Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock

Objective: To investigate the impact of exogenous beta-adrenergic receptor stimulation on splanchnic blood flow, oxygen kinetics, glucose-precursor fl ux, and liver metabolism in septic shock. Design: Prospective trial. Setting: University hospital intensive care unit. Patients: Six patients with hyperdynamic (cardiac index >4.0 L/ min/m(2)) s eptic shock, all requiring norepinephrine to maintain blood pressure >65 mm Hg. Interventions: We compared norepinephrine and phenylephrine titrated to ach ieve similar systemic hemodynamics and gas exchange. Splanchnic hemodynamic s, oxygen kinetics, and metabolic parameters were measured before, during, and after replacing norepinephrine with phenylephrine, Measurements and Main Results: Splanchnic blood flow and oxygen kinetics we re derived from the steady-state indocyanine-green clearance based on hepat ic dye extraction and arterial and hepatic venous blood gases. Endogenous g lucose production rate was derived from the plasma appearance rate of stabl e-isotope-labeled glucose using a primed-constant infusion. Splanchnic lact ate, alanine thigh-performance liquid chromatography) uptake, and hepatic m onoethylglycinexylidide (MEGX) (fluorescence polarization immunoassay) form ation rates were calculated from splanchnic blood flow and arterial-hepatic venous concentration differences. Replacing norepinephrine with phenylephrine induced no change in systemic h emodynamics or gas exchange. While splanchnic oxygen consumption and alanin e uptake rate remained unaffected, splanchnic blood flow, oxygen delivery, and lactate uptake rate were significantly decreased. Glucose production ra te also decreased significantly. A return to norepinephrine restored splanc hnic blood flow, oxygen delivery, and lactate uptake rate to baseline value s, while glucose production rate remained depressed. Hepatic MEGX formation rate was not influenced during the investigation, Conclusions: Exogenous beta-adrenergic receptor stimulation determines spla nchnic blood flow, oxygen delivery, and glucose precursor flux but not spla nchnic oxygen utilization in septic shock. Gluconeogenesis is not directly affiliated to hepatosplanchnic oxygen kinetics. The different response of g lucose and MEGX production rates, metabolic pathways of the periportal and perivenous region, may document intrahepatic heterogeneity associated with hepatocellular metabolic compartmentation.