Chin Med J (Engl), 1992 Jan, 105(1), 34 - 8 The role of Kupffer cells in the development of hepatic dysfunction during sepsis; Meng XJ et al.; The effect of Kupffer cell blockade on hepatic function during sepsis was evaluated in this study . Methyl palmitate suspension 100 mg/100 g administered intravenously suppressed the phagocytic activity as the phagocytic index K decreased from 0.0493 +/- 0.0089 to 0.0150 +/- 0.0035 in rats . Sepsis was produced by the method of cecal ligation and needling perforation (CLP) . At the end of 15 hours after CLP the hepatic adenosine triphosphate (ATP) level and ketone body ratio decreased significantly . But in rats pretreated with methyl palmitate 24 hours prior to CLP, the ATP level returned to the normal control level (1.6906 +/- 0.06-2.2323 +/- 0.13 mumol/g) and ketone body ratio remained at significantly higher values (0.26 to 0.68) . After CLP, the liver lipoperoxide (LPO) concentration increased and glutathione (GSH) contents decreased significantly . When the septic rats were pretreated with methyl palmitate, both the LPO and GSH returned to the normal control level (62.69 +/- 1.7 to 44.62 +/- 2.12 and 159.85 +/- 9.7 to 222.27 +/- 11.34) . It is concluded that the hepatic dysfunction is modulated at least to a greater extent by many of the toxic mediators released by the activated Kupffer cells during sepsis. J Am Board Fam Pract, 1992 Jan-Feb, 5(1), 89 - 91 Association of Escherichia coli sepsis and galactosemia in neonates; Barr PH; Galactosemia in newborns and infants is associated with the following symptoms: jaundice, hepatomegaly, failure to thrive, feeding difficulties, hypoglycemia, convulsions, lethargy, amino-aciduria, cataracts, hepatic cirrhosis, ascites, and mental retardation . If the preliminary evaluation indicates galactosemia, there is high risk for E . coli sepsis and death . Strong consideration should therefore be given for early antibiotic therapy in infants with suspected galactosemia in spite of the absence of clinical signs or symptoms of sepsis. Nutr Hosp, 1992 Jan-Feb, 7(1), 17 - 22 {Artificial enteral nutrition in sepsis patients}; Ortiz Leyba C et al.; The importance of avoiding bacterial translocation in critical patients in order to reduce the risk of multiorganic failure has led to an insistence on maintaining the enteral nutrition method in different clinical situations . The present study examines the possible alternative of enteral nutrition using an intact protein polymer and medium chain triglyceride diet in critical patients with sepsis . For this purpose, a prospective study was conducted on 20 patients who received this diet for a period of 20 days . In 16 cases, a jejunostomy catheter was used, and in the remaining 4, a nasogastric tube . 6 of the total patients died . The results obtained show a recovery of the visceral markers (prealbumin, transferrin and retinol-binding protein) of significant statistical importance . The improvement in albumin was discarded due to simultaneous intake of seroalbumin received by the patients . The nitrogenated balance and height creatinin index improved, whereas there was no increase in hepatic enzymes . In conclusion, this enteral diet is a perfectly valid alternative to parenteral nutrition in septic patients. J Clin Neurophysiol, 1992 Jan, 9(1), 145 - 52 The electroencephalogram in sepsis-associated encephalopathy; Young GB et al.; To define the EEG and associated clinical features of septic encephalopathy, we studied 62 patients with positive blood cultures . Patients were divided into three clinical groups: nonencephalopathic (NE), mildly encephalopathic (ME), and severely encephalopathic (SE); the latter two groups had diffuse cerebral dysfunction . EEGs were classified into five groups: normal, excessive theta, predominant delta, triphasic waves, and suppression or burst suppression, in ascending order of severity . The EEG (1) was more sensitive than our clinical criteria for encephalopathy, (2) showed features that were, when considered with clinical and laboratory characteristics, compatible with a potentially reversible encephalopathy, and (3) had well-defined categories that correlated with percent mortality, even within a single clinical group . We conclude that the EEG is a sensitive index of brain function in septic encephalopathy and that it is especially useful in the intensive care monitoring of patients with sepsis. Am J Perinatol, 1992 Jan, 9(1), 28 - 33 Fetal monitoring in perinatal sepsis; Day D et al.; To evaluate the utility of conventional electronic fetal monitoring in detection of established perinatal sepsis, we conducted a case-controlled study of fetal monitor results in 18 patients delivering newborns with sepsis . Eleven of the 18 newborns (61%) demonstrated clinically reassuring fetal heart rate patterns, not significantly different from controls (p = 0.80) . No pattern predictive of presumed perinatal sepsis could be identified . Obstetric factors traditionally associated with increased risk of perinatal infection, such as long duration of labor, use of internal fetal monitoring, and increased number of vaginal examinations were not significantly different from controls . Preterm rupture of membranes greater than 24 hours occurred in less than 50% of the cases . Clinical diagnosis of chorioamnionitis was established in only one third of the patients who delivered newborns with sepsis . In this study, use of conventional electronic fetal monitoring did not accurately identify newborns with presumed intrauterine infection. Arch Dis Child, 1992 Jan, 67(1 Spec No), 44 - 7 Reduced use of surface cultures for suspected neonatal sepsis and surveillance; Dobson SR et al.; Data on infection in a neonatal unit were collected prospectively for seven years . After the first four years, the number of surface cultures obtained from neonates with suspected sepsis and for surveillance was reduced . Rates of systemic infection (sepsis and meningitis) were not significantly different in the four years before and the three years after this change . Reduction in surface culture information made no observable difference to detection of colonisation in neonates with early onset sepsis (within first 48 hours of life) nor to antibiotic choice in late onset sepsis . Decisions concerning the length of antibiotic course in suspected infection were not adversely affected . Reduction in the number of surface cultures led to considerable saving of time, effort, and cost while appearing safe in terms of clinical practice and outcome. Scand J Infect Dis, 1992, 24(3), 361 - 8 Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis; Hamilton G et al.; The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis . Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure . The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days . Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0) . These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) Haemostasis, 1992, 22(1), 17 - 24 Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers; Okamoto K et al.; To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC) . In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7% . F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy . Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter . The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis . In addition, the levels of serum albumin in the two groups were similar . These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy . It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Surg Suppl, 1992, (567), 43 - 6 Teicoplanin vs cephradine and metronidazole in the prophylaxis of sepsis following vascular surgery: an interim analysis of an ongoing trial; Antrum RM et al.; This paper presents further preliminary results of a trial of the prophylaxis of sepsis in 165 patients undergoing vascular surgery . The efficacy and safety of a single dose of teicoplanin was examined and compared with three doses of cephradine plus metronidazole . No significant differences were detected in the prophylactic efficacy in either group . The first interim report indicated abnormalities in liver function, maximum at 7 days, in both groups . These findings are confirmed in this second interim report . Raised levels of GGT and alkaline phosphatase are more prominent in patients receiving teicoplanin . Liver function improved by 28 days, however, suggesting that any abnormality is transient. Clin Immunol Immunopathol, 1992 Jan, 62(1 Pt 2), S11 - 7 The role of tumor necrosis factor in sepsis; Spooner CE et al.; There is an increasing incidence of sepsis among hospitalized patients . Also, high mortality associated with sepsis and septic shock persists despite appropriate antibiotic therapy . Recent investigations have demonstrated that bacterial antigens stimulate a cascade of cellular mediators or cytokine release . In sepsis and septic shock the response of these cytokines often exceeds natural downregulation and leads to multisystem organ failure and even death in an unacceptably high number of patients . Many investigative studies have shown that tumor necrosis factor (TNF) is the prime mediator of the inflammatory response seen in sepsis and septic shock . Sepsis management in the future will include immune modulating therapy directed against the deleterious effects of cytokines, specifically TNF . This article reviews the current problem of sepsis and the evidence to support the role of TNF in sepsis . also, recent studies employing monoclonal antibodies against TNF as well as considerations for future studies are discussed. Eur J Cancer, 1992, 29A(1), 81 - 6 Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis; Radford JA et al.; The incidence and risk of septic complications in 382 patients treated for small cell lung cancer with combination chemotherapy at a single centre have been analysed . Full protocol doses were employed throughout with no dose reduction after episodes of severe or life-threatening sepsis (SLTS) . 50 (13%) patients experienced 66 episodes of SLTS associated with 1978 cycles of chemotherapy (3.2% cycles affected) . 