R. W. Samsel

Absence of supply dependence of oxygen consumption in patients with septic shock

We tested whether oxygen consumption (VO2) was dependent on oxygen delivery (QO2) in 10 patients with septic shock when QO2 was changed by the use of the inotropic agent, dobutamine. The mean acute physiology and chronic health evaluation (APACHE) II score of the patients was 27.3 +/- 8.1 with a mean blood pressure on entry of 66.8 +/- 12.4 mm Hg, and all had been volume resuscitated to a pulmonary artery occlusion pressure of greater than 10 mm Hg. We measured VO2 by analysis of respiratory gases (VO2G) while calculating VO2 by the Fick equation (VO2F) at three different O2 deliveries. When the dobutamine infusion rate was increased from 2.5 +/- 4.0 to 12.3 +/- 6.0 micrograms/kg/min, thermodilution cardiac output increased from 7.7 +/- 2.6 to 10.1 +/- 2.7 L/min (P < .01). Accordingly, dobutamine increased QO2 from 13.5 +/- 3.8 to 18.2 +/- 4.3 mL/min per kg (increase of 36.4% +/- 19.7%; P < .01), but VO2G did not increase (3.2 +/- 0.5 to 3.2 +/- 0.6 mL/min per kg). During these same interventions, the VO2F tended to increase (2.9 +/- 0.7 to 3.4 +/- 0.8 mL/min per kg, P < .06), presumably a spurious correlation because of measurement errors shared by the calculation of VO2F and QO2. Neither lactic acidosis nor acute respiratory distress syndrome (ARDS) conferred supply dependence of VO2G, but the presence of ARDS was predictive of death in this cohort. It is concluded that VO2 is independent of QO2 in patients with septic shock and lactic acidosis. These data confirm that maximizing QO2 beyond values achieved by initial fluid and vasoactive drug resuscitation of septic shock does not improve tissue oxygenation as determined by respiratory gas measurement of VO2.

L-canavanine selectively augments contraction in aortas from endotoxemic rats

Contractile responses to KCl or phenylephrine were inhibited in endothelium-denuded aorta from endotoxin-treated rats. L-Canavanine, a selective inhibitor of inducible nitric oxide synthase, augmented contractile responses in vessels from endotoxin, but not saline-pretreated animals. In contrast to nitroarginine, L-canavanine did not inhibit endothelium-dependent relaxation induced by acetylcholine. Selective inhibitors of inducible nitric oxide synthase may be useful probes of vascular dysfunction in sepsis.

The effect of adrenergic agonists on the systemic response to hemorrhage

PURPOSE Systemic blood loss elicits a variety of reflex cardiovascular responses, which preserve cardiac output as possible and preserve arterial blood pressure when cardiac output decreases. When compensatory venoconstriction is exhausted, hemorrhage reduces oxygen delivery (QO2), and systemic vasoconstriction competes with local metabolic vasodilation to preserve tissue oxygen uptake (VO2). Through their effects on vascular tone and blood flow distribution, adrenergic agents might interfere with the physiological responses to reduced O2 delivery. This study was designed to determine the effects of dobutamine and norepinephrine on oxygen extraction and systemic vascular resistance during progressive hemorrhage. METHODS We infused dobutamine or norepinephrine into anesthetized, ventilated dogs and measured the systemic vascular resistance, oxygen consumption, and oxygen extraction ratio as oxygen delivery (blood flow) was reduced by blood withdrawal. Four groups were compared: control (saline), dobutamine (10 micrograms/kg/min), high-dose norepinephrine (1.0 microgram/kg/min), and low-dose norepinephrine (0.1 microgram/kg/min). RESULTS High-dose norepinephrine increased oxygen demand but did not alter extraction significantly at the critical point. Neither low-dose norepinephrine nor dobutamine affected oxygen extraction during hemorrhage. Dobutamine and norepinephrine both ablated the increase in systemic vascular resistance that accompanies hemorrhage. Low-dose norepinephrine was not different from control. CONCLUSIONS Norepinephrine and dobutamine appear to block reflex vasoconstriction, and mechanistic explanations for this finding remain speculative. Despite inhibition of reflex vasoconstriction, neither dobutamine nor norepinephrine significantly impaired oxygen extraction during hemorrhage.