Ketamine may be useful for patients with severe acute brain injury because it inhibits cortical spreading depolarization, a phenomenon linked to secondary brain injury. A systematic review of five randomized trials (total 149 participants) compared ketamine with sufentanil, fentanyl, other sedatives, or saline. The proportion of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81-2.58; very low certainty). All outcomes had a high risk of bias. The evidence is very low certainty, and large, low-bias trials are needed to determine ketamine's effects on functional outcome and serious adverse events.
In 100 mechanically ventilated adults with septic shock but without acute brain injury, a low-dose continuous ketamine infusion (0.3 μg/kg/hr) was added to standard sedation. Only one of three noninvasive intracranial pressure (ICP) measures—ICP derived from diastolic flow velocity—showed a statistically significant but very small increase over 24 hours. Cerebral perfusion pressure and vital signs (heart rate, blood pressure, respiratory rate) remained stable. Doses of midazolam, fentanyl, and norepinephrine decreased substantially, especially in the first 12 hours. The findings suggest low-dose ketamine can be used adjunctively without raising ICP or destabilizing hemodynamics, while reducing overall medication burden.