Impairment of cerebral autoregulation during venovenous extracorporeal membrane oxygenation in the newborn lamb

Abstract

To study the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cerebral autoregulation in the newborn lamb. Animal studies, using newborn lambs, with comparison of two randomized treatment groups. Newborn lambs of mixed breed, 1 to 7 days of age, were randomized into two study groups: control animals, with jugular vein ligation but no ECMO (n = 6), and ECMO animals placed on venovenous ECMO (n = 6). Laboratory animal facilities of the Department of Anesthesiology and Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD. Animals were anesthetized with pentobarbital, intubated, and ventilated, and monitoring catheters were inserted. Control animals had their right jugular vein ligated, and a cerebral autoregulation curve was performed after 1 hr of stabilization. ECMO animals were placed on venovenous ECMO and after 1 hr of stabilization, they had a cerebral autoregulation curve performed. Cerebral autoregulation was examined by increasing intracranial pressure, thereby decreasing cerebral perfusion pressure. Intracranial pressure was increased by infusion of artificial cerebrospinal fluid into the lateral ventricle of the brain. Four ranges of cerebral perfusion pressure were evaluated: a) baseline (1 hr after initiation of bypass in venovenous ECMO or completion of surgery in controls); b) cerebral perfusion pressure of 55 to 40 mm Hg; c) cerebral perfusion pressure of 39 to 25 mm Hg; and d) cerebral perfusion pressure of < 25 mm Hg. Cerebral blood flow (radiolabeled microspheres), cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. In ECMO animals, cerebral blood flow (cerebral hemispheres) decreased from a baseline measurement of 46 +/- 9 (SD) mL/100 g/ min to 29 +/- 12 mL/100 g/min at a cerebral perfusion pressure of < 25 mm Hg. In the control group, cerebral blood flow was unchanged from baseline at any range of cerebral perfusion pressure. Cerebral oxygen consumption was unchanged from baseline as cerebral perfusion pressure decreased in either group. When cerebral oxygen consumption was compared between the two groups, it was lower in the ECMO group at baseline and at a cerebral perfusion pressure of < 25 mm Hg. At a cerebral perfusion pressure of < 25 mm Hg, cerebral blood flow, cerebral oxygen delivery, and metabolic rate were lower in the ECMO group than in the control group, and fractional oxygen extraction and cerebral vascular resistance were higher, indicating that autoregulation was impaired. There was no difference between blood flow in the right and left cerebral hemispheres when autoregulation was impaired in the ECMO animals. These findings indicate that cerebral autoregulation was altered in animals on venovenous ECMO, with cerebral blood flow decreasing at a cerebral perfusion pressure of < 25 mm Hg, compared with control animals which showed no changes at the same cerebral perfusion pressure. This disruption of cerebral autoregulation decreased cerebral oxygen metabolism despite an increased oxygen extraction in ECMO animals.