Effects of PEEP ventilation on liver metabolism.

Abstract

To study the influence of positive endexpiratory pressure (PEEP) ventilation on metabolic parameters with specific regard to liver metabolism. Prospective experimental study on the effects of PEEP ventilation on hemodynamic and gas exchange as well as metabolic parameters, i.e. hepatic glucose production, arterial, hepatic and portal venous insulin, glucagon, free fatty acid (FFA), glycerol, beta-hydroxybutyrate and lactate concentrations. Experimental Laboratory Unit of the University Hospital. 10 Labrador Beagle dogs (18-22 kg) were studied. Animals were ventilated with PEEP of 0, 7.5, 15, and 0 mm Hg, each level lasting 2 h. PEEP 15 significantly increased heart rate from 110(70) to 220(55) beats/min and decreased cardiac output from 2.5 (2.0) to 1.5 (0.8) l/min. This was associated with significant increases in mean pulmonary artery pressure, pulmonary artery occlusion pressure, portal and hepatic venous pressure, whereas mean systemic pressure did not change. While whole-body oxygen consumption and respiratory quotient remained constant, whole-body oxygen delivery significantly decreased from 456(266) to 294(168) ml/min during PEEP 15 concomitant to augmented whole-body oxygen extraction (from 27(34) to 51(33)%). Oxygen extraction from the splanchnic organs increased from 41(31) to 81(30)%. Hepatic venous oxygen tension (PhvO2) and hemoglobin oxygen saturation (ShvO2) during PEEP 15 decreased from 41(18) to 28(47) mm Hg and from 60(31) to 18(66)%, respectively. Hepatic glucose production was significantly stimulated from 3.44(1.44) to 3.92(1.83) mg/kg/min at PEEP 15. Arterial and portalvenous glucagon/insulin ratios did not change. FFA and glycerol concentrations depending on PEEP levels were significantly higher in the hepatic artery and portal vein than in the hepatic vein. Compared to portal venous and arterial hepatic concentrations, hepatic venous beta-hydroxybutyrate significantly increased with rising PEEP levels. Low values of PhvO2 and ShvO2 during PEEP 15 gave evidence for hypoxia of the liver. This was associated with a stimulated hepatic glucose production rate accompanied by enhanced hepatic uptake and utilization of FFA serving as fuel substrates. As the rate of gluconeogenesis is a major determinant of hepatic oxygen consumption these metabolic effects of PEEP ventilation have to be considered during states of critical illness.