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Midazolam reduces agitation associated with ketamine sedation in adults

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Adding midazolam to ketamine for emergency department sedation in adults reduces the occurrence of agitation during recovery, investigators report in the Annals of Emergency Medicine online October 25.

“The main message is that ketamine can and should be used for painful procedures in adults,” lead author Dr. Carl H. Schultz commented by email. “The addition of midazolam will substantially improve the sedation process and make ketamine very useful in adults.”

Dr. Schultz, at UC Irvine School of Medicine, Orange, California, and colleagues in Turkey point out in their report that while ketamine has been used widely for procedural sedation and analgesia in children, its acceptance for adult emergency department patients “may be limited by physician apprehension about dreaming and hallucinations during recovery, and unpleasant reactions and nightmares, collectively referred to as recovery agitation.”

To see if midazolam reduces recovery agitation after ketamine administration in adult emergency patients, and whether the route of administration of ketamine made any difference, the researchers conducted a prospective study involving 182 such patients. They were randomized in a 2×2 factorial design to receive either midazolam 0.03 mg/kg or placebo intravenously, with ketamine at a dose of either 1.5 mg/kg IV or 4 mg/kg IM.

“We defined recovery agitation as any moaning, screaming, cursing, unpleasant dreams, or unpleasant hallucinations, regardless of severity,” the authors state. “Pleasant hallucinations were not counted as adverse events.”

Agitation occurred in only 8% of patients given midazolam compared to 25% of those given placebo, according to the report. The rates were not significantly different when comparing IV versus IM ketamine administration — 13% versus 17%.

Sedation time was longer with ketamine given IM than when administered intravenously, but midazolam did not prolong those times significantly. “People have said that if you use midazolam, it will prolong recovery,” noted Dr. Schultz. “We showed that is not true.”

After the procedures, nurses, doctors and patients in the study were asked to rate their overall satisfaction. Staff registered no differences in satisfaction scores, whereas 69% of patients in the midazolam group expressed satisfaction compared with 48% in the placebo group.

Dr. Schultz said that ketamine “is incredibly safe,” and that generally there are no adverse effects from midazolam co-administration at the doses used. While midazolam is not specifically approved by the US Food and Drug Administration for administration with ketamine, it is approved for sedation “so this is really not an issue,” he noted.

Given the results, should the strategy be used more widely? “Absolutely!” said Dr. Schultz. “I have been using ketamine in adults with midazolam for over 10 years but have had some difficulty convincing my colleagues that it is effective. Now I think we should be doing this routinely.”

Ann Emerg Med 2010.