The gut and the neutrophil have been emphasized to play mechanistic roles in the development of adult respiratory distress syndrome and multiple organ failure (MOF). While a massive single insult (one-hit model) can precipitate early MOF, the more classic presentation is multiple sequential insults (two-hit model) in which the inflammatory system is primed to respond to a secondary activating stimulus. We hypothesized that gut ischemia/reperfusion (I/R) primes the systemic inflammatory cascade and a subsequent activating stimulus results in distant organ injury. Adult male Sprague-Dawley rats underwent 45min of superior mesenteric artery occlusion and ensuing reperfusion (gut I/R) as the first insult. A second insult, low dose endotoxin (2.5mg/kg), was given at 6hr reperfusion and the effects on pulmonary capillary permeability (assessed by ¹²⁵I-albumin leak) and mortality were determined. Forty-five min of laparotomy (LAP) was the control for gut ischemia while saline injection 6hr later was the control for endotoxin. The animals were allocated into 4 groups: i) LAP+Saline, ii) I/R+Saline, iii) LAP+Endotoxin, and iv) I/R+Endotoxin. Only the combined insult, I/R+Endotoxin, increased ¹²⁵I-albumin lung leakage at 18hr reperfusion and the mortality rate of this group was 39% which was significantly higher than those of LAP+Saline (0%), I/R+Saline (0%) and LAP+Endotoxin (4%). In the next study, the effects of the priming event (gut I/R; 45min/6hr) on the lung and neutrophils were investigated. Neutrophil depleted animals were obtained by pretreatment with vinblastine (0.75mg/kg, iv, 3 days prior). Lung leakage was again measured by the ¹²⁵I-albumin leak while pulmonary neutrophil sequestration was quantitated by myeloperoxidase assay. Circulating neutrophil priming was reflected by the difference in superoxide production with and without the activating stimulus, N-formyl-methionyl-leucyl-phenylalanine. We observed that, a) 45min of gut ischemia provoked transient mild lung leakage at 6hr reperfusion which had normalized by 18hr, b) this transient lung leakage was abrogated by neutrophil depletion, c) both gut I/R and sham-laparotomy increased lung neutrophil accumulation, and d) only gut I/R markedly primed circulating neutrophils. These findings indicate that a relatively brief period of gut I/R primes the neutrophil, the lung and the host such that low dose endotoxin exposure activates inflammatory mechanisms, resulting in advanced pulmonary failure and mortality.

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The indications for emergency and critical care were considered from different survival rates of patients in fulminant viral hepatitis (FVH), who were divided to three groups according to the period from symptom onset to encephalopathy (pre-encephalopathy period; PEP). Our artificial liver support (ALS) systems consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) were applied to 32 FVH patients. Patients with PEP between onset and 10 days, 4 weeks and 8 weeks, were classified as an acute (A) group in 9 cases, a subacute (S) group in 13 cases and a moderate (M) group in 10 cases, respectively. Cases over 40 years old accounted for 100, 77 and 70%, respectively, of each group. Type B or NANB hepatitis was diagnosed in 56 or 44% of group A, 46 or 54% of group S and 20 or 80% of group M, respectively. Liver volume estimated by computed tomography on admission was less than 700cm³/m² in 63, 55 and 78%, respectively, of each group. On average, PE and HDF were performed 15 and 13 times in group A, 13 and 12 times in group S and 33 and 32 times in group M, respectively. Coma grades improved during ALS in 78, 85 and 80% of groups A, S and M, respectively. The mean level of total bilirubin in each group was 10.0, 20.7 and 21.0mg/dl on admission, respectively, and significantly decreased in group S (p<0.01) but increased in group M (p<0.05) during ALS. The mean respective serum creatinine levels were 3.0, 1.7 and 1.0mg/dl on admission, but significantly increased in group M (p<0.01) during ALS. Bacteremia or endotoxemia was detected in 22, 38 and 50% of groups A, S and M, respectively. Consequently, the respective survival rate were 67, 46 and 10% and there was a significant difference between group A and M (p<0.05). Severe cases, who had more than three prognostic indicators for liver transplantation reported from London or Berlin, accounted for 78, 69 and 90% of the respective groups, and associated survival rates were 86, 33 and 0%. Thus, our ALS would be very useful for restoring consciousness, and the survival rate of group A was 67% while that of group M was only 10%. Therefore, the indications for emergency and critical care including ALS should be expanded to patients with presumed FVH with PEP between onset and 4 weeks.

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Object: DIC is often seen in severe patients in our emergency and critical care center. DIC is often diagnosed using the diagnostic criteria established by the Ministry of Health and Welfare in Japan (1988), and we usually use these criteria. In the present study, we have attempted to develop new criteria for DIC based on TAT, PIC and platelets. Method: TAT, PIC, platelet and DIC scores of 100 patients with various severe diseases seen in the 1989-1991 period, were measured 298 times. We analyzed these data and now propose simple new criteria. Results: Sensitivity and specificity; (1) 0≤PIC≤0.8μg/ml; sensitivity was 95.7%, specificity 98.1%. (2) 0.8<PIC<2.0μg/ml; sensitivity was 82.4%, specificity 85.4%. (3) 2.0μg/ml≤PIC; sensitivity was 85.2%, specificity 98.8%. (4) Total; sensitivity was 89.9%, specificity 93.5%. Conclusion: Simple criteria for DIC, based on TAT, PIC and platelets, are very useful, and we propose the introduction of these simple new criteria for DIC.

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A case of spontaneous nontraumatic intrahepatic clostridial gas gangrene is reported. The patient, a 77-year-old male, complained of upper abdominal pain and dyspnea of abrupt onset. His general condition deteriorated rapidly and he died 2 hours after his admission. Abdominal X-P and CT showed abnormal intrahepatic gas accumulation and laboratory data revealed severe metabolic acidosis, massive hemolysis and abnormal hepatic function. A blood smear obtained at the time of death showed gram positive rods and blood culture yielded Clostridium perfringens and Escherichia coli. Autopsy findings included numerous gram positive rods in the liver, kidney, spleen, heart, bone marrow and submucosal layer of the G-I tract, and microabscess of the liver was noted. However, inflammatory cell infiltration was absent from all involved organs. These virulent clinical findings are specific to clostridial gas gangrene and are considered to be brought about by the production of clostridial exotoxins (especially α-toxin and θ-toxin). Infection progresses in a highly fulminant manner and the prognosis is much poorer than traumatic clostridial gas gangrene; the majority of patients die within 24 hours after onset. The reason for the high mortality rate is failure to make the diagnosis in the early stages, as early diagnosis and treatment are crucial.

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