20 (5.2%) patients died due to sepsis (SD) of whom only 4 had experienced SLTS with a previous cycle of treatment . The others died as a result of their first septic episode . A model comprising four variables, age (< or = 50 or > 50 years), Karnofsky performance status (KP < or = 50 or > 50), treatment (two- or three-drug regimen) and previous sepsis (SLTS or no SLTS with previous cycles) was found to satisfactorily describe the incidence of SLTS and SD in the study population and once validated in another patient groups this model should allow identification of high-risk individuals before treatment starts . If so, we propose that high-risk patients (age > 50 years, KP < or = 50, treatment with three-drug regimen) receive 50% of protocol doses in the first cycle of treatment with escalation to 75% and eventually 100% doses in subsequent cycles if sepsis does not supervene . Those with one or two risk factors present run a relatively low risk of SLTS or SD and we consider that full-dose chemotherapy should be used throughout in these individuals. Acta Clin Belg, 1992, 47(1), 30 - 41 Pulmonary arterial hypertension in sepsis and the adult respiratory distress syndrome; Spapen H et al.; Pulmonary arterial hypertension, defined as a mean pulmonary artery pressure exceeding 20 mmHg has been observed both in experimental animal and human sepsis, even before development of the adult respiratory distress syndrome . In this article we review several mechanisms that have been invoked for the pulmonary arterial hypertension associated with sepsis (and the adult respiratory distress syndrome): obstruction of the pulmonary microcirculation with microthrombi composed of platelets and leukocytes, and active pulmonary vasoconstriction induced by the autonomous nervous system, hypoxia or vasoactive humoral factors ("mediators") . Some of these mediators, in particular serotonin and arachidonic acid metabolites have been the subject of substantial research and therapeutic manipulation . Since pulmonary arterial hypertension imposes an increased afterload to the right ventricle and because right ventricular dysfunction appears to be a major determinant of the outcome of sepsis, the study of the mechanisms involved in pulmonary arterial hypertension may lead to improved management of sepsis and septic shock. Crit Care Med, 1992 Jan, 20(1), 11 - 6 Intra-abdominal sepsis alters tumor necrosis factor-alpha and interleukin-1 beta binding to human neutrophils; Simms HH et al.; OBJECTIVE: To determine the effects of intraabdominal sepsis on polymorphonuclear leukocyte tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) receptor expression . DESIGN: Prospective, randomized comparison between patients undergoing elective colon surgery vs . patients with intra-abdominal sepsis . SETTING: Tertiary-care center with all patients with intra-abdominal sepsis in a surgical ICU environment . PATIENTS: Group 1 (n = 7) represents control patients who underwent elective colon surgery without intra-abdominal sepsis . Group 2 (n = 10) represents patients with intra-abdominal sepsis . MEASUREMENTS AND MAIN RESULTS: Polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression +/- stimulation of the oxidative burst was measured using 125I TNF-alpha and 125I IL-1 beta . Superoxide anion production and candicidal activity were measured in the presence of TNF-alpha and IL-1 beta . Group 2 patients expressed fewer TNF-alpha and IL-1 beta receptors on their cell surface, and stimulation of oxidative burst reduced TNF-alpha and IL-1 beta receptor expression in group 2 more than in group 1 . Diminished TNF-alpha and IL-1 beta binding reduced superoxide anion production by group 2 polymorphonuclear leukocytes . Decreased TNF-alpha binding but not IL-1 beta, reduced polymorphonuclear leukocyte candicidal activity by group 2 polymorphonuclear leukocytes . CONCLUSIONS: a) Intra-abdominal sepsis reduces polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression . b) Expression of these surface receptors is altered by stimulation of the polymorphonuclear leukocyte oxidative burst . c) Diminished TNF-alpha and IL-1 beta receptor expression is associated with functional impairments in polymorphonuclear leukocyte activity. Klin Wochenschr, 1991 Dec 15, 69(21-23), 969 - 74 Reactive oxygen species, antiproteases, and cytokines in sepsis; Wendel A; Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order . As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day . Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid . A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor . Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage . By this sequence the final central mediator of shock and sepsis becomes systematically abundant . The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock. Klin Wochenschr, 1991 Dec 15, 69(21-23), 1004 - 8 Oxygen radicals--an important mediator of sepsis and septic shock; Brigham KL; There is considerable evidence to implicate aggressive species of oxygen in the pathogenesis of organ dysfunction consequent to sepsis and septic shock . The inflammatory process appears to participate ubiquitously in this setting . A characteristic of inflammation is the involvement of activated neutrophils and their generation of aggressive oxygen species . Such species may both directly injure cells proximal to the oxidant generating cells, and may inactivate any proteolytic mechanisms normally protective against proteolytic injury caused by neutrophil elastase and other proteolytic enzymes released during inflammation . The offending agent in sepsis is most commonly envisioned as bacterial lipopolysaccharide, or endotoxin . Infusion of endotoxin into animals can reproduce much of the pathophysiology of sepsis and septic shock . In addition, administration of endotoxin to cultured cells, particularly endothelial cells, can cause responses consistent with a sequence of events that occurs in intact animals and humans . In both experimental models, it appears that aggressive oxygen species are important actors in the scenario eventuating in cell or organ injury . Of importance, the toxic consequences of these free radicals probably occurs in relatively protected spaces, including microenvironments created by close adherence between inflammatory cells and endothelial cells and the cell interior . For those reasons, the potential for antioxidants as therapy should include consideration of the volume of distribution of such substances . It is probably important that antioxidants access excluded spaces including cell interiors in order to have their maximum effect in this setting . We have studied ina preliminary way the effects of n-acetyl-cysteine, a highly permeable free radical scavenger and anti-oxidant, in patients with established ARDS.(ABSTRACT TRUNCATED AT 250 WORDS) Chest, 1991 Dec, 100(6), 1703 - 11 Effect of PGE1 on altered distribution of regional blood flows in hyperdynamic sepsis; Raper RF et al.; Since the sepsis syndrome is associated with depressed vascular reactivity, it may be incorrect to assume that pharmacologically mediated changes in cardiac output will be proportionately distributed at the regional level of the circulation . We examined the effect of hyperdynamic sepsis and the concurrent administration of the vasodilatory prostaglandin (PGE1) on the regional distribution of blood flows (Q) in unanesthetized sheep rendered septic by cecal ligation and perforation . Systemic Q progressively increased throughout a 48-h study period after cecal ligation and perforation . Simultaneously, organ Q, measured by the radioactive microsphere technique, was depressed to the pancreas, but increased to the heart, gallbladder, brain, and colon; the increased Q to both heart and gallbladder was greater than the simultaneous increase in systemic Q in this septic study . With the infusion of PGE1 (1 microgram/kg/min), mean arterial perfusing pressures fell, while the cardiac index increased further over that recorded during the 48-h septic study . Despite this depression in arterial pressures, the only significant effect of PGE1 on the interorgan distribution of Q was in the renal circulation, where it was demonstrated that kidney Q fell . We conclude that (1) hyperdynamic and normotensive sepsis exerted nonhomogeneous effects on the distribution of organ Q, and (2) an increased systemic Q during PGE1 infusion was proportionately distributed to all organs, except the kidneys, where Q paradoxically fell . The latter finding suggests that the regulation of kidney Q may be depressed across the normal range of arterial perfusing pressures in the sepsis syndrome . Further investigation is essential to understand the effect of clinical interventions on the control of tissue O2 flux at both the regional and microregional levels of the circulation. Clin Orthop, 1991 Dec, (273), 113 - 8 Periprosthetic knee sepsis . The role of irrigation and debridement; Hartman MB et al.; Thirty-three infected total knee arthroplasties were treated by irrigation, debridement, and intravenous antibiotics . These cases were retrospectively reviewed with an average follow-up period of 4.5 years . There were 12 revisions and 21 primary arthroplasties in the series . Thirty-two knees were openly irrigated and debrided, and one was arthroscopically treated . In 20 of 33 knees, infection recurred--a reinfection rate of 61% . The authors attempted to identify factors influencing success and failure of infection eradication . There was a statistically significant improvement in the success rate of knees irrigated and debrided within four weeks of index surgery (p less than .05) . No statistically significant correlation was found between success and failure with regard to gender, age, preoperative diagnosis, previous surgery, length of intravenous antibiotics, or time from clinical symptoms to debridement . The authors believe that irrigation and debridement have a role in the immediate postoperative period . Caution should be used in periprosthetic knee infection appearing greater than four weeks from index surgery. Surg Clin North Am, 1991 Dec, 71(6), 1175 - 85 Management of intra-abdominal sepsis; Munson JL; The management of intra-abdominal sepsis includes drainage of septic foci, debridement of devitalized tissue, and prevention of continuing peritoneal contamination . An algorithm is presented as an aid to the thought process. Infect Dis Clin North Am, 1991 Dec, 5(4), 793 - 805 Sepsis syndrome . New insights into its pathogenesis and treatment; Bone RC; Recent insights into the pathogenesis of sepsis and its sequelae have opened up new approaches to treatment . For maximum effectiveness, however, treatment must be given as early as possible in the course of illness--but only to patients who are at high risk of developing shock . The definition of sepsis syndrome outlined in this article provides a method by which to identify such patients before the onset of shock. Am J Physiol, 1991 Dec, 261(6 Pt 2), R1507 - 12 Increase in hepatic blood flow during early sepsis is due to increased portal blood flow; Wang P et al.; Although hepatic blood flow increases significantly during early sepsis {as produced by cecal ligation and puncture (CLP)}, it is not known whether this is due to the increase in portal or hepatic arterial blood flows . To study this, rats were subjected to CLP, after which they and sham-operated rats received either 3 or 6 ml normal saline/100 g body wt subcutaneously (i.e., all rats received crystalloid therapy) . Blood flow in various organs was determined by using a radioactive microsphere technique at 5 and 20 h after CLP or sham operation . Portal blood flow was calculated as the sum of blood flows to the spleen, pancreas, gastrointestinal tract, and mesentery . Total hepatic blood flow was the sum of portal blood flow and hepatic arterial blood flow . A significant increase in portal blood flow and in