Naloxone: How Risky in Opioid Reversal?
ABSTRACT&COMMENTARY
Source: Osterwalder JJ. Naloxone for intoxications with intravenous heroin and heroin mixtures: Harmless or hazardous? A prospective clinical study. J Toxicol Clin Toxicol 1996;34:409-416.
Naloxone is used so commonly for patients with signs and symptoms of opioid overdose that most emergency physicians are comfortable with its dosing and administration. Despite this fact, few data exist on which to judge the safety and efficacy of naloxone. Osterwalder recently reported the results of a large-scale study of naloxone use for patients with suspected opioid toxicity. Five hundred thirty-eight patient visits for intravenous drug use were evaluated. Although 66.4% of these visits were judged to involve IV heroin use alone, the remainder involved combinations with other drugs, such as cocaine, cannabis, alcohol, benzodiazepines, and LSD. Ultimately, naloxone was administered 453 timeseither IV, IM, or in combinationin individual doses ranging from 0.1 mg to 2.8 mg. Thirty-nine patients also were given flumazenil along with their naloxone.
While the majority of patients did well, the author reports on nine patients with complications. Six patients were noted to have complications within five minutes of naloxone administration; three had complications that pre-dated treatment, but the patients deteriorated after naloxone was given. The six major complications included: asystole in a man with a PCO2 over 100 mmHg and a potassium of 5.1 mEq/L; violent behavior in a man given an unknown dose of naloxone for a GCS of 5; pulmonary edema in a hypothermic man with a GCS of 3; an uncomplicated seizure; multiple seizures three minutes after naloxone administration to a post-cardiac arrest survivor; and a single uncomplicated seizure in a patient with known epilepsy. Only the fifth (post-arrest) patient ultimately died. The author concludes that this is a high incidence of complications and suggests that smaller doses of naloxone and hyperventilation might reduce this complication rate.
COMMENT BY ROBERT S. HOFFMAN, MD
The flaws in this study are striking. It is unclear whether the events described are complications of naloxone or complications of disorders that brought the patients to the hospital. Because all six of these patients were given naloxone intravenously, it seems unlikely that complications occurring 3-5 minutes later can be attributed to the naloxone. Furthermore, since morphine-induced noncardiogenic pulmonary edema was described by Osler almost 100 years before the use of naloxone, it seems unnecessary to invoke naloxone in the genesis of heroin-induced pulmonary edema. Similarly, seizures in hypoxic, post-arrest, or epilepsy patients have little relationship to naloxone. This leaves the case of patient violence in a man given an "unknown" dose of naloxone. While this complication is probably causally related to naloxone dosing, it is neither new,1 unexpected, nor serious. While the true incidence of complications related to naloxone will never be known, several studies offer strong support for its safety. Yealy et al reported on 813 consecutive paramedic uses of naloxone for altered mental status in the prehospital setting.2 Only a 1% incidence of adverse reactions was noted, and all were felt to be inconsequential. Similarly, we collected data from literally thousands of cases featuring the administration of large doses of naloxone for indications other than opioid intoxication and found the complication rate to be essentially nonexistent.3 Thus, it seems only reasonable to conclude that naloxone is both safe and effective.
Complications of severe opioid overdose can and will occur, and may be made more obvious by reversing the opioid effects. Clinicians need to be careful when administering naloxone. It is prudent to apply temporary, soft physical restraints to patients if the situation permits. Also, oxygenation and ventilation need to be thoroughly and repetitively assessed. Finally, small graded doses of naloxone, beginning at 0.1 mg IV, seem preferable to large IV or IM boluses. If these precautions are taken, the complication rate associated with life-threatening opioid overdoses can be kept to small and acceptable numbers.
References
1. Gaddis GM, Watson WA. Naloxone-associated patient violence: An overlooked toxicity? Ann Pharmacother 1992;26:196-198.
2. Yealy MD, et al. The safety of prehospital naloxone administration by paramedics. Ann Emerg Med 1990;19:902-905.
3. Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness: Controversies in the use of a "coma cocktail." JAMA 1995;274:562-569.
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