Last updated on April 2018

Ketamine Infusion in Neurologic Deficit


Brief description of study

Subarachnoid hemorrhage (SAH) or bleeding in the brain as a result of ruptured aneurysm is a devastating type of stroke. Many patients who undergo emergent neurosurgery to repair the aneurysm and remove the bleeding suffer from complications in their subsequent hospital stay, the most frequent and morbid of which is delayed cerebral ischemia (DCI) or small strokes resulting from impaired blood flow to certain vital brain centers. This occurs because of changes to the brain's blood vessels that occur after the bleed. The arteries can become narrow (spasm) or small clots can form within the vasculature that disrupts normal blood flow. Patients are left with profound neurologic deficits from these secondary complications.

Anesthesiologists, neurosurgeons, and intensivists are in need of a way to protect the brain during this vulnerable period following aneurysm repair. One drug that may provide such protection is ketamine, a compound frequently used in operating rooms and intensive care units to provide anesthesia and analgesia. Ketamine works by blocking glutamate receptor ion channels that play a pivotal role in promoting brain cell death during strokes by flooding the brain with too much calcium and dangerous chemicals. This project is designed to test the efficacy of ketamine in protecting the brain following aneurysm repair by using a controlled infusion of the drug in the intensive care unit (ICU) when patients return from their operation.

Detailed Study Description

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating type of stroke, with significant long-term morbidity for patients who survive the initial bleed. The most frequent and morbid complication is delayed cerebral ischemia (DCI) resulting from angiographic vasospasm of the arteries of the circle of Willis. At present, there is no protective therapy aimed at neuronal preservation during this period of ischemia. The standard medical care is primarily to maintain intravascular volume status to improve cerebral perfusion during arterial narrowing, or calcium channel blockers for smooth muscle relaxation on the arterial wall. Experimental and clinical data suggest a primary mechanism of neuronal injury during ischemia is excitotoxicity, glutamate-induced cell death resulting from overstimulation of ionotropic N-methyl-D-aspartate (NMDA) receptors and resultant excessive calcium influx. Ketamine is a dissociative anesthetic with a mechanism of action of non-competitive antagonism of the NMDA receptor, routinely used in operating rooms and intensive care units as an analgesic and anesthetic. In addition to its anesthetic properties, ketamine is also an anti-inflammatory agent and a sympathomimetic, maintaining sedation without the adverse effects of hemodynamic instability. Identification of a neuroprotective entity for DCI following SAH would vastly improve the quality of life and shorten hospital stay for patients with a ruptured intracerebral aneurysm. It is critical to identify such agents so that patients survive their injury, spend shorter time in the ICU, and can return to work and maintain relationships.

Clinical Study Identifier: NCT02636218

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