Vasodilating prostaglandin E1 decreases critical oxygen delivery by increasing critical oxygen extraction in...

The abnormal dependence of O2 uptake (VO2) on O2 delivery (QO2) during severe sepsis, and the adult respiratory distress syndrome (ARDS) may be caused by impaired vascular reactivity, following release of vasodilating prostaglandins. Infusion of these compounds, however, may improve tissue oxygenation. We studied the effect of vasodilating prostaglandin E1 (PGE1; 0.2 microgram/kg/min) on the critical O2 extraction ratio (ERO2c) and the critical QO2 (QO2c) in a saline-controlled, crossover study in 12 barbiturate-anesthetized pigs. QO2, VO2 (independently from QO2), and blood lactate concentrations were measured during graded cardiac output reductions by incremental positive end-expiratory pressure (0-20 cm H2O PEEP, raised by 5 cm H2O at 15 min intervals). At 0 cm H2O PEEP, PGE1 decreased arterial blood pressure, mainly due to a fall in systemic vascular resistance. From 0 to 20 cm H2O PEEP, the fall in QO2 was greater in the PGE1 than in the saline series (P < 0.005), since ventricular filling and the rise in heart rate were less in the former. The decrease in VO2 (P < 0.005) did not differ between series. As estimated from bilinear regression on paired VO2/QO2 data in individual pigs, the QO2c was 9.8 +/- 3.6 (mean +/- SD) during PGE1 and 14.6 +/- 3.8 ml/kg/min during saline infusion (P = 0.008), with ERO2c 68% +/- 16% and 48% +/- 12%, respectively (P < 0.005). The QO2c, estimated from bilinear regression on paired lactate/QO2 data during the first treatment period, was 7.1 +/- 1.2 for PGE1 and 12.8 +/- 4.5 ml/kg/min for saline (P < 0.05), at similar lactate concentrations (2.0 +/- 0.5 and 1.7 +/- 0.5 mmol/liter, respectively). PGE1-induced vasodilation thus decreases QO2c, because of increased ERO2c, probably resulting from capillary recruitment, an increased surface area available for O2 exchange, and decreased O2 diffusion distances. Hence, a reduced ERO2 and abnormal supply dependence of VO2 during severe sepsis and ARDS are not caused by release of vasodilating prostaglandins. In contrast, our results partly explain improved tissue oxygenation with these compounds during abnormal VO2 supply dependence, following sepsis and ARDS.