Does O₂availability determine hepatic metabolic activity in septic shock?

Background

In septic shock the hepatic metabolic response to ß-adrenergic receptor Stimulation may not mirror that of splanchnic blood flow (Qspl) and O₂ delivery (DO₂spl) [1], possibly due to hepatocyte heterogeneity associated with metabolic compartmentation [2]. Therefore we investigated if reducing DO₂spl differentially affects metabolic pathways depending on the periportal or perivenous localization.

Methods

In up to now four patients with hyperdynamic septic shock (CI = 4 l/min m²) all requiring noradrenaline to maintain mean arterial pressure DO₂spl was selectively reduced without effect on systemic hemodynamics by switching from noradrenaline to phenylephrine. We determined splanchnic lactate (VLac) (enzymatic kit) as well as alanine (VAla) and glutamine (VGln) (liquid chromatography) clearance rates from Qspl and arterio-hepatic venous content difference, hepatic glucose production rate (HGP) from the appearance rate of stable isotope-labelled 6,6-D₂-glucose (ion-selective mass spectrometry), and monoethylglycinexylidide (MGEX) formation (immunofluorescence polarization).

Results

See table.

Conclusions

Reducing DO₂spl leads to decreased HGP probably due to decreased precursor flux and clearance. While the cytochrome P450 IIIA dependent MGEX formation located in the perivenous region returned to baseline levels after restoration of DO₂spl, HGP, a highly O₂ consuming pathway of the periportal region, remained depressed such as recently demonstrated during ventilation with PEEP [3]. Oxygen supply, hence, may determine hepatic metabolic activity and compartmentation in septic shock.

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