Pathogenesis of central nervous system disorder during artificial hyperventilation in compensated hypercarbia in dogs.

Abstract

An animal model and experimental protocol were developed to elucidate the pathogenesis of coma and convulsions observed during artificial hyperventilation of patients with chronic hypercarbia. Compensated hypercarbia was simulated by sustained elevation of PaCO2 to 80 torr and normalization of pHa by bicarbonate given i.v. Arterial [HCO3-] eqilibrated with CSF [HCO3-] within about 2 hrs CBF, CMRO2, CMRL, CSFpH and lactate concentration and other variables were determined at PaCO2 40 and 20 torr, before and after bicarbonate loading. Rapid normalization of PaCO2 in compensated hypercarbia resulted in CSF alkalosis (CSFpH 7.52), cerebral hypoxia (CBF 50 percent of control) and evidence of cerebral hypoxia (increased cerebral lactate production, cerebral venous Po2 of about 20 torr, abnormal EEG with convulsive patterns) without a significant change in CMRO2. CSF alkalosis and cerebral hypoxia were augmented by further reduction in PaCO2 to 20 torr. Under light halothane anesthesia CBF was higher, CMRO2 was the same and cerebral lactate production was greater than in awake dogs with comparable PaCO2. The results indicate that CNS failure during rapid normalization of PaCO2 in compensated hypercarbia is due to cerebral hypoxia, which is caused by cerebral vasoconstriction from CSF alkalosis and a shift of the hemoglobin oxygen dissociation curve to the left from alkalemia; both effects result in impaired oxygen delivery to brain cells. Thus, to avoid these dangerous effects in patients with chronic hypercarbia and acute decompensation, oxygenation should be prompt, but PaCO2 should be corrected gradually to avoid alkalemia; base excess, hypochloremia and hypokalemia also should be corrected.