainly associated with a lower blood concentration of essential amino acids . Rats induced septic, by cecal ligature and puncture, showed a blood amino acid pattern most similar to those acutely treated with LPS.

J Trauma, 1993 Jul, 35(1), 128 - 31
Essential fatty acids influence survival in sepsis; Johnson JA 3rd et al.; Metabolites of arachidonic acid, formed from omega-6 essential fatty acids (n-6), play a pathologic role in mortality from sepsis . Metabolites of eicosapentaenoic acid, formed from omega-3 essential fatty acids (n-3), are less potent inflammatory mediators . Dietary restriction of n-6 fatty acids or supplementation with n-3 fatty acids in the form of fish oil have been shown to decrease the production of n-6 metabolites . Male Sprague-Dawley rats (350-400 g) were divided to receive either rat chow (CHOW) or essential-fatty-acid-deficient chow (EFAD) and subdivided to receive 1 mL daily of either fish oil (N3), linoleic acid (N6), or normal saline (NS), via gastric gavage . Two weeks later, half of the animals in each group underwent cecal ligation and puncture (CLP) to induce peritonitis or sham (SHAM) celiotomy . Survival was tabulated for 7 days . Survival was significantly decreased for animals undergoing CLP for both the N6 and NS groups but not for the N3 group . Omega-3 fatty acids as the sole essential fatty acids or as a supplement to a "routine" diet, when fed to rats for 2 weeks before a septic challenge, improved survival in this peritonitis model.

J Trauma, 1993 Jul, 35(1), 104 - 8; discussion 108-9
Pulmonary biophysical effects of triiodothyronine augmentation during sepsis-induced hypothyroidism; Dulchavsky SA et al.; Sepsis may cause pulmonary dysfunction and altered metabolism; triiodothyronine (T3) replacement improves lung function and surfactant pool . We evaluated the biophysical effects of T3 replacement during sepsis-induced hypothyroidism . Male Holtzman rats underwent cecal ligation and puncture (CLP) or sham laparotomy (S); treatment was administered consisting of T3 (3 ng/h) or saline . Twenty-four hours after CLP, lungs were ventilation-perfused with oxygenated N-2-hydroxylpiperazine-N1-2-ethanesulfonic acid (HEPES) with 5 microCi 3-H choline (3-HC) for 1 hour . Perfusion pressures were continuously monitored; perfusate was monitored for 3-HC uptake and oxygen extraction . Triiodothyronine treatment abolished the sepsis-induced decrease in free T3 levels (S = 68 +/- 5 ng/dL, CLP < 15 ng/dL, CLP/T3 = 91 +/- 20 ng/dL) . Lung wet-to-dry ratios and vascular and tracheal pressures were maintained by T3 treatment . Choline incorporation was not altered by sepsis or treatment . Triiodothyronine treatment reduced the sepsis-induced increase in oxygen requirement and improved septic pulmonary compromise through a nonhypermetabolic effect.

Chest, 1993 Jul, 104(1), 230 - 5
A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome; Hebert PC et al.; A simple multiple system organ failure (MSOF) score may predict mortality of patients who have sepsis syndrome . Using an MSOF scoring system, we prospectively determined the presence or absence of respiratory, cardiovascular, renal, hepatic, gastrointestinal, hematologic, and neurologic organ failure on day 1 of sepsis syndrome in 154 consecutive patients who had sepsis syndrome in the ICU of a tertiary care, teaching hospital . We used 30-day hospital mortality as the primary outcome variable . Overall 30-day mortality was 34 percent . There was a strong linear association between number of organ system failures and 30-day mortality (p < 0.0001) . Mortality was 20 percent in patients who had less than 3 organ system failures (n = 111) and 70 percent in patients who had 3 or more organ system failures (n = 43) . Survival was assessed using the Cox proportional hazards model and was found to be significantly different (p < 0.01) between the two groups defined by the aforementioned dichotomy after adjustment for age and sex using time to death as the primary outcome . The increase in relative risk of death associated with 3 or more organ system failures was 2.77 (95 percent confidence interval, 2.74 to 2.83) . Using logistic regression, the adjusted odds ratios (OR) for covariates most predictive of mortality were hematologic (OR = 6.2), neurologic (OR = 4.4), hepatic (OR = 3.4), cardiovascular (OR = 2.6), and age (1.05 per year) . The logistic model using the seven organ system failures and age as covariates accurately predicted outcome 75 percent of the time with a sensitivity of 51 percent and specificity of 87 percent . In conclusion, a simple scoring system tabulating the number of organ system failures present on day 1 of sepsis syndrome predicts the mortality of patients who have sepsis syndrome with reasonable accuracy.

Chest, 1993 Jul, 104(1), 225 - 9
Gastric intramucosal pH . A better predictor of multiorgan dysfunction syndrome and death than oxygen-derived variables in patients with sepsis; Marik PE; OBJECTIVE: To determine the value of tonometrically measured gastric intramucosal pH (pHi) and accepted indices of systemic oxygenation in predicting multiorgan dysfunction syndrome (MODS) and death in critically ill patients with sepsis . DESIGN: Prospective, noninterventional study . SETTING: Multidisciplinary ICU of a tertiary care, teaching hospital . PATIENTS: Thirty critically ill ventilated patients with pulmonary artery catheters and nasogastric tonometers in place . MEASUREMENTS AND MAIN RESULTS: The pHi, arterial lactate concentration, arterial and mixed venous pH, APACHE II score, and oxygen-derived variables, including oxygen delivery (Do2) and oxygen consumption (Vo2) were determined within 24 h of the onset of sepsis . The patients were then followed until death or discharge from the ICU . The development of organ system dysfunction during the ICU stay was recorded . Fifteen patients developed MODS of whom 12 died . An additional three patients died . The pHi and arterial and mixed venous pH were significantly lower in those patients who developed MODS and in those patients who died . The Vo2 and Do2, however, were higher in these patients . Using stepwise discriminant analysis, only the pHi contributed to the prediction of both MODS and death . CONCLUSIONS: In patients with sepsis, indices of tissue oxygenation are better predictors of outcome than the hemodynamic and oxygen-derived variables obtained by invasive hemodynamic monitoring . These indices should be used to direct therapy.

Crit Care Med, 1993 Jul, 21(7), 1012 - 9
Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock; Kreymann G et al.; OBJECTIVE: To test the hypothesis that variations in oxygen consumption (VO2) and resting metabolic rate reflect the severity of bacterial infections and reflect the development of sepsis syndrome and septic shock . DESIGN: Observational study with sequential measurements of VO2 and resting metabolic rate by expiratory gas analysis . SETTING: Medical intensive care unit . PATIENTS: Thirty patients, treated primarily for presumed bacterial infection, were examined on 118 treatment days . INTERVENTIONS: None . MEASUREMENTS AND MAIN RESULTS: VO2 and resting metabolic rate were measured by expiratory gas analysis . For mechanically ventilated patients, a measurement system was developed, based on a paramagnetic oxygen sensor, an infrared CO2 sensor, and digital signal averaging . Measurements in spontaneously breathing patients were performed with a metabolic monitor . Patients were assigned by clinical criteria to the following groups: sepsis, sepsis syndrome, and septic shock . The lowest VO2 value of each patient in each stage was evaluated . Mean VO2 in 15 patients with sepsis was 180 +/- 19 (SD) mL/min/m2, in 11 patients with sepsis syndrome 156 +/- 22 mL/min/m2, and in eight patients with septic shock 120 +/- 27 mL/min/m2 (p < .001) . Mean resting metabolic rate in sepsis was +55 +/- 14%, in sepsis syndrome +24 +/- 12%, and in septic shock +2 +/- 24% (p < .001) . Mean oxygen delivery (DO2) was 501 +/- 116 mL/min/m2 in sepsis, 515 +/- 186 mL/min/m2 in sepsis syndrome, and 404 +/- 96 mL/min/m2 in septic shock . Oxygen extraction (VO2/DO2) was highest in sepsis (0.39 vs . 0.33 in sepsis syndrome and 0.29 in septic shock) . During recovery from sepsis syndrome or septic shock, a significant increase in resting metabolic rate to +61 +/- 22% was measured in nine patients . CONCLUSIONS: In sepsis syndrome, VO2 and resting metabolic rate are enhanced by 30% compared with normal basal metabolism, but they are markedly reduced compared with uncomplicated sepsis . The higher VO2 in uncomplicated sepsis is flow independent . The noninvasive measurement of VO2 and resting metabolic rate by expiratory gas analysis therefore can be used as a quantitative staging and monitoring parameter for the development of sepsis syndrome and septic shock.

Am Rev Respir Dis, 1993 Jul, 148(1), 164 - 72
Differential impairment of vascular reactivity of small pulmonary and systemic arteries in hyperdynamic sepsis; Martin CM et al.; We postulated that the redistribution of organ blood flow that occurs in hyperdynamic sepsis is secondary to organ-specific alterations in vascular reactivity . Chronically instrumented rats were randomized to cecal ligation and perforation (CLP) (n = 12) or to a control procedure (n = 11) . Cardiac output increased from 107 +/- 23 ml/min at baseline to 152 +/- 32 ml/min at 24 h after CLP (p = 0.037 versus control values) . Mean blood pressure did not change in either group . Small arterial ring segment (100- to 200-microns effective lumen radius) from the pulmonary, renal, celiac, and femora arteries were obtained for determination of in vitro responsiveness . Maximal contractile responses to three receptor-operated contractile agonists were significantly depressed in the pulmonary (p = 0.001) and the celiac (p = 0.001) arteries from CLP versus control rats . The renal artery showed a trend toward decreased responsiveness (p = 0.049), but not difference was seen in the femoral artery (p = 0.172) . EC50 values were unchanged . A similar, but less marked, pattern was observed for KCI-induced contractions in that depressed responses were noted in the pulmonary (p = 0.045) and celiac (p = 0.064) arteries . Vasodilator responses to acetylcholine were normal in all vessels . Nitroprusside relaxant responses were enhanced in the pulmonary artery (p = 0.022), but they were normal in the other vessels . We conclude that hyperdynamic, normotensive sepsis is associated with an organ-specific alteration of vascular smooth muscle function that particularly affects receptor-operated contractile responses . The differential expression of this altered vascular responsiveness between organs may contribute to the observed variance in regional blood flows in sepsis.

Arq Bras Cardiol, 1993 Jul, 61(1), 49 - 52
{Refractory heart failure and sepsis in a patient with hypertrophic cardiomyopathy}; Pinotti AF et al.; A twenty one years old man with obstructive hypertrophic cardiomyopathy with resting gradient and which develops subacute infectious endocarditis and acute mitral regurgitation by valvular apparatus destruction . During the course occurs refractory heart failure and sepsis . The association between these diseases and difficulties in management are analyzed, and literature is reviewed . It is emphasized the high mortality of this condition and indication for surgical referral, as well the necessity for infectious endocarditis prophylaxis in patients with obstruction at rest.

Indian J Pediatr, 1993 Jul-Aug, 60(4), 559 - 63
Evaluation of sepsis screen for diagnosis of neonatal septicemia; Sharma A et al.; Fifty clinically suspected cases of neonatal septicemia were studied for evaluating the role of sepsis screen . Sensitivity and specificity of C-reactive protein test, micro-ESR, gastric aspirate cytology for polymorphs and toxic granules in neutrophils were studied singly and in combinations of two and three tests . Positive blood culture was obtained in only 20% cases, thereby underlying the need for a sepsis screen in the diagnosis of neonatal septicemia, especially in areas where adequate micro-biological facilities are lacking.

JAMA, 1993 Jun 16, 269(23), 3024 - 9
Effect of stored-blood transfusion on oxygen delivery in patients with sepsis; Marik PE et al.; BACKGROUND--Red blood cell transfusion is commonly used to augment systemic oxygen delivery to supranormal levels in patients with sepsis . However, clinical studies have not consistently demonstrated that this therapeutic maneuver is accompanied by an increase in oxygen utilization at either the whole-body level or within individual organs . STUDY OBJECTIVES--To determine the effect of red blood cell transfusion on gastrointestinal and whole-body oxygen uptake . DESIGN--Prospective, controlled, interventional study . SETTING--Multidisciplinary intensive care unit of a tertiary care teaching hospital . PATIENTS--Twenty-three critically ill patients with sepsis undergoing mechanical ventilation . MEASUREMENTS AND MAIN RESULTS--Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method . Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability . Measurements were made prior to transfusion of 3 U of packed red blood cells . These were then repeated immediately following transfusion, as well as 3 and 6 hours later . There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours posttransfusion (including those patients with an elevated arterial lactate concentration) . However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients . More importantly, we found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r = -.71; P < .001) . In those patients receiving blood that had been stored for more than 15 days, the gastric intramucosal pH consistently decreased following the red blood cell transfusion . CONCLUSION--We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis . Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia . We postulate that the poorly deformable transfused red blood cells cause micro-circulatory occlusion in some organs, which may lead to tissue ischemia in some organs.

Bol Med Hosp Infant Mex, 1993 Jun, 50(6), 406 - 9
{Acute gastric distension due to sepsis in a newborn infant}; Cisneros-Garcia N et al.; The acute distention of stomach in the newborn is conditional by metabolic alterations like hypocalcemia or by septic states . We present the case of a newborn with antecedents of membrane rupture for 12 hours obtained by cesarean procedure, of 38 weeks by Capurro, score without perinatal asphyxia and 3320 g of birth weight, which evolutioned with respiratory distress and its first exams showed leukopenia, low platelet count and the cerebrospinal fluid showed 390 cells with polymorphonuclear predominium considering the diagnosis of neonatal sepsis and meningitis . At the second day he presented abdominal distention secondary to gastric camera dilatation, were made a laparotomy to descart congenital obstruction and only found gastric distention . In all newborn with acute gastric distention its important for first instance descart congenital intestinal obstruction and is on sidered this entity by exclusion . We recommend in this patients sepsis worshop . The treatment is drainage by orogastric tube and antibiotics . The prognosis is good once upon treating the basic problem.

Circ Shock, 1993 Jun, 40(2), 92 - 8
Alterations in circulating blood volume during polymicrobial sepsis; Wang P et al.; Although a great deal is known concerning the pathophysiology of sepsis, it is not clear whether circulating blood volume (CBV) is altered under such conditions . To study, this, rats were subjected to sepsis by cecal ligation and puncture (CLP) . Immediately after CLP or sham operation, the animals received 3 ml/100 g body weight normal saline subcutaneously . CBV was determined by using in vivo indocyanine green (ICG) clearance at 2, 5, 10, or 20 hr after CLP or sham operation . This technique does not require any blood sampling . Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT) were assayed enzymatically as indicators of hepatocyte damage . Hepatic microcirculation was assessed at a selected time point (10 hr post-CLP) by using laser Doppler flowmetry and colloidal carbon infusion techniques . The results indicate that CBV, as determined by ICG clearance, remained unchanged up to 10 hr following the onset of sepsis (i.e., early sepsis) but decreased significantly at 20 hr after CLP (late sepsis) . However, systemic hematocrit increased significantly at 5, 10, and 20 hr after CLP, indicating that plasma volume decreased at those time points . This suggests that there may be limitations in accurately assessing CBV at 5 and 10 hr after CLP, i.e., during the hyperdynamic circulatory state of sepsis, using the ICG clearance method . Moreover, SGPT and SGOT levels increased significantly at 10 hr, and the levels increased further at 20 hr post-CLP . In contrast, microvascular blood flow and carbon-perfused areas in the liver were significantly increased at 10 hr post-CLP.

Circ Shock, 1993 Jun, 40(2), 144 - 50
Role of angiotensin II in neonatal sepsis; Dunn CW et al.; Previous studies in adult animals have indicated that plasma angiotensin converting enzyme (ACE) activity is inhibited by endotoxin . Reduced ACE activity may decrease plasma angiotensin II (AII) levels, contributing to the refractory hypotension we have previously reported in neonatal septic shock . In this study, hemodynamic function, plasma renin activity (PRA), AII, prostacyclin (PGI2), and thromboxane B2 (TxB2) levels were measured in 17-20-day-old dogs before and 1, 2, and 3 hr after endotoxin administration (1 mg/kg, Escherichia coli lipopolysaccharide-B) . PRA and AII levels rose significantly 60 min post-endotoxin, returning to baseline values by 180 min; PGI2 and thromboxane B2 levels rose post-endotoxin and remained elevated . Indomethacin or captopril was given by oral gavage 30-35 min before endotoxin . Captopril significantly blunted the rise in PRA and AII, while indomethacin blocked the rise in PGI2 and TxB2 . Mean arterial blood pressure and cardiac output fell 60 min after endotoxin challenge without pharmacologic intervention and remained depressed . Our data suggest that renin and AII responses to endotoxin challenge remain intact in the neonatal subject . Maintenance of hemodynamics in indomethacin-pretreated dogs may be due to unopposed stimulation of the peripheral vasculature by AII . Thromboxane B2 in maintenance of vasomotor tone may be minimal in the young.

J Pediatr, 1993 Jun, 122(6), 955 - 8
Toxic reaction to salicylate in a newborn infant: similarities to neonatal sepsis; Buck ML et al.; A newborn infant had metabolic acidosis, tachypnea, and hypoglycemia . After the initial diagnosis of neonatal sepsis, she was given antibiotics but failed to respond . Further investigation revealed that her mother had taken aspirin throughout pregnancy . This case illustrates the similarities between symptoms of neonatal sepsis and those of a toxic reaction to salicylate.

J Surg Res, 1993 Jun, 54(6), 565 - 70
Lymphokine activated killer cells enhance IL-2 prevention of sepsis-related death in a murine model of thermal injury; Mendez MV et al.; It has previously been shown by this laboratory that immunomodulation of thermally injured animals with low-dose interleukin-1 (IL-2) and indomethacin (Indo) improves survival following septic challenge . Lymphokine-activated killer (LAK) cells have been shown to be effective in certain viral infections and to act in synergy with IL-2 in the treatment of certain types of cancer . We have studied the effect of LAK cells in combination with IL-2 and Indo in a murine model of thermal injury and sepsis . Male A/J mice received a 25% scald burn injury or sham burn and were randomized into five groups: (a) sham/vehicle, (b) burn/vehicle, (c) burn/IL-2 (250 U) + Indo (5 micrograms), (d) burn/LAK cells (2 x 10(6) cells), or (e) burn/LAK cells+IL-2+Indo and were treated accordingly for 6 days following injury . LAK cells were generated by in vitro IL-2 treatment of syngeneic spleen cells for 72 hr and cytotoxic activity was confirmed by standard 51Cr release assay using natural killer (NK)-sensitive and NK-resistant targets . In the groups receiving LAK cells they were administered on Day 1 and Day 6 postinjury . On Day 10, septic challenge by cecal ligation and puncture (CLP) or splenectomy, for in vitro studies, was performed . Five-day survival after CLP was 80% in the sham/vehicle group compared to 0% in the burn/vehicle group (P < 0.01) . IL-2/Indo and LAK/IL-2/Indo improved survival to 25% (P < 0.05) and 57.1% (P < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

J Surg Res, 1993 Jun, 54(6), 558 - 64
Intracellular glutamine concentration does not decrease in all muscles during sepsis; James JH et al.; The concentrations of glutamine and other amino acids were measured in plasma and intracellular fluid of soleus and extensor digitorum longus (EDL) muscles of rats 4, 8, and 16 hr after induction of sepsis by cecal ligation and puncture or after sham operation . Previous studies have shown that muscle protein breakdown is greatly increased in EDL, but not in soleus muscle, in this sepsis model . Corresponding to previous observations of protein breakdown in sepsis, muscle glutamine was markedly depleted (< 50%) in EDL by sepsis, while no significant fall in glutamine concentration in soleus was observed . Changes in muscle glutamine concentration in sepsis could not be attributed to changes in the precursor of glutamine, glutamic acid . Data were examined for changes consistent with hypothesized alterations in glutamine transport . Correlations among glutamine and other amino acids in muscle, histidine in particular, were consistent with a sepsis-induced alteration in activity of the sarcolemmal glutamine transporter, system Nm . These results thus strengthen the proposed connection between muscle glutamine content and muscle protein metabolism under catabolic conditions.

Crit Care Nurs Clin North Am, 1993 Jun, 5(2), 345 - 54
Antiendotoxin therapy in sepsis; Colletti RC et al.; Septic shock is the leading cause of death in critical care units . New research in the management of septic shock is focused on the use of immune-based therapy such as antiendotoxin monoclonal antibodies . The object of this therapy is to neutralize endotoxin and prevent the progression of the pathophysiologic events of sepsis . To date, the promise of this therapy has not been realized, but hopefully, ongoing research will provide optimism for treatment of this syndrome . Two agents, E5 and HA-1A, are discussed.

Br J Surg, 1993 Jun, 80(6), 772 - 3
Gunshot wounds of the colon: role of retained bullets in sepsis; Demetriades D et al.; The role in the development of local sepsis of retained bullets that have passed through the colon was investigated . Of 84 patients with gunshot wounds of the colon, the bullet was retained in the body in 40 and had left or was removed from the body in 44 . The groups were similar with regard to Revised Trauma Score, Injury Severity Score, Penetrating Abdominal Trauma Index and type of colonic trauma . The incidence of major local complications was 5 per cent in patients with a retained bullet and 7 per cent in those without . These results suggest that retained bullets that have penetrated the colon do not contribute to local septic complications.

Singapore Med J, 1993 Jun, 34(3), 245 - 6
Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit; Lee KH et al.; Disseminated intravascular coagulation (DIC) and thrombocytopenia are well-known complications of sepsis, but the relationship between these coagulation abnormalities and outcome have not been well documented . We studied the incidence of thrombocytopenia and DIC in our Medical Intensive Care Unit, and evaluated their usefulness as prognostic risk factors for mortality . Platelet count was not found to be an independent risk factor associated with overall mortality in the 107 patients studied . In the sub-group of 53 patients with sepsis, 22 (42%) developed DIC, 31 (58%) developed thrombocytopenia (< 150,000 x 10(9)/L) and 27 (51%) died . Thrombocytopenia was associated with presence of DIC (p = 0.003), but not with the type of infecting organism . The platelet count in non-survivors (mean +/- sem, 97 +/- 18 x 10(9)/L) was significantly lower than survivors (194 +/- 27 x 10(9)/L, p < 0.005) . Multiple regression analysis showed that thrombocytopenia was a risk factor for mortality, independent of the APACHE II score . The presence of DIC surprisingly was not an independent risk factor . We conclude that DIC and thrombocytopenia are common in our adult Medical Intensive Care patients with sepsis, but only the latter is a prognostic factor in addition to the APACHE II score . The incidence of DIC in our patients (mainly Chinese) seems to be more than that of 10 to 20% reported in other series of Caucasian patients . We would, therefore, like to emphasise the importance of platelet count as an prognostic risk factor in sepsis.

Chin Med J (Engl), 1993 Jun, 106(6), 458 - 62
Organ-association phenomena during sepsis . TNF and IL-6 in different macrophages; Meng XJ et al.; Sepsis was induced in rats by cecal ligation and perforation (CLP) . Five and 15 hours post CLP, alveolar macrophage (AM), Kupffer cell (KC), and peritoneal macrophage (PM) were isolated and cultured for 18 hours . Culture supernatant was examined for bioactivity of tumor necrosis factor (TNF) and interleukin 6 (IL-6) and response to lipoplysaccharide (LPS) stimulation in vitro . Results showed that AM produced more TNF during sepsis as compared with KC and PM . Stimulation with LPS in vitro was responded only by AM at 15 hr after CLP . Pattern of IL-6 production was different from TNF while KC produced the highest level of IL-6 after induction of sepsis.

Hepatology, 1993 Jun, 17(6), 1086 - 94
Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis; Doi F et al.; We investigated the pathogenesis of septic liver injury in rats caused by cecal ligation and puncture . In this model, numerous neutrophils accumulated in the liver in parallel with the development of liver dysfunction . The supernatants of hepatic macrophages isolated from these septic rats 24 hr after cecal ligation and puncture had enhanced chemotactic activities for human neutrophils . These results suggest that in sepsis, hepatic macrophages attract neutrophils to the liver . Human neutrophils preincubated in this macrophage supernatant had the following biological activities not seen in the sham-operated controls . (a) They became more adherent to cultured endothelial cells through up-regulation of adhesion molecules such as CD11b/CD18, (b) their chemiluminescence was markedly elevated . These functional changes of cecal ligation and puncture hepatic macrophages were the same as those in endotoxin-pretreated hepatic macrophages after isolation from normal rats . Therefore we suspect that hepatic macrophages are activated by portal vein endotoxin in sepsis . These activated hepatic macrophages secreted chemical mediators of inflammation, including leukotriene B4 and tumor necrosis factor . In conclusion, hepatic macrophages seem to interact closely with neutrophils and play an important role in the pathogenesis of septic liver injury.

JPEN J Parenter Enteral Nutr, 1993 May-Jun, 17(3), 277 - 83
Intestinal amino acid absorption during sepsis; Gardiner K et al.; Sepsis has been shown to cause a decrease in mesenteric blood flow in association with ultrastructural changes in the small intestine and impaired immune, barrier, and metabolic functions of the gut . These impairments in the structure and function of the gastrointestinal tract may have a detrimental effect on the morbidity and mortality of sepsis . Two recent studies have shown that the ability of the small intestine to absorb amino acids is also impaired during sepsis, but the systemic and cellular mechanisms of this impairment are not known . Release of cytokines induced by systemic bacteria or endotoxin may lead to a reduction in the synthesis of transporter proteins by the enterocyte at a time when there is reduced availability of both luminal (because of anorexia) and circulating (because of reduced mesenteric blood flow) substrates . Future research needs to investigate the systemic and local mediation of the sepsis-induced reduction in intestinal amino acid absorption and the possibility of correcting the defect by the administration of enteral nutrients, hormones, or drugs.

Am J Physiol, 1993 May, 264(5 Pt 2), H1402 - 10
Effects of E . coli sepsis and myocardial depressant factor on interval-force relations in dog ventricle; Jha P et al.; We examined whether depressed left ventricular (LV) contractility during Escherichia coli sepsis in dogs was due to a decrease in the fractional release of calcium from the sarcoplasmic reticulum (SR) or a reduction in calcium content in this organelle . To indirectly assess SR calcium availability in a right ventricular (RV) trabecular muscle preparation, we utilized functional indexes of cellular myocardial calcium metabolism, which included rapid-cooling contracture (RCC), an indicator of SR calcium content, and postrest contraction (PRC), an index of calcium availability from the release compartment of the SR . Measurements were made during steady-state stimulation at 0.5 and 1.5 Hz, during which time rest intervals of 30-240 s were periodically imposed . SR calcium availability was measured in RV trabeculae of dogs subjected to 4 h of E . coli sepsis and was compared with calcium availability measured in nonseptic dogs . We further characterized a filterable cardiodepressant substance (FCS), which has been previously shown to be associated with LV depression in this model, to determine whether it produced changes in calcium metabolism similar to those found in sepsis . The results showed that calcium availability from the SR of septic dogs was not impaired . Furthermore, FCS was found in the 10,000- to 30,000-mol wt fraction of plasma and produced changes in PRC in canine trabeculae that were similar to those produced during sepsis . We conclude that, as assessed by PRC and RCC, SR calcium content and release are not impaired in sepsis.

