The Ketamine Effect on ICP in Traumatic Brain Injury

Abstract

Our goal was to perform a systematic review of the literature on the use of ketamine in traumatic brain injury (TBI) and its effects on intracranial pressure (ICP). All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2013), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts pertaining to the administration of ketamine in human TBI patients that recorded effects on ICP. Secondary outcomes of effect on cerebral perfusion pressure, mean arterial pressure, patient outcome, and adverse effects were recorded. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total 371 citations. Seven articles, six manuscripts and one meeting proceeding, were considered for the review with all utilizing ketamine, while documenting ICP in severe TBI patients. All studies were prospective studies. Five and two studies pertained to adults and pediatrics, respectively. Across all studies, of the 101 adult and 55 pediatric patients described, ICP did not increase in any of the studies during ketamine administration. Three studies reported a significant decrease in ICP with ketamine bolus. Cerebral perfusion pressure and mean blood pressure increased in two studies, leading to a decrease in vasopressors in one. No significant adverse events related to ketamine were recorded in any of the studies. Outcome data were poorly documented. There currently exists Oxford level 2b, GRADE C evidence to support that ketamine does not increase ICP in severe TBI patients that are sedated and ventilated, and in fact may lower it in selected cases.

S(+)-ketamine

“…Contrary to earlier assumptions, therapy with S(+)-ketamine with controlled ventilation does not raise intracranial pressure [36]. As described, due to the blockade of the NDMA receptor, not only an anti-nociceptive effect but also a neuroprotective effect is achieved.…”

“…The spectrum of typical applications (see Table 5 for overview) includes the following conditions in particular:

Severe brain trauma

S(+)-ketamine is a suitable and safe substance in patients with brain injuries if ventilation and oxygenation are sufficient, even in the hands of less experienced emergency physicians. Contrary to earlier assumptions, therapy with S(+)-ketamine with controlled ventilation does not raise intracranial pressure [36]. As described, due to the blockade of the NDMA receptor, not only an anti-nociceptive effect but also a neuroprotective effect is achieved.

Patients in shock

Treatment with sedatives, analgesics and anesthetics is often associated with a significant impairment of hemodynamic status [37].

…”

Delayed sequence intubation: is it ready for prime time?

“…10,11 Although Weingart et al's case series shows promising results with no complications, it does not directly compare DSI to RSI, or to other methods of preoxygenating uncooperative patients. Given the known fallibility of case series and its small sample size, we believe that additional experimental research in this area is required prior to concurring with the authors' that "delayed sequence intubation seems safe and effective for use in emergency airway management."…”

Ketamine*

“…However, systematic reviews report no such concerns in ventilated patients with traumatic or non-traumatic brain injury. 82,83 Drug interactions Reports involving the CYP450 enzyme system are mostly limited to PO S-ketamine:…”