Barbiturates, particularly short-acting agents like thiopental, have historically played a significant role in anesthesia, although their clinical use has declined (thiopental has not been available in the United States since 2011; methohexital and pentobarbital remain). Barbiturates induce anesthesia by direct activation and potentiation of GABA_A receptors, similar to benzodiazepines, but with stronger effects on CBF and CMRO₂. Thiopental was once commonly used for the induction and maintenance of general anesthesia, particularly in settings requiring neuroprotection.
Barbiturate administration leads to reductions in CBF and CMRO₂, which helps protect the brain during ischemic episodes by lowering metabolic demands. Both autoregulation and CO₂ reactivity are preserved during barbiturate anesthesia. The CMRO₂ reduction is dose-dependent and bottoms out at an isoelectric EEG, where roughly half of baseline consumption (the part that supports synaptic activity) has been removed; the remainder maintains cellular integrity and is untouched by any anesthetic, only by temperature. Because barbiturates constrict normal vessels while vessels in ischemic tissue stay maximally dilated, flow may be redirected toward the ischemic region (the inverse steal, or Robin Hood, effect). Animal studies have demonstrated significant neuroprotective properties of barbiturates during cerebral ischemia, but clinical trials have produced mixed results. Timing appears to be critical, as the neuroprotective benefits may depend on administering the drug before or during the onset of ischemia. Retrospective analysis of the IHAST trial found no clear association between thiopental use and improved neurological outcomes, calling into question the clinical efficacy of barbiturates as neuroprotective agents.