J Trauma, 1993 May, 34(5), 676 - 82; discussion 682-3
Mechanisms of endotoxin-induced intestinal injury in a hyperdynamic model of sepsis; Xu D et al.; The goal of this study was to test the hypothesis that endotoxin-induced bacterial translocation is the result of a selective decrease in intestinal blood flow that causes an oxidant-mediated intestinal mucosal injury . To accomplish this goal, 116 instrumented rats receiving a nonlethal dose of endotoxin (5 mg/kg IP) or saline were studied . Organ blood flow and cardiac output were measured using the microsphere technique and intestinal permeability was measured both by the blood to luminal clearance of 51Cr-EDTA and by horseradish peroxidase . Cardiac output was higher in the endotoxin-treated group than in the saline group (76 +/- 12 versus 95 +/- 17 mL/min; p < 0.05) . Although endotoxin induced a hyperdynamic state, blood flow to the distal ileum and cecum was selectively decreased by 35%-50% (p < 0.01), whereas blood flow to the rest of the intestine, spleen, pancreas, and liver was normal . Furthermore, blood flow to the ileal mucosa was decreased to a greater extent than to the remainder of the gut wall (p < 0.05) . Small bowel permeability to 51Cr-EDTA was increased at sites of decreased blood flow (ileum) but not at sites of normal (jejunum) blood flow . Allopurinol, a competitive inhibitor of xanthine oxidase, ameliorated the endotoxin-induced decrease in ileal blood flow as well as the increase in ileal permeability . Thus these studies support the hypothesis that endotoxin-induced mucosal injury is the result of an ischemia reperfusion-mediated injury of the distal small intestine and cecum.

Chest, 1993 May, 103(5), 1628 - 9
Adult respiratory distress syndrome as a complication of postanginal sepsis; Cosgrove EF et al.; Adult respiratory distress syndrome (ARDS) was described in 1971 by Petty and Ashbaugh . Since that time it has been reported in association with many disease entities . We report a case in which a patient with postanginal sepsis, also known as Lemierre's syndrome, had development of ARDS.

Chest, 1993 May, 103(5), 1536 - 42
Time course of hemostatic abnormalities in sepsis and its relation to outcome; Lorente JA et al.; OBJECTIVES: To investigate the time course and the relation to prognosis of coagulation and fibrinolytic abnormalities in patients with septic shock . PATIENTS AND METHODS: Forty-eight consecutive patients admitted to the medical ICU with the diagnosis of septic shock (diagnosed by defined criteria) were studied . Mortality was 25 of 48 . Mean age was 57 +/- 7.3 years . Blood samples were obtained on days 1, 4, and 7 after hospital admission to measure tissue-type plasminogen activator antigen (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor antigen (PAI-1), plasminogen, alpha 2-antiplasmin, fibrinogen, antithrombin III, protein C, protein S, thrombin-antithrombin complexes (TAT), D-dimer, and von Willebrand factor-related antigen (vWF:Ag) . RESULTS: All patients showed marked abnormalities in both the coagulation and fibrinolytic systems . There were signs of coagulation activation and elevation of both activators and inhibitors of fibrinolysis . Nonsurvivors showed lower levels of protein C and antithrombin III and higher concentration of TAT than survivors . While both t-PA and PAI-1 concentrations were high in survivors and nonsurvivors, only survivors showed a progressive normalization of both parameters during the study period . Low plasminogen levels and plasminogen/alpha 2-antiplasmin ratio were found in both groups, presenting a trend toward normalization only in survivors . The differences reported were not apparent at the time of hospital admission . CONCLUSIONS: Septic shock is characterized by coagulation activation and fibrinolysis activation and inhibition . Nonsurvivors present a particular hemostatic profile characterized by a more marked activation of coagulation and a more intense inhibition of fibrinolysis . None of the abnormalities studied was significantly different between survivors and nonsurvivors at the time of hospital admission . In the presence of fibrin formation, nonsurvivors present a maintained imbalance in the fibrinolytic response determined by higher PAI-1 plasma concentration, probably contributing to their poor outcome.

Proc Natl Acad Sci U S A, 1993 May 1, 90(9), 3933 - 7
Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis?
Song SK, Karl IE, Ackerman JJ, Hotchkiss RS.
Severe bloodstream-borne infection--i.e., sepsis--and the resulting multiorgan failure are now the most common cause of death in many intensive care units . One of the most fundamentally important and controversial issues concerning the pathophysiology of sepsis is the role of intracellular free calcium concentration ({Ca2+}i) in this disorder . Because of the critical role of calcium as an intracellular second messenger and as a potential cellular toxin, resolution of this issue is crucial . Using 19F NMR spectroscopy and the calcium indicator 5,5'-difluoro-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate we demonstrate in the intact perfused organ, the rat thoracic aorta, that {Ca2+}i in aortic smooth muscle is increased > 2-fold during sepsis . Furthermore, we determined that sodium dantrolene, a drug that decreases release of calcium from the sarcoplasmic reticulum and that is lifesaving in malignant hyperthermia (a disorder due to increased {Ca2+}i), is able to reduce the elevated {Ca2+}i in sepsis to control values when added in vitro or when given in vivo to the animal . These results suggest that an increase in {Ca2+}i is an early event in sepsis and that increased {Ca2+}i may be responsible for, or contribute to, cellular injury . Dantrolene may offer a therapeutic strategy in the treatment of sepsis.

Pediatr Infect Dis J, 1993 May, 12(5), 372 - 6
Hematologic scoring system in early diagnosis of sepsis in neutropenic newborns; Rodwell RL et al.; The hematologic profiles of 1000 newborns were prospectively examined to identify infants with neutropenia (N = 170) according to the system of Manroe et al . (J Pediatr 1979;95:89-98) and to evaluate a hematologic scoring system (Rodwell et al . J Pediatr 1988;112:761-7) as a screening test for sepsis . Neutropenia was more commonly of noninfectious than infectious origin (83.5% vs . 16.5%; P < 0.001) . On the initial test a positive screen (scores > or = 3) identified 26 of 28 infants with sepsis or probable infection (sensitivity 93%; specificity 82%; positive and negative predictive values 50 and 98%, respectively) . Corresponding values for an elevated immature:total neutrophil ratio were 100, 75, 43 and 100% . Overall mortality with neutropenia was 15% and was higher with an infectious than a noninfectious etiology (39% vs . 11%, P < 0.001) despite early antibiotic therapy . The combination of a neutrophil count < or = 500/mm3 and scores > or = 3 or an elevated immature:total neutrophil ratio identified a poor prognostic group: 67% (8 of 12) and 70% (7 of 10) infants, respectively, with these findings died, 6 in the infected group . The hematologic scoring system or immature:total neutrophil ratio in combination with the degree of neutropenia provides valuable diagnostic and prognostic information which could be applied to identification of possible candidates for granulocyte transfusions or other experimental treatments.

Orthop Rev, 1993 May, 22(5), 597 - 9
Hip sepsis from retroperitoneal rupture of diverticular disease; Messieh M et al.; Retroperitoneal perforation of diverticular disease is very uncommon and can be difficult to diagnose because of possible pathways of communication between the retroperitoneal space and the thigh . An iliopsoas abscess from a ruptured diverticulum may drain into the hip joint if the capsule has been violated . Cases of abscesses or gas in the thigh have been reported in which thigh pain was the predominant symptom, overshadowing any abdominal signs . We report a case in which hip sepsis due to a ruptured diverticulum was the presenting feature.

Haemostasis, 1993 May-Jun, 23(3), 142 - 8
Coagulation, fibrinolytic and kallikrein systems in neonates with uncomplicated sepsis and septic shock; Roman J et al.; This study evaluates the contact system, coagulation inhibitors and fibrinolysis in 23 full-term newborns with sepsis (8 with septic shock) . The results were compared with a group of 20 healthy newborns . Blood samples were obtained at the time of clinical diagnosis and 3 days after the antibiotic therapy was started . The results showed that: severe infection was associated with activation of the contact system, depletion of anticoagulant proteins and elevation of C4b-binding protein levels . There was a shift in protein S to the complexed inactive form, and the thrombin-antithrombin complexes increased . These changes occurred in parallel to both activation and inhibition of fibrinolysis . These changes were more pronounced in the septic shock patients than in nonshock neonates . After therapy, this procoagulant state decreased among survivor patients while in those who died, the abnormalities in coagulation did not improve . Our study suggests that neonatal sepsis induces a hypercoagulable state that persists in nonsurvivor neonates despite a correct treatment.

Rev Med Chil, 1993 May, 121(5), 537 - 41
{Changes in coagulation in patients with sepsis}; Alarcon G et al.; Aiming to know the coagulation disorders that occur in patients with sepsis, a retrospective study of 75 such patients hospitalized in an Intensive Care Unit was performed . The coagulation profile requested by the attending physician, that included platelet count, prothrombin time, partial thromboplastin time, thrombin time, protamine sulphate test, fibrinogen and euglobin lysis time, was analyzed . Fourteen patients that were receiving prophylactic subcutaneous heparin were excluded from further analysis . Of the 61 remaining patients, 23 had hemorrhagic manifestations and 94.4% of these had multiple alterations in coagulation parameters . Eighty one percent of patients had abnormal prothrombin time and 73% thrombocytopenia . Isolated alterations were infrequent and consisted in thrombocytopenia (3.7%) and fibrinogen elevation (1.9%) . Fifty two percent of patients had shock and they had significantly lower platelet counts and higher prothrombin and thrombin times than patients without hemodynamic disturbances . Global mortality was 63.9% . No relation between coagulation disturbances and mortality was observed . Likewise, no differences in mortality between patients with or without shock was observed . It is concluded that coagulation is frequently disturbed in patients with sepsis, even without clinical hemorrhagic symptoms, that these abnormalities are more marked in patients in shock and that 53% of these are consistent with intravascular coagulation.

Biull Eksp Biol Med, 1993 May, 115(5), 499 - 502
{Plasma erythropoietic activity in children with sepsis}; Soboleva MK et al.; The low plasma erythropoietic (Epo) activity which is non-adequate to manifestation of anemia, and the lack of correlation between Epo activity and the degree of anemia and hypoxia were found in children with sepsis . The lowest Epo activity was determined in plasma of patients after repeatedly blood transfusion and in emaciated children . The non-specific Epo activity inhibitor was determined in acute period of sepsis in majority of patients . We suppose that the low Epo activity was due to the violation of Epo synthesis regulation mechanism or was connected with the presence of non-specific inhibitors . These results suggest recombinant Epo for the treatment of anemia in children with sepsis.

New Horiz, 1993 May, 1(2), 353 - 9
Splanchnic resuscitation: a strategy for preventing liver failure in sepsis; Anderson GL et al.; Liver failure is commonly encountered in the critically ill, septic patient . This hepatic dysfunction occurs as a wide spectrum of abnormalities, ranging from mild chemical derangements to fulminant liver failure . The syndrome of multiple system organ system failure due to sepsis is often complicated by alterations in splanchnic/hepatic function . Knowledge of gut pathophysiology with resultant changes in substrate metabolism, synthetic function, cytokine release, and the detrimental effects on other organ systems is rapidly expanding . The functions of these pathophysiologically produced factors include extensive autocrine, paracrine, and endocrine effects . Evidence suggests that adequate resuscitation during sepsis, which is measured by systemic end-points, may result in inadequate splanchnic blood flow and oxygen delivery . The addition of serial measurements of splanchnic end-points may limit the hepatic failure encountered in multiple system organ failure due to sepsis.

New Horiz, 1993 May, 1(2), 348 - 52
Nutrition during critical illness and sepsis; Bower RH; The requirements for nutrient substrates are altered in patients with infection and critical illness . Parenteral and enteral nutritional support are indicated in septic patients to preserve lean body mass and support metabolic processes while appropriate anti-infective therapy is administered . In general, such patients require greater amounts of protein and fewer calories than normal patients . Enteral nutrition in septic patients has been demonstrated to be safe and well tolerated if begun immediately after the onset of infection or after injury . The salutary effect of enteral nutrition on the gastrointestinal tract has been shown to enable severely injured patients to have a lower frequency of infectious complications than similar patients fed parenterally . A new enteral formula fortified with arginine, nucleotides, and fish oil has been demonstrated to reduce hospital stay and to reduce complications in patients who are fed for > or = 7 days when compared with conventional formula . The increased use of early enteral nutrition and special nutrient formulas has the potential to reduce hospital length of stay, complications, and the cost of care if used appropriately.

New Horiz, 1993 May, 1(2), 342 - 7
Adult respiratory distress syndrome and sepsis; Goldsberry DT et al.; In the 25 yrs since the original description of adult respiratory distress syndrome, much has been learned concerning the pathology and pathophysiology of the syndrome . Investigations into the humoral mediator of the syndrome are proceeding . Despite these advances and the advances in intensive care medicine, adult respiratory distress syndrome remains a considerable clinical challenge, especially when associated with sepsis.

New Horiz, 1993 May, 1(2), 324 - 41
Cardiovascular abnormalities in sepsis; Porembka DT; The cardiovascular response in sepsis is the result of subcellular dysfunction and impaired metabolism from the complex interaction of cytokine and mediator with cellular involvement . The typical cardiovascular abnormalities seen are tachycardia, hypotension (relative decrease in preload), increased cardiac index, decrease in left ventricular stroke work index, decrease in ejection fraction (which is load dependent), and an apparent decrease in contractility . After augmentation of preload, the ventricles dilate in a response similar to the Frank-Starling mechanism . By challenging these patients with the augmentation of preload and contractility to increase oxygen delivery would theoretically minimize microcirculatory dysfunction and lactic acid production . Survivors have an amplification of this biventricular response . This response would temporarily normalize within a week, while the nonsurvivors would still have increased hemodynamics (tachycardia) without the ventricular dilation as a compensatory response . Even though the survivor response is not predictable, therapeutic end-points have been proposed as a guide to therapy in these critically ill patients . Conflicting results have been reported regarding contractility and ventricular compliance measurements in septic models . The development of pressure-volume loops would be the ideal technique for the evaluation of ventricular diastolic compliance, true preload, and contractility (from the end-systolic pressure relationship, which is load independent) in sepsis . More research has to be done with this type of evaluation to further understand the dynamic cardiovascular response in sepsis . This question still persists . Why can't some patients be hemodynamically challenged to increase right and left ventricular end-diastolic volumes and oxygen delivery?

New Horiz, 1993 May, 1(2), 231 - 45
Percutaneous abscess drainage in the management of sepsis; Moulton JS et al.; Image-guided percutaneous drainage has become the procedure of choice for a wide variety of abscesses and other fluid collections, and is an invaluable therapeutic alternative for the management of septic patients . Growing experience, along with technical advances, has significantly broadened the potential applications of percutaneous abscess drainage . Important considerations include the use of modern imaging techniques to identify and characterize sources of sepsis, appropriate patient selection and definition of therapeutic goals, and dedicated involvement by the interventional radiology team . The current methods and applications of percutaneous abscess drainage are reviewed, both in general, and in terms of specific anatomic locations and disease processes.

New Horiz, 1993 May, 1(2), 214 - 30
Overview of diagnostic imaging in sepsis; Braley SE et al.; This article discusses available imaging modalities with an emphasis on patient preparation and techniques to optimize image quality . Appropriate imaging of localized sepsis is then discussed, with a description of imaging features of common causes of sepsis . Finally, an imaging approach is discussed in the septic patient without localizing features.

Am J Pathol, 1993 May, 142(5), 1458 - 70
Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis; Drake TA et al.; Disseminated intravascular thrombosis is a frequent complication of endotoxic shock, and modulation of endothelial cell hemostatic properties has been proposed to play a role in its pathogenesis based on studies of endothelial cells in culture . This study examined the in vivo expression of tissue factor (TF) and thrombomodulin (TM) in a baboon model of lethal Escherichia coli sepsis using immunohistochemistry with monospecific antibodies . Expression of E-selectin (E-sel) was also determined as a marker of endothelial cell activation . Correlation of immunoreactivity with procoagulant activity in lipopolysaccharide-stimulated cultured human endothelial cells showed that immunohistochemistry was sufficiently sensitive to detect as little as 5% of the maximum in vitro endothelial cell TF response . Vascular endothelium of control animals expressed TM but had no detectable TF or E-sel . Following E . coli infusion, widespread E-sel expression and microvascular fibrin deposition was evident within 6 hours . However, expression of TF by endothelial cells became detectable only in the splenic microvasculature, where endothelial specificity of TF expression was confirmed by dual immunofluorescence of TF with von Willebrand's factor and with TM . In the spleen, there was a dissociation of expression of TF and E-sel, with marginal zone vessels being TF-positive and E-sel-negative, whereas sinusoidal endothelium was E-sel-positive but TF-negative . TM expression was unchanged from controls . Additionally, expression of TF by lung alveolar epithelial cells, splenic macrophages, and epithelial cells of the renal glomeruli was observed to be enhanced in septic animals . This study documents endothelial cell expression of TF in vivo in a relevant pathological setting . At the same time, compared with endothelial cells in culture, there is in vivo both significantly greater control of TF expression than expected, given the strong positive stimuli present in lethal E . coli septic shock and an unpredicted heterogeneity of activation responses.

J Trauma, 1993 Apr, 34(4), 473 - 9; discussion 479-80
Autoregulation of hepatic macrophage activation in sepsis; West MA et al.; Endotoxin (LPS)-stimulated macrophages release mediators, such as tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which modulate the function of many different cells . We hypothesize that macrophage regulation is altered in sepsis and that mediators from LPS-stimulated macrophages "autoregulate" their activation state . Alterations in the LPS dose response relationships for inhibition of hepatocyte protein synthesis by hepatic macrophages (hMos) were examined to investigate factors that regulate hMo activation . In vitro pretreatment was compared using TNF alpha, PGE2, subactivating concentrations of LPS, or LPS plus indomethacin . Pre-exposure to LPS resulted in a dose-dependent loss of subsequent LPS-triggered activation of hMos in co-culture . Pretreatment with LPS and 1 mumol/L indomethacin partially restored hMo responsiveness . Pre-exposure to PGE2 significantly decreased LPS responsiveness of co-cultured hMos, suggesting that PGE2 produced by LPS-stimulated hMos may mediate this effect . Pretreatment of hMos with TNF alpha, but not IL-1 beta, significantly lowered the LPS concentration required for maximal hMo activation . We conclude that both macrophage mediators and LPS pretreatment alter macrophage activation state . These data suggest an "autoregulatory" role for mediators of LPS-stimulated macrophages in sepsis.

Sheng Li Xue Bao, 1993 Apr, 45(2), 158 - 63
{Changes of calcium transport capacity of myocardium and myocardial mitochondria during sepsis}; Dong LW et al.; On the isolated perfused heart model of septic rats, the present study showed that: (1) Calcium content and 45Ca-influx of myocardium increased 190%, 208% (P < 0.01) and that of mitochondria elevated 332%, 178% (P < 0.01) respectively with no change of myocardial 45Ca-release during sepsis . (2) 10(-8) mol/L calcitonin gene-related peptide (CGRP) or 10(-7) mol/L atriopeptin (ANP) added into the Krebs-Henseleit solution could effectively reduce 45Ca-influx to myocardium and mitochondria with no effect on myocardial 45Ca-release . (3) The calcium uptake reserve of mitochondria evaluated in vitro showed that the maximal calcium uptake and uptake velocity of mitochondria during sepsis were reduced 34.6%, 33.3% (P < 0.01) respectively . The data suggested that the net increase of myocardial Ca2+ content resulted from increase of 45Ca-influx with no change of 45Ca-efflux and the reduction of mitochondrial Ca2+ buffering capacity during sepsis were key events in the pathogenesis of intracellular Ca(2+)-overload . CGRP and ANP could effectively alleviate Ca(2+)-overload of myocardium and mitochondria . This may have some cellular protection action during sepsis.

Acta Paediatr, 1993 Apr, 82(4), 352 - 4
Serum TNF levels in neonatal sepsis and septic shock; Roman J et al.; Tumor necrosis factor (TNF-alpha) has been implicated as a principal mediator in the pathogenesis of septic shock . TNF-alpha was measured by immunoradiometric assay in serum samples from 23 full-term infants with sepsis (15 with severe infection and 8 with septic shock) and in 20 healthy full-term newborns . Serum TNF-alpha levels were significantly higher in the group with sepsis, at the time of admission to the neonatal intensive care unit, than in the healthy neonates . The highest TNF levels were found in those newborns with septic shock, particularly in those who died . Although the method is far too slow for any clinical routine work, our results suggest that the presence of elevated serum TNF-alpha levels could be considered a sensitive and specific test for predicting septic shock and its clinical outcome.

Arch Surg, 1993 Apr, 128(4), 390 - 5
Polymorphonuclear leukocyte activation . An early marker of the postsurgical sepsis response; Wakefield CH et al.; It has been suggested that major surgery induces polymorphonuclear leukocyte (PMNL) dysfunction, which exposes patients to the development of sepsis . Conversely, the sepsis response and multisystem organ failure in patients after surgery is thought to be mediated by activated PMNLs . In a preliminary attempt to investigate this paradox, we studied functional (hydrogen peroxide production) and phenotypic (the adhesion/complement receptor CD11b) markers of PMNL activation in 28 patients undergoing elective major resectional surgery; 11 (39%) of these patients developed postoperative sepsis (the septic group) . The mean (SEM) preoperative level of neutrophil CD11b expression (97.8 {6.2} mean channel fluorescence {MCF} and 101.42 {7.9} MCF; P = .74) and hydrogen peroxide production (109.51 {4.91} MCF and 104.53 {6.3} MCF; P = .5) were similar for the uncomplicated and septic groups, respectively . However, on the first postoperative day, both mean CD11b expression and hydrogen peroxide production were greater in those patients who subsequently developed postoperative sepsis (192.5 {38} MCF vs 128.6 {8.1} MCF for the septic group vs the uncomplicated group, respectively {P < .05}, and 120.43 {2.56} MCF vs 109.61 {3.05} MCF for the septic group vs the uncomplicated group, respectively {P < .0001}) . We suggest that an exaggerated PMNL activation response to surgery is an early event in those patients destined to develop postsurgical sepsis.

Khirurgiia (Mosk), 1993 Apr, (4), 57 - 61
{Determination of superoxide production by polymorphonuclear leukocytes for the diagnosis and prognosis of burn sepsis}; Alekseev AA et al.; The authors conducted 140 studies of the level of superoxide production by polymorphonuclear leukocytes in 60 patients with severe burns during various periods of the burn disease . Sepsis was diagnosed clinically in 13 of the examined patients . It is shown that study of the leukocyte superoxide-generating function is important for objective appraisal of the condition of the unspecific protestive factors in persons with burns, early diagnosis and prognostication of possible infectious complications, as well as for evaluation of the adequacy of the applied treatment, namely--a fall of the level of superoxide production below 2.0-1.7 nm/10(6) indicated the development of sepsis and coincided with suppuration of the burn wound.

Lancet, 1993 Mar 27, 341(8848), 777 - 80
Serum antioxidants as predictors of adult respiratory distress syndrome in patients with sepsis; Leff JA et al.; Adult respiratory distress syndrome (ARDS) can develop as a complication of various disorders, including sepsis, but it has not been possible to identify which of the patients at risk will develop this serious disorder . We have investigated the ability of six markers, measured sequentially in blood, to predict development of ARDS in 26 patients with sepsis . At the initial diagnosis of sepsis (6-24 h before the development of ARDS), serum manganese superoxide dismutase concentration and catalase activity were higher in the 6 patients who subsequently developed ARDS than in 20 patients who did not develop ARDS . These changes in antioxidant enzymes predicted the development of ARDS in septic patients with the same sensitivity, specificity, and efficiency as simultaneous assessments of serum lactate dehydrogenase activity and factor VIII concentration . By contrast, serum glutathione peroxidase activity and alpha 1Pi-elastase complex concentration did not differ at the initial diagnosis of sepsis between patients who did and did not subsequently develop ARDS, and were not as effective in predicting the development of ARDS . Measurement of manganese superoxide dismutase and catalase, in addition to the other markers, should facilitate identification of patients at highest risk of ARDS and allow prospective treatment.

J Trauma, 1993 Mar, 34(3), 417 - 21
Effect of thermal injury and sepsis on neutrophil function; Dong YL et al.; Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils . As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound . We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats . Despite having a higher concentration of neutrophils in the blood, both the burned and burned-infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively) . Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001) . This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group . The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned-infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively).

Br J Surg, 1993 Mar, 80(3), 289 - 97
Cytokines, sepsis and immunomodulation; Molloy RG et al.; Tissue injury and infection produce significant alterations in host metabolic and immune homeostasis . It is increasingly clear that many of these changes result from a complex cascade of mononuclear phagocyte-derived endogenous mediators . Among the more important is a group of host proteins called cytokines, which play an integral role in mediating the host response to tissue injury and infection . Of these proteins, tumour necrosis factor (TNF) and interleukin (IL) types 1 and 6 have received much attention for their pathophysiological roles in infection and trauma . Evidence is reviewed for the involvement of these cytokines in the characteristic alterations in the metabolic and immune responses to such injury . These endogenous mediators initiate an integrated fuel substrate and hormonal adjustment to trauma and sepsis, and help to provide optimal metabolic homeostasis for systemic host defences . Widespread tissue injury, especially when associated with fulminant sepsis, may, however, precipitate massive release of TNF, IL-1 and IL-6, triggering a series of reactions involving multiple organs, and culminating in the 'sepsis syndrome' . New therapies designed to downregulate this aberrant response, either by neutralizing endotoxin directly or by blocking the release or actions of these cytokines, are reviewed . Although these treatments hold much promise for the future management of severely traumatized and infected patients, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended.

J R Soc Med, 1993 Mar, 86(3), 148 - 51
The value of screening for diabetes in patients with skin sepsis; Baynes C et al.; Four hundred and eighty-two patients with spontaneous skin and superficial sepsis and 291 controls of similar age and sex underwent random capillary blood glucose measurements in order to assess whether screening for diabetes in patients presenting with skin sepsis to an Accident & Emergency Department detects a greater number of cases than that present in the background population . All subjects with a concentration > 7.8 mmol/l were subsequently followed up with a 75 g oral glucose tolerance test . Forty-two (8.7%) of the 482 skin sepsis patients had a capillary blood glucose > 7.8 mmol/l compared to eight (2.7%) of the 291 without sepsis (chi 2 = 9.71, P < 0.002) . Of these, 26 of the skin sepsis group and 7 of the control group attended for follow up . Of those who attended, 13 of the skin sepsis group had an abnormal glucose tolerance test (seven diabetes, six impaired glucose tolerance-IGT) compared to two (one diabetes, one IGT) of the control group (chi 2 = 2.87, P < 0.1) . The difference in cases of frank diabetes between the two groups was not statistically significant . Of the total eight diabetic cases identified, five (on direct questioning) had symptoms of hyperglycaemia (thirst, polyuria and/or weight loss) and two of the others were obese, one of whom had documented ischaemic heart disease . Thus, while most cases of diabetes in patients with skin sepsis could be detected by specifically asking about hyperglycaemic symptoms and performing a blood glucose estimation when these are present, we suggest that the screening of patients with skin sepsis over 40 years of age provides an opportunistic method of screening . This strategy should yield clinically significant numbers of abnormal cases.

Circ Shock, 1993 Mar, 39(3), 178 - 87
Effects of coenzyme Q10 on the mediator cascade of sepsis; Lelli JL et al.; Coenzyme Q10 (CoQ) has been promoted as an effective agent for reducing the deleterious effects of septic shock by acting as an oxygen free radical scavenger and thus stabilizing mitochondrial membranes and by inhibiting the arachidonic acid metabolic pathway and the formation of various prostaglandins . This study was undertaken to evaluate the effect of CoQ in a live Escherichia coli model of canine septic shock . Group I (E . coli, n = 5) animals received an LD100 dose of 10(9) live E . coli/kg and were given no further treatment . Group II (CoQ, n = 5) animals received a 20-mg/kg bolus of CoQ without further treatment . Group III (CoQ + E . coli, n = 5) animals received a 20-mg/kg bolus of CoQ 10 min prior to a bacterial infusion as in group 1 . Mean arterial pressure stabilized at 70% of baseline levels (P < .002), while cardiac output remained near 50% of baseline levels (P < .053) in group III compared to group I dogs . The arachidonic acid metabolites, prostaglandin E2, Thromboxane B2, and leukotriene B4 were significantly elevated in groups I and III (vs . group II) (P < 0.05) . The catecholamines, tumor necrosis factor (TNF) and interleukin 6 (IL-6) were significantly elevated in groups I and III (vs . group II) (P < 0.05) . Fluorescent products (lipid peroxidation activity) were elevated in group I (vs . groups II and III) at 120 and 180 min (P < 0.05) . We conclude that CoQ supports cardiovascular hemodynamics and prevents free radical mediated lipid peroxidation during live E . coli septic shock, and its effect is not due to altered levels of humoral or cytokine mediators.

