The most commonly used barbiturate is pentobarbital. Induced coma with use of barbiturates like thiopentone sodium or pentothal is called barbiturate coma or pentobarbital coma .
High-dose barbiturates have been used for more than 60 years in critically ill neurologic patients. The most common application has been to lower elevated intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).
Other uses include refractory status epilepticus, cerebral vasospasm after subarachnoid hemorrhage (SAH), comatose survivors of cardiac arrest, and patients with cerebral edema and elevated ICP from any etiology other than TBI.
Mechanism of Action
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.
Dosage, Monitoring, and Adverse Effects
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 of pentobarbital coma 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.
Pentobarbital coma is associated with a host of serious adverse effects. The latter is an important issue since the beneficial effects of the therapy may be negated by the hypotensive effect.
The most common side effects of barbiturate coma or pentobarbital coma include respiratory depression and hypotension.
In fact, many treated patients will need extra cardiovascular support including vasopressors and pulmonary artery catheter insertion to monitor cardiac function and volume status. Other adverse effects of pentobarbital coma include ileus, decreased clearance of bronchial secretion leading to pneumonia, and liver dysfunction.
All of these factors and the fact that there is no good evidence from randomized, controlled clinical trials that pentobarbital coma improves outcome in patients with various neurological pathologies have led many practitioners to consider this therapy as the last resort when other treatments have been exhausted.
As such, pentobarbital coma should be used only in patients with elevated ICP refractory to medical and surgical therapy and status epilepticus refractory to other treatments including propofol and midazolam drips.
Further references
Brain Resuscitation Clinical Trial I Study Group. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med. 1986;314:397, 403.
Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988;69:15, 23.
Finfer SR, Ferch R, Morgan MK. Barbiturate coma for severe, refractory vasospasm following subarachnoid hemorrhage. Intensive Care Med. 1999.
Goodman JC, Valadka AB, Gopinath SP, et al. Lactate and excitatory amino acids measured by microdialysis are decreased by pentobarbital coma in head-injured patients. J Neurotrauma. 1996;13:549.
Roberts I. Barbiturates for acute traumatic brain injury and pentobarbital coma. Cochrane Database Syst Rev. 2000;(2):CD000033.
The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of barbiturates in the control of intracranial hypertension and pentobarbital coma . J Neurotrauma. 2000;17:527.
Ward JD, Becker DP, Miller JD, et al. Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg. 1985;62.