eMJA: Randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose

Ariella Glaser,* Dwight Arakaki,^† Gar Ming Chan,^‡ Robert S Hoffman§

* Resident, Mount Sinai Medical Center, New York City, NY, USA; ^† Resident, Beth Israel Medical Center, New York City, NY, USA; ^‡ Fellow (and corresponding author), § Director, New York City Poison Control Center, New York City, NY, USA. garchanATpol.net

To the Editor: Two aspects of the recent article by Kelly et al comparing intranasal with intramuscular naloxone in suspected opioid overdose1 make their study difficult to interpret. The methods allowed for a great deal of bias. There was no attempt to blind evaluators to therapy, and knowing which therapy is to be used a priori may influence both therapy selection and perceived outcome.

The second flaw we noted was the use of the Glascow Coma Scale (GCS) in a non-trauma patient.2 An improvement in GCS score may represent increased wakefulness or even withdrawal. The use of the GCS does not make it possible to determine what degree of improvement or worsening the therapy resulted in. In the opioid-intoxicated patient, the “alert/verbal/pain/unresponsive” (AVPU) scale is more appropriate.

We agree that the use of needles in a high-risk patient is dangerous. However, if these patients do not respond to painful stimuli, there should be no danger at all.

Anne-Maree Kelly,* Debra Kerr,^† Paul Dietze^‡

* Director, ^† Deputy Director, Joseph Epstein Centre for Emergency Medicine Research, Western Hospital, Private Bag, Footscray, VIC 3011. ^‡ Research Fellow, Turning Point Alcohol and Drug Centre, Fitzroy, VIC. Anne-Maree.KellyATwh.org.au

In reply: The prehospital setting for research poses challenges that require some flexibility in study design. While it would have been preferable to have used blinded naloxone and placebo solutions for both routes of administration in our study, financial and operational constraints made this impossible, so some bias in evaluations is possible. However, this is not necessarily in favour of the intranasal route, as before the study many paramedics were very sceptical about the intranasal naloxone preparation. Therapy selection was by random allocation in sealed envelopes as described in our article.

The Glasgow Coma Scale score was chosen as an outcome measure because it was the parameter used operationally for treatment and disposition decisions in the ambulance service within which our study was conducted. We acknowledge its limitations in non-trauma patients.

The potential for needlestick injury in this situation is real. Patients with opioid intoxication may be in cramped locations and may be irritable on waking, increasing the risks involved with handling a “sharp”. Given the prevalence of blood-borne viruses in the injecting drug user population, strategies to reduce the risk of needlestick injury are highly desirable. Additionally, a strategy that has been suggested for preventing opioid-overdose-related deaths is to make naloxone more widely available in the community. 1 The intranasal formulation of naloxone may be appropriate for this, as it has significant advantages including reducing risks of blood-borne virus transmission and minimising the requirement for training and the secure storage of syringes and needles. 2