Ann Thorac Surg, 1993 Mar, 55(3), 706 - 10
Paranasal sinusitis: cryptic sepsis after coronary artery bypass operations; Picone AL et al.; Infections occurred in 52 of 400 patients (13%) undergoing coronary artery bypass operations from January 1987 to December 1990 . The hospital courses of 5 patients (1.3%) in whom occult infections of the paranasal sinuses developed were reviewed . Only 1 patient had specific clinical findings of acute sinusitis (purulent nasal discharge) . Computed tomography showed wall thickening, opacification, or air-fluid levels in one or more paranasal sinuses in each patient . All patients were successfully treated with surgical drainage and antibiotics . Risk factors for development of postoperative acute sinusitis include: prolonged tracheal intubation, airway colonization with nosocomial bacteria, inability to clear nasal secretions, sinus ostial obstruction, and critical organ system dysfunction . Physical examination and roentgenographic evaluation of the paranasal sinuses should be considered when postoperative sepsis of obscure etiology occurs.

J Crit Care, 1993 Mar, 8(1), 43 - 50
Oxygen delivery-consumption relationship in adult respiratory distress syndrome patients: the effects of sepsis; Spec-Marn A et al.; The oxygen consumption-delivery relationship (VO2/DO2) was studied in 15 sedated paralyzed patients with the adult respiratory distress syndrome (ARDS) due to multiple trauma and in whom sepsis was absent . Different levels (0 to 15 cm H2O) of positive end-expiratory pressure (PEEP) were applied . Oxygen delivery was calculated from cardiac index (thermodilution technique) and arterial oxygen content measurements . Oxygen consumption was calculated using Fick's equation . Regression lines were obtained for each patient . Oxygen supply dependency was defined as a significant (P < .05) relationship between changes in VO2 and DO2 with PEEP . Results were compared with those obtained in 18 ARDS patients in whom ARDS was due to sepsis . In nonseptic ARDS patients no significant relationship between changes in VO2 and DO2 with PEEP was found within the experimental range of DO2 on zero end-expiratory pressure (ZEEP) (347 to 845 mL/min/m2) . None of these patients had multiple organ system failure (MOSF), and 73% survived . In ARDS patients in whom sepsis was present, supply dependency was present only when DO2 on ZEEP ranged between 330 and 640 mL/min/m2 . All these patients developed MOSF and died . When DO2 on ZEEP ranged between 686 and 951 mL/min/m2 in septic ARDS patients, the supply dependency phenomenon was absent and only three patients developed MOSF and died (70% survivors) . In almost all patients PEEP reduced DO2 and therefore worsened O2 balance by either increasing O2 extraction ratio and approaching the critical threshold for supply dependency or dismissing DO2 from the range of non-supply dependency.

Rev Prat, 1993 Mar 1, 43(5), 559 - 63
{Cytokines and severe sepsis}; Baumgartner JD et al.; During severe sepsis syndromes, almost every gene coding for cytokines may be activated . The primary purpose of this activation is to defend the organism against infection, but sometimes these inflammatory mediators go out of control . The reasons why this may occur is unclear because the regulation of cytokines production is still poorly understood . Metabolic effects, production of endothelial adhesion molecules and triggering of neutrophils are some important consequences of cytokine overstimulation which may lead to the clinical picture of septic shock . The major cytokines involved in septic shock are tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) . Both may induce lethal shock in experimental models . The effects of these 2 cytokines are difficult to differentiate from one another because they share many similar biological effects, one can induce the synthesis of the other, and they are strikingly synergistic with each other . gamma-interferon may amplify the inflammatory response by stimulating the cells of monocytic lineage and by increasing TNF-receptor expression, thus participating in the pathogenesis of the septic syndrome . The role of other cytokines is still poorly known . Clinical studies with anti-TNF monoclonal antibodies or with an IL-1 receptor antagonist are under way.

Khirurgiia (Mosk), 1993 Mar, (3), 27 - 32
{Gunshot wound sepsis}; Nechaev EA et al.; The authors emphasize that the origin of gunshot sepsis has specific features which are due to the peculiar effect of modern gunshot injury on the organism, the development of primary and secondary polyorganic deficiency, immunodeficiency among others . According to the authors, gunshot sepsis is encountered in 3.6% of cases among various infectious-purulent complications of gunshot wounds, usually in injuries to the lower extremities and pelvis, with 52.3% lethality . Improvement of the outcomes of gunshot sepsis is connected with refined organization of medical aid to the injured on the stages of medical evacuation, monitoring operative control over the course of the wound process, the use of medicinal agents which raise the viability of the damaged tissues and the organism's immunoresistance, improvement of the methods of surgical debridement of gunshot wounds and detoxification of the organism.

Anesteziol Reanimatol, 1993 Mar-Apr, (2), 40 - 3
{Effects of hemosorption and ultraviolet irradiation of blood on morphological properties of erythrocytes in sepsis in the newborn}; Estrin VV et al.; The morphological structure of erythrocytes was studied using electron microscopy in babies with sepsis . It has been shown that in mild forms of the disease the deformed cells consisted mainly of erythrocytes capable of reversible transformation, while in babies with severe forms of sepsis and especially in those who died of sepsis the deformed cells were mostly prehemolytic and destructive erythrocytes, with the nature of intercellular interaction changed by the formation of cytoplasmatic bridges and enhanced aggregation . A therapeutic effect of hemosorption with ultraviolet blood irradiation is based on a decrease in the counts of hemolytic and destructive erythrocyte forms, which leads to a more prompt recovery of structural and functional erythrocyte properties in the postsorption period.

Ned Tijdschr Geneeskd, 1993 Feb 13, 137(7), 360 - 4
{Cost-effectiveness analysis of human monoclonal antibody HA-1A in patients with sepsis syndrome}; Van Hout BA et al.; The efficiency of prescribing HA-1A for sepsis patients is analysed by comparing direct medical costs and effects . Effects are estimated on the basis of published data from a randomised clinical trial . Costs are analysed by combining data from the same trial with expectations about hospital days . Average costs per life year gained are estimated at DF1 . 25,000 . Sensitivity analysis is applied and the efficiency of treating patients with HA1A is shown to depend highly on the expected duration of survival after successful treatment . This leads to the advice to take epidemiologic knowledge into special account before setting the indication for using HA-1A.

Gaoxiong Yi Xue Ke Xue Za Zhi, 1993 Feb, 9(2), 80 - 8
{Kinetic studies of protein kinase A in rat liver during early sepsis}; Sun YM et al.; Sepsis-induced glucose dyshomeostasis has been characterized by an initial hyperglycemia followed by a progressive hypoglycemia . It is well known that the liver plays a predominant role on regulating the homeostatic level of blood glucose . Furthermore, recent studies indicate that protein kinase A, activated by c-AMP, contributes to the role of glycagon in glucogenolysis and glyconeogenesis . Kinetic studies of protein kinase were completed . During late sepsis, in order to further understand the pathophysiology of hepatic glucose disturbances during sepsis . This study investigates the role of protein kinase A in the liver regulating carbohydrate metabolism during early sepsis . The work was performed by using an animal septic model, induced by cecal ligation and puncture (CLP) operation . Through the measurement of blood sugar, a two phase change in sugar level was found . That is, blood sugar significantly increased at 4.5 hrs after CLP operation (p < 0.05) and then significantly decreased at 18 hrs (p < 0.01) . In the kinetic studies of protein kinase A, the results showed that, during early sepsis, the activities of both type I (eluted at low ionic strength) and type II (eluted at high ionic strength) protein kinase A were unchanged . Moreover, the kinetic parameters, Vmax and S0.5, of protein kinase A showed no significant difference between two groups . As such, it is suggested that hyperglycemia during early sepsis is not connected to the regulation of protein kinase A.

Circ Shock, 1993 Feb, 39(2), 160 - 7
Induction of group II phospholipase A2 expression and pathogenesis of the sepsis syndrome; Vadas P et al.; Phospholipase A2 catalysed hydrolysis of phospholipid substrates is rate-limiting in the release of arachidonic acid for subsequent downstream metabolism to biologically active eicosanoids . Concomitant release of lysoplatelet activating factor (lyso PAF) serves as the precursor of PAF . Thus, phospholipase A2 (PLA2) is pivotal in the generation of a spectrum of biologically active lipids . Over the course of the past decade, studies have increasingly pointed to a pathogenetic association between endotoxin-induced PLA2 expression and ensuing circulatory shock and multisystem organ failure in animals with experimental endotoxemia as well as in patients with septic shock . The structural, functional, regulatory and biologic characteristics of PLA2 are reviewed in relation to septic shock and its complications and areas of controversy are highlighted.

Prof Nurse, 1993 Feb, 8(5), 288 - 91
Avoiding an unnecessary outcome . A comparative trial between IV3000 and a conventional film dressing to assess rates of catheter-related sepsis; Keenlyside D; A new transparent dressing, IV3000 is reported to be successful in preventing moisture accumulation around the catheter site . A trial was thus undertaken to compare its effectiveness in preventing catheter-related sepsis with a conventional film dressing.

Arch Surg, 1993 Feb, 128(2), 218 - 22; discussion 223
Postoperative intra-abdominal sepsis requiring reoperation . Value of a predictive index; Pusajo JF et al.; In this study we analyze the results of the use of a predictive index to decide whether to perform abdominal reoperation in the event of septic complications . During a 5-year period, a population of 542 critically ill patients received major abdominal surgery . Patients were divided into two groups: (1) the control group, for which the decision to reoperate was made routinely, based on clinical consensus of the medical team; and (2) the Abdominal Reoperation Predictive Index group, for which the decision to reoperate was made with the help of a mathematical index involving eight mainly clinical variables . The use of Abdominal Reoperation Predictive Index enabled mortality among patients undergoing reoperation to be lowered, the time elapsing between the first operation and relaparotomy to be reduced, and the length of stay in the intensive care unit to be shortened . We conclude that the systematic application of an index, without disregarding clinical judgment, allows the quality of attention to be improved, cost to be lowered, and the level of conflicts generated by the difficult decision to perform reoperation to be curtailed.

Crit Care Med, 1993 Feb, 21(2 Suppl), S4 - 8
Adequacy of gut oxygenation in endotoxemia and sepsis; Fink MP; OBJECTIVE: To provide a succinct overview of current notions regarding sepsis-induced alterations in mesenteric perfusion and oxygen transport . DATA SOURCES: Selected English-language articles dealing with mesenteric perfusion and gut mucosal function during sepsis or endotoxicosis in experimental animals or man . STUDY SELECTION AND DATA EXTRACTION: The review emphasizes findings obtained using a well-characterized porcine model of acute, resuscitated endotoxicosis . Other experimental and clinical studies are discussed as well . DATA SYNTHESIS: Total hepatosplanchnic perfusion and oxygen uptake are increased in most patients with compensated sepsis . No data are currently available from clinical studies regarding the effect of sepsis on mesenteric perfusion per se . Data are unavailable regarding either total hepatosplanchnic or mesenteric blood flow in patients with decompensated sepsis (i.e., septic shock) . Therefore, current ideas regarding mesenteric perfusion in sepsis derive primarily from studies using animal models . In a normodynamic porcine endotoxicosis model, mesenteric perfusion and oxygen delivery (DO2) are markedly decreased . The changes in flow and DO2 are accompanied by intestinal mucosal acidosis and increased permeability to hydrophilic solutes, suggesting that these latter phenomena are a consequence of lipopolysaccharide-induced mesenteric hypoperfusion . This idea is supported by the observation that maintenance of normal mesenteric blood flow ameliorates gut mucosal acidosis and hyperpermeability in endotoxic pigs . However, because transmesenteric oxygen consumption is unchanged in endotoxic pigs, the precise mechanistic relationship between hypoperfusion and altered barrier function remains puzzling . CONCLUSION: Mesenteric hypoperfusion may be an important factor leading to alterations in gut epithelial permeability in endotoxicosis and sepsis.

Crit Care Med, 1993 Feb, 21(2), 196 - 202
Human sepsis increases lymphocyte intracellular calcium; Zaloga GP et al.; OBJECTIVE: To determine whether free intracellular calcium is increased during human bacterial sepsis . DESIGN: Prospective controlled study of lymphocyte free intracellular calcium concentrations from patients with sepsis compared with critically ill nonseptic patients and healthy subjects . SETTING: A large multidisciplinary ICU of a university hospital . PATIENTS: Eleven patients with sepsis, six patients after cardiac surgery, six patients with head injury, and 22 healthy control subjects . INTERVENTIONS: Blood samples obtained for lymphocyte isolation and measurement of free intracellular calcium concentrations . MEASUREMENTS: Lymphocytes were isolated using Ficoll-paque centrifugation and free intracellular calcium concentrations were measured using the fluorescent dye fura-2 . We also evaluated the effect of septic serum, endotoxin, tumor necrosis factor (TNF), and lysophosphatidylcholine on lymphocyte free intracellular calcium concentrations . MAIN RESULTS: Mean (+/- SEM) lymphocyte free intracellular calcium concentrations were significantly (p < .05) higher in the septic patients (176 +/- 12 nM) compared with cardiac surgical (112 +/- 9 nM), head-injured (110 +/- 11 nM), or healthy control patients (112 +/- 5 nM) . Endotoxin (0.1 and 1.0 mg/mL) and TNF (10 and 100 ng/mL) did not alter lymphocyte free intracellular calcium values . Lysophosphatidylcholine (100 and 200 microM) significantly increased lymphocyte free intracellular calcium in a dose-dependent manner . Septic serum had no effect on resting lymphocyte free intracellular calcium concentrations but potentiated the free intracellular calcium response to lysophosphatidylcholine . CONCLUSIONS: Lymphocyte intracellular calcium homeostasis is altered during human sepsis . In addition, circulating factors present in septic serum are capable of altering cellular calcium handling.

Crit Care Med, 1993 Feb, 21(2), 191 - 5
Detrimental effects of high-dose methylprednisolone sodium succinate on serum concentrations of hepatic and renal function indicators in severe sepsis and septic shock . The Methylprednisolone Severe Sepsis Study Group; Slotman GJ et al.; OBJECTIVE: To evaluate the effects of high-dose methylprednisolone sodium succinate on biochemical markers of hepatic and renal function in patients with severe sepsis and septic shock . DESIGN: Retrospective analysis of serial serum chemistries in 382 patients who were entered prospectively into a randomized, placebo-controlled, double-blind clinical trial of high-dose methylprednisolone or placebo in the sepsis syndrome . SETTING: The original study was conducted at 19 academic centers . PATIENTS: Adult patients in severe sepsis or septic shock who met the study entry criteria, which included a clinically defined source of infection and signs of systemic sepsis, were enrolled into the study . Three hundred eighty-two patients were evaluated . INTERVENTIONS: Patients received either methylprednisolone (30 mg/kg) or placebo by iv infusion every 6 hrs for four doses . Hemodynamic variables and serum concentrations of creatinine, urea nitrogen, bilirubin, and aspartate aminotransferase (AST) were recorded on entering the study, at 12 and 24 hrs, and at 3, 7, and 14 days after the first infusion of methylprednisolone or placebo . These data were analyzed retrospectively . MAIN OUTCOME MEASUREMENTS: Hemodynamic and biochemical data were analyzed to determine whether or not hepatic and renal function in the sepsis syndrome had been influenced by methylprednisolone treatment . RESULTS: Differences between methylprednisolone and placebo in hemodynamic variables, the occurrence rate of shock and recovery from shock, mortality rates and serum concentrations of creatinine and AST were not statistically significant . At 12 and 24 hrs, and at 3 and 7 days after the first drug infusion (of methylprednisolone or placebo), blood urea nitrogen was increased from baseline values in a significantly (p < .01) greater proportion of the methylprednisolone-treated patients compared with placebo-treated patients . The frequency of increased serum bilirubin concentrations was significantly (p < .01) greater among methylprednisolone patients vs . the placebo group at 12 and 24 hrs . CONCLUSIONS: The frequency of acutely increased blood urea nitrogen and bilirubin concentrations in severe sepsis was increased significantly with high-dose methylprednisolone therapy . Similar frequencies of circulatory shock in the study groups excluded differences in global perfusion as a cause of this phenomenon . Possible adverse effects of pharmacologic concentrations of methylprednisolone in critically ill patients should be considered in planning treatment.

Circ Shock, 1993 Feb, 39(2), 153 - 9
Oxidative stress in skeletal muscle during sepsis in rats; Peralta JG et al.; Skeletal muscle is a target organ during sepsis; nevertheless, there is no evidence of a possible free radical overproduction with tissue damage in this situation . We studied Sprague Dawley female rats in two groups: a septic group with cecal ligation and double cecal perforation and a control group that was sham operated . Hind limb adductor muscles spontaneous chemiluminescence was measured at 2, 4, 6, 12, 24, and 30 hr after the surgical procedure as the expression of oxygen excited species generation . Muscle samples were also taken and activity of the principal antioxidant enzymes--superoxide dismutase (SOD), catalase, and glutathione peroxidase--as well as myeloperoxidase, an index of neutrophil infiltration was determined . CPK seric assays at 12 and 24 hr were used to reflect muscle injury and revealed high levels . Previously administered bovine superoxide dismutase was employed to prevent or attenuate oxidative stress . The results showed that light emission by rat skeletal muscle doubled from 4 to 12 hr of sepsis and could be attenuated with SOD pretreatment . Observed changes may be attributed to the production of oxygen free radicals that do not depend on local neutrophil infiltration . The detoxifying antioxidant enzyme activities in skeletal muscle were diminished (Mn SOD 46% at 6 hr, catalase 83% at 12 hr glutathione peroxidase 55% at 12 hr), which would also facilitate muscle septic damage.

Clin Auton Res, 1993 Feb, 3(1), 5 - 13
Spectral analysis of heart rate variability in the sepsis syndrome; Garrard CS et al.; Sympathetic and parasympathetic activity was evaluated on 39 occasions in 17 patients with the sepsis syndrome, by measurement of the variation in resting heart rate using frequency spectrum analysis . Heart rate was recorded by electrocardiography and respiratory rate by impedance plethysmography . The sepsis syndrome was established on the basis of established clinical and physiological criteria . Subjects were studied, whenever possible, during the period of sepsis and during recovery . Spectral density of the beat-to-beat heart rate was measured within the low frequency band 0.04 to 0.10 Hz (low frequency power, LFP) modulated by sympathetic and parasympathetic activity, and within a 0.12 Hz band width at the respiratory frequency mode (respiratory frequency power, RFP) modulated by parasympathetic activity . Results were expressed as the total variability (total area beneath the power spectrum), as the spectral components normalized to the total power (LFPn, RFPn) or as the ratio of LFP/RFP . During the sepsis syndrome, total heart rate variability and the sympathetically mediated component, LFPn were significantly lower than during the following recovery phase (ANOVA, p < 0.0001, p < 0.01 respectively) . Both APACHE II (Acute Physiological and Chronic Health Evaluation) and TISS (Therapeutic Intervention Scoring System) scores showed an inverse correlation with total heart rate variability, logLFP, LFPn and the LFP/RFP ratio (p < 0.002 to 0.0001) . Sympathetically mediated heart rate variability was significantly lower during the sepsis syndrome and was inversely proportional to disease severity.

Gematol Transfuziol, 1993 Feb, 38(2), 15 - 8
{The metabolic activity of the erythrocytes and the characteristics of ferrokinetics in children with sepsis}; Soboleva MK et al.; The examination of septic children has revealed characteristics of iron and red cell metabolism: deep and persistent hypotransferrinemia, normo- or hypersideremia, normal ferritin levels . Red cells of septic children contain low concentrations of ATPase, histidine, lipoproteins, there is compensatory enhancement of 2,3-DPG, G-6-PD SH-group activity . In terminal sepsis the activity of the above parameters drastically falls entailing hemolysis, anemia and severe hypoxia.

New Horiz, 1993 Feb, 1(1), 96 - 109
Colony-stimulating factors in the modulation of sepsis; Gillan E et al.; Colony-stimulating factors, a complex family of cytokines often referred to as hematopoietic growth factors, are a family of glycoprotein hormones that regulate production and differentiation of hematopoietic cells . The study of colony-stimulating factors was originally confined to stimulation and formation of clonal colonies in in vitro culture systems . The study of hematopoietic growth factors has since evolved into an expanding number of clinical applications in the treatment of patients with hematopoietic and immunologic diseases . Increased occurrence rates of infection have been demonstrated to be associated with both severity and duration of neutropenia . Sepsis has also been associated with phagocytic functional abnormalities . Both neutropenia and neutrophil dysfunction have been shown, in part, to be corrected by granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor . In clinical trials to date, neither of these growth factors has shown significant toxicity . This article discusses the possible use of these and other growth factors in the treatment of sepsis.

New Horiz, 1993 Feb, 1(1), 13 - 22
Cytokines and sepsis: pathophysiology and therapy; Shapiro L et al.; Current therapies for sepsis are unsatisfactory, with a 50% mortality rate in patients with septic shock, regardless of etiology . Persuasive evidence shows that the majority of damage induced during sepsis is pursuant to induction and overproduction of endogenous cytokine immune mediators . Interleukin-1 and tumor necrosis factor act synergistically as strategic triggers of the cascade of cytokine-induced pathophysiology . Anticytokine therapeutic strategies, directed primarily at interleukin-1 and tumor necrosis factor modulation, have produced preliminary but exciting results in treating sepsis and other inflammatory diseases.

New Horiz, 1993 Feb, 1(1), 127 - 36
Intravascular volume and fluid therapy for severe sepsis; Astiz ME et al.; Hypovolemia is one of the principal defects contributing to cardiovascular instability and circulatory failure during septic shock . Fluid infusion is the mainstay of initial resuscitation . Large amounts of fluids may be required and should be titrated to optimal hemodynamic effects while attempting to minimize the development of pulmonary and systemic edema . Hemoglobin and hematocrit should be carefully monitored, with transfusions being used as necessary to maintain adequate levels of systemic oxygen delivery . Crystalloids and colloids are equally effective, although the volume of fluids required with crystalloids is two to four times that of colloids . In older patients, where high filling pressures may be required for optimal hemodynamic effect, colloids may be associated with a lower frequency of pulmonary edema.

New Horiz, 1993 Feb, 1(1), 120 - 6
Anticytokine therapies in sepsis; Lowry SF; The pro-inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), are widely assumed to participate in the initial systemic manifestations of sepsis . While the toxicities of excessive cytokine activity have been well described in animal models, clinical evaluations often fail to detect circulating forms of these mediators in critically ill patients . It is now evident that a diverse array of host mechanisms serve to attenuate or block excessive cytokine influences . This homeostatic response includes the generation of natural antagonists, such as soluble receptors of TNF and an antagonist of IL-1 that prevents binding of the cytokine to its receptor . Recombinantly derived forms of these natural cytokine antagonists have proven effective in preventing many of the adverse consequences of sepsis . Prospective clinical trials of these agents are currently underway . While results of such trials are not fully available at present, it is likely that one or more therapies directed against TNF and IL-1 may prove effective in the management of septic shock.

Scand J Infect Dis, 1993, 25(2), 245 - 8
Glucocorticoid receptors in mononuclear cells of patients with sepsis; Sigal GA et al.; Glucocorticoid receptor (GR) hormone-binding activity was studied by a whole-cell method in mononuclear cells (MNC) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis . 4 patients were receiving dopamine, which did not affect the GR count . The patients' plasma cortisol concentrations were normal or slightly elevated . Despite a wide range, the mean GR count and affinity in MNC from septic patients did not differ from those in normal controls, suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis.

Am Surg, 1993 Jan, 59(1), 65 - 8
Decreased red blood cell deformability and impaired oxygen utilization during human sepsis; Powell RJ et al.; Sepsis is characterized by decreased microcirculatory flow and increased peripheral shunting . Previous studies have shown red blood cell deformability (RCD) is decreased during sepsis . The purpose of this study was to evaluate the effect of changes in RCD on hemodynamics and oxygen utilization during sepsis . RCD, arteriovenous oxygen difference (DA-VO2), mixed venous oxygen saturation (MVO2), intrapulmonary shunt (QS/QT), cardiac index, and systemic vascular resistance were measured in 10 trauma patients, all of whom had or developed clinical sepsis . Data are expressed as mean +/- SD . Patients with normal RCD (> 0.75) were compared with those with low RCD (< 0.75) . Patients with low RCD had a significantly higher incidence of sepsis (100% vs . 20%, P < 0.05, Student's t test or Fisher's Exact Test), lower DA-VO2 (2.4 +/- 0.9 vs . 4.8 +/- 1.5 P < 0.05, Student's t test or Fisher's Exact Test), and higher MVO2 (79 +/- 8 vs . 65 +/- 11 P < 0.05, Student's t test) or Fisher's Exact Test) than those patients with normal RCD . There was a direct correlation between RCD and DA-VO2 (r = 0.852, P < 0.001) . MVO2 correlated inversely with changes in RCD (r = 0.813, P < 0.001) . No significant correlation existed between RCD and cardiac index or systemic vascular resistance . Patients with low RCD demonstrated impaired oxygen utilization; changes in RCD correlated closely with changes in DA-VO2 and MVO2 . These data suggest that decreased RCD may have an etiologic role in the impaired oxygen utilization that occurs during sepsis.

Acta Anaesthesiol Scand Suppl, 1993, 98, 20 - 4
Manipulation of the immunoinflammatory reaction in clinical sepsis; Sjolin J; For many years patients with sepsis and septic shock have been treated with antibiotics, fluids, surgery (if indicated) and, in the more severe cases, inotropic and ventilatory support . During recent years there has been an intensive development of new treatments based on increased knowledge of the pathophysiology . This presentation will focus on treatments modulating the immunoinflammatory response, which are either available in clinical practice today or which will be available in the near future . It is concluded that optimal therapy depends on the stage of the septic disease as well as the gram stain of the causative bacteria.

Surg Today, 1993, 23(2), 137 - 43
Rat liver peroxisomal and mitochondrial fatty acid oxidation in sepsis; Yamamoto T; Time course changes in hepatic mitochondrial and peroxisomal fatty acid oxidative capacities, as well as changes in the related enzyme activities, were investigated in rats with sepsis induced by cecal ligation and puncture . Palmitoyl-L-carnitine oxidation was not altered, but carnitine palmitoyl-transferase (CPT) dependent palmitoyl-CoA (plus L-carnitine) oxidation was slightly increased in the liver mitochondria of the septic rats . Hepatic CPT activity, being the rate-limiting step of mitochondrial beta-oxidation, was also enhanced by sepsis . In contrast, cyanide-insensitive peroxisomal beta-oxidation and the carnitine acetyltransferase and catalase activities associated with the peroxisomal-enriched fraction were markedly reduced by abdominal sepsis . Cyanide-insensitive beta-oxidation in control livers showed optimal specificity for lauroyl- and myristoyl-CoA and this pattern remained unchanged by sepsis . However, oxidation rates were reduced for all acyl-CoA esters tested, being more pronounced with longer carbon chain length acyl-CoA substrates . These results indicate that in early sepsis, hepatic mitochondrial fatty acid oxidative capacity was increased, probably due to enhanced CPT activity, whereas peroxisomal beta-oxidation was seriously disturbed along with reduced catalase activity.

