No one will deny that emergency medicine is currently experiencing a protracted love affair with the arylcyclohexylamine known as ketamine. It is used for procedural sedation, to manage acute pain, and as an induction agent in patients undergoing emergent intubation. It is a common participant in some of the most popular pharmacological mashups in the emergency department like rocketamine or ketofol.
Ketamine possesses a number of properties that make it an ideal agent for patients who typically undergo intubation in the emergency department, but it has been traditionally avoided in patients with intracranial pathology due to the fear of increasing intracranial pressure (ICP).
Ketamine's effects on ICP were first noted in articles published in 1972 describing its potentially detrimental influences in patients undergoing anesthesia for neurodiagnostic procedures. (Br J Anaesth 1972;44:1298; Br J Anaesth 1972;44:1200.) This series of articles described a small cohort of patients with anatomical obstruction to cerebrospinal fluid (CSF) who experienced a marked increase in their CSF after ketamine was administered. In typical dogmatic fashion, these observations have been passed from generation to generation, and inappropriately applied to the emergent induction of patients with traumatic brain injury (TBI).
I am not the first to notice ketamine's unfair treatment. In fact, many have pointed out the poor quality of evidence indicting this dissociative anesthetic. Cohen, et al., published a systematic review in 2015, exploring the entirety of the literature on ketamine's effects on ICP and, more importantly, the clinical consequences observed. (Ann Emerg Med 2015;65:43.e2.)
The authors identified 10 studies, including a total of 953 patients. Most of these studies were small, and only a few were randomized, but the authors found no studies reporting a clinically important rise in ICP. Neither did they identify any study demonstrating a difference in neurological outcomes.
A new study by Upchurch, et al., also helps dispel the dogma and vindicate ketamine. They retrospectively examined all trauma patients who underwent rapid sequence intubation (RSI) in their emergency department over a four-year period. (Ann Emerg Med 2017;69:24.e2.) During this time, the institution changed its standard induction agent in trauma patients requiring endotracheal intubation from etomidate to ketamine.
A total of 968 patients were included in the analysis, 526 receiving etomidate and 442 receiving ketamine. Approximately one-third of each group went on to be diagnosed with traumatic brain injury. The authors did not find a difference in overall mortality in patients who received ketamine compared with those who received etomidate. Nor did they find an increase in mortality in the subset of patients with TBI who received ketamine as their induction agent.
If I still haven't convinced you, more evidence came from Jabre, et al., in a randomized controlled trial comparing ketamine and etomidate as the induction agent for critically ill patients undergoing RSI. (Lancet 2009;374:293.) Similar to Upchurch's study, the authors noted no difference in any clinically important endpoint, including 28-day mortality, in-hospital mortality, or ICU-free days. The authors reported no detrimental effects when ketamine was utilized as the induction agent in the subset of patients who were intubated because of trauma again.
These data are not perfect, but they are certainly far more robust than the data suggesting that ketamine is deleterious in patients with neurological insult. The original research on which this dogma was based was performed with patients with different physiological circumstances from those presenting to the emergency department and requiring endotracheal intubation.
Moreover, even in these patients, no clinically important harms were reported except rather transient rises in a surrogate marker. What is clear is that patients with TBI do not tolerate episodes of hypoxia or hypotension, both of which are not uncommon during emergency department RSI.
Ketamine offers a number of potentially beneficial characteristics when intubating the critically ill in the emergency department. It is far more of a hemodynamically neutral induction agent when compared with many of the other agents used for RSI in the ED. It has minimal effects on the patient's respiratory drive when dosed appropriately. Limiting its use simply because of surrogate data obtained on a highly select patient population rarely encountered in the emergency department is needlessly restricting our resuscitative tools to help our most critically ill patients.
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