EFFECTS OF NOREPINEPHRINE AND DOBUTAMINE ON OXYGEN-TRANSPORT AND CONSUMPTION IN A DOG-MODEL OF ENDOTOXIC-SHOCK

Objectives: Severe septic shock is associated with an imbalance between oxygen demand and oxygen supply (DO2) in the presence of an impaired oxygen extraction. Vasopressors are often used to restore a minimal perfusion pressure and inotropic agents are often used to increase myocardial contractility. However, optimal adrenergic support remains controversial. The present study investigated the effects of norepinephrine and dobutamine on DO2, oxygen consumption (VO2), and oxygen extraction in a dog model of endotoxic shock. Design: Prospective, randomized, cross-over trial. Setting. University intensive care laboratory. Subjects: A total of 14 mongrel dogs anesthetized with pentobarbital and mechanically ventilated with air. Interventions. The dogs received 2 mg/kg Escherichia coli endotoxin intravenously. After 30 mins, fluid administration with 0.9% saline was started to restore baseline filling pressures. The dogs randomly received dobutamine and norepinephrine. Each agent was infused for 20 mins followed by a drug free interval of 30 mins so that each dog could serve as his own control. Results for norepinephrine were grouped as low dose (0.1 and 0.2 mug/kg/min) and high dose (0.5 and 1.0 mug/kg/min). Results for dobutamine were also grouped as low dose (5 mug/kg/min) and high dose (10 mug/kg/min). Measurements and Main Results: Norepinephrine increased both mean arterial pressure (MAP) and cardiac output without a significant change in systemic vascular resistance. Only high-dose norepinephrine increased DO2 (from 969 +/- 62 to 1240 +/- 49 mL/min [p < .001]) and VO2 (from 176 +/- 15 to 194 +/- 14 mL/min [p < .001]). Dobutamine increased both cardiac output and MAP. Both low- and high-dose dobutamine increased DO2 (from 891 +/- 91 to 1142 +/- 99 mL/min [p <.001] and from 847 +/- 54 to 1317 +/- 75 mL/min [p < .001], respectively) and VO2 (from 172 +/- 14 to 182 +/- 15 mL/min [p <.001] and from 168 +/- 13 to 184 +/- 14 mL/min [p <.001], respectively). The increase in VO2, for a given increase in DO2 was higher with high-dose norepinephrine compared with high-dose dobutamine. When all doses were taken together, DO2 increased more with dobutamine than norepinephrine. Oxygen extraction decreased with all doses for both norepinephrine and dobutamine. Conclusions: In this endotoxic shock model, both norepinephrine and dobutamine can increase DO2 and VO2 but dobutamine caused a more consistent increase in these parameters. The decrease in oxygen extraction was relatively similar with dobutamine and norepinephrine. The present study does not support a significant beneficial effect of norepinephrine on the tissue extraction capabilities in endotoxic shock.