Nutrition, 1993 Jan-Feb, 9(1), 33 - 6
Substrate supply as determinant of O2 extraction in sepsis and nonseptic trauma; Giovannini I et al.; Metabolic and hemodynamic measurements performed in 72 septic (S) and 40 nonseptic (NS) surgical patients undergoing total parenteral nutrition were analyzed to assess the role of substrate supply as a determinant of O2 extraction (O2Ex) . In S, O2Ex was inversely related to cardiac index (CI); at any given CI, significant increases in O2Ex with simultaneous increases in O2 consumption (VO2) were related to increasing doses of amino acids, with a less remarkable effect of fat and no effect of glucose dose . In NS, O2Ex was also inversely related to CI; however, at any given CI, there was no evident substrate-supply dependency of O2Ex, which was more normally related to P50 . The increase in VO2 per gram of administered amino acids, at any CI and O2 transport index, was 817 ml in S and 267 ml in NS . These results suggest that the impaired O2Ex and VO2 in S may at least partly reflect abnormalities in substrate utilization and that amino acid support may have a role in modulating these abnormal O2Ex patterns by providing preferential substrate for oxidative metabolism.

Acta Paediatr, 1993 Jan, 82(1), 26 - 9
The risk of bilirubin encephalopathy, as estimated by plasma parameters, in neonates strongly suspected of having sepsis; Ebbesen F et al.; The study comprises 18 mature newborns, strongly suspected of having sepsis, and a control group of 18 mature, healthy newborns with the same postnatal age . The object of the investigation was to compare the risk of development of bilirubin encephalopathy between the two groups, as estimated by plasma parameters . The sepsis group had significantly lower reserve albumin concentration for binding of MADDS (p < 0.01) and significantly lower total albumin concentration (p < 0.01) . No significant differences were observed in unconjugated bilirubin concentration and plasma pH . It is suggested that mature newborns with sepsis have a slightly increased risk of developing bilirubin encephalopathy.

J Perinatol, 1993 Jan-Feb, 13(1), 8 - 13
Fibronectin levels in premature infants with late-onset sepsis; Edwards MS et al.; Physical features do not reliably distinguish premature infants with bacterial infections from those with noninfectious conditions . We evaluated the association of depressed plasma fibronectin with sepsis among hospitalized very low birth weight infants (< 1500 gm) . Reference values were determined by sequential plasma sampling from 60 healthy very low birth weight infants . Among 17 very low birth weight infants with proved late-onset sepsis (mean age, 20 days; range, 10 to 42 days), 9 had plasma fibronectin levels more than 1 SD below the age- and birth weight-associated mean . Overall, the sensitivity and specificity of the finding of depressed fibronectin levels were 53% and 94%, respectively . These data suggest that depression of plasma fibronectin occurs commonly in association with late-onset sepsis among hospitalized premature infants.

Br J Anaesth, 1993 Jan, 70(1), 58 - 62
Comparison of thoracic electrical bioimpedance and thermodilution for the measurement of cardiac index in patients with severe sepsis; Young JD et al.; Cardiac index was measured using thoracic bioimpedance (CIbi) and thermodilution (CItd) in 19 patients with proven sepsis, undergoing artificial ventilation of the lungs . There was a poor correlation between the techniques (r = 0.36, 242 data sets, regression line CIbi = 0.16 CItd + 2.56 litre min-1 m-2) . The overall bias (CItd-CIbi) was 1.69 litre min-1 m-2 with limits of agreement (precision) of +4.17 to -0.79 litre min-1 m-2 . In individual patients the bias was from -0.46 to 4.56 litre min-1 m-2 with the limits of agreement from +/- 0.29 to +/- 2.55 litre min-1 m-2 around the bias values . The two techniques cannot be used interchangeably in this group of patients.

Crit Care Med, 1993 Jan, 21(1), 84 - 9
Heparin in experimental hyperdynamic sepsis; Meyer J et al.; OBJECTIVE: To evaluate the hypothesis that heparin administration increases cardiac output and improves oxygenation in experimental hyperdynamic sepsis in sheep . DESIGN: Prospective trial . SETTING: Laboratory at a large university-affiliated medical center . SUBJECTS: A total of 14 sheep weighing 28 to 44 kg . INTERVENTIONS: All 14 chronically instrumented sheep received a continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) over 24 hrs . Seven sheep received a fixed bolus of beef lung heparin (5000 units) every 4 hrs intravenously . The other seven sheep served as controls . MEASUREMENTS AND MAIN RESULTS: The heparinized animals showed a triphasic cardiovascular response . Cardiac index increased (p < .05), and systemic vascular resistance index decreased (p < .05) at 2 hrs after the start of the endotoxin infusion (early phase, 0 to 2 hrs) . Both variables returned to approximately baseline levels at 4 hrs (second period, 2 to 4 hrs) . A hyperdynamic state (in terms of an increased cardiac index), a decreased systemic vascular resistance index, and a decreased mean arterial pressure (MAP) (p < .05 for all) was observed in the third phase (8 to 24 hrs) . In the control group, cardiac index, systemic vascular resistance index, and MAP showed no changes in the first period, but a slight decrease in cardiac index and a slight increase in systemic vascular resistance index in the second period . The onset of the hyperdynamic state was less pronounced in the control group and cardiac index was lower (p < .05); likewise, systemic vascular resistance index was increased (p < .05) when compared with heparinized animals . Both groups developed pulmonary hypertension during the endotoxin infusion . The gas exchange in the heparin group was significantly impaired in the first and second periods, but returned to baseline levels in the hyperdynamic phase, whereas the oxygenation of the nonheparinized animals showed only minor changes in the first and second phases, but deteriorated significantly during the third phase of endotoxemia . CONCLUSIONS: In this experimental model of hyperdynamic sepsis, heparin significantly influenced the cardiopulmonary performance . Heparin preserved gas exchange and increased cardiac output but lowered systemic vascular resistance and MAP in the hyperdynamic state.

Arch Surg, 1993 Jan, 128(1), 89 - 94; discussion 94-5
Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis; Ayala A et al.; We examined whether (1) there is an association between elevated circulating levels of transforming growth factor-beta (TGF-beta) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-beta release) or TGF-beta could ablate these changes . Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation . Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-beta value and depressed splenocyte interleukin 2 release . Administration of monoclonal antibodies against interleukin 6, but not against TGF-beta (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-beta at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release . Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-beta, thereby attenuating host immunosuppression during sepsis.

Arch Surg, 1993 Jan, 128(1), 65 - 6; discussion 66-7
The relationship between platelet count, sepsis, and survival in pediatric burn patients; Housinger TA et al.; Early identification of sepsis can be difficult in severe burns because of the systemic changes that routinely accompany these burns . This review examined the value of a falling platelet count in predicting the development of sepsis . Thirty-two pediatric patients who sustained lethal burn injuries were compared with 32 patients with similar burns who survived . Daily platelet count was evaluated in conjunction with clinical course . Thirty-one of the 32 non-survivors developed a platelet count less than 0.1 x 10(12)/L . Only 10 of the survivors had a similar occurrence . Platelet count decline preceded other signs of sepsis in all cases . A platelet count below 0.1 x 10(12)/L for more than 4 days was uniformly associated with death . All patients who died succumbed to multisystem organ failure, consistent with sepsis . These results emphasize platelet count as an independent predictor of sepsis and death.

Am J Surg, 1993 Jan, 165(1), 46 - 50; discussion 51-2
Pathogenesis of pancreatic sepsis; Medich DS et al.; Although pancreatic sepsis is the most common cause of major morbidity and mortality associated with acute pancreatitis, the pathogenesis of such infections is unknown . Since intraperitoneal foci of inflammation are known to promote bacterial translocation, we hypothesized that acute pancreatitis promotes bacterial translocation that leads to infection of the inflamed pancreas and peripancreatic tissues . Non-lethal acute pancreatitis was induced in rats, and the translocation of live bacteria to the pancreas, mesenteric lymph nodes, liver, and spleen was determined . The presence of orally fed fluorescent beads, sensitive inert markers of translocation, was also determined in the pancreas and mesenteric lymph nodes . Live bacteria were recovered from 33% of the pancreata of rats with acute pancreatitis but from none of the control rats . Beads were visualized in 91% of the pancreata of rats with acute pancreatitis but in none of the pancreata from control rats . Beads were not visualized in the mesenteric lymph nodes of rats with acute pancreatitis, suggesting a transperitoneal route of migration . We conclude that acute pancreatitis promotes bacterial translocation leading to transperitoneal infection of the pancreas . These results support the use of selective decontamination of the gut and peritoneal lavage for the prevention of pancreatic infections in acute pancreatitis.

Am J Surg, 1993 Jan, 165(1), 150 - 4
Sepsis impairs gut amino acid absorption; Sodeyama M et al.; Sepsis has been shown to adversely affect the barrier and metabolic functions of the small intestine as well as to reduce mesenteric blood flow and cause histologic damage . However, the effect of sepsis on gut absorptive function has been largely ignored . In this study, intestinal absorption of arginine and an amino acid analogue, aminoisobutyric acid, was studied using in vivo and in vitro techniques in an experimental model of sepsis . In vivo studies showed a significant impairment in the absorption of both amino acids from the intestinal lumen 24 and 72 hours after cecal ligation and puncture . Uptake of these amino acids by everted gut sacs prepared from septic animals was also significantly reduced . This reduction in absorptive capacity of the gut may limit the ability of enteral feeding alone to supply nutritional requirements during sepsis and may also contribute to the associated morbidity and mortality.

Am J Hematol, 1993 Jan, 42(1), 132 - 7
Agranulocytosis during antibiotic therapy: drug sensitivity or sepsis?
Pisciotta AV.
Forty-three patients reviewed from the literature and five cases of agranulocytosis during antibiotic therapy studied by the author are presented . Time required to develop agranulocytosis with antibiotics was < 19 days in comparison to > 40 days required with nonantibiotic drugs . In all, agranulocytosis occurred concomitantly with drug treatment and became normal as treatment was discontinued . Retrospective rechallenge studies suggest that agranulocytosis may be dose related . In all cases PMNs were almost completely deleted and marrows were devoid of granulocyte precursors . In contrast, leukopenia secondary to overwhelming sepsis displayed persisting granulocytes in peripheral blood and marrow . While leukagglutinins were not found in nine cited cases, four serums were toxic to test PMNs as measured by suppression of postphagocytosis respiratory burst . Clindamycin directly suppressed development of CFU-G in one sensitive patient but not in 16 normal controls . The hazard of antibiotics in suppressing granulocytopoiesis is emphasized by these observations.

Ann Neurol, 1993 Jan, 33(1), 94 - 100
The neurological complications of sepsis; Bolton CF et al.; Encephalopathy and polyneuropathy occur in 70% of septic patients . The encephalopathy is diffuse, appears early, is often severe, but reverses quickly with successful treatment of the sepsis . The electroencephalogram is a sensitive indicator of the incidence and severity of the encephalopathy, but computed tomograms of the brain and cerebrospinal fluid findings are unremarkable . Critical-illness polyneuropathy develops later and in association with multiple-organ failure . Recovery is more gradual . Difficulty in weaning from the ventilator is an important early manifestation . Electromyography should be routinely performed to establish the diagnosis . The polyneuropathy is a primary axonal degeneration, predominantly of distal motor fibers . A persistent deficit may eventuate in severe cases . Whether muscle is affected as consistently as brain and peripheral nerve, and by the same process, has not been determined . Medications used in critical care units, notably sedatives and neuromuscular blocking agents, often confuse the clinical picture . The neurological pathophysiology is unknown but current evidence suggests that nervous system dysfunction arises through the same mechanisms as for systemic organs in the septic syndrome.

Am J Med Qual, 1993 Spring, 8(1), 2 - 5
Usefulness of a discharge diagnosis of sepsis in detecting iatrogenic infection and quality of care problems; Barbour GL; To address the question of how often a diagnosis of sepsis in the discharge summary represents a condition present on hospital admission as opposed to an acquired condition, medical records from Veterans Affairs medical centers were reviewed . A random sample of discharged summaries coded for sepsis were obtained from five different hospitals . One hundred forty-one summaries involving 128 patients from 1989 were evaluated . Twenty-seven (18.7%) of the summaries were judged to be improperly coded . Of the remaining 114 summaries, 61 (53.5%) contained information supporting sepsis as an admission condition . Comparison of other clinical attributes of these summaries indicates that patients with sepsis on admission have some characteristics that are different from those of patients who acquire sepsis during care . These attributes include a history of chemotherapy, an overall shorter length of stay, and a lower death rate . Sepsis, as a discharge diagnosis, cannot be assumed to represent an iatrogenic condition or to be the result of poor care since more than half of the cases reviewed indicated that the condition was present at admission.

Indian J Gastroenterol, 1993 Jan, 12(1), 1 - 4
Role of zipper in the management of abdominal sepsis; Singh K et al.; BACKGROUND: Continuous peritoneal lavage, staged laparotomies and radical peritoneal debridement have been used to reduce mortality from severe abdominal sepsis . Recently, open abdomen technique using a 'zipper' with or without mesh for abdominal lavage has shown promising results . AIMS: To evaluate open abdominal technique using a zipper in patients with advanced diffuse peritonitis with impending or established multiple organ failure . METHODS: Modified open abdomen technique using zipper with or without mesh was used for abdominal closure in eight patients with severe generalized peritonitis (APACHE-II score range 27-30) . RESULTS: Zipper was inserted at first laparotomy in three patients, at second exploration in four and at the time of third laparotomy in one case . Two patients required strips of mesh in addition to zipper . Six of eight patients survived and were discharged after an average period of 27 days . Two deaths were due to multisystem organ failure . In four patients additional surgical procedures like closure of perforation, temporary ileostomy and resection anastomosis of small bowel was carried out through the zipper . Zipper-mesh were removed an average of 10.5 days after insertion . Three patients developed incisional hernia at 6 months follow-up . CONCLUSION: This technique merits further controlled trials to ascertain its indications and benefits.

Blood Purif, 1993, 11(2), 128 - 33
Interleukin-1, TNF alpha and their naturally occurring antagonists in sepsis; Moldawer LL; Recent evidence has demonstrated that specific inhibitors of the proinflammatory cytokines, IL-1 and TNF alpha, circulate in the blood of healthy individuals and concentrations of these inhibitors are elevated in inflammation . Initial characterization reveals that one of the classes of IL-1 inhibitors that circulates is the newly described IL-1 receptor antagonist (IL-1ra) . A class of newly described TNF inhibitors is the soluble type I (p55) and type II (p75) TNF receptor (sTNFR) . In patients with nonlethal infections, both IL-1ra and sTNFR appear to circulate at levels that can block the quantities of IL-1 and TNF alpha produced . However, such concentrations of inhibitors are inadequate to prevent the deleterious host responses to exaggerated proinflammatory concentrations seen in lethal septic shock . Nevertheless, administering either IL-1ra or soluble TNF receptors to raise plasma concentrations 1,000-fold can prevent the pathologic sequelae associated with excessive cytokine production.

Agents Actions, 1993, 39 Spec No, C125 - 7
Additive effects of a bradykinin antagonist, NPC 17761, and a leumedin, NPC 15669, on survival in animal models of sepsis; Otterbein L et al.; The effects of coadministration of NPC 17761 (D-Arg-Arg-Pro-Hyp-Gly-Phe-Ser-D-Hype (transthiophenyl)-Oic-Arg), a potent bradykinin antagonist, and NPC 15669 (N-{9H-(2,7-dimethylfluoren-9-yl-methoxy)carbonyl}-L-leucine), a leukocyte recruitment inhibitor, were examined in rodent models of experimental shock . In mice, ED50 doses of NPC 17761 (0.12 mg/kg) and NPC 15669 (4 mg/kg), administered together, increased survival (83%) and inhibited leukopenia (60% at 4 h) in response to a lethal dose of endotoxin . In rats, independent administration of NPC 15669 (10 mg/kg, i.v . bolus) or NPC 17761 (0.1 mg/kg/h, 4 h) did not significantly increase survival (36 +/- 4 and 46 +/- 9 h, respectively) versus controls (27 +/- 1 h) . However, co-treatment essentially "cured" (survival > 1 week) all septic animals, suggesting synergistic effects of the two agents.

Klin Khir, 1993, (6), 26 - 8
{Diagnosis and specifics of the clinical course of acute surgical sepsis}; Kavkalo DN; The results of observations on 176 patients with sepsis are presented . Criteria for diagnosis of acute surgical sepsis are substantiated, it symptoms, peculiarities of the course and outcome described . The criteria for differential diagnosis of diffuse purulent peritonitis and peritoneal sepsis on the basis of a mechanism of the polyorganic failure syndrome development are presented.

Otolaryngol Pol, 1993, 47(6), 529 - 33
{An atypical case of Wegener's granulomatosis complicated by sepsis and coxitis}; Makowski A et al.; There is presented an atypical case Wegener's granulomatosis of maxillo-nasal region without bony destruction . The case is unusual because of sepsis and purulent coxitis . The patient responded well to treatment with vincristine and cyclophosphamide . ANCA assays have very good sensitivity and specificity for Wegener's granulomatosis.

Klin Khir, 1993, (9-10), 43 - 5
{Evaluation of effectiveness of programmed laparostomy in the treatment of diffuse suppurative peritonitis and peritoneal sepsis}; Domanskii BV et al.; The results of treatment of 630 patients with peritonitis of different etiology are presented . In 170 patients with purulent peritonitis, the programmed laparostomy was used in the complex of treatment . A good immediate and long-term result was noted . Lethality reduced by 17.3%.

Intensive Care Med, 1993, 19 Suppl 2, S58 - 63
Neuromuscular complications of sepsis; Bolton CF; Sepsis and multiple organ failure are major problems in medical and surgical intensive care units . Critical illness polyneuropathy occurs in 70% of these patients . Difficulty in weaning from the ventilator is an early sign . Electrophysiological studies are necessary to establish the diagnosis; these studies show an axonal degeneration of peripheral nerve fibres . Recovery occurs in weeks or months, depending upon severity . Muscle biopsy reveals denervation atrophy . Sepsis itself does not induce a neuromuscular transmission defect, but neuromuscular blocking agents may increase the severity of critical illness polyneuropathy . If steroids are used in addition to neuromuscular blocking agents, a severe myopathy may result . Other effects on muscle are cachectic myopathy and panfascicular muscle fibre necrosis . A variety of combinations of these conditions may affect the same patient . Only well-designed prospective studies will determine the true effect of these medications on the neuromuscular system in septic patients.

Antibiot Khimioter, 1993 Jan, 38(1), 62 - 8
{Leukinferon in the comprehensive therapy of sepsis in newborns}; Nesterov VV et al.; Leukinferon was used in adoptive immunotherapy of sepsis in risk group newborns by activation of the donor leukocyte suspension in combination with etiotropic, antitoxic and other agents of chemotherapy . It accelerated the recovery at the average of 7 days in comparison with the control (the routine treatment) . The favourable time course of the major immunological indices such as leukocytosis and absolute and relative counts of lymphocytes mainly due to correction of the T-lymphocyte count, NBT and LII impaired by the pathological process was recorded at the average 4 days earlier against the control . By the end of the treatment normalization of the above mentioned indices proved to be more complete . Neither complications of the septic process nor side effects of the immunotherapy were observed.

Intensive Care Med, 1993, 19(6), 323 - 8
Preliminary observations on the neuromuscular abnormalities in patients with organ failure and sepsis; Coakley JH et al.; OBJECTIVE: To estimate the incidence and nature of neuromuscular abnormalities in a representative group of ITU patients . DESIGN: Prospective sequential study . SETTING: Teaching hospital ITU . PATIENTS: 23 patients who eventually stayed > 7 days on ITU who had no contraindication to muscle biopsy and whose relatives gave informed consent . MEASUREMENTS AND RESULTS: Muscle histopathology, neurophysiological studies, record of all drugs administered, APACHE II score, organ system failure score, presence or absence of sepsis, clinical evaluation of neuromuscular problems, time to hospital discharge . Heterogeneous neuromuscular abnormalities were present in 22 out of 23 patients studied and included axonal neuropathy, denervation, generalised fibre atrophy, non-specific myopathy and necrotising myopathy . CONCLUSION: Neuromuscular abnormalities are almost invariable in longstay intensive care patients and the resulting weakness may seriously delay hospital discharge . Various abnormalities were seen but no obvious aetiological factors were identified . The origin of the abnormalities is probably multifactorial.

Curr Opin Gen Surg . 1993;:19-25.
Surgical infections: blocking the mediator cascade responsible for sepsis and septic shock; Fink MP; In conventional usage, "sepsis" denotes a clinical syndrome caused by excessive release of a variety of proinflammatory mediators, including tumor necrosis factor alpha, interleukin-1, and metabolites of arachidonic acid . Because this condition can be precipitated by infectious or noninfectious causes (eg, acute pancreatitis), a recent consensus conference has advocated replacing the term sepsis with the phrase systemic inflammatory response syndrome . Improvements in our understanding of the pathophysiologic basis for systemic inflammatory response syndrome have resulted in the development of a number of novel approaches for treating, preventing, or limiting its deleterious consequences . Although much of this work remains confined to the laboratory, several of these approaches are undergoing (or recently have undergone) clinical evaluation . Among these are the use of monoclonal antibodies against endotoxin, monoclonal antibodies against tumor necrosis factor, recombinant proteins that antagonize the effects of or bind to circulating interleukin-1 or tumor necrosis factor, and drugs that inhibit the enzyme cyclooxygenase, which is responsible for the formation of certain key metabolites of arachidonic acid.

J S C Med Assoc, 1992 Dec, 88(12), 570 - 2
Immobilization hypercalcemia in an adult patient with pancreatitis and sepsis: case report; Latham BB et al.; We describe an adult patient who developed persistent hypercalcemia while bedridden for more than three months with pancreatitis and sepsis . On the basis of hypercalciuria, suppressed serum intact PTH, suppressed serum 1,25-dihydroxy vitamin D3 and no clinical evidence of malignancy, the diagnosis of immobilization hypercalcemia was established His hypercalcemia improved during treatment with saline, calcitonin and/or etidronate . With active mobilization and weight-bearing exercises, serum calcium finally normalized . We discuss clinical and laboratory features as well as current modalities of treatment of this rare form of hypercalcemia in adults.

Eur J Pediatr Surg, 1992 Dec, 2(6), 368 - 9
Continuous arteriovenous hemofiltration (CAVH) in a premature newborn as treatment of overhydration and hyperkalemia due to sepsis; Schroder CH et al.; If renal replacement therapy is required in the neonatal period, peritoneal dialysis is generally applied . In some cases, for example after extensive abdominal surgery, peritoneal dialysis is not possible . Continuous arteriovenous hemofiltration may then be an attractive alternative . The present paper describes the positive results in a 1265 g premature baby.

South Med J, 1992 Dec, 85(12), 1247 - 8
Trichosporon beigelii: a potential cause of sepsis in premature infants; Giacoia GP; Trichosporon beigelii is an emerging pathogen, often resistant to amphotericin B, that causes disseminated infection in immunocompromised patients . Early identification of this organism and knowledge of sensitivity patterns to antifungal agents may decrease the high mortality rate for immunocompromised patients with disseminated trichosporosis . I have reported a case of septicemia associated with T beigelii in a premature twin infant who had been granulocytopenic since birth.

Clin Investig, 1992 Dec, 70(12), 1079 - 81
Disseminated toxoplasmosis with sepsis in AIDS; Buhr M et al.; A 24-year-old woman with acquired immunodeficiency syndrome was admitted with septic fever of unknown origin and a 2-week history of diarrhea . Clinical diagnostic procedures did not reveal the cause of sepsis . Broad-spectrum antibiotics and intensive symptomatic therapy could not prevent progressive deterioration . The patient developed septic shock and consumptive coagulopathy and died 6 days after admission . Autopsy revealed disseminated infection with toxoplasma gondii and multiple organ manifestations . We conclude that disseminated toxoplasmosis should be considered in AIDS patients with septic disease of unknown origin . Extremely elevated lactate dehydrogenase may suggest disseminated toxoplasma gondii infection . New procedures such as polymerase chain reaction for detection of toxoplasmosis may be helpful diagnostic tools.

Ann Surg, 1992 Dec, 216(6), 648 - 55
Effects of recombinant human growth hormone in patients with severe sepsis; Voerman HJ et al.; The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis . It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital . Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects . Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission . The study period was eight days . During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01) . Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05) . Within 24 hours after cessation of treatment, differences between GH and controls disappeared . 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups . The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment . Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance . Side effects other than insulin resistance were not observed . Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis . These effects are not sustained after cessation of treatment.

Chest, 1992 Dec, 102(6), 1882 - 3
Evolving aortic mass in a patient with sepsis and systemic embolization . Detection by transesophageal echocardiography; Dubin JD et al.; An elderly patient with sepsis and systemic embolization is described . An intraluminal aortic mass was discovered by transesophageal echocardiography that appeared to be the source of infection in this patient . Transesophageal echocardiography can be a useful diagnostic test in patients with sepsis and systemic embolization of unknown etiology.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1992 Dec, 8(4), 272 - 5, 328-9
{Changes in plasma free amino acid concentration in burned patients with sepsis}; Li JY; The sequential changes in plasma free amino acid concentration were analyzed and compared in burned patients with sepsis (n = 12) and without sepsis (n = 19) . After burn injury, phenylalanine, methionine, lysine, and the Phe/Tyr ratio were significantly increased in two groups (P < 0.05-0.01) . Threonine, serine, histidine, arginine, proline and BCAA/AAA ratio were significantly decreased in two groups (P < 0.05-0.001) . The Phel Tyr ratio in patients with sepsis was much higher than that in patients without sepsis on postburn days 14 and 21 (P < 0.05), while the BCAA/AAA ratio in patients with sepsis was much lower than that in patients without sepsis on postburn day 14 (P < 0.01) . The level of proline in patients with sepsis was much higher than that in patients without sepsis on postburn days 3 and 7 (P < 0.05) . It is suggested that these results, in collaboration with other clinical and laboratory findings, may be helpful in foretelling the probable development of sepsis in patients with major burns.

S Afr J Surg, 1992 Dec, 30(4), 178 - 81
{Does a correlation exist between positive wound cultures at the end of an operation and later wound and prosthetic sepsis?}; De Jager MP et al.; A prospective study was carried out on 51 patients in whom a reconstructive vascular procedure was performed in order to determine whether any correlation between positive wound cultures at the end of the operation and later wound and/or prosthetic sepsis exists . Swabs were taken from all surgical wounds and cultured for aerobic and anaerobic organisms . The patients were monitored for 72-89 months and all instances of wound or prosthetic sepsis thoroughly investigated . The incidence of positive wound cultures was 13%, with a variety of organisms present . No increased incidence of wound or prosthetic sepsis was observed in patients with positive wound cultures . The incidence of wound sepsis was 3.7% and of prosthetic sepsis 2% . No correlation was found between organisms cultured during operation and organisms isolated from septic wounds . The 1 case of prosthetic sepsis (at 19 months postoperatively) was probably due to secondary haematogenous infection.

Circ Shock, 1992 Dec, 38(4), 253 - 63
Hyperdynamic sepsis in baboons: II . Relation of organ damage to severity of sepsis evaluated by a newly developed morphological scoring system; Schlag G et al.; The purpose of our study was to set up a baboon hyperdynamic sepsis model with live bacteria administration, which produces within 8 hr an organ failure comparable to human pathological conditions . Twelve adult male baboons were instrumented and studied for 8 hr under pentobarbital (2-3 mg/kg BW/hr) anesthesia breathing spontaneously . The animals were divided into two groups: 1) Live Escherichia coli were infused intravenously at a dose of 1.0-2.0 x 10(10) CFU/kg BW over 8 hr; 2) Live E . coli were infused i.v . at a dose of 5 x 10(8) CFU/kg BW over 2 hr . Organ damage was monitored by a newly developed scoring system . Organ damage was clearly dependent on the concentration of the bacterial challenge . Bacterial challenge at a dosage of 5.0 x 10(8) produces insignificant hemodynamic effects, while the 1.0-2.0 x 10(10) animals demonstrated massive hemodynamic alterations and needed much higher fluid support . The higher E . coli dosage was associated with an overwhelming organ damage seen, e.g., from the lung weight (12 g/kg BW vs . 9.6 g/kg BW with the lower dosage) or from the organ failure score, which is based on macroscopic pathology, histological data and organ weight . The percentage of animals with one, two, or three organ failures (organ failure score > or = 2) was higher in baboons with the higher dosage/kg BW . Therefore, we believe that the less severe organ damage in the acute phase after 8 hr with live bacteria 5 x 10(8) CFU/kg BW infusion over 2 hr is better to monitor the efficacy of newly developed therapeutic regimens, since in another set of experiments this model still produces lethal organ damage (80%) in a subchronic setting over 72 hr.