total hepatic blood flow was observed at 5 h after CLP (i.e., early sepsis), and this was not altered by doubling the volume of crystalloid resuscitation after the induction of sepsis . In contrast, hepatic arterial blood flow during early sepsis was found to be similar to control; however, it was significantly reduced in late sepsis (i.e., 20 h after CLP) . Cardiac output was significantly higher than the control in early sepsis . However, even in late sepsis, cardiac output and total hepatic blood flow were not significantly different from controls . These results indicate that the increased total hepatic blood flow during early hyperdynamic sepsis is solely due to the increased portal blood flow. J Trauma, 1991 Dec, 31(12), 1663 - 70 Interleukin 6--a potential mediator of lethal sepsis after major thermal trauma: evidence for increased IL-6 production by peripheral blood mononuclear cells; Schluter B et al.; We studied the plasma levels of the acute phase mediator interleukin 6 (IL-6) in 21 severely burned patients (burn injuries ranging from 24% to 75% total body surface area) . The posttraumatic course of the IL-6 plasma levels was closely related to the clinical outcome . The nonseptic survivors as well as survivors with suspected sepsis (n = 14) exhibited maximal amounts of IL-6 (251 +/- 32 pg/mL) during the first 3 days post-burn, which subsequently returned to values within the normal range (days 30 to 50; 26 +/- 8 pg/mL) . In the nonsurvivors (n = 7) IL-6 concentrations permanently increased (up to 1,921 +/- 356 pg/mL) until death (days 10 to 19) resulting from sepsis with consecutive multiple organ failure . Peripheral blood mononuclear cells (PBMCs) of patients expressed IL-6-specific mRNA in vivo at high levels in contrast to the PBMCs of healthy donors . In addition, the spontaneous and PHA-induced in vitro production of IL-6 by patients' PBMCs was enhanced compared with healthy controls, whereas no significant differences were obtained with bacterial endotoxin (LPS) . The findings suggest that interleukin 6 is a potential mediator of lethal sepsis after major thermal trauma. Kokyu To Junkan, 1991 Dec, 39(12), 1209 - 14 {Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration}; Yahagi M et al.; We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines . {METHODS} Twenty-nine Japanese White rabbits were divided into 2 groups . Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E . coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17) . BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study . We used {3H} dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol . B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist . In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts . {RESULTS} In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM) . MAP and HR were slightly decreased in E-LPS but not significantly . Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM) . Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected . In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines . {CONCLUSION} These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock. Metabolism, 1991 Nov, 40(11), 1147 - 51 Tissue metabolite levels in different types of skeletal muscle during sepsis; Angeras U et al.; The effect of sepsis on energy and metabolite levels in the white, fast-twitch extensor digitorum longus (EDL) and the red, slow-twitch soleus (SOL) muscles was studied in rats . Sepsis was induced by cecal ligation and puncture (CLP) . Control rats were sham-operated . Sixteen hours later, metabolite levels in muscle tissue were determined . Adenosine triphosphate (ATP) levels and energy charge were reduced during sepsis in SOL, but were unchanged in EDL muscles . In contrast, phosphocreatine (PCr) concentration was reduced during sepsis in EDL, but not in SOL . Tissue glycogen levels were reduced and lactate concentrations were increased in both muscles during sepsis . Results suggest that sepsis affects energy metabolism differently in different types of skeletal muscle . Tissue lactate accumulation may be consistent with muscle hypoperfusion following CLP, although other mechanisms may also be involved. Chest, 1991 Nov, 100(5), 1397 - 403 Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome; Pacht ER et al.; The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema . Reactive oxygen species such as hydrogen peroxide and hypochlorous acid may play a key role in the pathogenesis of the acute lung injury . Glutathione (GSH) is a tripeptide that is able to react with and effectively neutralize oxidants such as hydrogen peroxide and hypochlorous acid . The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7 mumols +/- 7.8 mumols vs 91.8 mumols +/- 14.5 mumols; p = 0.002) . In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 +/- 0.003 nmol of GSH per microgram of total protein vs 0.026 +/- 0.005 nmol of GSH per microgram of total protein; p = 0.002) . Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of GSH may predispose these patients to enhanced lung cell injury. Crit Care Med, 1991 Nov, 19(11), 1339 - 47 Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study . The Ibuprofen Study Group; Haupt MT et al.; OBJECTIVE: To evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: Three university hospital medical ICUs . PATIENTS: Twenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter . INTERVENTIONS: Thirteen patients received placebo and 16 received ibuprofen that consisted of 600 mg (n = 11) or 800 mg (n = 5) iv over 20 mins, followed by three 800-mg doses administered as a rectal solution every 6 hrs . The initial iv dose was given within 4 hrs of the presumptive diagnosis of sepsis . MEASUREMENTS AND MAIN RESULTS: The peak circulating total ibuprofen concentration after the iv dose (49.4 +/- 4.5 micrograms/mL, mean +/- SEM) was higher than peak concentrations after the three rectal doses (17.0 +/- 2.7, 16.4 +/- 3.0, 16.0 +/- 3.1 micrograms/mL) . Both routes of ibuprofen administration were well tolerated . Frequent monitoring for gastrointestinal bleeding and assessment of renal and hepatic function failed to demonstrate significant differences between ibuprofen and placebo . Because a trend for reduced creatinine clearance was observed at 8 hrs in the ibuprofen group, nephrotoxicity of this drug in sepsis cannot be excluded . Temperature decreased significantly within 4 hrs of the initial dose of investigational therapy in patients who received ibuprofen (38.5 +/- 0.3 degrees to 37.0 +/- 0.2 degrees C, p less than .001) . However, despite this significant change in temperature, we were unable to detect significant differences in hemodynamic and respiratory values or survival when ibuprofen-treated patients were compared with controls . CONCLUSIONS: Ibuprofen was well tolerated when administered iv and rectally to patients with severe sepsis, although drug absorption was poor with the rectal route . Significant antipyretic effects of ibuprofen were demonstrated . Although an excellent safety profile characterized ibuprofen in this study, the absence of ibuprofen-associated toxicity may have been secondary to poor rectal absorption of the drug . Our results support the continued clinical investigation of ibuprofen in sepsis, using an all-intravenous route of administration. J Clin Invest, 1991 Nov, 88(5), 1452 - 9 Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome; Fasano MB et al.; Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome . We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively) . There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN . Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression . In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN . Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis . Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation . Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome. JPEN J Parenter Enteral Nutr, 1991 Nov-Dec, 15(6), 630 - 6 Histopathologic study of cholestasis induced by total parenteral nutrition or intraperitoneal sepsis in rats; Shu ZJ et al.; Wistar rats were divided into two groups, intraperitoneal sepsis group (group IS) and total parenteral nutrition group (group TPN), to evaluate the characteristics of pathologic alterations in rats with cholestasis . Biochemical assay showed that cholestasis developed in both groups after 10 days . Light microscopic examination of liver specimens revealed that the degeneration in the intermediate and external zone of hepatolobules was the major alteration in group IS, and group TPN showed characteristic dilation of central veins and hepatic sinuses and the proliferation of Kupffer cells with marked phagocytosis . Electron microscopic pictures presented the enlargement of bile canaliculi with altered microvilli in group IS and many highly electron-dense bile particles within cytoplasm and secondary lysosomes near dilated bile canaliculi in group TPN . It is concluded that there were different histopathologic alterations of liver specimens in TPN-supported animals and septic animals when cholestasis developed . It is unsuitable to take intraperitoneal sepsis as a unique factor of cholestasis in TPN-supported rats . Bile stasis is only one sign of TPN-induced hepatic lesion, which needs further exploration to determine its causes and mechanisms. J Appl Physiol, 1991 Nov, 71(5), 1979 - 89 TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis; Eichacker PQ et al.; We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies . Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls) . Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study . Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study . Animals given TNF had early (0-4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%) . In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema . In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days . Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2 . In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock . The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury . Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock. Am Surg, 1991 Oct, 57(10), 656 - 62 Patterns of liver test abnormalities in patients with surgical sepsis; Brooks GS et al.; The progression of changes in biochemical liver test results during moderate and severe sepsis (SS) was studied prospectively in 43 patients admitted to a surgical intensive care unit . Using predetermined criteria, severity of sepsis was assessed by physicians blinded to the liver test results . Linear regression analysis showed that bilirubin levels increased at a rate approximating 0.95 mg/dl/day in patients with SS, whereas alkaline phosphatase levels did not rise initially in these patients . Following peak hyperbilirubinemia, however, alkaline phosphatase levels increased at approximately 4 IU/L/day . In patients with moderate sepsis (MS), bilirubin levels increased slowly (approximately 0.4 mg/dl/day) but alkaline phosphatase levels increased rapidly (approximately 29 IU/L/day) . Following peak hyperbilirubinemia, alkaline phosphatase levels did not change . These data define patterns of liver test abnormalities of clinical importance . Rapidly rising bilirubin levels with little change in alkaline phosphatase levels are associated with SS, whereas markedly elevated alkaline phosphatase levels may indicate MS or resolution of SS . In critically ill surgical patients subjected to many potential hepatic insults, recognition of liver dysfunction with these patterns should alert the clinician to the possibility of underlying sepsis. Br J Surg, 1991 Oct, 78(10), 1187 - 8 Subareolar dissection for duct ectasia and periareolar sepsis; Hartley MN et al.; Excision of the major duct system of the breast for symptoms owing to mammary duct ectasia may be curative, but recent reports have been less optimistic . A retrospective study (1978-1990) of 46 women (median age 38 years, range 18-78 years) who underwent subareolar dissection with antibiotic cover for symptoms associated with duct ectasia is presented . Thirty-three women presented without symptoms of overt sepsis (periareolar lump, nipple discharge or nipple retraction) . Following subareolar dissection, six developed recurrent symptoms and five required further surgery . Thirteen women presented initially with abscesses . Eight abscesses recurred following incision and drainage, and one developed a mammillary fistula . Following subareolar dissection, six developed recurrent sepsis requiring further surgery. Am Surg, 1991 Oct, 57(10), 618 - 23 Prevention of central venous catheter sepsis: a prospective randomized trial; Bonawitz SC et al.; A prospective randomized trial was undertaken to evaluate the influence of routine 72-hour catheter exchange and the use of an implantable collagen cuff in preventing central venous catheter infection in critically ill patients requiring multiple lumen central venous access . Patients were randomized to one of four groups, which determined whether the central venous catheter placed would be removed at 3 or 7 days and whether an implantable collagen cuff would be used or not . Upon removal, cultures of the central line tip, the insertion site, and peripheral blood were obtained . One hundred and fifty-nine catheters were studied in 85 patients during a 14-month period . There were 26 (16.4%) episodes of catheter colonization and four (2.5%) episodes of catheter infection in the entire population . Catheter colonization rates (same organisms cultured from catheter tip and skin site) were 14.5 per cent at 3 days and 18.4 per cent at 7 days . Infection rates (same organism cultured from catheter tip and peripheral blood culture) were 2.4 per cent at 3 days and 2.6 per cent at 7 days . With regard to the use of the collagen cuff, colonization rates were 14.5 per cent with the use of the cuff and 18.1 per cent without the use of the cuff . Infection rates were 5.3 per cent with the use of the cuff and 0 per cent without the use of the cuff . None of these differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Physiol, 1991 Oct, 261(4 Pt 2), R965 - 72 Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker {18F}fluoromisonidazole; Hotchkiss RS et al.; Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis . We employed the novel hypoxic marker {18F}fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat . A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion . No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats . Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs . 20% decrease, P less than 0.05) and an increased retention of {18F}fluoromisonidazole in skeletal muscle of the septic rats . We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis . The greater reduction in muscle blood flow and the increased retention of {18F}fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia. Circ Shock, 1991 Oct, 35(2), 65 - 77 Imbalance between plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha during subacute endotoxin-induced hyperdynamic sepsis or multiple organ failure syndrome in sheep; Pittet JF et al.; We compared the time course of plasma and pulmonary lymph levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha during the development of either the hyperdynamic phase of sepsis or of the multiple organ failure syndrome (MOFS) associated with sepsis in 26 chronically instrumented awake sheep with intravascular catheters and a chronic pulmonary lymph fistula . Using a continuous i.v . infusion of Escherichia coli endotoxin administered at a rate of 20 ng.kg-1.min-1 (group E20, n = 9) resulted in hyperdynamic septic shock with more than 75% of animals surviving after 72 h of continuous endotoxin administration . Infusing endotoxin at a higher dosage (40 ng.kg-1.min-1; group E40, n = 9) resulted in the development of respiratory failure and MOFS with death occurring within 55 hr of endotoxemia . Eight similarly instrumented sheep served as controls . Administration of endotoxin produced within 4 hr in both endotoxin groups a significant increase in arterial plasma concentration of TxB2, which was not significantly different between both endotoxin groups . Thereafter, plasma TxB2 concentrations progressively decreased in the E20 group to reach at 36 hr values significantly lower than those measured in control sheep not given endotoxin . In the E40 group, plasma TxB2 concentrations returned to baseline values during the development of a MOFS . The time course of TxB2 concentrations in pulmonary lymph in both endotoxin groups was similar to that measured in each group in plasma . 6-Keto-PGF1 alpha concentrations in arterial plasma and pulmonary lymph were significantly higher than in controls during the first 20 hr following the start of endotoxin infusion in both endotoxin groups and were not different between these groups . Thereafter, plasma and pulmonary lymph 6-keto-PGF1 alpha concentrations progressively returned to baseline values in the E20 group and remained at these levels up to the end of the study period (72 hr) . In the E40 group, plasma 6-keto-PGF1 alpha concentrations also decreased to baseline values during the second day of endotoxemia but then significantly increased in sheep that survived more than 36 hr and developed a hypodynamic septic state . During the first 24 hr of endotoxemia, the plasma TxB2/6-keto-PGF1 alpha ratio was similar in controls and in both endotoxin groups . During the second study day, TxB2/6-keto-PGF1 alpha ratio progressively decreased in both endotoxin groups to reach and maintain values significantly lower than those measured in controls at 36 hr in the E40 group and at 52 hr in E20 group.(ABSTRACT TRUNCATED AT 400 WORDS) Inflammation, 1991 Oct, 15(5), 355 - 67 Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis; Green JA et al.; Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock . Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis . The relationship between these phospholipases is unclear . We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2 . This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis . These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity . The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis . We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme . This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis . Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease. Indian Pediatr, 1991 Oct, 28(10), 1159 - 64 Diagnostic and prognostic utility of C-reactive protein, alpha-1-antitrypsin and alpha-2-macroglobulin in neonatal sepsis: a comparative account; Suri M et al.; C-reactive protein (CRP), alpha-1-antitrypsin (alpha-1-AT) and alpha-2-macroglobulin (alpha-2-MG) levels were evaluated serially in 25 healthy and 20 septicemic neonates and then compared as early diagnostic aids and prognostic indicators in this illness . Compared to healthy controls, septicemic neonates had significantly higher mean CRP levels (p less than 0.01) . Neonates with septicemia, who recovered, had higher mean CRP levels than the group which died (p less than 0.05) . As an early diagnostic aid CRP had a low Youden index, whereas for prognosis its index was higher . Septicemic neonates also had significantly higher mean alpha-1-AT levels (p less than 0.05), 12-24 hours after onset of illness, as compared to healthy neonates . Alpha-1-antitrypsin could not be used as an early diagnostic aid in septicemia, but was useful for predicting outcome . Mean alpha-2-macroglobulin levels did not show significant variation in healthy and septicemic neonates . Lower mean alpha-2-MG levels were observed in neonates recovering from septicemia . As an early diagnostic aid alpha-2-MG had a low Youden index, whereas for prognosis its index was higher . CRP had a higher Youden index than alpha-2-MG for early diagnosis of neonatal septicemia and had a higher index than both alpha-1-AT and alpha-2-MG for predicting outcome in septicemia . Serial use of CRP alone is, therefore, recommended for both purposes. Jpn J Clin Oncol, 1991 Oct, 21(5), 353 - 9 The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor; Oshita F et al.; The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy . The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60% . In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses . It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%) . The administration of antibiotics was required for about 7 days to patients with febrile episodes . Sepsis was experienced in five courses, in which the neutrophils were all zero . All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy. Schweiz Med Wochenschr, 1991 Sep 21, 121(38), 1387 - 92 {Tumoral calcinosis with superinfection and sepsis}; Oeggerli P et al.; Tumoral calcinosis (TC) is a rare syndrome involving ectopic calcifications in the vicinity of the large joints . In about one third of patients the disorder is familial and is associated with hyperphosphatemia, elevation of 1,25-dihydroxy-vitamin-D levels and peculiar dental lesion . TC is inherited in an autosomal-recessive manner . In a normophosphatemic male patient with alcoholic cirrhosis of the liver, TC occurred first in the thoracic wall . Seven years after excision of the first lesion, a large tumor mass around the right hip developed . Infection of the calcified masses with Staph . aureus led to extensive abscess formation, septicemia and death at the age of 64 . Clinical, dental and biochemical examination of the 7 descendants of the patient revealed no constitutional signs of the disease, thus identifying our patient as a sporadic case . Clinical and pathological findings in the patient are discussed and the literature is reviewed. Ann Intern Med, 1991 Sep 15, 115(6), 457 - 69 The pathogenesis of sepsis; Bone RC; Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses . Many mediators of the pathogenesis of sepsis have recently been described . These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade . Neutrophil and platelet activation may also play a role . Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins . Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other . A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role . Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design . Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators . Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8 . Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults . Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response. Baillieres Clin Gastroenterol, 1991 Sep, 5(3 Pt 1), 611 - 37 Intra-abdominal sepsis: the role of surgery; Gallinaro RN et al.; The role of the surgeon in intra-abdominal sepsis is multifactorial . A comprehensive understanding of the incidence and pathophysiology of diseases which cause intra-abdominal sepsis is the key to the diagnosis and treatment of such ailments . In simplest terms, the aetiology has two basic mechanisms: (a) violation of the 'bug-body barrier' and (b) obstruction to the flow of a body fluid with subsequent bacterial overgrowth . Either of these mechanisms may affect any of the organs within the abdomen, leading to sepsis . The peritoneal cavity is a dynamic structure which responds to insults in certain predictable manners which notify the alert physician that danger is present . Recognition of these signs through history and physical examination are the most important aspects of diagnosis . Confirmation of suspicions can be obtained with radiological modalities, but they are not a substitute for clinical judgement . Treatment of intra-abdominal sepsis should always begin with resuscitation and systemic antibiotics . Alleviation of the septic source is mandatory, and this may be achieved either operatively or non-operatively (i.e . percutaneous or endoscopic procedures) . When the patient does not improve after the initial procedure, then a missed focus of infection must be investigated . In some cases, a planned or staged second operation may be needed to further debride necrotic tissue . Antibiotics should be of adequate spectrum and bioavailability to kill the species of bacteria most likely to cause the infection . This regimen may be altered when culture and sensitivity reports are completed . Finally, patients whose immune system function has been altered by disease or treatment must be assumed very ill until proven otherwise . These are general guidelines in the management of patients with intra-abdominal sepsis . Individual cases may necessitate slight modifications, but all require a high level of vigilance and expertise in order to combat a very lethal disease. Midwifery, 1991 Sep, 7(3), 102 - 6 Puerperal sepsis: its contribution to maternal mortality; Kwast BE; Puerperal sepsis is the second most common cause of maternal mortality in the developing world . In this paper the extent of the problem is described and factors affecting puerperal sepsis are identified . Methods of reducing the incidence of puerperal sepsis are suggested . This paper is based on one originally given at the ICM/WHO/UNICEF pre-congress workshop in Kobe, Japan, October, 1990. Br J Surg, 1991 Sep, 78(9), 1031 - 8 Postsplenectomy sepsis and its mortality rate: actual versus perceived risks; Holdsworth RJ et al.; A collective critical review of the literature on postsplenectomy sepsis from 1952 to 1987 has been undertaken . The reports cover a cohort of 12,514 patients undergoing splenectomy but of these only 5902 reports were sufficiently detailed to allow a useful analysis . The incidence of infection after splenectomy in children under 16 years old was 4.4 per cent with a mortality rate of 2.2 per cent . The corresponding figures for adults were 0.9 per cent and 0.8 per cent respectively . The present analysis of well documented patients has shown that severe infection after splenectomy for benign disease is very uncommon except in infants (infection rate 15.7 per cent) and children below the age of 5 years (infection rate 10.4 per cent) . Many of these reported postsplenectomy infections may have been coincidental . It is also apparent that children contract a different type of infection after splenectomy than adults, predominantly a meningitis which is less frequently fatal . Adults, in contrast, appear to develop a septicaemic type of illness associated with a higher mortality rate . This survey has also shown that children are reported to be more susceptible to pneumococcal sepsis than to infection caused by any other organism . Although the removal of the spleen in otherwise normal people does not appear to be associated with an increased frequency of infection, the presence of a coexistent disorder, notably hepatic disease, can increase the risk substantially. Baillieres Clin Gastroenterol, 1991 Sep, 5(3 Pt 1), 587 - 609 Intra-abdominal sepsis: the role of radiology; Adam EJ et al.; A wide range of imaging tools is available for the investigation of abdominal sepsis . Plain films and barium studies alone are generally regarded as inadequate and most patients will require ultrasound, CT or nuclear medicine studies to locate the source of sepsis . The choice of imaging modality depends on several factors, most important of which are the clinical condition of the patient and the presence or absence of localizing signs and symptoms . Ultrasound has the advantage of being portable and is therefore probably the best initial imaging method for the critically ill patient . It should also be the first investigation in patients with signs and symptoms localizing to the right upper quadrant, renal areas, subphrenic spaces or pelvis . Transvaginal ultrasound is particularly useful in examining the pelvis . CT is the imaging modality of choice for the pancreas and retroperitoneum and in patients who are poor candidates for ultrasound or in whom visualization on ultrasound is inadequate . In patients with PUO or evidence of sepsis without localizing signs or symptoms, nuclear medicine studies in the form of 67Ga citrate or labelled white cell scans are useful to localize the septic focus, although in most cases CT or ultrasound will subsequently be required for detailed anatomical definition . Imaging techniques have an increasingly important role to play in the treatment of sepsis, and guided aspiration and drainage may be performed with a high degree of accuracy under ultrasound or CT guidance, eliminating the need for surgical intervention in many individuals. Pediatr Infect Dis J, 1991 Sep, 10(9), 663 - 8 Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates; Lassiter HA et al.; The significance of low serum IgG and complement proteins in very low birth weight (VLBW; less than 1500 g) neonates is not known . Therefore serum IgG, C3, C4 and Factor B were quantitated weekly by rate nephelometry in 15 VLBW neonates who developed proven nosocomial bacterial or candidal sepsis (Group A) and 27 VLBW neonates who did not develop sepsis (Group B) . In the first week of life the serum IgG of neonates in Group A was 295 +/- 33 mg/dl (mean +/- SEM) and in Group B it was 440 +/- 21 mg/dl (P less than 0.01) . In the second week, the IgG of Group A was 270 +/- 32 mg/dl and that of Group B was 473 +/- 38 mg/dl (P less than 0.01) . If the IgG was less than 350 mg/dl in the first week or less than 230 mg/dl in the second week, the relative risk of acquiring sepsis was greater than or equal to 5 (95% confidence interval in the first week, 1.7 to 11.2) . The serum IgG was measured before the onset of sepsis in 14 of the 15 neonates in Group A . In the week before sepsis the IgG of the 14 neonates was less than 440 mg/dl (range, 45 to 433 mg/dl) in all cases, was below the mean IgG of Group B in 12 of 14 cases (P = 0.006 vs . Group B) and was greater than 2 SD below the mean IgG of Group B in 4 of 14 cases (P = 0.0003 vs . Group B).(ABSTRACT TRUNCATED AT 250 WORDS) J Bone Joint Surg Br, 1991 Sep, 73(5), 783 - 6 Total arthroplasty of the hip after childhood sepsis; Kim YH; Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood . The average age of the patients was 36.4 years (range 19 to 50) . The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80) . Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection . The mean functional rating of the hips was 58 points before operation and 90 at the final review . Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration . Acetabular allografts were required in 27 hips (60%) . All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all. Eur J Immunol, 1991 Sep, 21(9), 2177 - 84 Dissociation between plasma and monocyte-associated cytokines during sepsis; Munoz C et al.; We report our investigations of circulating interleukin (IL) 1 beta, IL 6 and tumor necrosis factor (TNF)-alpha, as well as cell-associated IL 1 alpha, IL 1 beta and TNF-alpha in plasma and monocytes of 21 patients with sepsis syndrome and 6 patients with non-septic shock . Longitudinal studies reveal that (a) the most frequent detectable plasma cytokines were TNF-alpha and IL 6, (b) the presence and the kinetics of circulating cytokines were independent of one other, (c) detectable levels of cytokines could be found for a long period of time, and (d) significantly higher levels of IL 6 were found for non-surviving patients . Because of the in vivo half-life of cytokines and of the existence of numerous specific high-affinity receptors, it is quite probable that detectable plasma cytokines represent the excess of produced mediators which have not been trapped by the target cells . TNF-alpha (410 +/- 65 pg/10(6) monocytes) and IL 1 beta (153 +/- 60 pg/10(6) monocytes) were frequently found associated to monocyte lysates (88% and 50%, respectively) . Despite the fact that IL 1 alpha is the most abundant cytokine found associated to monocytes following in vitro activation, IL 1 alpha was rarely found in monocytes of intensive care unit patients (29%) . No correlation was found to exist between the levels of plasma cytokines and cell-associated cytokines . Some patients had plasma TNF-alpha or IL 1 beta in the absence of the corresponding monocyte-associated cytokine . This observation suggests that cells other than monocytes can participate in the production of circulating cytokines . At the end of the longitudinal study (day 14 +/- 2), only 2/12 surviving patients still had plasma TNF-alpha, whereas 8/12 had monocyte-associated TNF-alpha . These results indicate that activation of monocytes still occurs in patients for whom no plasma cytokines can be detected . Thus, in addition to the measurement of plasma cytokine, measurement of cell-associated cytokine appears useful to assess cytokine production and monocyte activation in vivo. Crit Care Med, 1991 Sep, 19(9), 1114 - 9 Differential detection of plasma hydroperoxides in sepsis; Keen RR et al.; OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis . DESIGN: Exploratory, open-label study . SETTING: Critical care unit at a university medical center . PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters . Seven patients were diagnosed with pulmonary infections and five patients had intra-abdominal infections . INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient . Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase . MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005) . CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma . Assays for hydroperoxides may be useful when relatively free of other tissue trauma. Anesth Analg, 1991 Sep, 73(3), 289 - 94 Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats; Beebe DS et al.; Hyperthermia from septic shock may be indistinguishable from malignant hyperthermia . Dantrolene may be given in septicemia if the diagnosis is unclear . To determine if dantrolene is safe to use in sepsis, two studies were performed . In study 1, 18 anesthetized dogs in which profound septic shock was induced with 5 mg/kg of intravenous Escherichia coli endotoxin were randomized to receive (30 min later) intravenous injections of 10 mg/kg of dantrolene solution, the diluent of dantrolene, or maintenance intravenous fluids alone . The use of dantrolene solution and the diluent of dantrolene resulted in similar but transient statistically significant increases in the cardiac filling pressures and cardiac outputs and decreases in the vascular resistances compared with the control dogs . In a second study, 185 rats were randomized into five equal groups . Groups 1, 2, and 3 received 15 mg/kg of intraperitoneal Escherichia coli endotoxin followed 30 min later by 10 mg/kg of dantrolene solution, the diluent of dantrolene, or normal saline . Groups 4 and 5 received normal saline followed by dantrolene or normal saline . The survival of groups 1, 2, and 3 was less at 24 h (P less than 0.0001) than that of either control group, but was not significantly different from one another . The results suggest dantrolene can be administered safely under clinical conditions where the cause of hyperthermia and shock cannot clearly be ascribed to malignant hyperthermia or septicemia. Indian J Pediatr, 1991 Sep-Oct, 58(5), 661 - 4 Neonatal sepsis due to vertical transmission from maternal genital tract; Ayengar V et al.; High vaginal swabs (HVS) of 1792 expectant mothers were sent for culture at the time of delivery, prior to first vaginal examination . The newborns were followed-up for development of superficial or deep infections . Appropriate cultures of the babies who developed infections were sent . Bacterial growth of predominantly gram-ve organisms was obtained in 1026 (57%) HVS . Infection developed in 48 (27%) babies in 1st 72 hours of life, of which 28 had deep infection while the rest had superficial infection . Vertical transmission of organisms was documented in 24 (1.3%) mother-baby dyads and the same was 72% in newborns who were at risk of developing sepsis by septicemia scoring, showing a significantly higher incidence of vertical transmission and subsequent sepsis in high risk newborns. Infection, 1991 Sep-Oct, 19(5), 317 - 23 Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock; Boekstegers P et al.; In 40 intensive care patients, tissue oxygen partial pressure distribution within skeletal muscle was measured in order to estimate peripheral oxygen availability . In septic patients with multiple organ failure (n = 20) mean skeletal muscle pO2 was abnormally high (48.8 +/- 8.5 mmHg, p less than 0.001) in contrast to patients with limited infection without sepsis (28.3 +/- 5.9 mmHg, n = 10) . Mean muscle pO2 also discriminated between septic and cardiogenic shock (22.6 +/- 6.9 mmHg, p less than 0.001) . The characteristic pattern of oxygen availability in septic patients--but not in patients with limited infection--was high skeletal muscle pO2 high whole body oxygen delivery and low whole body oxygen extraction, which was not influenced by the type of pathogenic agent of sepsis . In our patients in severe stage of sepsis, we did not observe local skeletal muscle hypoxia due to microcirculatory disorder . High mean skeletal muscle pO2 suggested reduced oxygen consumption within tissue rather than reduced oxygen transport to tissue in sepsis. Anesteziol Reanimatol, 1991 Sep-Oct, (5), 32 - 4 {Changes in the amino acid spectrum of the blood in patients with sepsis in the process of complex intensive therapy}; Spas VV et al.; Amino acid fund has been studied during complex therapy of 25 patients with sepsis . In 15 patients complex therapy included detoxicating hemosorption (3-5 sessions), in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions) . Complex therapy employing hemosorption led to a decrease in serine plasma level . Changes in the amino acid fund of the whole blood were insignificant . Leucine, isoleucine, threonine and phenylalanine blood levels were significantly increased . The introduction of ultraviolet blood irradiation into complex therapy of patients reduced traumatic effect of sorption detoxication on blood cells and enhanced detoxicating effect. J Surg Res, 1991 Aug, 51(2), 158 - 64 Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage; Meldrum DR et al.; Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions . Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL-6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation . To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate . Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline . The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed . The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively . However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05) . Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Surg, 1991 Aug, 214(2), 141 - 8 The complex pattern of cytokines in sepsis . Association between prostaglandins, cachectin, and interleukins; Ertel W et al.; Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis . Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group . Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL) . Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours) . Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05) . These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis. Surg Clin North Am, 1991 Aug, 71(4), 749 - 64 Sepsis . What it is and how to recognize it; Mileski WJ; Sepsis, shock, and resuscitation may result in various degrees of ischemia-perfusion injury that may produce widespread organ dysfunction through complex interactions and activation of host immunoinflammatory processes . As the pathophysiologic mechanisms of the inflammatory response are better defined, we may be able to modulate the generalized inflammatory state we know as sepsis and prevent the development of multiple organ failure syndrome . At present, however, the mainstay of therapy remains prompt resuscitation to eliminate regions of hypoperfusion and to limit as much as possible those factors that predispose to further organ injury while the source of inflammatory stimulation is being identified and controlled. Crit Care Med, 1991 Aug, 19(8), 1060 - 6 Reduced alveolar macrophage production of tumor necrosis factor during sepsis in mice and men; Simpson SQ et al.; BACKGROUND AND METHODS: Tumor necrosis factor (TNF) has been implicated as a major humoral mediator of sepsis and endotoxin shock . TNF is secreted by cells of the reticuloendothelial system, including alveolar macrophages . Alveolar macrophage TNF production has been postulated to play a pathogenetic role in the development of adult respiratory distress syndrome (ARDS) in sepsis . To evaluate alveolar macrophage production of TNF during sepsis and endotoxin shock, we studied the effects of sepsis and/or in vivo lipopolysaccharide on the in vitro production of TNF by pulmonary alveolar macrophages . Human pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from six septic and five nonseptic patients, cultured in the presence or absence of lipopolysaccharide (1 ng/mL), and assayed for TNF activity in a bioassay using fibroblast lysis . A murine model of sepsis was also utilized to study pulmonary alveolar macrophage TNF production under more controlled conditions . Normal mice were given ip injections of either lipopolysaccharide or saline . After 2 hrs, pulmonary alveolar macrophages were obtained and cultured in saline or various concentrations of lipopolysaccharide (0.001 to 10 micrograms/mL) . RESULTS: There was no difference in baseline TNF activity, expressed as per cent lysis at 1:10 dilution, between pulmonary alveolar macrophages from control and septic patients (35.7 +/- 5.5% vs . 24.4 +/- 9.3%, respectively) (p greater than .05) . However, when stimulated with lipopolysaccharide in vitro, the pulmonary alveolar macrophages from nonseptic patients produced significantly (p less than .01) more TNF (82.8 +/- 3.6%) than did pulmonary alveolar macrophages from patients with the septic syndrome (35.2 +/- 3.8%) . Similar findings were obtained using the murine sepsis model . The baseline TNF activity in pulmonary alveolar macrophages from control mice was 22.9 +/- 7.0% (mean +/- SEM) and from lipopolysaccharide-injected mice was 26.8 +/- 3.3% (p greater than .05) . Stimulation with 1 ng/mL lipopolysaccharide in vitro produced an increase in TNF activity in both groups, but the increase was greater in the control mice (68.1 +/- 5.7%) than in the lipopolysaccharide-injected mice (47.5 +/- 5.3%) (p less than .01) . When the murine pulmonary alveolar macrophages were stimulated with higher concentrations of lipopolysaccharide (0.1 to 10 micrograms/mL), pulmonary alveolar macrophages from lipopolysaccharide-injected mice produced less than 25.5% of the TNF produced by pulmonary alveolar macrophages from control mice . CONCLUSIONS: These studies indicate that sepsis and endotoxin injection result in a rapid decrease in the ability of pulmonary alveolar macrophages from both humans and mice to produce and secrete TNF in response to lipopolysaccharide . We speculate that a downregulation of TNF production or of macrophage responsiveness to lipopolysaccharide has occurred . These results suggest that sustained TNF production by macrophages is not required for lung injury in sepsis. Zhonghua Nei Ke Za Zhi, 1991 Aug, 30(8), 484 - 6, 521 {Bacterial sepsis and nosocomial infection: a study of 70 patients}; Deng GH et al.; 74 episodes of bacterial sepsis in 70 patients were analysed from July 1988 to June 1989 . The incidence of sepsis is 0.7% of the whole admitted patients . Compared to a similar previous study from April 1982 to March 1983, the incidence of sepsis decreased (P less than 0.01), and the incidence of nosocomial sepsis remained unchanged, whereas its mortality decreased (P less than 0.05) . The host defenses are important in predisposing to sepsis and determining prognosis . Antibiotic sensitivity test revealed that some bacterial strains were resistant to new beta-lactam antibiotics. Am J Physiol, 1991 Aug, 261(2 Pt 1), G287 - 94 Increased glucose uptake by intestinal mucosa and muscularis in hypermetabolic sepsis; Lang CH et al.; The purpose of the present study was to determine the