Synopsis: Intravenous ketamine, added to standard emergency department therapy for acute severe asthma, had no significant effect on symptom score, airway function, or hospital admission rate.

Source: Howton JC, et al. Ann Emerg Med 1996; 27:170-175.

This study from the emergency department at Alameda County Medical Center in Oakland, CA, involved 53 consecutive adult patients who presented with acute asthma attacks and still had peak expiratory flow rates less than 40% of the predicted values after an intensive regimen including three doses of nebulized albuterol. In addition to standard therapy for acute asthma, which included oxygen and intravenous corticosteroids, the patients were randomized to receive either placebo or ketamine. Measurements at intervals during the initial three hours included respiratory rate, peak expiratory flow, 1-sec forced expiratory volume (FEV1), and dyspnea assessed by Borg visual analog scale. Patients and emergency physicians completed a questionnaire after the episode to rate various aspects of the two treatment regimens.

The initial dose of ketamine, 0.2 mg/kg as an initial IV bolus, followed by 0.5 mg/kg delivered by infusion over a three-hour period, proved to be too high, as three of the first six patients in the ketamine group suffered dysphoric reactions. Thereafter, the bolus dose was cut in half, and only the last 44 patients were used in data analysis. The authors designed the study to provide sufficient power to detect a 20% difference between the treatment groups with an alpha of 0.05 and a beta of 0.2.

The study patients demonstrated significant improvement within each treatment group for respiratory rate, peak expiratory flow, FEV1, and Borg scale. However, no differences could be detected over time between treatment groups. Patients receiving ketamine gave the treatment a slightly higher subjective rating than patients in the placebo group (P = 0.0285), but there was no difference in physician assessments, nor in hospital admission rates. The authors conclude that ketamine does not add to the airway effects of standard emergency asthma treatment and does not reduce the need for subsequent hospital admission.

COMMENT BY DAVID J. PIERSON, MD

Most patients with acute severe asthma respond promptly to aggressive treatment with aerosolized beta-agonist bronchodilators, systemic corticosteroids, and other components of "standard" therapy. Even when the attack cannot be broken in the emergency department and the patient is admitted to the ICU, continuation of this standard regimen nearly always works, even in that minority of patients who require intubation and mechanical ventilation. However, when the therapeutic response is delayed, the question of whether to add an "alternative" therapy such as intravenous magnesium, heliox, or an inhalational anesthetic frequently arises. None of the therapies just mentioned has ever been shown to be effective by a properly-designed clinical trial. This paper reports a randomized clinical trial of another such "alternative" therapy—intravenous ketamine.

Ketamine, commonly used as an induction agent prior to administration of general anesthetics, was fortuitously discovered to have bronchodilator properties in 1971. Its use in refractory acute asthma has been reported anecdotally several times, but this is the first prospective, randomized evaluation of its possible benefit in this setting. The authors were unable to demonstrate any measurable effect on symptoms, airway function, or the need for hospitalization when the dose of ketamine was low enough to avoid dysphoric reactions. Because these reactions can be extremely unpleasant and can subsequently recur, the use of higher doses does not seem justifiable since highly effective, less toxic therapy for acute asthma already exists.