Circ Shock, 1992 Dec, 38(4), 238 - 44
Calcium transport by rat liver plasma membranes during sepsis; Lau YT et al.; The effects of sepsis on the ATP-dependent Ca2+ transport in rat liver plasma membranes were investigated . Sepsis was induced by cecal ligation and puncture (CLP) . Control rats were sham-operated . The results show that the ATP-dependent Ca2+ transport by liver plasma membranes was not affected during early sepsis (9 hr after CLP) but was decreased by 30-50% (P < 0.05) during late sepsis (18 hr after CLP) . Kinetic analysis of the data indicates that during late sepsis, the Vmax values for ATP and for Ca2+ were decreased by 38.5% (P < 0.05) and 41.8% (P < 0.05), respectively, while the Km values for ATP and Ca2+ remained unchanged . Mg2+ stimulated ATP-dependent Ca2+ transport . The Mg(2+)-stimulated activity was unaffected during early sepsis but was decreased by 34-63% (P < 0.05) during late sepsis . These data demonstrate that ATP-dependent Ca2+ transport in rat liver plasma membranes was impaired during late sepsis and that the impairment is associated with a mechanism not affecting the affinity of the Ca2+ transporter for ATP and Ca2+ . Since plasma membrane ATP-dependent Ca2+ transport plays an important role in the regulation of intracellular Ca2+ homeostasis in hepatocytes, an impairment in the ATP-dependent Ca2+ transport by liver plasma membranes during late sepsis may have a pathophysiological significance in contributing to the development of altered hepatic metabolism during septic shock.

JPEN J Parenter Enteral Nutr, 1992 Nov-Dec, 16(6), 581 - 5
Prevention of catheter-related sepsis during parenteral nutrition: effect of a new connection device; Inoue Y et al.; A prospective study was carried out to determine the clinical effect of a newly devised catheter connection method (I system) and piggyback access system . Previous studies have demonstrated that the I system avoided bacterial contamination in vitro during tubing change that Luer-Lock connectors did not . The purpose of this study was to investigate the ability of this device coupled with a new closed-system piggyback technique for multipurpose access to reduce catheter-related sepsis in clinical practice . Two hundred and thirty patients receiving total parenteral nutrition were divided into two groups . Group I (n = 106) used the I system connector and group L (n = 124) used a Luer-Lock connector . Catheters in both groups were used for multipurpose access for infusion and blood sampling . In group L, a three-way stopcock and/or pig-gyback system was used for multiple access . In group I, a newly designed closed-system piggyback was used . The incidence of catheter-related sepsis was significantly lower in group I (1.89%/catheter) than in group L (12.10%/catheter) (p < .01, chi 2 analysis), and the average duration of use of each catheter was significantly longer in group I than in Group L (p < .01 by generalized Wilcoxon test) . The results of this clinical study suggest that the newly designed connection method and piggyback access system are able to reduce catheter-related sepsis.

Nutrition, 1992 Nov-Dec, 8(6), 434 - 9
Regulation by insulin of muscle protein metabolism during sepsis and other catabolic conditions; Hasselgren PO et al.; The anabolic effect of insulin in skeletal muscle reflects increased protein synthesis and reduced protein degradation . Insulin stimulates protein synthesis mainly at the translational level by enhancing peptide chain initiation . The mechanism by which the hormone reduces protein breakdown is less well understood, but inhibition of the lysosomal pathway is probably an important component . Sepsis results in pronounced muscle catabolism, mainly reflecting increased protein breakdown, particularly myofibrillar protein breakdown, and a less prominent inhibition of protein synthesis . There is evidence that muscle protein breakdown becomes resistant to the effect of insulin during sepsis, probably at the postreceptor level . This insulin resistance may be mediated by increased beta-adrenoreceptor activity . In contrast, the stimulatory effect of insulin on muscle protein synthesis and amino acid transport is maintained during sepsis . The regulatory effect of insulin on muscle protein metabolism may be affected by other catabolic conditions as well, e.g., fasting, denervation, burn injury, and trauma.

J Pediatr Surg, 1992 Nov, 27(11), 1399 - 403
Is the metabolic response to sepsis in skeletal muscle different in infants and adults? An experimental study in rats; Zamir O et al.; In this study we compared the effect of sepsis on muscle protein metabolism in infant (3 to 4 weeks) and adult (3 to 4 months) rats . Sepsis was induced by cecal ligation and puncture (CLP) . Control animals underwent sham operation . Sixteen hours after CLP or sham operation, metabolic studies were performed in incubated intact extensor digitorum longus muscles from infant rats or in strips of the same muscle from adult rats . Protein synthesis rate was determined as incorporation of 3H-phenylalanine into protein; total and myofibrillar protein breakdown rates were determined as release of tyrosine and 3-methylhistidine, respectively . Mortality rate following CLP was similar in both age groups . Basal protein synthesis rate was 3 times higher, total protein breakdown rate was 50% higher, and myofibrillar protein breakdown rate was 3 times higher in infant than in adult animals . However, the relative changes in protein turnover rates induced by sepsis were similar in infant and adult rats: protein synthesis rate decreased by approximately 30%, total protein breakdown increased by 40% to 50%, and myofibrillar protein breakdown increased severalfold . The data suggest that despite prominent differences in basal protein turnover rates between infant and adult rats, the effect of sepsis on muscle protein metabolism is not age dependent.

Clin Geriatr Med, 1992 Nov, 8(4), 913 - 24
Sepsis; Bender BS; Septic shock is associated with a very high mortality in elderly patients . This is likely due to the age-related anatomic and physiologic changes and the presence of comorbid diseases . Medical management of patients with septic shock consists of antibiotics, fluids, vasopressors, and careful monitoring . Judicious use of antiendotoxin monoclonal antibodies may be a beneficial adjunctive therapy.

Crit Care Med, 1992 Oct, 20(10), 1395 - 401
Hypothermia in the sepsis syndrome and clinical outcome . The Methylprednisolone Severe Sepsis Study Group; Clemmer TP et al.; OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock . DESIGN: Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death . SETTING: Multi-institutional medical and surgical ICUs . PATIENTS: Patients meeting predetermined criteria for severe sepsis syndrome . INTERVENTIONS: Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo . MEASUREMENTS AND MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population . When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs . 60%), increased serum bilirubin concentration (35% vs . 15%), prolonged prothrombin times (50% vs . 23%), shock (94% vs . 61%), failure to recover from shock (66% vs . 26%), and death (62% vs . 26%) . The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission . CONCLUSIONS: This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock . This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

J Intensive Care Med, 1992 Nov-Dec, 7(6), 275 - 82
Critical appraisal of therapeutic interventions in the intensive care unit: human monoclonal antibody treatment in sepsis . Journal Club of the Hamilton Regional Critical Care Group; Cook DJ et al.; Using the medical literature to solve patient problems is challenging and rewarding . For intensive care physicians, this evidence-based medicine approach is more compelling when basic critical appraisal skills are developed . We highlight the important methodological points for interpreting the literature on treatment, using a cogent example from the critical care literature--monoclonal antibody therapy in sepsis . It is likely that as we move into the 1990s, growth in the number of articles on immunotherapy in the sepsis syndrome will parallel the growth of the general biomedical literature.

Clin Pediatr (Phila), 1992 Oct, 31(10), 578 - 82
Correlating CBC profile and infectious outcome . A study of febrile infants evaluated for sepsis; Bonadio WA et al.; The cases of 1,009 febrile infants who were evaluated for sepsis as outpatients during a seven-year period were reviewed to correlate their complete blood count (CBC) profiles with the infectious outcomes . Eighty-one infants had serious bacterial infections (SBIs); the remainder (928) were culture-negative . The infants with SBIs had a significantly greater mean total white blood cell (WBC) count and absolute band count (ABC) than did those who were culture-negative, whereas the difference in mean percent of polymorphonuclear leukocytes was not significant . The sensitivity of the ABC was significantly superior to that of total WBC count in predicting the outcome of SBI . The diagnostic data provided by the ABC can aid physicians in determining the predictive value of CBC profiles for infectious outcome in febrile infants receiving outpatient sepsis evaluation.

Am J Physiol, 1992 Oct, 263(4 Pt 1), E703 - 11
Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism; Lang CH; Bacterial infection decreases insulin-mediated glucose uptake (IMGU) by skeletal muscle and produces whole body insulin resistance . Because circulating catecholamines are elevated by the septic insult, the present study was performed to determine the potential role of the beta-adrenergic system in eliciting these changes . Before induction of sepsis, an infusion containing saline, propranolol, or atenolol was started and continued throughout the experimental protocol . Sepsis increased the basal rate of glucose production and utilization and impaired IMGU by peripheral tissues . The peripheral insulin resistance in septic rats was manifested by an increase in the dose producing 50% of maximal response and a decrease in the maximal responsiveness . Infusion of propranolol, a nonselective beta-adrenergic antagonist, attenuated the sepsis-induced increase in basal glucose turnover by 70% and completely prevented the decrease in IMGU by the whole body . In contrast, atenolol, a selective beta 1-antagonist, did not alter the glucose metabolic response to infection . Under basal conditions, propranolol prevented or attenuated the increase in glucose uptake by the gastrocnemius, diaphragm, skin, liver, lung, spleen, and ileum normally observed in septic rats . In addition, propranolol prevented the decrease in IMGU by various muscles and skin in septic animals . These results suggest that adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the sepsis-induced increases in basal whole body glucose turnover and plays a prominent role in the development of peripheral insulin resistance in this condition.

Biochem J, 1992 Sep 1, 286 ( Pt 2), 585 - 9
Increased intestinal protein synthesis during sepsis and following the administration of tumour necrosis factor alpha or interleukin-1 alpha; von Allmen D et al.; The influence of sepsis on intestinal protein synthesis was studied in rats . Sepsis was induced by caecal ligation and puncture (CLP); control rats were sham-operated . Protein synthesis was measured in vivo in the jejunum and ileum following a flooding dose of {14C}leucine . At 8 h after CLP the protein synthesis rate was increased by approx . 15% in jejunal mucosa, and at 16 h after CLP, the protein synthesis rate was increased by 50-60% in the mucosa and seromuscular layer of both jejunum and ileum . In a second series of experiments, rats were treated with recombinant tumour necrosis factor alpha (rTNF alpha) or recombinant interleukin-1 alpha (rIL-1 alpha) administered at a total dose of 300 micrograms/kg body weight over 16 h . Control rats received corresponding volumes of solvent . Treatment with rTNF alpha resulted in an approx . 25% increase in mucosal protein synthesis in jejunum . Following treatment with rIL-1 alpha, protein synthesis increased by 25% in jejunal mucosa and almost doubled in ileal mucosa . The results suggest that sepsis stimulates intestinal protein synthesis and that this response may, at least in part, be mediated by TNF and/or IL-1.

Am J Med, 1992 Sep, 93(3), 277 - 82
Single- versus triple-lumen central catheter-related sepsis: a prospective randomized study in a critically ill population; Farkas JC et al.; PURPOSE: A prospective randomized study was conducted over a 23-month period in an adult medical-surgical intensive care unit to determine whether triple-lumen catheters reduce the need for peripheral vascular access and whether they are associated with a higher rate of infection than single-lumen catheters . PATIENTS AND METHODS: After the insertion route, internal jugular or subclavian, was selected by the physician, patients were randomized either to single-lumen or triple-lumen catheter groups . Complementary peripheral vascular access was allowed in both groups . Catheters were removed according to preestablished defined reasons: suspicion of catheter-related sepsis, uselessness of central venous access, duration of catheterization of more than 21 days, discharge from the intensive care unit, or death . RESULTS: Data on 129 central venous catheters were collected from 91 consecutive patients . Twenty-five of 68 patients from the single-lumen group and 1 of 61 patients from the triple-lumen group needed peripheral vascular access (p less than 0.001) . Catheter-related sepsis rates, defined either by clinical signs and positive qualitative tip cultures (8.9% versus 11.5%) or by quantitative tip cultures (16.2% versus 11.5%), were identical in the single-lumen and triple-lumen groups (type II error: 8%) . CONCLUSION: In intensive care units, the use of triple-lumen catheters is associated with a dramatic decrease in the need for peripheral vascular access . The incidence of central venous catheter-related sepsis appears identical for single- and triple-lumen catheters.

Crit Care Med, 1992 Sep, 20(9), 1315 - 21
Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis; Berg S et al.; BACKGROUND AND METHODS: Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver . Increased plasma hyaluronan concentrations have been found in patients with sepsis . We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis . RESULTS: Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 {SEM} to mean maximum concentrations of 964 +/- 255 micrograms/L {p less than .01}) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L) . A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01) . Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs . 285 +/- 43 micrograms/L {p less than .05}) . CONCLUSIONS: Experimental sepsis is associated with an increase in serum hyaluronan values . The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause . An association between high hyaluronan values and nonsurvival in sepsis is possible.

Am J Kidney Dis, 1992 Sep, 20(3), 223 - 30
Endotoxemia, renal hypoperfusion, and fever: interactive risk factors for aminoglycoside and sepsis-associated acute renal failure; Zager RA; Sepsis and aminoglycoside administration remain leading causes of clinical acute renal failure (ARF) . In recent years, a number of experimental studies from different laboratories have indicated that specific components of the septic state, most notably fever, endotoxemia, and renal hypoperfusion, can interact to induce synergistic renal damage, acting in concert to produce acute tubular necrosis and ARF . If sepsis-associated ARF has a multifactorial basis, then a number of interventions directed at one or more of its etiologic components could confer protection . In this brief review, evidence to support these pathophysiological and therapeutic considerations are presented.

Am J Kidney Dis, 1992 Sep, 20(3), 214 - 22
Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock; Quezado ZM et al.; Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR) . For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased . In survivors, these abnormalities reverse to normal within 7 to 10 days . The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia . In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization . However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury . The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time . The pathophysiology of this disease is complex . Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock . Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate . Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.

Am J Kidney Dis, 1992 Sep, 20(3), 207 - 13
Sepsis-associated renal vasoconstriction: potential targets for future therapy; Badr KF; Systemic sepsis is associated with acute deterioration in renal function despite normal or increased cardiac output . The kidney is often structurally normal, but severe renal vasoconstriction underlies a marked decrease in the glomerular filtration rate (GFR) . The mechanisms underlying renal vasoconstriction in sepsis include locally and systemically released vasoconstrictors . Novel peptide and lipid-derived mediators that have been implicated in experimental models of sepsis include endothelin (ET)-1, thromboxane A2 (TXA2), leukotrienes (LTs), and, most recently, noncyclooxygenase-derived prostaglandin F2 (PGF2) analogues . Plasma ET-1 levels are elevated in septic patients and following endotoxin administration in experimental animals; antagonism of the endogenous actions of ET-1 is associated with improvement in renal perfusion and function during experimental endotoxemia . Antagonists of the TXA2 receptor and/or TXA2 synthesis in vivo have been associated with selective improvement in renal vascular tone and preservation of GFR during experimental endotoxemia in several mammalian species . Furthermore, antagonism of the TXA2 receptor inhibits the actions of endogenously released free radical-generated PGF compounds . The latter are the most potent renal vasoconstrictors among the family of arachidonic acid derivatives . Sulfidopeptide LTs, in particular LTC4 and LTD4, are also implicated in the renal vasoconstriction that attends sepsis in rats and other experimental animals . LT hepatobiliary elimination is suppressed during sepsis and endogenous LT production is enhanced . Antagonism of LTD4 receptors is associated with amelioration of renal vasoconstriction . Taken together, these novel potential mediators of renal vasoconstriction during sepsis constitute specific molecular targets for future therapeutic interventions.

Surgery, 1992 Sep, 112(3), 549 - 61
The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis; Bersten AD et al.; Because sepsis is characterized by a depression in vascular reactivity, we hypothesized that changes in organ blood flows (Q) would differ between the nonseptic and septic state during the infusion of sympathomimetics . Therefore we examined the (sepsis x organ Q) interaction during the infusion of five sympathomimetics in 36 mature, awake sheep before and after cecal ligation and perforation produced hyperdynamic sepsis . A 3-hour infusion of dobutamine, norepinephrine, dopamine, dopexamine, or salbutamol was compared with that of placebo during both nonseptic and septic studies; drug infusion was titrated to an increase in cardiac index of greater than 20% . Increased plateau infusion doses of norepinephrine (+305%), salbutamol (+275%), dopamine (+70%), and dobutamine (+49%) were required to achieve predefined treatment guidelines during the septic versus nonseptic study . Few differences in the regional effects of individual sympathomimetics were found in the nonseptic study, although infusion of sympathomimetics was accompanied by a redistribution of systemic Q toward the heart and away from the brain, kidney, small intestine, liver, and pancreas . In the septic study, however, the sympathomimetic infusions were not accompanied by the redistribution of Q away from small intestine and liver that was demonstrated in the nonseptic study . Therefore (1) the depressed vascular reactivity in hyperdynamic sepsis altered the dose profile of exogenous sympathomimetics required to augment systemic Q, and (2) the (sepsis x sympathomimetic) interaction was characterized by a depression in the anticipated redistribution of organ Q from "nonvital" to "vital" circulations.

Metabolism, 1992 Sep, 41(9), 961 - 9
Individual regulation of different hepatocellular functions during sepsis; von Allmen D et al.; The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis . This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats . Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated . After 16 hours, livers were perfused in situ, and bile flow, synthesis rates of albumin and alpha 1-acid glycoprotein (a major acute-phase protein in rats), and release of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) into perfusate were determined . Within the same livers, sepsis resulted in a 54% increase in the synthesis of alpha 1-acid glycoprotein and approximately 30% inhibition of albumin synthesis concomitant with 50% lower bile flow . The concentrations of GOT and GPT in the perfusate increased slightly during the experiments, both when control and septic livers were perfused . The maintained tissue levels of adenosine triphosphate (ATP) and the uptake of Evans blue dye by less than 1% of the hepatocytes, although a late test of viability, suggest that both control and septic livers remained viable during perfusion . The results are consistent with the concept that different hepatocellular functions are individually regulated during sepsis . Thus, impairment of certain hepatocellular functions does not necessarily imply generalized liver failure.

Metabolism, 1992 Sep, 41(9), 934 - 40
Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens; Voerman HJ et al.; The metabolic response to sepsis is dependent on the hormonal status . However, reported plasma hormone levels vary widely among studies . The persistence of pulsatile secretion, as occurs normally, may explain the observed variability . To study whether pulsatile hormone secretion persists during sepsis and how it affects assessment of the hormonal status from single measurements, we measured growth hormone (GH), prolactin, cortisol, insulin, and C-peptide at 20-minute intervals for 24 hours in eight consecutive patients with severe sepsis . Twenty-four-hour averages (mean +/- SD) were 3.3 +/- 2.5 ng/mL for GH, 640 +/- 461 nmol/L for cortisol, 18.2 +/- 4.8 mU/L for insulin, and 3.4 +/- 2.9 U/L for C-peptide, at a pulse frequency between 3.3 +/- 2.7 for C-peptide and 10.2 +/- 3.4 for insulin, and an increase of the maximal value in a pulse above the preceding nadir of 131% +/- 13% for cortisol and 376% +/- 386% for GH, as assessed with Cluster analysis . Prolactin levels were below the detection limit in all but one patient, probably due to the administration of dopamine . To determine the accuracy of less frequent blood sampling regimens, we simulated different sampling strategies and compared them with the 24-hour averages . The accuracy of single samples proved inadequate for all hormones . Sampling every 20 minutes for periods of 4, 8, or 12 hours improved accuracy, but intermittent sampling every 1, 2, 4, or 6 hours during a 24-hour period yielded even more accurate results.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1992 Sep, 11(9), 702 - 5
Therapy of bacterial sepsis, meningitis and otitis media in infants and children: 1992 poll of directors of programs in pediatric infectious diseases; Klass PE et al.; To determine current opinions among experts in pediatric infectious diseases for treatment of bacterial sepsis, meningitis and acute otitis media, we polled directors of training programs in January, 1992 . Responses were received from 69 centers in the United States and Canada . For initial treatment of presumed bacterial meningitis, the third generation cephalosporins alone or combined with ampicillin have become drugs of choice in all age groups . Most infectious disease programs include dexamethasone in the management of presumed bacterial meningitis for children 2 months of age and older . Third generation cephalosporins are also drugs of choice for presumed sepsis: combined with ampicillin for infants 5 weeks of age; used alone for children 5 months and 12 years of age . Amoxicillin remains the preferred drug for initial treatment of acute otitis media . The combination of amoxicillin and clavulanic acid is favored in the setting of an increased proportion of beta-lactamase-producing bacterial pathogens . Comparison of these results with polls in 1987 and 1989 indicates a shift in recommendations of therapy of presumed bacterial sepsis and meningitis from ampicillin alone or combined with an aminoglycoside or chloramphenicol to use of a third generation cephalosporin alone or combined with ampicillin.

Infect Dis Clin North Am, 1992 Sep, 6(3), 677 - 92
Fungal sepsis; Burchard KW; Immunocompromise can result from trauma, burns, cancer, cancer chemotherapy, and immunosuppressive therapy . Immunocompromise increases the risk of invasive infection from opportunistic fungi . The key to successful management of these infections is early recognition, aggressive therapy, and when indicated, surgical therapy . This article describes the common opportunistic fungal infections aspergillosis, zygomycosis, and candidiasis, which may arise in surgical patients or which may require surgical intervention for diagnosis or therapy.

Circ Shock, 1992 Sep, 38(1), 42 - 9
Effect of sepsis on intracellular sodium activity, sodium concentration, and water content in thermal injured rat; Chiao JJ et al.; The effects of sepsis on intracellular Na+ activity, Na+ concentration, and H2O partition in skeletal muscle were investigated in a burn rat model . Studies were performed on either postburn day 3 or day 7 during evolving burn wound sepsis . Data are compared among 3 groups of rats: burned and infected (BI), burned not infected (B), and sham burn (C) . After 3 days postburn both Na+ activity and concentration decreased in the BI group as compared with B and C groups . By postburn day 7, the BI group developed septic shock and had increased intracellular Na+ activity and concentration . The resting membrane potentials of skeletal muscle cells depolarized . The finding of an increased cell membrane relative permeability of Na+ to K+ could account for the increase in Na+ influx into cells . In addition, intracellular and total muscle H2O contents decreased and extracellular H2O increased . Hypernatremia, hyperchloremia, and hyperosmolality were also observed in the BI group . However, the fact that there was no significant difference between B and C groups indicates that the late derangements were due to septic shock rather than simple burn injury . Thus, the deleterious effects of the evolving burn wound sepsis on Na+ homeostasis might be due to the detrimental effect of increased intracellular Na+ activity on mitochondrial respiratory control with subsequent impairment of cellular functions.

Circ Shock, 1992 Sep, 38(1), 1 - 8
Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions; Simms HH et al.; The purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function . Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision . PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN . (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs . F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs . F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi . PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production . Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals . Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN . These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.

Gaoxiong Yi Xue Ke Xue Za Zhi, 1992 Sep, 8(9), 460 - 70
{Kinetic studies of protein kinase A in rat liver during late sepsis}; Jin YW et al.; The covalent modification of receptor proteins via phosphorylation and dephosphorylation is one of the principal mechanisms controlling carbohydrate metabolism and is known to be regulated by various protein kinases . Recent studies indicated that many hormones may exert their effects on cellular metabolism by regulating intracellular c-AMP levels and by activating a c-AMP dependent protein kinase, i.e., protein kinase A . The metabolic disturbances during sepsis are characterized by an initial hyperglycemia followed by a progressive hypoglycemia and a depletion of hepatic glycogen content . The latter is coupled with a slowdown in glycogenesis, an accelerated glycogenolysis, and a depression in gluconeogenesis in the liver . Since the liver is the major organ that regulates the homeostatic level of blood glucose, it is conceivable that the sepsis-induced glucose dyshomeostasis might be mediated by changes in protein kinase activity and the kinetic characteristics of enzymes . The present experiment was designed to study the correlation between protein kinase A and the pathophysiology of hepatic glucose dyshomeostasis during sepsis . Sepsis was induced in rats by cecal ligation and puncture (CLP) . Late sepsis occurred 18 hours after CLP . Protein kinase A was extracted from the rat livers by acid precipitation and ammonium sulfate fractionation, and then partially purified by DEAE-cellulose . The results show that in the late sepsis, type-I protein kinase A (eluted at low ionic strength) activity was significantly decreased by 34-52% (P < 0.01) . The kinetic parameters such as Vmax's for ATP, histone, and c-AMP were also significantly decreased from the control values of 6.1 +/- 0.9, 5.4 +/- 0.8, and 5.1 +/- 1.9 nmoles/mg.min . to 3.6 +/- 0.5, 2.8 +/- 0.3, and 2.5 +/- 0.5 nmoles/mg.min., respectively . Analysis using Hill's equation indicates that the S0.5 and n (Hill coefficient) values of the various substrates and activators for type-I protein kinase A remained unchanged . In the case of type-II protein kinase A (eluted at high ionic strength), the Vmax, S0.5, and n values for ATP, histone, and c-AMP were unchanged during late sepsis . The results of the present study indicate that the activities and kinetic characteristics of type I protein kinase A in rat liver are modified during late sepsis . Since protein kinase A is known to regulate glucose metabolism through adrenergic receptor mediation, these findings may have a pathophysiological significance in the understanding of hepatic glucose dyshomeostasis during sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)

Surgery, 1992 Aug, 112(2), 475 - 9
Triiodothyronine treatment maintains surfactant synthesis during sepsis; Dulchavsky SA et al.; BACKGROUND . Pulmonary compromise with altered surfactant metabolism is frequently noted during sepsis; triiodothyronine is necessary for normal surfactant synthesis . We evaluated the role of physiologic replacement of triiodothyronine during sepsis-induced hypothyroidism on surfactant synthesis and lung structural integrity . METHODS . Male Sprague Dawley rats (average weight, 330 gm) underwent sham laparotomy or cecal ligation and puncture; treatment was administered to rats that underwent cecal ligation and puncture by Alzet osmotic pump consisting of triiodothyronine (3 ng/hr) or saline control . The rats were killed 24 hours after serum triiodothyronine determination by radioimmunoassay (normal, 60 to 160 ng/dl) . Surfactant was obtained by saline lavage . Lipid content was determined by Folch extraction; phospholipid content was verified by chromatography . Blinded histologic analysis of lung confluence and alveolar sparing was done in separate subgroups . Results are +/- SE . RESULTS . Control rats with sepsis were hypothyroid at 24 hours; rats given triiodothyronine were euthyroid (rats that underwent sham laparotomy, 67.7 +/- 4.9 ng/dl; control rats, 37.6 +/- 5.7 ng/dl; and triiodothyronine, 85.7 +/- 19 ng/dl; p less than 0.05 compared with triiodothyronine by analysis of variance) . Surfactant production was significantly improved by triiodothyronine compared with control (60.7 +/- 22.6 mg vs 23.2 +/- 11.3 mg; p less than 0.05 by analysis of variance) . Lung histologic integrity was maintained by triiodothyronine treatment during sepsis . CONCLUSIONS . Triiodothyronine supplementation may be beneficial in septic-induced pulmonary dysfunction.

