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