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Three Part Question

In [patients acutely intoxicated with opioids] does [intramuscular/subcutaneous or intravenous naloxone] reduce [the need for subsequent doses and risk of death from recurrent opioid toxicity]?

Clinical Scenario

A 30 year old male who is a known opioid addict is brought to the emergency department after an overdose of heroin, with a GCS of 3, a respiratory rate of 4 breaths per minute, and pinpoint pupils. You are aware that many addicts self-discharge on reversal of opioid intoxication (possibly due to precipitation of acute withdrawal symptoms), and that because naloxone has a shorter duration of action than most opioid agonists, there is a risk of harm to the patient if he becomes renarcotized away from the hospital. You wonder if use of the intramuscular or subcutaneous route reduces this risk by prolonging the duration of action of naloxone.

Search Strategy

Medline 1966-02/02 using the OVID interface.
[{exp naloxone OR "naloxone".mp} AND {exp narcotics OR "opioid".mp OR "opiate".mp OR (morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR pentazocine OR pethidine OR phenazocine OR tramadol).mp} AND {exp overdose OR "overdos$".mp OR exp poisons OR "poison$".mp OR "acute intoxic$".mp OR "acute toxic$".mp}] LIMIT to human AND English.

Search Outcome

185 papers were found of which two addressed the question directly.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Sporer KA et al, 1996, USA	609 patients treated with prehospital naloxone for clinical evidence of opioid overdose. 487 were given IM; 69 IV; 53 both routes	Observational	Response rate (increased GCS or RR) within 5 minutes of naloxone administration	94% IM; 90% IV; 98% both	Not randomised The doses given were not standardised Complication rates were recorded but no attempt was made to compare between routes of administration
Wanger K et al, 1998, Canada	Patients treated with prehospital naloxone for clinical suspicion of opioid od. 74 patients given 0.4mg IV; 122 given 0.8mg SC	Observational	Need for further doses of naloxone	Significantly less need for further doses with SC route (15% cf 35%)	Not randomised (treatment groups sequential) Poor follow-up (?missed delayed complications/prolonged withdrawal symptoms)
			Time from arrival at scene to time patients RR >10/min	No time difference

Comment(s)

Both studies were set in the prehospital environment and different criteria were used to define opioid intoxication, which means that it is difficult to assess applicability to other patient populations. In Sporer's study there were 16 patients who were found to be asystolic at the scene; these have been excluded from this discussion because no note was made of which treatment was given, and, in any case, none of this group survived. Although, in Wanger's study, there was a perception by the paramedics that patients were less violent after sc naloxone, the iv dose was given relatively rapidly. In theory, titrating the iv bolus slowly against clinical effects should allow more gradual emergence from opioid-induced coma and, if withdrawal symptoms do occur, then they should be shorter-lived; the study does not settle the concerns regarding the erratic and unpredictable absorption from im/sc injection sites compared with the iv route.

Clinical Bottom Line

There is no evidence from these studies to suggest that the subcutaneous or intramuscular routes are inferior to IV administration of naloxone, but significant theoretical concerns have not been addressed, requiring further research. They may be useful alternative routes if intravenous access is difficult to obtain.

References

1. Sporer KA, Firestone J, Isaacs SM. Out-of-hospital treatment of opioid overdoses in an urban setting. Acad Emerg Med 1996;3(7);660-7.
2. Wanger K, Brough L, MacMillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed opioid overdose. Acad Emerg Med 1998;5(4);293-9.