Clin Infect Dis, 1992 Aug, 15(2), 327 - 9
Severe pneumococcal sepsis and meningitis in human immunodeficiency virus-infected adults with sickle cell disease; Godeau B et al.; Pneumococcal infection is frequent in children with sickle-cell disease (SCD) but is less common in adults . Infection due to human immunodeficiency virus (HIV) is also a risk factor for pneumococcal infection . The purpose of this study was to determine the clinical course of HIV infection in adults with SCD . During a 6-year period, 283 adults suffering from SCD were screened for HIV type 1 and HIV type 2 infections . The clinical course of HIV infections in these patients was retrospectively analyzed at the term of the study . HIV type 1 infection was detected in eight patients . The mean follow-up period after diagnosis of HIV infection was 4.6 years . None of the patients had AIDS . Five episodes of severe pneumococcal infection were observed in four of these eight patients (septic shock in two patients and three episodes of meningitis in two patients); two patients died of meningitis . Only one severe pneumococcal infection (meningitis) was observed in the 275 non-HIV-infected patients with SCD (P = .000001) . Our results show that pneumococcal infection appears to occur frequently and is often serious in HIV-infected adults with SCD.

Am J Physiol, 1992 Aug, 263(2 Pt 1), E368 - 73
Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats; Yoshida S et al.; The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated . Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days . On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine . Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of {U-14C}leucine to determine the mucosal fractional protein synthesis rates . The following results were obtained . 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum . 2) Glutamine supplementation attenuated these changes . 3) There were no visible changes to the colon either from glutamine supplementation or sepsis . 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis . 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

Circ Shock, 1992 Aug, 37(4), 291 - 300
Pentoxifylline treatment of sepsis in conscious Yucatan minipigs; Law WR et al.; Recent evidence suggests that pentoxifylline (PTX) may be useful in the treatment of sepsis . We examined effects of PTX in a conscious swine model of sepsis . Yucatan minipigs (20-30 kg) were anesthetized and instrumented with catheters in the vena cava, aortic arch, pulmonary artery (Swan-Ganz thermodilution catheter), and peritoneum . Twenty-four hours after surgery, sepsis was induced by intraperitoneal (ip) injection of Escherichia coli bacteria (2 x 10(10) cfu/kg) . Nonseptic pigs received intraperitoneal saline (5 ml/kg) . PTX treatment (3 mg/kg/hr, iv; 1 mg/ml in 0.9% saline) and maintenance fluid (5 ml/kg/hr, iv) were started with bacterial infusion . An additional 60 cc/kg 0.9% saline bolus was administered iv at 1 hr . Pigs were monitored before and 1, 2, 5, and 24 hr after bacterial injection . Intraperitoneal injection of bacteria led to significant reductions in blood pressure and cardiac output and elevations in pulmonary wedge pressure and pulmonary vascular resistance . These effects were attenuated by PTX treatment . All septic animals demonstrated elevated creatinine, blood urea nitrogen, circulating endotoxin (LPS), and tumor necrosis factor concentrations, reductions in white blood cell and platelet counts, and peritonitis . None of these responses was altered by PTX treatment . We conclude that PTX may prove to be a useful therapeutic tool in the early treatment of septic shock but is limited in the scope of its effects.

Diagn Microbiol Infect Dis, 1992 Aug, 15(6), 499 - 503
Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis; Ascher DP et al.; We reviewed our experience with paired quantitative and standard blood cultures in the evaluation of children with suspected central-line sepsis with the hypothesis that by employing both systems we would increase our yield of pathogenic isolates . A total of 913 paired cultures were reviewed, representing 267 pathogenic isolates and 58 individual episodes of sepsis . The isolates were analyzed for recovery rates for each system and by combining both systems . The Isolator system proved to be equal to the BACTEC system for the recovery of all groups of pathogenic isolates . The combined use of both the quantitative and the standard culture systems demonstrated a statistically significant advantage (p less than 0.001) for the recovery of pathogens as compared with either system alone . The use of either system alone would have missed 15% of the total pathogenic isolates . Quantitative colony counts were helpful in identifying the line as the source of infection in 35 to 58 episodes of sepsis and were often beneficial in the clinical management central venous line infection . We recommend the use of the Isolator 1.5 ml combined with a conventional broth-bottle system in selected pediatric patients to enhance the recovery of pathogenic organisms.

Immun Infekt, 1992 Aug, 20(4), 128 - 33
{The role of interleukin 1 in infection and sepsis}; Beuscher HU et al.; Interleukin(IL-)-1 is the prototype of a proinflammatory cytokine, produced in response to infection and other forms of trauma . At low concentrations IL-1 brings about increases in a number of defense mechanisms, particularly immunologic and inflammatory responses . However, over- or continued production of IL-1, as seen for example during septic infection, significantly contributes to pathological reactions such as hemodynamic shock . Thus, it is not surprising that IL-1 activities are tightly regulated, most notably at the levels of transcription and secretion . Additional regulation is provided by the action of a protein, that blocks the binding of IL-1 to its receptors . This protein, termed IL-1-receptor antagonist (IL-1ra) has been cloned recently, and may provide the possibility of specific therapeutic measures.

J R Coll Surg Edinb, 1992 Aug, 37(4), 232 - 4
Management of perianal sepsis in a district general hospital; Fielding MA et al.; Perianal sepsis remains a common surgical problem . A total of 121 patients undergoing surgery for perianal abscess and/or fistulae over a 2-year period was studied . Of these, 50 patients (41.3%) had suffered from previous perianal sepsis (not necessarily resulting in hospital attendance) . Ninety-one patients underwent incision and drainage of abscesses (ischiorectal and perianal) for the first time, whereas eight patients underwent drainage of recurrent abscesses . Fistulae were identified when the abscess was drained in 14 of 91 patients, and a further ten patients subsequently developed fistulae . Twenty-two patients presented with a discharging fistula . A high yield of bowel organisms was present in patients with coexisting fistulae (88%), recurrent abscesses (75%) and in those who subsequently developed fistulae (83%) . We confirm that such a growth can be used to identify patients who will benefit from further examinations.

J Infect Dis, 1992 Aug, 166(2), 336 - 43
Effect of granulocyte colony-stimulating factor on sepsis-induced changes in neutrophil accumulation and organ glucose uptake; Lang CH et al.; Neutropenia was seen in rats made septic by subcutaneous (sc) injection of Escherichia coli . The sepsis-induced increase in glucose uptake by tissues distant from the site of infection was not associated with increased myeloperoxidase (MPO) activity . Only the skin and muscle at the site of infection demonstrated an increase in both glucose uptake and MPO activity . Granulocyte colony-stimulating factor (G-CSF) attenuated the sepsis-induced decrease in circulating neutrophils . Both glucose uptake and MPO activity of skin and muscle adjacent to the infection site showed a smaller increase in G-CSF treated rats . In contrast, septic rats injected with G-CSF exhibited a greater number of leukocytes and a larger reduction in the number of bacteria in the sc lavage fluid . These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil function and also increases their recruitment to the site of infection, resulting in improved bacterial killing and host defense.

Surgery, 1992 Aug, 112(2), 412 - 8
The possible inhibitory role of the leucine-zipper DNA binding protein c-fos in the regulation of hepatic gene expression after sepsis; Barke RA et al.; BACKGROUND . The leucine-zipper c-fos has been implicated in the regulation of gene expression . We investigated the possible role of c-fos in the regulation of hepatic gene expression after sepsis . Based on previous data demonstrating that sepsis inhibits hepatic gene expression of carnitine palmitoyltransferase (CPT), we hypothesized that c-fos may play a role in the inhibition of CPT gene expression after sepsis . METHODS . We studied c-fos gene expression after peritoneal sepsis induced by cecal ligation and puncture (CLP) or sham-CLP . To investigate the possible inhibitory role of c-fos on CPT gene transcription, we investigated the effect of c-fos on c-jun-driven CPT promoter-chloramphenicol acyltransferase reporter gene expression in a HepG2 hepatoma cell cotransfection model . To investigate the possible role of cyclic adenosine monophosphate (cAMP) in the regulation of c-fos in vivo, we treated either the sham-CLP group or the CLP group with either vehicle or cAMP . RESULTS . Peritoneal sepsis in the rat model resulted in a four-fold increase in hepatic c-fos mRNA and c-fos protein . In the cotransfection model, c-fos significantly inhibited c-jun-induced chloramphenicol acyltransferase activity . Treatment with cAMP resulted in a 50% decrease in c-fos protein in either the sham-CLP or CLP group . CONCLUSIONS . We conclude that (1) sepsis increases hepatic c-fos transcription and translation, (2) c-fos inhibits c-jun-induced CPT gene expression, and (3) cAMP probably does not directly mediate the increase in c-fos after sepsis.

Am J Physiol, 1992 Jul, 263(1 Pt 2), R19 - 23
Sepsis produces early depression of gut absorptive capacity: restoration with diltiazem treatment; Singh G et al.; Although gut permeability increases and bacterial translocation occurs under certain pathological conditions, it remains unknown whether gut absorptive capacity (GAC) is altered early after the onset of sepsis . The aim of the present study was to investigate this and also to determine whether diltiazem has any effect on GAC in early sepsis . Rats were lightly anesthetized and cecal ligation and puncture (CLP) was performed . A nasogastric tube was inserted, cannulation of various blood vessels was carried out, and the animals were allowed to recover from anesthesia . One hour after CLP, one group of animals received a 1-ml bolus of normal saline intravenously, and another group received diltiazem, 400 micrograms/kg body wt . Sham animals had no CLP performed . GAC was determined by the D-xylose absorption test at 2 and 4 h after CLP . One hour after the administration of D-xylose via the nasogastric tube, its concentration in portal blood was determined colorimetrically . Results show that GAC is significantly depressed at 2 and 4 h after CLP despite the maintenance of normal blood pressure, central venous pressure, and portal pressure . Administration of diltiazem restored GAC to normal levels at 4 h after CLP . Thus diltiazem is a useful adjuvant in the treatment of sepsis because it restores gut absorptive capacity to normal and allows for early enteral nutrition.

Am J Physiol, 1992 Jul, 263(1 Pt 1), G38 - 43
Differential alterations in microvascular perfusion in various organs during early and late sepsis; Wang P et al.; Although cellular dysfunction occurs very early in sepsis, it remains controversial whether this is solely due to a decrease in tissue perfusion . Recent studies have indicated that while active hepatocellular function was depressed, hepatic surface microvascular blood flow (MBF) increased in early sepsis but decreased in late sepsis as produced by cecal ligation and puncture (CLP) . However, it is not known whether microvascular hyperperfusion in early sepsis and microvascular hypoperfusion in late sepsis are common events in other organs under such conditions . To study this, rats were subjected to sepsis by CLP, after which these and the corresponding shams received 3 ml/100 g body wt normal saline . Microvascular perfusion and MBF in various tissues were assessed by colloidal carbon infusion and laser-Doppler flowmetry, respectively, at 5 h (i.e., early sepsis) or 20 h (late sepsis) after CLP or sham operation . Carbon-perfused areas were quantitated by an Optomax image analyzer . The results indicate that the carbon-perfused areas and MBF in the liver, renal cortex, spleen, and small intestinal serosa (only MBF) increased significantly 5 h after CLP . In late sepsis, however, the carbon-perfused areas and MBF were found to be significantly decreased . A highly linear relationship was observed between the changes of carbon-perfused areas and MBF during sepsis in the tested organs . Thus the microvascular responses in the fluid-resuscitated sepsis model are characterized by hyperperfusion in the early stage and hypoperfusion in the late stage of sepsis in the tested tissues . The cellular dysfunctions observed during the early stage of sepsis are, therefore, not due to any reduction in tissue perfusion.

Arch Intern Med, 1992 Jul, 152(7), 1381 - 9
Modulators of coagulation . A critical appraisal of their role in sepsis; Bone RC; Widespread intravascular coagulation is common in patients with sepsis . Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor . The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems . Multiple agents are being studied to correct these abnormalities . Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin . Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue . Bradykinin may offset hypotension in sepsis . Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis . Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin . There are no data to support the use of heparin or fibronectin, except in limited circumstances.

Chest, 1992 Jul, 102(1), 208 - 15
Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients; Shoemaker WC et al.; In a series of 253 high-risk surgical patients, we measured the oxygen consumption (VO2) at frequent intervals before, during, and immediately after surgical operations and calculated the rate of VO2 deficit from the measured VO2 minus the VO2 need estimated from the patient's own resting preoperative control values corrected for both temperature and anesthesia . The calculated oxygen deficit was related to multiple organ failure, complications, and outcome . The 64 patients who died all had organ failure; their cumulative VO2 deficit averaged 33.2 +/- 4.0 L/m2 (+/- SEM) at its maximum, which occurred 17.8 +/- 2.2 h after surgery . In the 31 survivors with organ failure, the cumulative VO2 deficit averaged 21.6 +/- 3.7 L/m2 at its maximum, which occurred 10.1 +/- 2.7 h after surgery (p less than 0.05) . In the 158 survivors without organ failure or major complications, the maximum cumulative VO2 deficit averaged 9.2 +/- 1.3 L/m2 at 4.1 +/- 0.6 h after surgery (p less than 0.05) . In a prospective randomized clinical trial, a protocol group maintained at supranormal hemodynamic and oxygen transport values had significantly reduced oxygen debt (7.6 +/- 3.4 L/m2 vs 17.3 +/- 6.8 L/m2; p less than 0.05), fewer organ failures, and lower mortality (4 percent vs 33 percent; p less than 0.05) compared with a control group maintained at normal hemodynamic values . The data demonstrate a strong relationship between the magnitude and duration of the VO2 deficit in the intraoperative and early postoperative period and the subsequent appearance of organ failure and death . The latter may be reduced when oxygen debts were prevented or minimized by augmenting naturally occurring compensations that increased oxygen delivery.

Chest, 1992 Jul, 102(1), 184 - 8
Gastric tonometry in patients with sepsis . Effects of dobutamine infusions and packed red blood cell transfusions; Silverman HJ et al.; We wanted to determine the efficacy of dobutamine infusions and Prbc transfusions on splanchnic tissue oxygen utilization by measuring gastric pHi . Physiologic parameters and pHi measurements via the use of a gastric tonometer were obtained in 21 septic patients before and after the administration of a dobutamine infusion (5 micrograms/kg/min) or the transfusion of two units of Prbc . Subsets of measurements with normal (greater than 7.32) and with low (less than 7.32) pHi were separately analyzed for each intervention . In the dobutamine low pHi group, pHi increased significantly from 7.16 +/- 0.03 to 7.24 +/- 0.03 (n = 9, p less than 0.05) . In contrast, pHi failed to increase in the Prbc low pHi subgroup (7.16 +/- 0.05 to 7.17 +/- 0.04 {n = 10, p greater than 0.80}) . We conclude that dobutamine rather than Prbc transfusions should be administered to reverse gastric intramucosal acidosis.

Surgery, 1992 Jul, 112(1), 37 - 44
Oxygen kinetics in experimental sepsis; Hirschl RB et al.; Systemic oxygen delivery (DO2) is normally four to five times higher than oxygen consumption (VO2), and VO2 is independent of DO2 . If DO2 is decreased to less than twice VO2, a state of anaerobic metabolism and supply dependency occurs . Some authors have reported that this biphasic relationship is altered in the adult respiratory distress syndrome or sepsis to a condition of continuous supply dependency . If that were true, it would affect both our understanding and management of metabolism during sepsis . Therefore we measured VO2 and DO2 in a dog peritonitis model . DO2 was regulated with controlled pericardial tamponade . During sepsis VO2 increased 28% from a mean baseline of 5.6 to 7.3 cc O2/kg/min (p less than 0.005) . As progressive cardiac tamponade was applied during sepsis, the DO2/VO2 ratio fell . When the DO2/VO2 ratio was greater than 2.4, VO2 remained independent of DO2 . At DO2/VO2 ratios less than 2.4, VO2 was dependent on the level of DO2, and it diminished rapidly as DO2 decreased . Oxygen saturation in mixed venous blood (SvO2) consistently reflected the DO2/VO2 ratio in a fashion similar to that in normal dogs . A ratio of DO2/VO2 of 2.4 corresponded with an SvO2 of 42% +/- 12%, which was identified as a statistically significant critical SvO2 that marked onset of VO2 supply dependence . In this dog septic model, VO2 is independent of DO2 when DO2 is adequate . A state of continuous supply dependency does not exist . SvO2 reflects the status of the DO2/VO2 relationship in the septic state.

Surgery, 1992 Jul, 112(1), 24 - 31
Prophylaxis of infection with intravenous immunoglobulins plus antibiotic for patients at risk for sepsis undergoing surgery for colorectal cancer: results of a randomized, multicenter clinical trial; Cafiero F et al.; BACKGROUND . The results of a randomized, multicenter clinical trial with perioperative short-term antibiotic plus intravenous immunoglobulins (IVIG + A) versus antibiotic alone (A) for prevention of postoperative infections in patients at risk for sepsis undergoing surgery for colorectal cancer are presented . METHODS . The patients at risk for sepsis were selected by an original multiparametric test based on delayed-hypersensitivity skin testing and serum protein electrophoretic subfractions . This screening had shown 76% positive predictability in a previous validation assessment . Eighty patients at risk for sepsis were selected prospectively from 210 patients undergoing surgery for colorectal cancer; 43 patients were randomly assigned to the IVIG + A group and 37 to the A group . IVIG was administered on the day before operation, on the first and fifth postoperative days . RESULTS . There was a clear-cut reduction of postoperative infections in the IVIG + A group: 21 infections in 20 patients versus 37 infections in 29 patients in the A group (p less than 0.004) . With regard to serum immunoglobulin (Ig) G monitoring, basal IgG levels were significantly lower in patients given IVIG + A who had postsurgical infections (p less than 0.005) compared with patients with a regular outcome, whereas the same was not true in the A group of patients . CONCLUSIONS . A significant decrease (p less than 0.001) of postoperative IgG was evidenced in the A group of patients who had infections as opposed to a significant increase (p less than 0.001) of postoperative IgG in IVIG + A patients with a normal outcome.

Clin Orthop, 1992 Jul, (280), 200 - 7
Etiology of deep sepsis in total hip arthroplasty . The significance of hematogenous and recurrent infections; Schmalzried TP et al.; Between January 1970 and August 1986, 3051 total hip arthroplasties (THAs) were performed at the authors' institution . Forty-seven hips in 43 patients developed deep infection . Using clinical and laboratory criteria, patients were classified into four modes of infection: (1) surgical contamination, which included hips (N = 13) with a suspicious clinical course (e.g., persistent elevation of sedimentation rate, early radiographic signs of loosening) without another identifiable source; (2) hematogenous spread, which included septic hips (N = 19) with a temporally related infectious source and an organism consistent with that source; (3) recurrent sepsis, septic failure in a previously infected hip (N = 13); and finally, (4) infection from direct or contiguous spread, which occurred in an additional two patients . Thus the majority of infections were nonsurgical . Patients with surgically acquired infections tended to present earlier, were less likely to require a Girdlestone procedure for salvage, and were more likely to be reimplanted (p = 0.024) . The incidence of surgical infections decreased with the use of improved antiseptic techniques . The incidence of hematogenous infection, however, increased during the time that a cohort was followed . Additionally, in a previously septic hip, septic failure may occur as late as seven years after THA.

Arch Surg, 1992 Jul, 127(7), 859 - 63
Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2; Gough DB et al.; A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity . Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied . Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture . Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture) . Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better . At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10) . By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively) . Responses at day 7 approached those of controls given sham cecal ligation and puncture . Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.

J Emerg Med, 1992 Jul-Aug, 10(4), 445 - 53
The sepsis workup for the febrile child; Su E; The sick infant or toddler who presents with a high fever or suspected sepsis must have all possible sources for bacterial infection excluded by clinical evaluation or laboratory studies as quickly and safely as possible . The process is frightening and often painful for the child . The process can be difficult for the physician because of the smallness of anatomic structures in children and the infrequent performance of pediatric procedures by many emergency physicians . This article uses a case report to illustrate features of the sepsis workup . Methods and sites that have been used with the most frequent success are described and alternatives and pitfalls are listed.

J Surg Res, 1992 Jul, 53(1), 55 - 61
Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage; Ertel W et al.; Although hemorrhage depresses splenocyte (SPL) functions and increases susceptibility to sepsis, it is not known whether increased tumor necrosis factor (TNF) or prostaglandin (PG) production are responsible for it . To study this, mice (C3H/HeN) were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 min, resuscitated, and treated with ibuprofen (1.0 mg/kg body weight) or vehicle (saline) . Hemorrhage reduced (P less than 0.05) SPL proliferation by 60%, SPL release of interleukin-2 (IL-2) by 47%, interferon-gamma (IFN-gamma) by 67%, TNF by 54%, and interleukin-6 (IL-6) by 46% compared to sham . In addition, splenic macrophage (sM phi) release of interleukin-1 (IL-1) and TNF was decreased by 58 and 67% (P less than 0.05), respectively . However, ibuprofen treatment increased (P less than 0.05) SPL proliferation, lymphokine (IL-2, IFN-gamma, and IL-6) synthesis, and IL-1 release by sM phi compared to hemorrhage alone . Furthermore, ibuprofen enhanced the release of TNF by SPL (+175%, P less than 0.05) and sM phi (+68%) compared to the vehicle group . Ibuprofen also decreased (P = 0.011) the susceptibility to sepsis following hemorrhage . These results indicate that PGs are involved in hemorrhage-induced suppression of cellular immunity and in the increased mortality of such animals following a septic challenge.

Am J Physiol, 1992 Jun, 262(6 Pt 2), F965 - 71
Sequential changes in renal oxygen consumption and sodium transport during hyperdynamic sepsis in sheep; Weber A et al.; The sequence of changes in systemic and renal oxygen delivery (QO2) and consumption (VO2) and renal function in an ovine model of progressive hyperdynamic sepsis was investigated . Nine chronically instrumented awake sheep were given a continuous intravenous Escherichia coli endotoxin infusion (20 ng.kg-1.min-1) for 3 days . After 8 h of the infusion, systemic arterial blood pressure and vascular resistance stayed decreased by 30% (P less than 0.001) . Systemic QO2 progressively increased to a maximum of 157% of baseline values at 24 h and was associated with a decreased O2 extraction ratio from 33 +/- 2 (SE) to 23 +/- 2% (P less than 0.05), resulting in an unchanged systemic VO2 . Renal blood flow and renal QO2 decreased by 40% during the first 12 h, returning to and staying at baseline values after 24 h . Renal VO2 decreased significantly by 35% at 12 h and then partially recovered to baseline values . Plasma creatinine clearance was maximally reduced to 25% of baseline values at 12 h and thereafter remained significantly (P less than 0.01) below 50% of baseline values . Both total and fractional sodium excretion fell at 12 h by 95 and 74%, respectively, and remained reduced over time, indicating conserved tubular function . The ratio of moles of sodium reabsorbed to moles of O2 consumed by the kidney was transiently reduced, from 33.4 +/- 4.1 to 12.4 +/- 3.6 at 12 h (P less than 0.05), indicating a relative increase in energy expenditure for tubular transport or renal synthetic activities, but recovered to baseline values after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Crit Care Med, 1992 Jun, 20(6), 891 - 8
Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis; Bone RC; OBJECTIVE: Damage to the vascular system is a major finding of sepsis and its sequelae . This damage is caused, in part, by the recruitment and adhesion of neutrophils to the endothelium and their release of destructive molecules . Mediators released by various cell types, including the neutrophil itself, control these destructive actions of the neutrophil . The complement system is one such group of mediators . Through the use of medications that decrease neutrophil activation and adherence and block complement activation, it may be possible to control the course of sepsis . DATA SOURCES: The issues discussed in this paper come from a wide variety of sources, including several broad-based clinical studies of humans with inflammatory disease . Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics . STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent new discoveries . Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals . Few clinical studies have been performed using these agents . DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including important basic science and clinical journals such as Science, Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine . DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies . These contradictions are discussed and may often be due to different protocols and different definitions of the various clinical states . CONCLUSIONS: Pentoxifylline has been shown to decrease neutrophil adhesion and provides increased survival rate in various animal models of sepsis . Early studies regarding monoclonal antibodies to adhesion molecules are exciting . However, the possible effects of these agents in sepsis has yet to be studied . Drugs have been discovered that show potential to block the numerous destructive agents released by degranulating neutrophils.

Crit Care Med, 1992 Jun, 20(6), 884 - 90
Phospholipids and their inhibitors: a critical evaluation of their role in the treatment of sepsis; Bone RC; OBJECTIVE: The clinical condition sepsis and its sequelae are caused by numerous mediators that are released by various cell types . The purpose of this review is to describe the results of various studies performed with agents that either inhibited or stimulated the synthesis of, or affected the receptor-binding characteristics of a specific class of these mediators, the phospholipids . DESIGN: Antagonists to platelet-activating factor and thromboxane A2 receptors, monoclonal antibodies to phospholipase A2, agents which increased levels of prostaglandins, and cyclooxygenase, lipoxygenase, and other specific pathway inhibitors, which block the production of leukotrienes and thromboxane A2, were used in the studies described to affect the physiologic correlates of sepsis animal models and human studies . DATA SOURCES: The matters discussed in this paper come from a wide variety of sources, including many broad-based clinical studies of humans with inflammatory disease . Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics . STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent discoveries . Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals . Clinical studies are generally of large numbers of patients showing overt signs of sepsis . DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including such major basic science journals as Science, and clinical journals such as the Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine . DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies . These contradictions are discussed in this review, and may often be due to the use of different protocols and definitions of the various clinical states . CONCLUSIONS: Increases of some mediators, such as platelet-activating factor, thromboxane A2, and the leukotrienes are associated with animal models of sepsis and seem to have a negative effect on the course of sepsis . Antagonists and blockers of these mediators increased survival in these studies . More research is needed to identify how these mediators of inflammation are associated with sepsis, and what the effects of blocking their actions will have on sepsis.

Crit Care Med, 1992 Jun, 20(6), 864 - 74
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis; Sepsis induces an early increased spontaneous release of hepatocellular stimulatory factor (interleukin-6) by Kupffer cells in both endotoxin tolerant and intolerant mice; Department of Surgery, Michigan State University, East Lansing 48824Previous studies have shown that hepatocellular function is significantly depressed early during sepsis and that this is associated with a marked increase in the circulating levels of the hepatocellular stimulatory factor (IL-6) . It remains unknown, however, whether or not Kupffer cells (KC) are activated during sepsis and whether these cells are the major contributors to the increased circulating levels of this cytokine . The objectives of this study were, therefore, to determine whether or not during sepsis: (1) KC are stimulated in vivo to release IL-6, as compared to other cytokines; (2) KC differ from splenic macrophages (SM phi) in their ability to release cytokines; and (3) there is a difference in macrophage (M phi) cytokine release between endotoxin (ET)-tolerant (C3H/HeJ) and ET-intolerant (C3H/HeN) mice . To assess this, KC and SM phi were harvested at 1 or 24 hr from mice which had been subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) or sham-operation . Following depletion of the nonadherent cells, KC and SM phi cultures were incubated for 24 hr in the presence or absence of 10 micrograms of ET/ml, and the levels of interleukin (IL)-1, IL-6, and TNF release were determined by bioassays . Sepsis induced an early (at 1 hr) in vivo stimulation of KC but not SM phi IL-6 release, irrespective of ET-tolerance/intolerance . However, the release of IL-1 or TNF was not markedly different for either CLP or sham KC.(ABSTRACT TRUNCATED AT 250 WORDS)

Circ Shock, 1992 Jun, 37(2), 134 - 44
Altered endothelial mechanisms blunt skeletal muscle microcirculatory responses to live E . coli sepsis in 1K1C hypertension; Lubbe AS et al.; While renovascular (1K1C) hypertension significantly attenuates small arteriole dilation to sepsis in skeletal muscle of rats, maximal dilation of these small arterioles is not altered in response to an endothelium-independent vasodilator (nitroprusside) . This suggests that 1K1C hypertension modifies a receptor-level mechanism to reduce small arteriole vasodilation during sepsis . To test this hypothesis, we used hydroquinone (HQ) to block an endothelium-derived relaxing factor (EDRF) in skeletal muscle arterioles of sodium pentobarbital (45 mg/kg BW)-anesthetized 1K1C-renovascular hypertensive male Sprague-Dawley rats which were then made septic . We found that responses of large and small arterioles to sepsis were blunted in hypertensive rats and that these responses were unchanged during the presence of HQ . This suggests 1) that blockade of some vasodilator mechanisms does not unmask an enhanced vasoconstrictor influence during sepsis in 1K1C hypertension and 2) that EDRF mechanisms are blunted by 1K1C hypertension . To further test this second idea, we examined the responses of small arterioles to acetylcholine (ACH) in normotensive and renovascular (1K1C) hypertensive rats before and after EDRF blockade . Skeletal muscle small arterioles were essentially not reactive to ACH in the hypertensives and HQ did not change this response . However, some vasodilation in hypertensives occurred under very high ACH concentrations even during the presence of HQ . These data suggest that sepsis-induced small arteriole dilation in skeletal muscle is blunted because endothelium-mediated responses are impaired in renovascular hypertension . Nevertheless, EDRF-independent mechanisms appear to be left intact during this form of hypertension.

