Changes in Cerebral Blood Flow After Endotoxin in Humans and Sheep

Abstract

Neurologic dysfunction is common in early sepsis. To better understand cerebral autoregulatory responses during sepsis, we studied cerebral hemodynamics, cerebral oxygen delivery (CDO2), and the cerebral metabolic rate for oxygen (CMRO2) in volunteers and in unanesthetized sheep during experimental endotoxemia. In ten healthy volunteers, we used a Kety-Schmidt technique to measure cerebral blood flow (CBF) at baseline and at hourly intervals for 5 h after a bolus of Escherichia coli endotoxin (4ng/kg). We also measured CMRO2, CDO2, and cerebral vascular resistance (CVR) at these time points. Volunteers developed marked systemic and hemodynamic responses after endotoxin, including an elevated body temperature, cardiac index (CI), and heart rate (HR), and a decreased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). CBF, CDO2, CMRO2, and CVR were un-changed throughout the 5-h study period. In a separate study, we measured CBF (using radiolabeled or colored microspheres), and CMRO2, CDO2, CVR, and cerebral perfusion pressure (CPP) at baseline and at 1.5, 4, and 24 h in 18 sheep during continuous E. coli endotoxin infusion (10ng/kg per hour). Eight sheep became hyperdynamic with an increased body temperature, CI, and HR, and a decreased SVRI. In the hyperdynamic sheep, CBF, CDO2, CMRO2, and CPP were elevated and CVR was decreased after 4 h of continuous endotoxin. Ten sheep did not become hyperdynamic although body temperature, white cell count, and pulmonary artery pressure had significantly increased. CBF, CDO2, CMRO2, CPP, and CVR were un-changed in these sheep.