OBJECTIVE (a) To investigate the relationship between gut ischemia parameters (gastric intramucosal pH [pHi], mucosal-arterial carbon dioxide difference [PCO2-gap]), and endotoxin or cytokine release during hemorrhagic shock; (b) to compare the predictive value of pHi, PCO2-gap and arterial lactate concentrations. METHODS Prospective study. METHODS Surgical intensive care unit of a university hospital. METHODS 20 multiple trauma patients with severe hemorrhagic shock. METHODS Intramucosal measurements and blood samples were obtained on admission to the emergency room and repeatedly over 48 h. RESULTS Endotoxin was measured using a chromogenic limulus amoebocyte assay. Cytokine [tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6)] values were evaluated by immunoradiometric assays. Only 3 patients had positive blood cultures but endotoxins were detected at least once in all patients. Endotoxin levels were similar in survivors and non-survivors over the study period and were not related to pHi or PCO2-gap. Initially, high levels of IL-6 were observed in both nonsurvivors and survivors [median 1778 pg/ml (range 435-44,540) vs 2068 pg/ml (range 996-92,300)]. IL-6 levels progressively decreased in the survivors but not significantly. On admission, TNF alpha concentrations were similar in nonsurvivors and survivors (42 +/- 35 vs 46 +/- 27 pg/ml). From the 24th h, TNF alpha values were higher in the nonsurvivors than in the survivors (24 h: 72 +/- 38 vs 34 +/- 17 pg/ml, p < 0.05). The greatest IL-6 levels were found for a pHi < 7.20 (28.5 +/- 36.5 vs 1.8 +/- 1.3 ng/ml, p < 0.05) or a PCO2-gap > 7.5 mmHg (1 kPa) (32.5 +/- 37.5 vs 1.7 +/- 1.3 ng/ml, p < 0.01). With the same pHi threshold, no difference was found in endotoxin levels. The lactate concentrations were predictive for outcome from the 12th h (9.5 +/- 5.9 vs 3.6 +/- 2.3 mmol/l, p < 0.05). CONCLUSIONS During severe hemorrhagic shock, endotoxin translocation from the gut was a common phenomenon that seemed independent of both pHi values and outcome. It could not explain IL-6 and TNF alpha release. In severe hemorrhagic shock, neither pHi nor PCO2-gap provides additional information to the lactate measurements.