Am J Physiol, 1992 Jun, 262(6 Pt 1), C1513 - 9
Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles; Vary TC et al.; Sepsis is associated with severe muscle wasting . Mechanisms responsible for sepsis-induced alterations in muscle protein metabolism were investigated in vivo and compared with changes induced by nonseptic inflammation . The rate of protein synthesis in mixed hindlimb muscles was not altered in inflammation but was inhibited 50% in sepsis . This inhibition did not result from a decreased RNA content . Instead, the translational efficiency was significantly reduced by 50% in skeletal muscle of septic animals compared with control . The effect of sepsis to lower the rate of protein synthesis was further examined using individual muscles containing different fiber types . Both the protein concentration and protein synthetic rate in fast-twitch muscles were reduced by sepsis, whereas neither of these parameters was affected in slow-twitch muscles or heart . The decreased translational efficiency did not result from a change in the rate of peptide-chain elongation . Instead, the sepsis-induced inhibition of protein synthesis resulted from a restraint in peptide-chain initiation because sepsis caused a 1.6-fold increase in free ribosomal subunits . Overall, sepsis, but not inflammation, caused an inhibition of protein synthesis primarily in muscles composed of fast-twitch fibers . The mechanism involved in the reduced rates of protein synthesis in muscles resulted from an inhibition of peptide-chain initiation, with no change in peptide-chain elongation.

Chest, 1992 Jun, 101(6), 1644 - 55
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis . The ACCP/SCCM Consensus Conference Committee . American College of Chest Physicians/Society of Critical Care Medicine; Bone RC et al.; An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae . New definitions were offered for some terms, while others were discarded . Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized . Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered . The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality . Appropriate methods and applications for the use and testing of new therapies were recommended . The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.

Schweiz Med Wochenschr, 1992 May 16, 122(20), 768 - 75
{Sepsis syndrome: progress and therapeutic perspectives}; Schaller MD; To reduce the very high mortality rate due to septic shock, a new clinical entity has been defined: sepsis syndrome . The aggressive treatment of any sepsis syndrome should prevent the evolution towards a state of shock and thus reduce the risk of a fatal outcome . It consists in broad spectrum antibiotic therapy associated with hemodynamic support (volume resuscitation, vasopressors and inotropic agents) at the first signs of cardiocirculatory failure . Several pharmacological or immunological interventions--antagonists directed at mediators and multiple cytokines involved in the pathogenesis and perpetuation of sepsis syndrome and septic shock--have been successful experimentally . However, new therapies, such as those using monoclonal antibodies against endotoxins of TNF, cannot yet be considered established.

Ann Surg, 1992 May, 215(5), 460 - 5; discussion 465-6
Total IgE in plasma is elevated after traumatic injury and is associated with sepsis syndrome; DiPiro JT et al.; Gamma E immunoglobulin (IgE) is associated with allergic reactions, but has not been described as being activated after trauma or sepsis . Total plasma IgE concentrations were determined in 32 patients with major traumatic injury, 29 patients undergoing elective abdominal operations, and 30 healthy volunteers . Mean total IgE concentrations were 271.7 ng/mL, 52.3 ng/mL, and 41.3 ng/mL, respectively (p less than 0.01 for each comparison with the trauma group) . Total IgE concentrations in trauma patients at the time of admission were not significantly different from elective surgical controls, and tended to increase during the intensive care unit stay . In the trauma group, total IgE concentration was significantly greater in the 18 patients that developed sepsis syndrome compared with those that did not (p = 0.034) . These data suggest that allergic mechanisms may be involved in the physiologic response to major traumatic injury and sepsis syndrome, or that other cells known to be involved in the immune responses to trauma and sepsis (macrophages, platelets, and B lymphocytes) may become activated by IgE-dependent mechanisms.

Am J Physiol, 1992 May, 262(5 Pt 1), E728 - 35
Sepsis-induced cascade of cytokine mRNA expression: correlation with metabolic changes; Byerley LO et al.; The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined . From 0 to 2 h, serum glucose significantly decreased while plasma glucagon increased . By 8 h, plasma glucagon, serum insulin, and glucose appearance were significantly elevated . Gene expression of phosphoenolpyruvate carboxykinase increased 1 h after E . coli but by 4 h was significantly decreased . TNF-alpha mRNA (liver and spleen) and serum peptide levels peaked 1-2 h after the septic challenge and then decreased substantially by 6-8 h . Spleen IL-6 and gamma-IFN mRNA expression reached a maximum 4 h after E . coli challenge, whereas serum IL-6 levels were elevated by 2 h after injection of the bacteria . The increase in TNF-alpha mRNA and serum peptide levels correlated with the early fall in serum glucose and rise in plasma glucagon . Alterations in the rate of glucose appearance and plasma glucagon were observed later and coincided with the increased mRNA expression of IL-6 and gamma-IFN . Thus the metabolic alterations observed in the septic rat are associated with a complex cascade of several cytokines.

Eur J Clin Chem Clin Biochem, 1992 May, 30(5), 263 - 9
Characterization of two phospholipases A2 in serum of patients with sepsis and acute pancreatitis; Kortesuo PT et al.; Pancreatic phospholipase A2 and non-pancreatic ascitic phospholipases A2 were studied in sera of healthy individuals and of patients suffering from sepsis or acute pancreatitis . In gel filtration experiments, immunoreactive ascitic phospholipase A2, as determined in serum by a time-resolved fluoroimmunoassay, eluted either unassociated with an apparent M(r) of 10,000-14,000 or associated with proteins of high molecular mass . Catalytically active ascitic phospholipase A2 was associated with high molecular weight proteins . In acute pancreatitis the catalytically active and immunoreactive pancreatic phospholipase A2 eluted mainly as a protein of M(r) of 14,000 . The results of the gel filtration experiments indicate that pancreatic phospholipase A2 is not associated with other proteins in human serum, whereas ascitic phospholipase A2 is associated with protein(s) of relative high molecular weight, or exists in different polymeric forms . We also purified phospholipase A2 from sera of healthy individuals by ion exchange chromatography and HPLC . The enzyme was homogenous, displayed an M(r) of approximately 13,500 as judged by SDS-polyacrylamide gel electrophoresis, and reacted with an antibody raised against ascitic phospholipase A2.

J Am Vet Med Assoc, 1992 May 1, 200(9), 1339 - 43
Relation between pharmacokinetics of amikacin sulfate and sepsis score in clinically normal and hospitalized neonatal foals; Wichtel MG et al.; Pharmacokinetic values after IV administration of amikacin sulfate were determined for clinically normal and hospitalized foals during the first week of life . The relations between drug disposition and sepsis score and serum creatinine concentration also were studied . In clinically normal foals, differences in sepsis score, serum creatinine concentration, and pharmacokinetic variables of amikacin were not found between foals 1 to 3 and 4 to 7 days old . In hospitalized foals, sepsis score, serum creatinine concentration, area under the curve, area under the moment curve, and mean residence time were greater, and total clearance was decreased, compared with values in clinically normal foals . Sepsis score and serum creatinine concentration were inversely correlated to amikacin clearance and appeared to be useful indicators of altered drug disposition.

Surgery, 1992 May, 111(5), 551 - 4
Management of ruptured abdominal aortic aneurysm and concomitant biliary sepsis; Friedman SG et al.; Since 1984 three patients have been treated for a ruptured abdominal aortic aneurysm and acute biliary sepsis . The biliary tract disease included two cases of gangrene of the gallbladder, one with perforation . Two patients had cholangitis . All patients underwent repair of the ruptured aneurysm and cholecystectomy under the same anesthetic . Two individuals required common duct exploration: one at the time of the initial operation and the other 6 days later . Despite a high incidence of postoperative complications in these elderly men, all survived surgery and are alive and well after periods of 1 to 7 years . There have been no graft infections.

Magn Reson Med, 1992 May, 25(1), 67 - 77
Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo . III . Alterations of muscle blood flow and metabolism during sepsis; Song SK et al.; In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated . Sepsis decreased muscle {PCr} by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but {ATP} was unchanged, 6 mmol/kg tissue wet wt (P = 0.2) . The derived free cytosolic {ADP} in the two groups was similar, {ADP}septic = 0.023 +/- 0.004 SD and {ADP}control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14) . Likewise {Pi} in the septic and control groups was not statistically different, {Pi}septic = 1.1 +/- 0.5 SD and {Pi}control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2) . Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH . Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in {PCr} . Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.

Am Rev Respir Dis, 1992 May, 145(5), 1016 - 22
High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis; Suter PM et al.; Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS) . To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock . During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01 . Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS . BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml) . BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001) . In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Nippon Rinsho, 1992 May, 50(5), 1112 - 6
{MRSA sepsis of premature infants}; Tanaka G; During the 12 year period from 1978 to 1990, 112 mature newborn and premature infants were diagnosed as sepsis in our nursery . The first case of MRSA sepsis was found in 1985 . Since then, cases abruptly increased in number and 31 cases were found in total . Seven cases died and 24 were cured . Antibiotics such as AMK, MINO, IPM were effective . As the sensitivity of these drugs has been gradually dropping, we believe that VCM will be selected as the first choice . Early diagnosis and therapy are most important . Daily measurement of low level CRP (0.1 to 1.0 mg/dl) is useful and careful management is necessary in the course of significant PDA.

Indian Pediatr, 1992 May, 29(5), 571 - 5
Thermoregulatory alterations as a marker for sepsis in normothermic premature neonates; Bhandari V et al.; To evaluate the core-peripheral temperature alterations as a marker for sepsis in normothermic premature newborns, 50 normal term neonates and 11 preterms with sepsis and 11 normal preterms (controls) were studied . Axillary, rectal and sole temperatures were recorded in all babies using a single mercury-in-glass thermometer by a single observer . There was significant widening of the rectal-sole and axillary-sole temperatures in the preterms with sepsis (p less than 0.001) . There was no significant difference (p greater than 0.05) between the axillary and rectal temperatures in the term, normal preterms or those with sepsis . With an overall accuracy of 90.9%, a rectal-sole temperature difference of greater than or equal to 2.3 degrees C (100% sensitivity) or greater than or equal to 3.2 degrees C (100% specificity) is a useful marker to differentiate normothermic preterms with or without sepsis . Using the axillary-sole temperature difference, the respective values were greater than or equal to 2.2 degrees C and greater than or equal to 3.0 degrees C.

Haematologica, 1992 May-Jun, 77(3), 253 - 6
Fulminant sepsis in adults splenectomized for idiopathic thrombocytopenic purpura; Rodeghiero F et al.; BACKGROUND AND METHODS . Splenectomy is still a mainstay in the treatment of idiopathic thrombocytopenic purpura (ITP) . Although the risk of fulminant sepsis after splenectomy in children and in adults has been known for a long time, the true prevalence of fulminant sepsis in adults splenectomized for ITP has still not been well established, despite many anecdotal reports . In this paper we have tried to estimate this risk by reviewing the available literature and by analyzing a large cohort of adults splenectomized for ITP at our Institute since 1970 . RESULTS . Two cases of fulminant sepsis (a 21-year-old man and a 24-year-old woman) were traced in a group of 133 splenectomized adults, with a crude incidence of 1.5% or, equivalently, of 0.17 cases per 100 patient-years . No case of sepsis occurred in a control group of 323 non splenectomized ITP adults . This estimation seems sufficiently precise for the large population analyzed and the duration and completeness of follow-up (1,126 patient-years, mean 101 months, 2 patients lost from follow-up), and it is in agreement with the estimations yielded by a literature review (1.8%) . CONCLUSIONS . The risk of fulminant sepsis seems to be a real hazard in adults splenectomized for ITP, and a conservative approach in recommending splenectomy seems advisable . Antipneumococcal vaccination should also be recommended.

Eur J Clin Microbiol Infect Dis, 1992 May, 11(5), 403 - 7
Value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis; Capdevila JA et al.; A prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter . A total of 107 central venous catheters from 64 patients were used for the study . Blood was obtained simultaneously through the suspected infected device and from a peripheral venipuncture . The catheter was removed and its tip cultured semiquantitatively . Catheter-related sepsis occurred in 17 patients . Using as cut-off value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn peripheral blood, a sensitivity of 94%, specificity of 100% and positive predictive value of 100% were obtained . A single bacterial count greater than 100 cfu/ml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative peripheral blood culture of the same organism was also highly suggestive of catheter-related sepsis . Differential quantitative blood culture is a reliable method for the diagnosis of catheter-associated sepsis without catheter removal.

Stomatologiia (Mosk), 1992 May-Dec, (3-6), 39 - 41
{The extracorporeal connection of a donor spleen in the treatment of suppurative diseases of the face and neck complicated by sepsis}; Gubin MG et al.; Analyzes the results of extracorporeal connection of donor spleen in 9 patients with purulent diseases of the face and neck, complicated with sepsis . Presents the indications for the use of this treatment modality and its technique . Describes the changes in the clinical picture and time course of the basic homeostasis parameters over the course of therapy . Reduction of mortality rates to make them as low as 12.5% demonstrates a high efficacy of the suggested treatment as part of multiple-modality complex used in the treatment of odontogenic and surgical sepsis.

Orthop Clin North Am, 1992 Apr, 23(2), 265 - 77
Prevention and treatment of sepsis in total hip replacement surgery; Nasser S; In spite of improvements in prevention and treatment, sepsis following joint replacement still remains . Deep sepsis can lead to additional operative procedures, prolonged disability, and potential death . A universally effective treatment regimen is unknown . Prevention, therefore, remains the only truly effective means of treatment for sepsis.

Am J Physiol, 1992 Apr, 262(4 Pt 2), H1164 - 73
Interaction of sepsis and sepsis plus sympathomimetics on myocardial oxygen availability; Bersten AD et al.; The ability to regulate myocardial blood flows (Q) in accord with changing myocardial O2 needs may be depressed in sepsis . This could be an important concern when sympathomimetics are used to augment systemic oxygen delivery (QO2) in this syndrome as increased myocardial O2 needs may accompany an infusion of this class of drugs . Therefore after measuring the effect of sepsis on myocardial O2 metabolism, we then infused various sympathomimetics to evaluate the sepsis+sympathomimetic interaction on myocardial QO2 . We measured Q to the left (LV) and right (RV) ventricles by the radioactive microsphere technique in 36 unanesthetized mature sheep, before and during the infusion of dopamine, dobutamine, dopexamine, norepinephrine, salbutamol, or placebo . Randomly selected for infusion, these drugs were titrated to augment the thermodilution-derived cardiac index (CI) by greater than 20% . This study was repeated 24-48 h after cecal ligation and perforation had resulted in a hyperdynamic septic state {change (delta) in CI = sepsis - baseline = +54%; P less than 0.01} . During the septic study, both Q-LV (delta = +80%; P less than 0.01) and Q-RV (delta = +84%; P less than 0.01) were increased above baseline values; the augmented Q to both LV and RV was directly correlated with the arterial perfusion pressure (PA) x CI product and the mean pulmonary artery pressure (PPA) x CI product, respectively . Only 23% of study animals demonstrated net transmyocardial lactate production during the septic study . When the infusion of sympathomimetics was accompanied by an increase in the PPA x CI and PA x CI products, a further increase in both Q-RV and Q-LV, respectively, occurred . Also, neither the ventricular endocardial-to-epicardial flow ratios nor transmyocardial lactate extraction were modified by the sympathomimetics infusion . We conclude that the septic response to infection in this animal model was not accompanied by significant abnormalities in the metabolic regulation of myocardial QO2 (R . E . Cunnion, G . L . Scher, and M . M . Parker, Circulation 73: 637-644, 1986).

Crit Care Med, 1992 Apr, 20(4), 458 - 67
Intestinal platelet trapping after traumatic and septic shock . An early sign of sepsis and multiorgan failure in critically ill patients?
Sigurdsson GH, Christenson JT, el-Rakshy MB, Sadek S.
OBJECTIVES: Patients resuscitated after severe traumatic or septic shock were studied with reference to the behavior of radiolabeled platelets in vital organs, the occurrence of sepsis, and multiorgan failure . These findings were compared with findings of patients who had sustained severe head trauma, but had reportedly not been in shock . DESIGN: Prospective, clinical trial of consecutive patients . SETTING: Multidisciplinary ICU . PATIENTS: Thirteen critically ill patients who were considered at high risk for developing multiorgan failure . These patients had all been resuscitated after major trauma (Injury Severity Score 50.2 +/- 7.2) or severe septic shock (group A, Acute Physiology and Chronic Health Evaluation {APACHE II} score 21.7 +/- 4.4) . For comparison, six patients with head trauma, who were considered at low risk for multiorgan failure were studied (group B, Injury Severity Score 26.0 +/- 5.1 and APACHE II score 12.3 +/- 2.4) . MEASUREMENTS: Platelet trapping was studied in multiple organs by external detection of platelets labeled with 111indium-oxine . Measurements were started on the third day and continued for seven consecutive days or until death . RESULTS: Eight of 13 patients in group A developed sepsis and multiorgan failure and six of these eight patients died 8 to 29 days after the initial insult . No patient in group B developed multiorgan failure, and all survived . The patients in group A had significant increases in platelet trapping in the liver and the lungs, but the increase was significantly (p less than .01) greater in the nonsurvivors than in the survivors . All the nonsurvivors had markedly increased platelets sequestration in the intestine (less than 10 times the activity in blood), but none of the survivors had increased platelet sequestration in the intestine (p less than .01) . This increase was recorded 1 to 4 days before the first clinical signs of sepsis and 3 to 7 days before the development of multiorgan failure . No patient in group B had increased activity in the liver or in the intestine, and only one patient had a slight increase in the lung . CONCLUSIONS: The results indicate that, in patients resuscitated after severe traumatic or septic shock, increased sequestration of platelets in the intestine, as measured by external detection of radioisotope-labeled autologous platelets, may precede clinical signs of sepsis and multiorgan failure and may possibly predict the outcome.

Ann Surg, 1992 Apr, 215(4), 356 - 62
Cytokine serum level during severe sepsis in human IL-6 as a marker of severity; Damas P et al.; Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit . Among these patients, 19 developed septic shock and 16 died, 9 of them from septic shock . Interleukin 1 beta (IL-1 beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every 1 or 2 hours when septic shock occurred . Although IL-1 beta was never found, TNF alpha was most often observed in the serum at a level under 100 pg/mL except during septic shock . During these acute episodes TNF alpha level reached several hundred pg/mL, but only for a few hours . In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/mL) . There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level . Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above 1000 pg/mL . Thus, IL-6 appears to be a good marker of severity during bacterial infection.

Arch Surg, 1992 Apr, 127(4), 460 - 7
Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma; Waydhas C et al.; The relation of (multiple) organ failure (OF) to the release of inflammatory mediators and the incidence of infection and sepsis was studied prospectively in 100 patients with multiple trauma (injury severity score = 37) . Sixteen patients died of OF, 47 patients survived OF, and 37 patients had no OF . Fifteen (24%) of the patients with OF showed no signs of infection . In patients with early onset of OF (n=45), infection followed with a lag of 2 or more days . In 16 (44%) of these patients, infection led to a deterioration in organ function . With late onset of OF (n=18), infection preceded OF in nine patients . Polymorphonuclear leukocyte-elastase, neopterin, C-reactive protein, lactate, antithrombin III, and phospholipase A discriminated significantly among the three outcome groups . Of all factors, only polymorphonuclear leukocyte-elastase showed a difference between patients with and without infection or sepsis, respectively . These data indicate that infection might not play a crucial role in the pathogenesis of posttraumatic OF in a substantial portion of patients with trauma . Early OF, especially, seems to be mainly influenced by the direct sequelae of tissue damage and shock (eg, the release of inflammatory mediators) . Since infection and sepsis did not lead to an augmented release of mediators in patients with trauma, the role of both entities remains unclear.

JAMA, 1992 Mar 18, 267(11), 1503 - 10
Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis; Hotchkiss RS et al.; Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal "delivery-dependent" oxygen consumption . Two hypotheses have been advanced to explain these metabolic abnormalities: (1) cellular hypoxia resulting from abnormal microcirculatory blood flow or (2) defect(s) in energy-producing metabolic pathways of cells . Results of our studies on rat muscle, liver, heart, brain, and plasma suggest that there is no evidence of bioenergetic failure in these septic tissues and that the increase in lactate production is not necessarily due to cellular hypoxia . The adequacy of cellular oxygenation and bioenergetics was verified using in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, {18F}fluoromisonidazole, and microfluorometric enzymatic techniques . Findings from these studies as well as results from several clinical investigations indicate that neither hypothesis can adequately account for the metabolic features typical of sepsis and that the pathophysiology of sepsis awaits further clarification . These studies and important clinical implications are discussed.

Circ Shock, 1992 Mar, 36(3), 191 - 9
Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophages to release inflammatory mediators (interleukins-1 and -6 and tumor necrosis factor); Ayala A et al.; While a number of clinical studies indicate that elevated serum cytokine {interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)} levels are associated with enhanced mortality in sepsis, the time course and the role that different macrophage (M phi) populations play in releasing these cytokines remain to be determined . To study this, polymicrobial sepsis was induced in C3H/HeN mice by cecal ligation and puncture (CLP) . The animals were then sacrificed at 1, 4, or 24 hr post-CLP . Blood was taken for serum cytokine level determination . Macrophages, of either peritoneal (PM phi) or alveolar (AM phi) origin, were harvested by lavage, and their innate vs . inducible cytokine productive capacities were assessed by incubation with or without endotoxin (lipopolysaccharide; LPS) . Serum levels of TNF were significantly enhanced 1 hr post-CLP (CLP = 3.8 +/- 2.4* vs . sham = 0.4 +/- 0.9 U/ml; P less than 0.05 by t test) . However, not until 4 hr post-CLP were marked increases in IL-6 observed (CLP = 318.0 +/- 209.0* vs . sham = 1.1 +/- 0.5 U/ml), which remained elevated through 24 hr post-CLP (CLP = 11.3 +/- 15.0* vs . sham = 0.03 +/- 0.02 U/ml) . Cytokine release (IL-1, IL-6, TNF) from PM phi (without the addition of LPS) was detectable only in cells harvested 1 h following CLP . Alveolar M phi from septic mice showed little in vivo activation . Septic PM phi IL-1 and IL-6 production was markedly depressed at all time points with LPS stimulation, but TNF release remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Res Clin Pract, 1992 Mar, 15(3), 213 - 8
Sepsis inhibits insulin-stimulated glucose transport in isolated rat adipocytes; Igarashi M et al.; To assess the mechanism of insulin resistance in sepsis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes . Male Sprague-Dawley (SD) rats weighing 200-220 g were submitted to cecal ligation under chloral hydrate anesthesia, followed by double punctures with 18-G needle into the ligated portion to produce peritonitis . Age-matched SD rats without operation were used as the controls . After starvation for 16 h, blood samples were taken from the inferior vena cava for bacterial culture and assayed for plasma glucose and IRI levels, and then adipocytes were isolated from the dissected epididymal fat tissues . Plasma levels of both glucose and IRI in septic rats were higher than those in the controls . The {125I}-insulin binding rate of the adipocytes in septic rats was similar to that of the controls . However, {3H}-2-deoxy-D-glucose uptake by adipocytes was markedly decreased in the septic group (approximately 45% of the control group at the plateau) . In conclusion, this study suggests that insulin resistance in the septic state results, at least partly, from impairment in the post-binding level of the insulin receptor.

Dimens Crit Care Nurs, 1992 Mar-Apr, 11(2), 75 - 89
Advances in immunotherapy of sepsis; Klein DM et al.; Septic shock, with its associated high morbidity and mortality, has long been a challenge to the critical care nurse . A promising new development in the treatment of this condition is the use of monoclonal antibodies to inactivate two prime mediators that induce the cascade of events that culminate in septic shock and multiple organ failure: bacterial endotoxin and tumor necrosis factor (TNF) . The effectiveness of this immunotherapy depends on its timely administration, which necessitates the early identification of sepsis.

Ann R Coll Surg Engl, 1992 Mar, 74(2), 134 - 7
The influence of suturing and sepsis on the development of postoperative peritoneal adhesions; O'Leary DP et al.; Postoperative peritoneal adhesions are a major cause of morbidity . The purpose of this study was to investigate the potential contributions of suturing and sepsis to their formation in animals undergoing laparotomy . Suturing the peritoneum with plain catgut was associated with a high incidence of adhesions to the wound at 8 days (11/15), but this was significantly less at 25 days (5/15, P less than 0.04) . Use of monofilament nylon, or non-suture, were each associated with a low incidence of adhesions . Wound strength was significantly greater at 25 days than at 8 days (P less than 0.0005), but did not differ between groups . In a separate experiment, bacterial infection, even in the absence of a particulate carrier, proved to be a potent cause of postoperative peritoneal adhesions (8/9, P = 0.02) compared with uninfected controls (3/10) . Suturing the peritoneum in the presence of infection caused an especially high incidence of adhesions to the wound (8/9, P = 0.004 vs 2/10 unsutured) . It is concluded that the lowest incidence of adhesions to the wound is likely to be obtained, both in uninfected and in infected cases, if the peritoneum is not sutured during closure of abdominal wounds, and that such an approach does not compromise wound strength.

Arch Surg, 1992 Mar, 127(3), 265 - 72
Hypocalcemia during sepsis . Relationship to resuscitation and hemodynamics; Burchard KW et al.; The ionized calcium (IC) and parathyroid hormone response to polymicrobial intra-abdominal sepsis and the relationship between IC and hemodynamic alterations with and without crystalloid resuscitation were investigated . Thirty swine underwent cecal ligation and incision (n = 19) or sham laparotomy (n = 11), with seven animals that had cecal ligation and incision administered Ringer's solution (50 mL/kg) after each set of measurements recorded on days 0, 1, 2, 4, and 8 . An early decrease in mean arterial pressure and cardiac index in animals that had cecal ligation and incision reversed with resuscitation . The IC also fell early and parathyroid hormone level increased in both the unresuscitated and resuscitated septic groups . However, correlation coefficients of mean arterial pressure and cardiac index with IC ranged from .034 to .287 in the septic animals and were lower in the group that had sham laparotomy . We conclude that polymicrobial intra-abdominal sepsis results in decreased IC and an elevated parathyroid hormone level . Hemodynamics do not correlate with IC levels, and resuscitation can be achieved without calcium administration.

J Trauma, 1992 Mar, 32(3), 389 - 96; discussion 396-7
Hepatocellular dysfunction persists during early sepsis despite increased volume of crystalloid resuscitation; Wang P et al.; Although hepatocellular dysfunction occurs early in sepsis despite fluid resuscitation, it is unknown if an increased volume of resuscitation protects hepatocellular function . To study this, rats were subjected to sepsis by cecal ligation and puncture (CLP) . These and sham-treated rats then received either 3 or 6 mL/100 g BW normal saline subcutaneously . Studies were performed at 5 hours (i.e., early sepsis) or 20 hours (late sepsis) after CLP . Hepatic blood flow was determined by radioactive microspheres, 3H-galactose clearance technique, and laser Doppler flowmetry in both groups . Active hepatocellular function (i.e., Vmax and Km) was assessed by an in vivo indocyanine green clearance technique . The results indicate that: (1) hepatic blood flow increased markedly in early sepsis; (2) Vmax and Km decreased significantly at 5 hours and 20 hours after CLP; and (3) the increased volume of fluid resuscitation did not improve the depressed active hepatocellular function 5 hours following CLP . Cardiac output and hepatic microcirculation, however, were significantly increased in early sepsis . These results confirm the notion that the depression in hepatocellular function in early sepsis is not the result of any reduction of hepatic perfusion . The dissociation of increased hepatic blood flow from depressed hepatocellular function remains despite the larger volume of resuscitation . The hepatocellular dysfunction that occurs even in early sepsis cannot be corrected simply by increasing the volume of crystalloid resuscitation.

