Paradoxical reaction following intravenous midazolam premedication in pediatric patients - a randomized placebo controlled trial of ketamine for rapid tranquilization.

Background: Paradoxical reactions to benzodiazepines include restlessness, violent behavior, physical assault, act of self-injury and need for restraints. These may occur at variable times after administration. This study was designed to determine the incidence of paradoxical reactions following intravenous midazolam premedication in pediatric patients and to compare the efficacy of extra doses of midazolam with low-dose intravenous ketamine to rapidly tranquillize them.

Methods: A total of 706 ASA I, II children scheduled for elective surgery were given intravenous midazolam premedication. Children who developed a paradoxical reaction were randomly divided into three equal groups to receive: (i) extra midazolam, (ii) ketamine, or (iii) placebo as the test drug for treatment of paradoxical reaction. Ease of rapid tranquillization and need for a rescue tranquillizer (i.e. ketamine; irrespective of patient group) were compared among the three groups.

Results: Twenty-four (3.4%) children developed paradoxical reaction after midazolam premedication. Those who received ketamine as the test drug responded rapidly to ketamine. But the responses of the other two groups to their test drug were poor and the majority of them required ketamine as rescue tranquillizer (six in midazolam, seven in placebo, but no patient in the ketamine group; P < 0.05).

Conclusions: The results of this study demonstrate that ketamine is an effective drug for the treatment of paradoxical reaction following intravenous midazolam premedication. The exact mechanisms of these reactions and how it is aborted by ketamine are not clear.