OBJECTIVE (1) To determine the effects of resuscitation of patients with severe sepsis to conventional hemodynamic end points and normal blood lactate levels on postresuscitation sequential assessments of gastric intramucosal pH (pHi). (2) To determine whether trends in pHi are reflected in trends in systemic hemodynamic, oxygen utilization, and acid-base assessments. METHODS Prospective cohort study. METHODS Medical ICU in an inner-city, university-based medical center. METHODS Twelve recently admitted patients with severe sepsis and signs of circulatory shock who were successfully resuscitated to normal hemodynamic end points and lactate levels and who were also monitored with pulmonary artery catheters and gastric tonometers. METHODS Because of the observational nature of this study, no specific interventions were employed. The physician staff administered i.v. fluids and pharmacologic agents, during and after the resuscitative period, to treat infection and to achieve and maintain hemodynamic stability. Mechanical ventilation and supplemental oxygen were provided as needed. The hemodynamic and physiologic monitoring employed was determined by the managing physicians and established medical ICU routines. RESULTS A total of 12 patients were studied. Systemic hemodynamic, oxygen utilization, and acid-base assessments and pHi were recorded following resuscitation, and every 12 h thereafter. pHi decreased from 7.33 +/- 0.08 (mean +/- SD) following resuscitation to 7.26 +/- 0.04 at 24 h, 7.20 +/- 0.07 at 36 h (p < 0.05), and 7.24 +/- 0.08 at 48 h. Corresponding statistically significant and clinically relevant changes in systemic hemodynamic, oxygen utilization, and acid-base variables were not observed. The hospital mortality of this patient group was high (10 of 12; 83%). CONCLUSIONS Gastric intramucosal acidosis develops and persists for at least 48 h in patients resuscitated from septic shock to conventional resuscitative end points, including the normalization of lactate levels. These regional changes were not reflected in corresponding changes in systemic acid-base and oxygen utilization variables. Direct determinations of pHi and therapy directed toward the resolution of splanchnic ischemia may be required to improve the outcome in these patients.