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Tuesday, February 16, 2016

THE SUCCESS OF KETAMINE IN REFRACTORY SEIZURES, WHERE BENZODIAZEPINES FAIL



๐Ÿ”ดIn status epilepticus is there is a reduction in expression of “benzodiazepine-sensitive” GABAA-R d2 subunits 

๐Ÿ”ดAlso there is a 20-fold loss of potency in benzodiazepine receptors after 30 minutes.

๐Ÿ”ดBut there is an increase in the expression of excitatory NMDA receptors occurs, leading to seizure propogation

๐Ÿ”ดContinued seizures result in BBB dysfunction facilitating leakage of albumin into the CNS, with a resultant proconvulsant effect by stimulating astrocytes to release NMDA and causing cerebral vasoconstriction.

๐Ÿ”ดWith continuing seizures, inhibitory GABA receptors are internalized in clathrin-coated vesicles, and excitatory NMDA receptors are mobilized to the membrane. This receptor trafficking may result in decreased inhibitory control and increased excitation that may foster status epilepticus. 

๐Ÿ”ดThe strong NMDA antagonist effect of ketamine has anticonvulsant effects and has the potential to prevent glutamate-mediated neurotoxicity. 

๐Ÿ”ดWilliams et al used a dose of 5 mg/kg/h in patients to control the seizures. The literature shows that doses as high as 7.5 mg/kg/h used for up to 14 days were safe.

๐Ÿ”ด"With ketamine use, a concern about increasing intracranial pressure has been raised in ventilated patients. However, ketamine may not significantly elevate intracranial pressure and may provide some degree of neuroprotection by inhibiting the NMDA-receptor activation and interfere with the inflammatory response to injury when used in typical sedative or anesthetic doses."

๐Ÿ”ดKetamine may be the ideal agent for the control of seizure in patients with refractory seizures and septic shock in the intraoperative setting.

REFERENCE:

Use of Ketamine for Control of Refractory Seizures During the Intraoperative Period ; Williams, George W. MD; Cheng, Yuen C. MD; Sharma, Aanchal MD, Journal of Neurosurgical Anesthesiology, October 2014, Volume 26, Number 4





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