High-dose barbiturates have various effects on the brain that may explain their apparently neuroprotective properties. It has been suggested that the most important property is that of coupling cerebral blood flow to regional cerebral metabolic demands. It is postulated that lowering cerebral metabolic requirements would lower cerebral blood volume, which in turn will result in lower ICP. Other mechanisms may include inhibition of free-radical-mediated lipid peroxidation and amelioration of glutamate release. High-dose barbiturates also suppress both clinical and electrical seizure activity.

A number of therapeutic regimens using pentobarbital have been used. One common strategy uses an initial loading dose of 10 mg/kg over 30 to 40 minutes followed by a maintenance drip of 0.5 to 2.0 mg/kg/h. The most reliable monitoring technique is continuous electroencephalogram (EEG) monitoring. Patients who undergo pentobarbital coma have no useful clinical examination; therefore, EEG is most helpful at titrating the therapy. Usually, the infusion rate of pentobarbital is titrated to a burst suppression pattern on the EEG record. There is no agreement regarding the depth of the EEG suppression that must be accomplished. However, many experts recommend an EEG burst suppression pattern of 5 to 10 seconds. There is also no general agreement on the duration of pentobarbital coma. Certainly
the duration will depend on the condition being treated. For instance, patients with refractory ICP elevations will have to be treated as long as the abnormal intracranial compliance is present, which may be for several days. On the other hand, many patients with status epilepticus may need between 24 and 96 hours of treatment to control seizures. However, some patients with status epilepticus may also require days or weeks of treatment.