following: 1) whether the sepsis-induced increase in glucose uptake was a generalized response along the entire length of the gastrointestinal tract; 2) the relative contribution of the mucosa and muscularis to the enhanced uptake; and 3) whether reducing intestinal blood flow would attenuate the elevated rate of glucose uptake . Hypermetabolic sepsis increased in vivo glucose uptake in all sections of the gastrointestinal tract (57-93%) except the stomach . The rates of glucose uptake per gram of tissue by the mucosa and muscularis were not different . However, because the mucosa accounted for the majority of the whole intestine mass, this layer was responsible for 76-78% of the glucose uptake by the entire small intestine . Intestinal blood flow, determined with the use of radiolabeled microspheres, increased by 127% in sepsis . In both groups, approximately 70% of the total intestinal blood flow was distributed to the mucosa . Somatostatin was infused to produce splanchnic vasoconstriction and decreased the sepsis-induced increment in intestinal flow to the mucosa and muscularis (38 and 54%), whereas the enhanced rate of glucose uptake was not altered . Somatostatin also produced a severe insulinopenia . These results indicate that hypermetabolic sepsis increases glucose uptake to a similar extent along the length of the small and large intestine and that the majority of this increase is due to an enhanced uptake by the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) Circ Shock, 1991 Aug, 34(4), 356 - 63 Intraabdominal sepsis: enhanced autooxidative effect on polymorphonuclear leukocyte cell surface receptor expression; Simms HH et al.; We investigated the effects of untreated intraabdominal sepsis on the interrelationship between PMN oxidative metabolism and cell surface receptor expression . Female swine underwent either sham laparotomy (n = 7) or cecal ligation and incision (n = 9) with assays conducted on postoperative days (POD) 0, 1, 4, and 8 . Superoxide anion production, intracellular H2O2 production, and the cell surface expression of Fc gamma RII, III, CR1, and CR3 were measured . In addition, phagocytosis of serum-opsonized zymosan was used as a multivalent ligand for CR3 and subsequently Fc gamma RII, III, and CR1 expression were assayed to determine if intraabdominal sepsis induces a linkage between complement and Fc gamma receptor expression . Superoxide anion production increased between POD 0 and 4 and fell between POD 4 and 8 in animals with untreated intraabdominal sepsis . Intracellular H2O2 production rose between POD 0 and 1 and then fell progressively in animals with untreated intraabdominal sepsis . Simulation of the oxidative burst using glucose/glucose oxidase reduced Fc gamma RII and III expression in both sets of animals with a greater reduction seen by POD 4 in animals with intraabdominal sepsis . CR1/CR3 expression was increased with glucose/glucose oxidase by POD 4 in the presence of intraabdominal sepsis . Xanthine/xanthine oxidase did not alter cell surface receptor expression . Phagocytosis of serum-opsonized zymosan decreased subsequent Fc gamma RII expression in animals with intraabdominal sepsis by POD 4.(ABSTRACT TRUNCATED AT 250 WORDS) Br J Surg, 1991 Aug, 78(8), 961 - 3 Gallbladder sepsis after stent insertion for bile duct obstruction: management by percutaneous cholecystostomy; Ainley CC et al.; Of 364 patients undergoing insertion of a biliary endoprosthesis in 1989, six (1.6 per cent) developed gallbladder sepsis . Three patients had cholangiocarcinoma, two had carcinoma of the pancreas and one had a benign biliary stricture . Two of the five patients with malignancy had gallbladder stones, and the patient with a benign stricture developed stones after 3 years of stenting . Three patients developed gallbladder sepsis early after endoprosthesis insertion (less than 6 days), while in the other three it occurred late (greater than 6 months) . All six patients failed to respond to antibiotics and were successfully managed by percutaneous cholecystostomy; the patient with a benign biliary stricture also had cholecystolithotomy . The gallbladder drainage tubes were removed or became dislodged at intervals varying from 2 weeks to 6 months without complications . Percutaneous cholecystostomy is the treatment of choice for gallbladder sepsis unresponsive to antibiotics in patients with a biliary endoprosthesis in situ. Surgery, 1991 Aug, 110(2), 318 - 25; 325-6 Sepsis alters skeletal muscle energetics and membrane function; Jacobs DO et al.; The effects of sepsis on skeletal muscle energetics and membrane function are poorly understood, and the time course of changes in energy metabolism are unclear . To clarify these relationships, high energy phosphate ratios, intracellular pH, and phosphocreatine breakdown rates were measured in vivo in the gastrocnemius muscle of adult male Wistar rats after cecal ligation and puncture or sham operation with 31P magnetic resonance spectroscopy . Adenosine triphosphate (ATP) concentration and Na(+)-K+ ATPase and creatine kinase activities were determined in vitro . Within 24 hours, Na(+)-K+ ATPase activity increased by 60% in rats with cecal ligation and puncture, all of which had positive bacterial cultures, as compared to none of the sham-operated controls . Phosphocreatine/ATP ratios decreased by 20% in association with a quantitatively similar increase in phosphocreatine breakdown (9.7 +/- 0.5 vs 11.9 +/- 0.5 mumoles/gm wet wt/sec; p = 0.01) . ATP concentrations were maintained, and intracellular pH did not change significantly . In this model, changes in phosphocreatine breakdown were not related to total creatine kinase activity, which did not change significantly, or increases in adenosine 5'-diphosphate (ADP) concentration (62 +/- 8 vs 92 +/- 8 mumols/L; p = 0.02) . Thus, in early sepsis before a measurable decrease in pH occurs, ATP is utilized at an increased rate to help maintain ionic balance and/or to support other metabolic processes . Phosphocreatine stores are used to buffer ATP concentrations. Postgrad Med, 1991 Jul, 90(1), 199 - 202, 205-8 Sepsis and septic shock . Deadly complications that are on the rise; Murray MJ et al.; Most patients are already hospitalized when sepsis and septic shock develop, and in spite of therapy, at least 50% die . Although newer therapeutic agents are being evaluated, current management consists of antibiotics, fluids for volume resuscitation, inotropic agents, and surgery for septic foci . Greater emphasis on preventive measures is recommended. Crit Care Med, 1991 Jul, 19(7), 882 - 6 Postoperative sepsis: reexplore or observe? Accurate indication from diagnostic abdominal paracentesis; Halpern NA et al.; OBJECTIVE: To determine if postoperative diagnostic abdominal paracentesis is a useful clinical tool in the abdominal evaluation of the critically ill septic patient . DESIGN: Retrospective review . SETTING: Surgical ICU patients in a Veterans Administration medical center . PATIENTS: Ten patients were studied from a total of 1,053 patients admitted to the surgical ICU between September 1985 and May 1989 . INTERVENTIONS: Diagnostic abdominal paracentesis performed by the open or closed approaches . MEASUREMENTS AND MAIN RESULTS: Results are presented in three patient groups (A, B, and C): Group A (n = 4) had positive diagnostic abdominal paracentesis . Abdominal causes for the sepsis were found at reexploration . One of these four patients survived . Group B (n = 3) had negative diagnostic abdominal paracentesis . No abdominal septic source was found at reexploration; all three patients died . In group C (n = 3), diagnostic abdominal paracentesis was negative, patients were not reexplored, and all survived . Diagnostic accuracy correlated with three variables: a) the gross appearance and smell of the fluid, b) WBC count greater than 5000 or less than 500/mm3, and c) Gram stain demonstrating bacterial organisms . CONCLUSIONS: Diagnostic abdominal paracentesis proved accurate, reliable, simple, safe, and rapid in evaluating the abdomen in the postoperative septic patient . The use of this procedure should be considered in postoperative septic patients in whom an abdominal source for the sepsis needs to be excluded. JPEN J Parenter Enteral Nutr, 1991 Jul-Aug, 15(4), 460 - 3 Tunneled central venous catheter sepsis: risk factors in a pediatric hospital; Mulloy RH et al.; All tunnelled central venous catheters (TCVC) placed at the Alberta Children's Hospital in Calgary, Alberta, between November 1984 and July 1987, were retrospectively reviewed to study the association of catheter infection with a number of factors including age, diagnosis, catheter use, and areas caring for children . One hundred children received 130 silastic catheters placed for a total of 17,861 days . Each catheter survived a median of 100 days . Thirty-one episodes of catheter sepsis were identified (one episode for each 576 days of catheter use) . Children under 2 years of age had more than two times the risk of catheter infection (p less than 0.01) . Children with malabsorption had a greater risk (45.7%) than did those with infection (25.0%) or cancer (15.5%) . The use of catheters for total parenteral nutrition (TPN) or for multiple purposes markedly increased the risk of catheter infection . The risk of infection of TCVC appears to be great in the young child, in particular, in those requiring TPN or multiple intravenous infusions . Use of TCVC in these children should be avoided if possible. Circ Shock, 1991 Jul, 34(3), 311 - 8 Hyperdynamic sepsis in baboons: I . Aspects of hemodynamics; Schlag G et al.; The baboon has a number of advantages as a shock model, as its physiological as well as its biochemical behaviour is similar to man . Therefore we have tried to set up a model to mimic the early hyperdynamic phase of clinical sepsis . Seven baboons, 21-25 kg body weight were kept under EEG servocontrolled anesthesia for 8 hr . During this time live E . coli (ATC #33985) 2 x 10(10) BW/8 hr were continuously infused intravenously . Adequate fluid supply with Ringer's solution (up to 40 ml/kg/hr) was given to keep the pulmonary artery wedge pressure at baseline levels; this procedure resulted in a hyperdynamic response with a cardiac output (CO) 20-35% above baseline and a decrease (20-39%) in mean arterial pressure (MAP), leading to a 50% decrease in peripheral resistance . The pulmonary vascular changes were reflected in an increase of the mean pulmonary pressure (PA) to 42% above baseline and a marked rise in pulmonary vascular resistance (PVR) to 50% above baseline with no additional changes in pulmonary gas exchange . After 8 hr both CO and MAP were inversely correlated (r = 0.9-1) with dramatically increased catecholamine plasma levels (15 times above baseline) . With continuous infusion of live E . coli (blood levels 10(5)-10(6) CFU/ml) and massive fluid supply we have successfully mimicked hyperdynamic sepsis with severe organ failure after an 8-hr observation period. Blood, 1991 Jun 15, 77(12), 2660 - 7 Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis; Kaufman N et al.; Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available . We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody . The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L . A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented . Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex . Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks . Two other HAE patients did not show elevated levels at quiescent periods . The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks. Aust N Z J Surg, 1991 Jun, 61(6), 469 - 71 Sepsis after Ivalon sponge rectopexy: an unusual case; Gupta S et al.; A case with an unusual presentation of sepsis after Ivalon sponge rectopexy is reported . A strong index of suspicion is important for correct diagnosis . Early removal of infected sponge allows quick resolution of the sepsis without recurrent prolapse. Am J Physiol, 1991 Jun, 260(6 Pt 2), H1857 - 63 Chronic alcohol consumption enhances sepsis-induced cardiac dysfunction; McDonough KH et al.; Chronic alcoholism causes a cardiac contractile dysfunction which, in rats, may occur after 6 mo to 1 yr of alcohol consumption . Sepsis, on a more acute basis, can also induce intrinsic cardiac dysfunction . We tested the hypothesis that 2 mo of chronic alcohol feeding, while not directly causing overt depression of the myocardium, might sensitize the heart to a known cardiac stress, i.e., sepsis . We proposed that sepsis, induced in an alcoholic animal, would cause a more severe myocardial depression than in a nonalcoholic rat . Thus rats were fed a liquid diet with 36% of the total calories as alcohol for 8-10 wk and were then anesthetized and received an injection of live Escherichia coli (approximately 10(10) E . coli) through a dorsal subcutaneous catheter followed by a second dose approximately 5 h later . The following day, hearts were removed and, using the isolated working heart preparation, intrinsic contractile performance was assessed by generating ventricular function curves . Four groups of animals were studied . Hearts from the nonalcoholic-nonseptic group and the alcoholic-nonseptic group showed identical cardiac work (cardiac output x peak systolic pressure at the highest preload was 6,113 +/- 324 and 5,955 +/- 406 ml.min-1.mmHg-1, respectively) . Work in the nonalcoholic-septic and the alcoholic-septic groups was decreased by 30 and 50%, respectively (4,806 +/- 478 vs . 2,917 +/- 435 ml.min-1.mmHg-1 at the highest preload) . Thus 2 mo chronic alcohol consumption caused no overt cardiac dysfunction by itself but did exacerbate the myocardial injury induced by sepsis. J Trauma, 1991 Jun, 31(6), 768 - 73; discussion 773-4 Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis; Barton RG et al.; We tested the hypothesis that substitution of omega-3 fat for dietary omega-6 fat would reduce mortality and decrease Kupffer cell prostaglandin E2 (PGE2) production in a rat model of chronic sepsis . Rats were fed via gastrostomy for 12 days with isonitrogenous, isocaloric diets containing 15% of calories as either safflower oil (omega-6) or a 10:1 mixture of menhaden oil (omega-3) and safflower oil . After five days of feeding, animals received an intra-abdominal abscess of defined bacterial content . Survivors were killed on post-laparotomy day 6 in conjunction with liver perfusion and protease liver digestion for Kupffer cell isolation . Kupffer cell PGE2 production was measured by radioimmunoassay after 18 hours of cell culture and again after stimulation with 0 LPS, 10 ng/ml LPS, and 10 micrograms/LPS . Mortality was decreased in menhaden oil-fed animals compared with safflower oil-fed animals (16% vs . 35%) . Kupffer cell PGE2 production was decreased in menhaden oil-fed animals at 18 hours (354 +/- 54 vs . 570 +/- 95 pg/0.1 ml; p = 0.09) and after stimulation with 10 micrograms/ml LPS (140 +/- 41 vs . 288 +/- 45 pg/0.1 ml; p = 0.03) compared with safflower oil-fed animals. J Trauma, 1991 Jun, 31(6), 753 - 8; discussion 758-9 T3 preserves respiratory function in sepsis; Dulchavsky SA et al.; Sepsis produces profound hypothyroidism . This hypothyroid state is associated with altered lung metabolism and structural integrity . We studied the respiratory function of rats during sepsis-induced hypothyroidism with or without T3 treatment . Forty-four male Holtzman rats underwent cecal ligation and puncture (CLP) . Treatment was administered at six hours after surgery consisting of intraperitoneal injection of T3 (15 micrograms/kg, n = 19) or saline (n = 25) . At 20 hours (Group A) or 30 hours (Group B) following CLP, respiratory drive was assessed by serial occlusion pressure technique (P0.1) . The rats were killed and static elastance determined by serial air inflation to 10 cc . The lungs were excised for weight determination . The P0.1 values were significantly greater in T3-treated animals over controls in Group A (9.3 +/- 0.7 vs . 6.6 +/- 2.2, p less than 0.05 by t test); elastance was significantly improved by T3 treatment in Group B (p less than 0.05 by two-way ANOVA) . Lung weight, pH, pO2, pCO2, respiratory rate (RR), and mortality were not significantly different between groups . Control animals were hypothyroid by 20 hours after CLP (T3 less than 12.5 ng/dL) whereas T3-treated animals were euthyroid (T3 = 145 +/- 43 ng/dL) . Pulmonary dysfunction frequently accompanies sepsis; the euthyroid state appears protective . We found a significantly improved respiratory drive in septic animals with T3 treatment . Lung elastance was similarly improved in late sepsis with T3 treatment . The data suggest that T3 treatment preserves respiratory function in septic rats as evidenced by respiratory drive and compliance. Crit Care Med, 1991 Jun, 19(6), 753 - 7 Amino acid alterations and encephalopathy in the sepsis syndrome; Sprung CL et al.; OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy . DESIGN: Retrospective analysis . SETTING: Medical wards and medical ICU of a university hospital . PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium . INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined . MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs . 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs . 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs . 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs . 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05) . Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality . APACHE II scores were higher in the septic shock patients (30 +/- 2 vs . 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs . 12%, p less than .01) . Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs . 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs . 61 +/- 7 mmol/L, p less than .05) than patients who survived . CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease. AJR Am J Roentgenol, 1991 Jun, 156(6), 1163 - 6 Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy; Lee MJ et al.; Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection . Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15 . Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign . All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy . Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors . Bile cultures were positive in four patients . Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes . A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder . No complications related to catheter insertion occurred in this group of patients . Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence . Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile. Circ Shock, 1991 Jun, 34(2), 252 - 62 Awake porcine model of intraperitoneal sepsis and altered oxygen utilization; Hoban LD et al.; We have characterized an awake swine model of septic shock . Hemodynamic, serum chemistry, and oxygen metabolism parameters were compared between eight septic and five sham animals . Eight male Yucatan miniature swine, weighing 20-28 kg, were anesthetized and catheters were placed in the pulmonary artery, external jugular, and the carotid artery . On day 2, 1.1-4.0 x 10(10) cfu Escherichia coli/kg were administered via an intraperitoneal catheter . Hemodynamic parameters were monitored hourly for 6 hours in awake animals . The animals were then placed back into the animal holding facility for clinical observation until the 24 hour post infusion measurements were taken . Septic animals were initially hypodynamic, with a decrease in cardiac index (CI) from a baseline value of 152.8 +/- 24.8 to 87.9 +/- 17.8 ml/kg/min (P less than .05) and an increased systemic vascular resistance index (SVRI) from a control value of 48.1 +/- 9.5 to 65.0 +/- 16.7 dynes*sec*cm-5/kg . At 24 hours post infusion, the animals were hyperdynamic with the CI increased to 211.0 +/- 27.2 ml/kg/min (P less than .05) and a decreased SVRI to 30.64 +/- 3.9 dynes*sec*cm-5/kg (P less than .05) . Oxygen utilization (VO2) increased during sepsis from 6.6 +/- 0.8 to 8.1 +/- 0.8 ml/kg/min at 6 hours (P less than .05) and remained elevated at 24 hours at 7.7 +/- 0.4 (P less than .05) . Increased oxygen consumption was attained with an increase in oxygen extraction (O2 ext) from 0.34 +/- 0.03 to 0.56 +/- 0.07 (P less than .05) during the first 6 hours of sepsis . At 24 hours, increased oxygen utilization was maintained by high oxygen delivery state . Significant alterations in serum chemistries in conjunction with post mortem evidence of multiple organ system failure were observed . Mortality on or before 4 days post infusion was 50% and positive blood cultures were obtained in 38% of the animals studied . This awake swine model serves as an excellent model to study metabolic pathophysiology and the treatment of septic shock. Circ Shock, 1991 Jun, 34(2), 247 - 51 Amrinone during porcine intraperitoneal sepsis; Hermiller JB et al.; Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v . (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis . Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study . Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure . Intravenous amrinone modestly augmented cardiac index without altering heart rate . Mean systemic and pulmonary arterial pressures decreased . Systemic and pulmonary vascular resistance fell significantly (P less than 0.05) . Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05) . During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index . Consequently, cardiac output and oxygen delivery increased modestly . Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis. Surg Clin North Am, 1991 Jun, 71(3), 549 - 65 Nutrition and metabolism in sepsis and multisystem organ failure; Baue AE; Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure . When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated . Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount . Organ and nutritional support to prevent complications is necessary . The gastr