title: Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure.
abstract: Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.
authors.affiliation: Department of Surgery, University of Cincinnati, OH 45267-0558.
authors.forename: P N
authors.initials: PN
authors.lastname: Purcell
authors.forename: R D
authors.initials: RD
authors.lastname: Branson
authors.forename: T J
authors.initials: TJ
authors.lastname: Schroeder
authors.forename: K
authors.initials: K
authors.lastname: Davis
authors.forename: D J
authors.initials: DJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D016638:Critical Illness; D004195:Disease Models, Animal; D004285:Dogs; D005069:Evaluation Studies as Topic; D005260:Female; D006439:Hemodynamics; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D008102:Liver Circulation / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*
chemical_list: D008012:Lidocaine; C001173:monoethylglycinexylidide