Pharmacologic neuroprotection/burst suppression has been of great interest for decades in the setting of acute cerebral insults. It has been studied in the setting of both global and focal cerebral injury. The interest stems from the knowledge that burst suppression with anesthetic agents (barbiturates, propofol, midazolam, isoflurane) results in a large reduction (approximately 50%) in the cerebral metabolic rate of oxygen(CMRO2) (1-3). Animal models have shown efficacy and this naturally led to human trials (1-3). Anesthetic burst suppression has been studied in comatose survivors of cardiac arrest (3) with no evidence of benefit. Lower level evidence showing no benefit exists for cerebral aneurysm surgery (4). There is insufficient evidence in the setting of stroke or traumatic brain injury to determine benefit or harm (5).
Current indications for pharmacologic burst suppression based on low level evidence include : Refractory Status Epilepticus (6), Refractory Intracranial Hypertension (such as in traumatic brain injury) (7), and Intraoperative Neuroprotection during cerebrovascular (such as carotid endarterectomy) surgery (8). Insufficient evidence exists to determine benefit or harm in the setting of prolonged cerebral ischemia due to cerebral aneurysm surgery (prolonged temporary clip application), cerebral bypass surgery with prolonged vascular clamping and cerebral ischemia, or cardiac/aortic surgery with cerebral blood flow disruption/ischemia.
Therapy (barbiturate, propofol, or halogenated anesthetic) is titrated to an electroencephalographic (cEEG) endpoint. Complete pharmacologic suppression results in a flat-line EEG. Typically, a 1:10 burst to suppression ratio is chosen as an arbitrary endpoint, but this is neither evidence based nor a universal practice. In other words, a 10 second screen of EEG would have 1 second of burst activity and 9 seconds of flat-line EEG. Optimal dosing is unknown and there is no evidence base to guide therapy (6).
In the operating room, barbiturate burst suppression with pentobarbital or thiopental results in delayed emergence from anesthesia that can take days. Propofol burst suppression can be shut off intraoperatively after full restoration of cerebral blood flow and may still allow for anesthetic emergence and even extubation by the end of the procedure.
References
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- Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial I Study Group. N. Engl. J. Med.: 1986, 314(7);397-403 PubMed Link
- Bradley J Hindman, Emine O Bayman, Wolfgang K Pfisterer, James C Torner, Michael M Todd, IHAST Investigators No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial. Anesthesiology: 2010, 112(1);86-101 PubMed Link
- I Roberts Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev: 2000, (2);CD000033 PubMed Link
- Andrea O Rossetti, Daniel H Lowenstein Management of refractory status epilepticus in adults: still more questions than answers. Lancet Neurol: 2011, 10(10);922-30 PubMed Link
- Miguel A Melgar, Nitin Mariwalla, Hassan Madhusudan, Martin Weinand Carotid endarterectomy without shunt: the role of cerebral metabolic protection. Neurol. Res.: 2005, 27(8);850-6 PubMed Link
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