Barbiturate therapy in acute brain injury

Abstract

Barbituric acid was first synthesized in 1864, and since that time its derivatives have been in common use for induction of sedation, hypnosis, seizure control, and anesthesia. In recent years barbiturates have been used widely for control of intracranial pressure in a variety of clinical situations, and there has been extensive controversy regarding the effectiveness of barbiturates in protecting against or ameliorating ischemic or anoxic brain damage. Despite numerous studies, there is no clear evidence that these agents protect the brain from such injury. This review addresses some of the known physiologic and metabolic effects of barbiturates, the results of experimental studies using a number of models for focal and global ischemia and anoxia, and clinical reports pertaining to the use of barbiturate coma. Cerebral blood flow is closely coupled with cerebral metabolic rate for oxygen in the awake state; barbiturates reduce both) 3 This effect increases as dose increases; at levels sufficient to produce burst suppression on the EEG, flow can be reduced to as little as one-third normal, and CMRO2 to as low as 45% normal. Barbiturates do not uncouple the effect of CMRO2 on blood flow; in fact, the cerebrovascular effects of barbiturates appear to be the result of reduction in CMRO2 rather than the direct effects on cerebral blood vessels? No further change in these variables occurs if the dose is increased beyond that required to induce an isoelectric EEG, because barbiturates affect only the oxygen consumption required for electrical activity and not that needed for maintenance of cellular integrity? In contrast, lidocaine, a drug that blocks sodium channels and prevents efflux of potassium in ischemic brain, inhibits CMRO2 and cerebral glucose consumption, and continues to exert its effect after the EEG has become fiat. This suggests that lidocaine is a more effective agent in protecting isehemic brain? In clinical situations in which increased intracranial pressure