ObjectiveExcessive release of nitric oxide has been implicated as being an important factor contributing to systemic arterial hypotension in septic shock. Hemoglobin is an effective nitric oxide scavenger. The purpose of this study was to test the hypothesis that treatment with cross-linked human hemoglobin can ameliorate systemic arterial hypotension and improve organ perfusion in a porcine model of normodynamic endotoxemic shock.DesignProspective, randomized, controlled trial.SettingLaboratory at a university medical center.SubjectsFourteen, male, random-bred swine.InterventionsAll animals were challenged with Escherichia coli lipopolysaccharide (400 micro gram/kg) infused from t equals 0 to 90 mins. Pigs in group 1 (n equals 7) were infused with cross-linked human hemoglobin (150 mg/kg) at t equals 30 mins. Pigs in group 2 (n equals 7) were infused at t equals 30 mins with 150 mg/kg of dextran (average molecular weight 70,000 daltons) as a 5% (weight per volume) solution.Measurements and Main ResultsAfter infusion of endotoxin, mean arterial pressure decreased significantly (p less than .05) but baseline cardiac index was maintained in both groups. In hemoglobin-treated pigs (group 1), mean arterial pressure was higher than in controls (group 2) from t equals 60 to 120 mins (p less than .05). There were no significant differences between the two groups in systemic vascular resistance index, renal blood flow, mesenteric blood flow, systemic oxygen delivery, or systemic oxygen extraction. Ileal mucosal blood flow was lower (p less than .07) in group 1 than in group 2. Mean pulmonary arterial pressure increased relative to baseline in both groups, but was significantly greater in group 1 as compared with group 2. Compared with controls, infusion of hemoglobin significantly exacerbated endotoxin-induced arterial hypoxemia (p less than .05).ConclusionsTreatment with hemoglobin improved mean arterial pressure in endotoxemic swine without significantly impairing blood flow to the renal or mesenteric vascular beds. Infusion of hemoglobin, however, significantly exacerbated endotoxin-induced pulmonary hypertension and arterial hypoxemia. Additional pharmacologic strategies may be necessary to ameliorate the potential adverse pulmonary effects of administering hemoglobin solutions to patients with sepsis.(Crit Care Med 1996; 24:807-814)