Effects of PEEP Ventilation on Liver Metabolism

Abstract

Objective: To study the influence of positive endexpiratory pressure (PEEP) ventilation on metabolic parameters with specific regard to liver metabolism. Design: Prospective experimental study on the effects of PEEP ventilation on nemo-dynamic gas exchange as well as metabolic parameters i. e. hepatic glucose production, arterial, hepatic and portal venous insulin, glucagons, free fatty acid (FFA), glycerol β-hydroxybutyrate and lactate concentrations. Setting: Experimental Laboratory Unit of the University Hospital. Animals: 10 Labrador Beagle dogs (18-22 kg) were studied. Interventions: Animals were ventilated with PEEP of 0, 7.5, 15, and 0 mmHg, each level lasting 2 h. Results: 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) 1/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) hemoglobin oxygen saturation (ShvO₂) during PEEP 15 decreased from 41(18) to 28(47) mmHg 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 portalvenous glucagon/insulin ratios did not change. FFA and glycerol concentrations depending on PEEP levels were significantly higher in the hepatic artery portal vein than in the hepatic vein. Compared to portal venous and arterial hepatic concentrations, hepatic venous β-hydroxybutyrate significantly increased with rising PEEP levels. Conclusions: Low values of PhvO₂ 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 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.

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

“…Furthermore, in a study by Schricker et al [ 78 ], it was found that PEEP affected liver metabolism by promoting hepatic gluconeogenesis and enhancing oxidative hepatic lipid utilization for energy coverage in the liver[ 78 ]. A parallel increase in the splanchnic oxygen extraction rate was reported in response to a decline in hepatic oxygen delivery caused by a PEEP-dependent decrease in cardiac output[ 78 ].…”

“…Furthermore, in a study by Schricker et al [ 78 ], it was found that PEEP affected liver metabolism by promoting hepatic gluconeogenesis and enhancing oxidative hepatic lipid utilization for energy coverage in the liver[ 78 ]. A parallel increase in the splanchnic oxygen extraction rate was reported in response to a decline in hepatic oxygen delivery caused by a PEEP-dependent decrease in cardiac output[ 78 ]. This mechanism has been corroborated by various human studies which have shown that increasing levels of PEEP reduced splanchnic blood flow, thereby jeopardizing oxygen delivery to the abdominal viscera; yet, splanchnic oxygen consumption was usually maintained through a compensatory increase in splanchnic oxygen extraction[ 79 ].…”

Liver sinusoidal endothelial cells: Their unique role in immune tolerance

“…Brienza et al1 showed that PEEP ventilation decreased the total venous return, probably through an increase in the venous back pressure at the outflow end of the liver, and a decrease in the portal vein flow. A study by Schricker et al2 revealed that PEEP ventilation increased hypoxia of the liver. These studies engendered concern that PEEP ventilation might adversely affect a newly transplanted liver.…”