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Ketamine the New (and Safe) Go-to for RSI

Sorelle, Ruth MPH

doi: 10.1097/

Though it was developed more than 50 years ago as a rapid-acting anesthetic, ketamine is fast becoming the drug of choice for rapid sequence intubation, even in patients with neurological problems.

“Ketamine is about the most commonly used anesthetic around the world, even in developing countries,” said Marcel Durieux, MD, PhD, a professor of anesthesiology and neurological surgery at the University of Virginia in Charlottesville. He and Sabine Himmelseher, MD, of the Klinik fuer Anaesthesiology, Klinikum rechts der Isar, Technische Universitåt in Munich, Germany, concluded in a recent report that ketamine can be used in patients with neurological injury, a reversal of dogma. (Anesth Analg 2005;101[2]:524.)

“With a little understanding of the drug, you can use it in many settings,” said Dr. Durieux. “It is an easy and safe drug to give. It was even used when extracting someone from a car here. It provides good pain control over a limited period of time versus an opioid, which can have dangerous complications.”

A review of the literature by Frederick Zeilder, MD, an assistant professor of neurosurgery at the University of Manitoba, Canada, and colleagues found credible evidence as well for ketamine, specifically that it does not increase intracranial pressure in adults and children with nontraumatic neurological illness when the patients are sedated and ventilated. (J Crit Care 2014;29[6]:1096.) The idea also generated a fair amount of buzz at the most recent Social Media in Critical Care (SMACC) conference in Berlin last year.

Physicians were concerned for a long time, however, about using ketamine in patients with neurological injury, head trauma, and stroke because they already have high intracranial pressure, he said, noting that studies in rats had supported that. (Anesth Analg 2005;101[2]:524.) “We worry a lot in the emergency room,” Dr. Durierux said.

Studies of 246 articles over the past 25 years examined the use of ketamine in brain injury. (Anesth Analg 2005;101[2]:524.) Analysis of the findings showed that ketamine increased cerebral blood flow and metabolism in volunteers who breathed on their own. When ventilation and sedation were controlled, however, ketamine did not raise intracranial pressure, leading the researchers to conclude that it can be used safely in neurologically impaired patients if a gamma-aminobutyric acid (GABA) receptor agonist were administered and nitrous oxide were avoided.

“We didn't feel comfortable saying that this lack of effect on brain pressure would hold true without the GABA inhibitor,” said Dr. Durieux. Most patients would receive a sedative that may in some cases be responsible for maintaining intracranial pressure.

“We regulate our breathing to maintain the level of carbon dioxide, which is a potent dilator of blood vessels,” said Dr. Durieux. “Why would your body do that? When a part of the body is working harder, it uses more oxygen and produces more carbon dioxide and thus needs more blood. The problem is that ketamine, to a small extent, slows breathing down and means that people cannot breathe out carbon dioxide as well. But when ventilation is controlled, none of that happens. When high doses of ketamine are given to patients with brain injury, nothing happens to their brains.”

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Wesley Self, MD, MPH, an associate professor of emergency medicine at Vanderbilt University School of Medicine, and his colleagues compared the use of etomidate and ketamine for induction of rapid sequence intubation in adult trauma patients from January 2011 to December 2014, a period that spanned a shift from etomidate to ketamine as a standard induction agent for rapid sequence intubation. (Ann Emerg Med 2017;69[1]:24.)

The retrospective study included 968 patients; 526 received etomidate and 442 received ketamine. The study found that 20.4 percent of patients induced with ketamine died, compared with 17.3 percent of those who received etomidate. The study began after some emergency physicians expressed concern that etomidate might suppress adrenal function and wanted to substitute ketamine, but determined that etomidate-associated adrenal suppression was not clinically important.

“This was not designed to be an absolute, definitive study. Another trial is indicated,” said Dr. Self, adding that more patients are needed to determine if there is really a difference in mortality. “That would require more patients and a different design,” he said.

“Ketamine had a reputation of increasing intracranial pressure,” Dr. Self added. “It stimulates the sympathetic nervous system and increases blood pressure. Because of that, we thought it might increase pressure in the brain. More recently, those ideas have been disproven.”

Weigh that against the adrenal suppression associated with etomidate, he said. “Patients who are severely injured might be hurt by adrenal suppression,” he said. “That was the main reason to do this study. We switched from one drug to the other to see if we could get mortality to go down.”

The upshot was that there was little difference between the two and no indication that the change would affect mortality, Dr. Self said.

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