Infect Immun, 1992 Mar, 60(3), 976 - 82
Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice; Hyde SR et al.; Previous work in our laboratory demonstrated increased sensitivity of senescent (24-month-old) mice to cecal ligation and puncture (CLP) sepsis compared with that of mature (12-month-old) mice . In this study the median lethal dose of the strain of Escherichia coli most frequently isolated during CLP sepsis was determined . No significant age-associated difference in the mean lethal dose or the mean survival time was noted; however, sham surgery before injection of E . coli decreased the mean lethal dose by at least 100-fold . With surgical manipulation, the average time to death after bacterial injection simulated more closely that observed after CLP surgery . Host responses to CLP sepsis were investigated by measuring the levels of corticosterone, glucose, and tumor necrosis factor (TNF) in the sera of mature and senescent mice at 2-h intervals after surgery . Corticosterone levels increased gradually during the course of sepsis in mature mice; however, senescent mice demonstrated a pronounced elevation in hormone levels at 2 and 4 h after surgery . At subsequent sampling intervals the corticosterone levels remained elevated, although they were similar for both ages . At all sampling intervals, the glucose levels in serum were lower in senescent mice than in mature mice . Pronounced hypoglycemia (less than 80 mg/dl) was observed in senescent mice at 8 h postsurgery . TNF was detected in serum within a narrow time frame in both age groups at 6, 8, and 10 h postsurgery . Although elevated TNF levels in serum were not seen in every mouse in each group (approximately 50%), the data hinted that senescent animals produced larger quantities of TNF during CLP sepsis than did mature animals . E . coli lipopolysaccharide (1 mg/kg) was injected intraperitoneally, and the TNF levels in serum and peritoneal lavage fluid were measured at 30, 60, and 90 min . Senescent mice demonstrated a level of TNF in serum at 90 min after lipopolysaccharide treatment that was 20-fold higher than that of mature mice (299,877 pg/ml versus 15,594 pg/ml) . The amount of TNF produced locally in the peritoneum was also substantially higher in senescent mice than in mature animals (1,716 pg/ml versus 776 pg/ml) . The increased production of TNF in senescent animals, despite elevated circulating corticosterone levels, suggested an age-related defect in glucocorticoid-directed downregulation of TNF production . This was confirmed in lipopolysaccharide-treated animals given exogenous dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)

Chest, 1992 Mar, 101(3), 865 - 6
Fatal sepsis following peripheral intravenous cannula embolus; Freiberg DB et al.; This is a case report of multiple septic complications of a peripheral intravenous cannula as a direct result of proximal embolization of a fragment of the cannula to the heart and major vessels.

Anesteziol Reanimatol, 1992 Mar-Apr, (2), 41 - 3
{Immunologic indices in patients with sepsis and their changes in response to complex intensive therapy}; Spas VV et al.; Immune status has been studied in the course of intensive care in 48 patients . It has been established that hemosorption may enhance already existing changes in immune homeostasis in patients with sepsis . Therefore, immunostimulating therapy with tactivin and group B vitamins (B1, B6, B12) or ultraviolet (UV) blood irradiation in combination with group B vitamins administration have been included into therapy . Simultaneous use of tactivin, group B vitamins and UV blood irradiation was not advisable due to reduction of immunostimulating effect . Consecutive use of the immunity-stimulating methods seems expedient.

Eur J Surg, 1992 Mar, 158(3), 157 - 64
The influence of biliary obstruction and sepsis on reticuloendothelial function in rats; Ding JW et al.; Obstructive jaundice is frequently associated with septic complications and renal impairment . The present study was performed in order to evaluate reticuloendothelial system (RES) function in obstructive jaundice and the influence of a septic challenge . Male Sprague-Dawley rats were allocated into four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of the common bile duct (CBD) alone and CBD+CLP, respectively) . Mortality, blood clearance and organ distribution of 125I labelled Escherichia coli were determined . Mortality in sepsis (CLP) significantly increased in jaundiced animals (p less than 0.033) . Blood clearance of radiolabelled E . coli was significantly impaired in both jaundiced groups . In jaundiced animals, hepatic localisation and renal uptake of E . coli significantly increased (p less than 0.001), while radioactive counts in bile significantly decreased (p less than 0.01) . Changes in organ distribution of bacteria did not depend on alterations in blood flow . Thus, RES function was impaired in jaundiced animals and mortality increased in a concomitant septic challenge in jaundiced animals.

J Am Vet Med Assoc, 1992 Feb 15, 200(4), 503 - 6
Disposition of gentamicin administered intravenously to horses with sepsis; Sweeney RW et al.; Plasma concentration of gentamicin was measured 1, 4, and 6 hours after IV administration in 35 hospitalized adult horses on days 1, 3, 5, and 10 of treatment . The mean apparent elimination rate constant beta was 0.53 +/- 0.10 h-1 on day 1 for horses with normal plasma creatinine concentration and 0.41 +/- 0.13 h-1 for horses with abnormally high plasma creatinine concentration . There was no significant difference between beta of the hospitalized horses and of 6 healthy horses treated with gentamicin, but total clearance for the hospitalized horses with normal plasma creatinine concentration was significantly greater than that of the healthy horses and the hospitalized horses with abnormally high plasma creatinine concentration . Gentamicin clearance was significantly correlated with plasma creatinine concentration for healthy horses and hospitalized horses, and beta was significantly correlated with plasma creatinine concentration for hospitalized horses . Twelve of the 35 hospitalized horses required an adjustment in gentamicin dosage . Ten required a reduction, 1 an increase, and 1 a change in dosage and interval with no net change in total daily dose . One horse of 35 (2.9%) developed signs compatible with nephrotoxicosis on day 14 of treatment, despite appropriate gentamicin concentrations on day 10.

J Trauma, 1992 Feb, 32(2), 141 - 7
A study of the relationship among survival, gut-origin sepsis, and bacterial translocation in a model of systemic inflammation; Deitch EA et al.; Several factors, including uncontrolled inflammation, gut barrier failure, and sepsis, have been implicated in the development of multiple organ failure . To investigate the relative importance and interrelationships among some of these factors, increasing doses of the inflammatory agent zymosan were used to induce a systemic inflammatory state in mice . At nonlethal doses (0.1 and 0.5 mg/g body weight), zymosan caused injury to the intestinal mucosa, increased intestinal xanthine oxidase activity, and promoted bacterial translocation in a dose-dependent fashion . Inhibition or inactivation of xanthine oxidase activity was effective in reducing mucosal injury and bacterial translocation when zymosan was injected at 0.1 mg/g but not at 0.5 mg/g body weight . At a dose of 1 mg/g, the lethal effects of zymosan appeared to be related to gut-origin sepsis, since cefoxitin (1 mg/g) reduced the seven-day mortality rate from 100% to 20% (p less than 0.01) . However, at a zymosan dose of 2 mg/g, antibiotics did not improve survival . Zymosan thus induced gut barrier failure and systemic infection in a dose-dependent fashion . Additionally, the mechanism of zymosan-induced bacterial translocation and the relationship of gut-origin sepsis to survival appeared to be related to the magnitude of the inflammatory insult (the dose of zymosan).

J Lab Clin Med, 1992 Feb, 119(2), 159 - 68
Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis; Nuijens JH et al.; Increased vasopermeability and vasodilation, presumably the result of endothelial perturbation, are considered among the basic pathogenetic mechanisms in septic shock . Neutrophils have been implicated as a source for mediators in endothelial injury . We measured elastase-alpha 1-antitrypsin (alpha 1AT) complexes and lactoferrin as markers for release of neutrophil granule contents in plasma from patients with sepsis on admission to the Intensive Care Unit, and we delineated the relationship of neutrophil activation to other inflammatory parameters and to hemodynamic and biochemical parameters . Levels of elastase-alpha 1AT and lactoferrin significantly correlated with each other (r = 0.58; p less than 0.008), and were increased (greater than 3.33 and 5 nmol/L, respectively) in 96% and 71% of the patients, respectively . Lactoferrin, but not elastase-alpha 1AT, correlated with the number of white blood cells (r = 0.38; p = 0.008) . Elastase-alpha 1 AT levels were significantly higher (p = 0.008), whereas white blood cell counts were lower (p = 0.015) in patients with shock when compared with patients without abnormal blood pressure . Both elastase-alpha 1AT and lactoferrin levels correlated with lactate levels (r = 0.33; p = 0.024 and r = 0.30; p = 0.04), suggesting a role for neutrophil activation in the pathogenesis of hypoxygenation . In addition, elastase-alpha 1AT correlated with the concentrations of interleukin 6 (IL-6) (r = 0.46; p = 0.001) and C3a (r = 0.38; p = 0.009), suggesting that cytokines and complement may contribute to the degranulation of neutrophils in sepsis . Elastase-alpha 1AT complexes were inversely related to C1-inhibitor (r = -0.33; p = 0.028) and to platelet numbers (r = -0.42; p = 0.003) . Levels of elastase-alpha 1AT complexes in plasma appeared to be of prognostic significance; levels were higher in 27 patients who died than in 21 patients who survived (p = 0.01) . The mortality in 27 patients with concentrations below 10 nM was 37%, whereas it was 81% in 21 patients with higher levels . The overall mortality in this study was 56% . These results provide further evidence that activation and degranulation of neutrophils, induced by multiple agonists, are involved in the development of fatal complications in patients with sepsis.

Crit Care Med, 1992 Feb, 20(2), 263 - 75
Magnesium-adenosine triphosphate in the treatment of shock, ischemia, and sepsis; Harkema JM et al.; PURPOSE: To review the rationale for adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration in shock, ischemia, and sepsis; the beneficial effects on cellular and organ functions and survival; and possible mechanisms of these effects . DATA SOURCES: Current literature review . STUDY SELECTION: Articles deemed most pertinent, current, and representative were utilized . DATA SYNTHESIS: Despite apparent, adequate resuscitation of hypovolemic shock and sepsis in experimental animals and patients, persistent cellular and organ dysfunction is apparent . Disturbances in organ microcirculation and tissue hypoxia appear to play an important role . These disturbances occur when the energy needs are increased . Because of the theoretical benefits of ATP-MgCl2 as an energy source, as well as a vasodilator, the administration of ATP-MgCl2 has been investigated extensively, and considerable evidence suggests that ATP-MgCl2 restores the depressed cell and organ functions following ischemia, hypovolemic shock, and sepsis . CONCLUSIONS: ATP-MgCl2 improves cellular and organ function and survival following experimental shock, ischemia, and sepsis . Studies also indicate that ATP-MgCl2 can be administered safely in experimental animals and in normal human volunteers, as well as in patients following various adverse circulatory conditions . Further trials should be undertaken to determine the effects on cell and organ function in patients following traumatic shock and sepsis.

Surgery, 1992 Feb, 111(2), 177 - 87
Interferon-gamma attenuates hemorrhage-induced suppression of macrophage and splenocyte functions and decreases susceptibility to sepsis; Ertel W et al.; Although it is known that interferon-gamma synthesis and macrophage functions are depressed after hemorrhage, it remains to be determined whether systemic administration of interferon-gamma has any effect on hemorrhage-induced depression of macrophage and splenocyte functions . To study this, C3H/HEN mice were bled to a mean blood pressure of 35 mm Hg, maintained for 60 minutes, and followed by adequate fluid resuscitation . The mice then received either 1000 units interferon-gamma or saline solution (vehicle) . Peritoneal (pM phi) and splenic (sM phi) macrophages and splenocytes were isolated 24 hours later . PM phi antigen presentation was measured by coculturing pM phi with the D10.G4.1 cell clone . Major histocompatibility complex class II (Ia) antigen expression was determined by direct immunofluorescence . Cytokine release by pM phi, sM phi, and splenocytes was assessed with specific bioassays . For survival studies, mice were subjected to sepsis 3 days after hemorrhage . Treatment with interferon-gamma restored (p less than or equal to 0.05) hemorrhage-induced suppression of pM phi antigen presentation capacity and Ia antigen expression and increased (p less than or equal to 0.05) interleukin-1 and tumor necrosis factor release by pM phi and sM phi, as well as splenocyte proliferation (p less than or equal to 0.05) . Interferon-gamma also decreased (p less than or equal to 0.007) the susceptibility to sepsis after hemorrhage . Thus interferon-gamma represents a potent agent for treating hemorrhagic shock-induced immunosuppression and for increasing the ability of the host defense system to combat bacterial infections after hemorrhage.

J Nucl Med, 1992 Feb, 33(2), 254 - 5
Spread of infectious complications of odontogenic abscess detected by technetium-99m-HMPAO-labeled WBC scan of occult sepsis in the intensive care unit; Kao CH et al.; We report a rare case of odontogenic abscess, detected while the patient was in the intensive care unit (ICU), which resulted in sepsis and the patient's death due to mediastinitis, skull osteomyelitis, and deep neck cellulitis . The detection of infectious focus in occult sepsis in ICUs is usually difficult because many diagnostic procedures cannot be conveniently performed . The use of 99mTc-hexamethylpropyleneamineoxime-labeled white blood cells scan allowed accurate diagnosis and appropriate surgical drainage.

Arch Surg, 1992 Feb, 127(2), 191 - 6; discussion 196-7
Does endotoxin tolerance prevent the release of inflammatory monokines (interleukin 1, interleukin 6, or tumor necrosis factor) during sepsis?
Ayala A, Kisala JM, Felt JA, Perrin MM, Chaudry IH.
Mice were subjected to sepsis by cecal ligation and puncture to determine whether macrophages from endotoxin-tolerant C3H/HeJ mice are also activated systemically to release inflammatory monokines associated with septic mortality . Blood levels of both tumor necrosis factor and interleukin 6 were significantly elevated during the first 1 to 4 hours of sepsis as compared with sham controls . Peritoneal macrophages from septic mice exhibited a marked spontaneous release of interleukin 1, interleukin 6, and tumor necrosis factor at 1 hour . However, the addition of endotoxin to macrophage cultures taken from septic mice had no further stimulatory effect . Sham controls alternatively showed no significant innate monokine release, but their macrophages did release increased monokine numbers in response to endotoxin . These results indicate that the spontaneous macrophage release of these monokines is comparable with that previously observed in endotoxin-sensitive mice, suggesting a common mechanism by which macrophages are primed by traumatic injury by an agent other than endotoxin to release monokines during sepsis . Thus, the administration of agents that decrease or prevent the deleterious effects of systemic inflammatory mediators during sepsis could be useful adjuvants in those clinical situations where the bacterial origin is unknown.

Arch Surg, 1992 Feb, 127(2), 170 - 4
Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis; Zamir O et al.; The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats . Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles . Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis . In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed . Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation . Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture . The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals . Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.

Arch Surg, 1992 Feb, 127(2), 152 - 7; discussion 157-8
Modulation of macrophage hyperactivity improves survival in a burn-sepsis model; O'Riordain MG et al.; Macrophage hyperactivity with increased production of tumor necrosis factor, interleukin 6, interleukin 1, and prostaglandins has been demonstrated in the injured patient, but the effect of this on the clinical outcome is unclear . We studied the effect of combination interleukin 1 beta and indomethacin sodium therapy on macrophage hyperactivity and survival after sepsis in a murine burn model . Macrophage interleukin 1, interleukin 6, and tumor necrosis factor alpha production were all significantly increased 10 days after thermal injury . Treatment with recombinant human interleukin 1 beta in combination with indomethacin significantly reduced this overproduction of cytokines to normal levels, and this was associated with an improvement in survival after septic challenge (52% survival in interleukin 1 beta-indomethacin-treated group compared with 22% in burned vehicle control mice) . Burned mice that received either interleukin 1 beta or indomethacin alone demonstrated tumor necrosis factor and interleukin 6 production and survival intermediate between the interleukin 1 beta-indomethacin-treated group and the vehicle control group . Control of macrophage hyperactivity is associated with improved survival from subsequent sepsis and offers a potential new strategy for the treatment of immune dysfunction in thermally injured patients.

Am J Physiol, 1992 Feb, 262(2 Pt 1), C445 - 52
Regulation of hepatic protein synthesis in chronic inflammation and sepsis; Vary TC et al.; The regulation of protein synthesis was determined in livers from control, sterile inflammatory, and septic animals . Total liver protein was increased in both sterile inflammation and sepsis . The rate of protein synthesis in vivo was measured by the incorporation of {3H}phenylalanine into liver proteins in a chronic (5 day) intra-abdominal abscess model . Both sterile inflammation and sepsis increased total hepatic protein synthesis approximately twofold . Perfused liver studies demonstrated that the increased protein synthesis rate in vivo resulted from a stimulation in the synthesis of both secreted and nonsecreted proteins . The total hepatic RNA content was increased 40% only in sterile inflammation, whereas the translational efficiency was increased twofold only in sepsis . The increase in translational efficiency was accompanied by decreases in the amount of free 40S and 60S ribosomal subunits in sepsis . Rates of peptide-chain elongation in vivo were increased 40% in both sterile inflammation and sepsis . These results demonstrate that sepsis induces changes in the regulation of hepatic protein synthesis that are independent of the general inflammatory response . In sterile inflammation, the increase in protein synthesis occurs by a combination of increased capacity and translational efficiency, while in sepsis, the mechanism responsible for accelerated protein synthesis is an increased translational efficiency.

J Hosp Infect, 1992 Feb, 20(2), 67 - 78
Vascular catheter-related sepsis: diagnosis and prevention; Johnson A et al.; Although catheter-related sepsis (CRS) is an important cause of nosocomial infection and the major complication of intravenous catheter use, there is, as yet, no consensus concerning either a useful definition of CRS or the optimal method of catheter management and prevention of infection . Semiquantitative culture of catheter tips is a useful method of diagnosis of CRS but other techniques such as quantitative catheter blood cultures and Gram staining of the catheter have roles in selected patients . The most significant impact on the prevention of CRS is made by the introduction of an intravenous therapy team . The site and method of catheter insertion, type of dressing and antisepsis, catheter flushing and use of prophylactic antibiotics are also important issues . Techniques such as guide-wire exchange and catheters such as triple lumen and total implantable venous access devices have their own infection problems . Many new and interesting approaches to the prevention of CRS are being formulated . To facilitate further progress, a standardized definition for diagnosis, and revised recommendations for prevention of CRS would be helpful.

Clin Sci (Lond), 1992 Feb, 82(2), 205 - 9
Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat; Evans RD et al.; 1 . Administration of tumour necrosis factor (cachectin) and of interleukin-1-alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis . There were parallel increases in the plasma level of triacylglycerols . Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations . 2 . In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines . The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats . The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha . Parallel changes occurred in hepatic ketone bodies . 3 . It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.

Biochem Biophys Res Commun, 1992 Jan 15, 182(1), 269 - 75
A rationale for the prophylactic use of monophosphoryl lipid A in sepsis and septic shock; Gustafson GL et al.; Monophosphoryl lipid A (MLA), a substructure of bacterial lipopolysaccharide (LPS), is being developed as a prophylactic for sepsis and septic shock . In the present study it was shown that MLA induced a rapid accumulation of IFN-gamma in mice that correlated with an in vivo priming of macrophages . Primed macrophages could be induced in vitro to synthesize nitric oxide, a key mediator of macrophage cytotoxicity . Due to its rapid clearance, MLA was not present in circulation at the time when IFN-gamma accumulated, suggesting that MLA could not synergize with IFN-gamma to systemically activate macrophages in vivo . MLA treatment tolerized mice against the IFN-gamma response--ie., treatment of mice with MLA on day 1 blocked LPS from inducing IFN-gamma on days 2-4 . The significance of these results in relation to MLA's ability to enhance non-specific resistance and block LPS lethality in animals is discussed.

Am Surg, 1992 Jan, 58(1), 32 - 6
Pericardiotomy improves left ventricular compliance during sepsis-induced pulmonary artery hypertension; Coons MS et al.; Sepsis-induced pulmonary artery hypertension (SIPAH) causes an increase in right ventricular (RV) afterload, dilatation of the RV, leftward shift of the interventricular septum (IVS), and therefore decreases left ventricular compliance (LVC) . This study was designed to evaluate the role of pericardiotomy during SIPAH as an alternative to vasodilators (which cause a detrimental increase in shunt fraction) to improve LVC . Systemic and pulmonary hemodynamics, pulmonary function, RV, and LVC were acquired at baseline (BL), during SIPAH with closed pericardium (PAHCP) and after opening the pericardium (PAHOP) . Systemic hemodynamics and pulmonary function did not change significantly during the experiment . The infusion of live bacteria induced a significant rise in mean pulmonary artery pressure from 16 +/- 5.3 at BL to 36.8 +/- 3.3 and 35.0 +/- 6.4 mm Hg during PAHCP and PAHOP, respectively, (P less than 0.05) . Pulmonary vascular resistance index and right ventricular stroke work index (RVSWI) displayed a similar rise in response to SIPAH (P less than 0.05 vs BL) . Pericardiotomy did not affect pulmonary hemodynamics or RVSWI . Right ventricular contractility did not increase following pulmonary hypertension while the pericardium was closed (440 +/- 78 vs 410 +/- 125, P less than 0.05); however, it rose, although not significantly, to 615 +/- 326 after pericardiotomy . RV time tension index displayed a rise during SIPAH with the pericardium intact and returned to baseline values after pericardiotomy; however, these changes were not significant . RVC did not change significantly throughout the experiment . In contrast, LVC decreased significantly after SIPAH and significantly improved after pericardiotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Surg, 1992 Jan, 127(1), 70 - 5; discussion 75-6
Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis; Ertel W et al.; Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages . Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined . Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated . Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight) . Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later . Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours . Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release . Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice . Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage.

Am J Surg, 1992 Jan, 163(1), 181 - 4; discussion 184-5
Effect of sepsis or cytokine administration on release of gut peptides; Zamir O et al.; The effect of sepsis on plasma levels of various gut peptides was studied in rats . Sepsis was induced by cecal ligation and puncture (CLP); control animals underwent sham operation . Sixteen hours after CLP or sham operation, portal and systemic blood was drawn, and plasma levels of gastrin, vasoactive intestinal peptide (VIP), secretin, peptide YY (PYY), gastrin-releasing peptide (GRP), and substance P were determined by radioimmunoassay . Plasma levels of gastrin, VIP, PYY, and secretin were elevated in septic rats compared with nonseptic animals, with the highest levels noted in portal blood . There was no effect of sepsis on GRP or substance P levels . In other experiments, human recombinant interleukin 1 alpha (IL-1 alpha) or recombinant tumor necrosis factor alpha (TNF alpha) was injected intraperitoneally (300 micrograms/kg body weight in 3 divided doses over 16 hours) . There was no change in plasma levels of gut peptides after IL-1 alpha injection . TNF alpha induced elevation of PYY levels in portal plasma with no change in other gut peptide levels . The results suggest that sepsis stimulates release of certain gut peptides and that TNF, but not IL-1, may be partly responsible for this response . The mechanism of the release of gut peptides and its significance in the pathophysiologic changes induced by sepsis remain to be determined.

Crit Care Med, 1992 Jan, 20(1), 28 - 34
Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome; Byrne K et al.; OBJECTIVE: To determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure . Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients . DESIGN: Prospective study . SETTING: University hospital ICUs . PATIENTS: Thirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis . MEASUREMENTS AND MAIN RESULTS: All patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera . Lung-to-heart ratio of tracer was calculated and expressed as the slope index . Increase in slope index indicated increased pulmonary albumin flux . Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was greater than 30 mm Hg . Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups . A subgroup of patients in the septic group had a normal slope index . Septic patients with an increased slope index had a significantly (p less than .01) longer duration of mechanical ventilation (36 +/- 5 vs . 7 +/- 1 days), spent longer in the ICU (67 +/- 9 vs . 11 +/- 1 days), and had a longer hospital stay (113 +/- 20 vs . 35 +/- 5 days) than septic patients with a normal slope index . CONCLUSIONS: Gamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP less than 30 mm Hg from patients with sepsis-induced ARDS . Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (greater than 2 SD above control mean) had a markedly increased morbidity.

Scand J Infect Dis, 1992, 24(2), 197 - 204
Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans; Dofferhoff AS et al.; Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines . In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis . Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock . Levels of C4 were decreased in only 1 of the 20 septic patients . Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01) . C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05) . C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01) . Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels . We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6 . Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients . TNF levels remained stable or increased in the non-survivors . We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

J Natl Med Assoc, 1992 Jan, 84(1), 81 - 4
Neonatal bone infarction following cord sepsis: case report; Monu JU et al.; An unusual case of infarction of the tibia in a neonate who presented with sepsis following poor cord management at birth is reported . He was managed as for necrotizing enterocolitis and had limited debridement of infarcted limb because the parents refused amputation of the limb . This patient was a diagnostic problem . Necrotizing fasciitis and in retrospect purpura fulminans are considered as possible diagnoses and are discussed briefly.

Arkh Patol, 1992, 54(1), 14 - 9
{Aspects of modeling, etiology and pathogenesis of experimental sepsis}; Tepliakov VG et al.; An experimental model of sepsis is developed that allows one to reproduce septicopyemia and septicemia taking into account the biological properties of bacteria which determine sepsis dynamics, its form and localization of metastatic pyemic foci . The dependence of the sepsis manifestation upon the functional state of polynuclear leucocytes is revealed . The irreversibility of the process after the bacterial colonisation of the inner organs is shown a general increase of the histohematic barrier permeability facilitates the release of flora, mainly intestinal one, into the circulation and organs.

Intensive Care Med, 1992, 18(1), 6 - 10
Diagnostic bronchoalveolar lavage in patients with pneumonia produces sepsis-like systemic effects; Pugin J et al.; Fever following fiberoptic bronchoscopy occurs in 10-25% of the patients and its origin is not well understood . We prospectively examined changes in body temperature (T degrees), mean systemic arterial pressure (MAP) and oxygenation after 2 bronchoalveolar lavages (BAL, bronchoscopic and non-bronchoscopic) for 34 procedures in 25 intubated patients . In patients with pneumonia (11 investigations) we observed a rise in T degrees 3 h after bronchoscopic and non-bronchoscopic BAL, p less than 0.0001, a decrease in MAP, p = 0.008 and arterial oxygenation, p = 0.002 . Of patients with pneumonia 73% had a rise in T degrees of more than 1 degrees C compared with only 17% of those without pneumonia (p = 0.005) . Patients without pneumonia (23 procedures) had no significant changes in T degrees, MAP and arterial oxygenation following the 2 BAL procedures . Changes in T degrees correlated significantly with those in MAP, and with the level of endotoxin in bronchoscopic BAL fluid . These findings suggest that BAL in patients with pneumonia may cause intravascular translocation of toxins or mediators producing pyrogenic and hypotensive effects.

Intensive Care Med, 1992, 18(1), 15 - 9
Tc-99m HMPAO labelled WBCs in the detection of occult sepsis in the intensive care unit; Kao CH et al.; In a retrospective study involving 25 patients with occult sepsis in the ICU of Taichung Veterans General Hospital, the sensitivity and specificity of the new diagnostic method, Tc-99m HMPAO labelled white blood cells (WBCs) scan, were compared with other evaluating methods including clinical information, radiograph, ultrasound, bacterial culture, operative findings and pathological report . It was found that Tc-99m HMPAO labelled WBCs scans gave a sensitivity of 96.0%, a specificity of 84.4% and an overall accuracy of 87.3%, as well as the probable causes of false positive and false negative diagnoses were discussed . In conclusion, Tc-99m HMPAO labelled WBCs scans provide a reliable method for imaging of occult sepsis in the ICU.

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