Original Contribution
Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses

https://doi.org/10.1016/j.ajem.2008.12.009Get rights and content

Abstract

Introduction

This study proposes that intranasal (IN) naloxone administration is preferable to intravenous (IV) naloxone by emergency medical services for opioid overdoses. Our study attempts to establish that IN naloxone is as effective as IV naloxone but without the risk of needle exposure. We also attempt to validate the use of the Glasgow Coma Scale (GCS) in opioid intoxication.

Methods

A retrospective chart review of prehospital advanced life support patients was performed on confirmed opioid overdose patients. Initial and final unassisted respiratory rates (RR) and GCS, recorded by paramedics, were used as indicators of naloxone effectiveness. The median changes in RR and GCS were determined.

Results

Three hundred forty-four patients who received naloxone by paramedics from January 1, 2005, until December 31, 2007, were evaluated. Of confirmed opioid overdoses, change in RR was 6 for the IV group and 4 for the IN group (P = .08). Change in GCS was 4 for the IV group and 3 for the IN group (P = .19). Correlations between RR and GCS for initial, final, and change were significant at the 0.01 level (ρ = 0.577, 0.462, 0.568, respectively).

Conclusion

Intranasal naloxone is statistically as effective as IV naloxone at reversing the effects of opioid overdose. The IV and IN groups had similar average increases in RR and GCS. Based on our results, IN naloxone is a viable alternative to IV naloxone while posing less risk of needle stick injury. Additionally, we demonstrated that GCS is correlated with RR in opioid intoxication.

Introduction

In 1991, the Occupational Health and Safety Administration mandated the implementation of alternative drug delivery systems to minimize needle stick injuries and decrease the exposure of blood borne pathogens to emergency health workers [1]. The risk of exposure to blood borne pathogens is especially high in the emergency medical services (EMS) environment. The annual blood contact for individual EMS providers is estimated to be as high as 12.3 exposures per year in populations with more than 90% of the HIV statuses unknown [2]. In high-risk populations, such as intravenous (IV) drug abusers, alternative practices are vital in maintaining the safety of the EMS personnel while providing adequate care to the patients.

Intranasal (IN) medication delivery is a safe and direct means to provide medication to patients without using needles. Some advantages compared with parenteral include avoidance of painful injection, avoidance of risks associated with IV access, rapid onset, and high levels of patient acceptability [3].

Human studies elucidate naloxone pharmacokinetics [4], [5], [6]. The onset of IV naloxone is 1 to 2 minutes; it has a clinical duration of 20 to 90 minutes that varies with dosage and administration route [7]. Intranasal administration of naloxone bypasses hepatic first-pass metabolism because absorption is direct via nasal mucosa, due to richly supplied vasculature and low barrier to drug permeation [8]. Intranasal drug delivery also has the potential to target brain delivery, bypassing the blood brain barrier [9].

Pharmacokinetic data for IN administration in humans is lacking. Currently, data in rats describe 100% bioavailability for IN naloxone, with similar elimination half-life to IV naloxone [10]. In this animal study, peak plasma concentrations for IN naloxone occurred within 3 minutes of administration. This evidence corroborates supporting this route of administration. Clinical outcome data also support the use of IN naloxone in reversing opioid effects in both the overdose setting and for opioid dependency [11], [12], [13].

Multiple articles suggest IN naloxone has a strong evidence base as a first-line therapy for people with suspected opioid overdose in the prehospital setting. The 2006 Best Evidence Topic Report [14], published in the Emergency Medicine Journal, summarizes the findings in these articles published since 1992. The review concludes IN naloxone has minimal adverse side effects and is a safe route of administration.

From 2002 to 2005, several case series were published on IN naloxone [15], [16]. Limitations of these studies included small patient number, variable exclusion/inclusion criteria, differing route and timing of naloxone, and inconsistent methods of response measurement quantified. A 2005 article concluded that IN naloxone was a good first-line therapy for patients suspected of opioid overdose, with findings of rapid reversal of overdose in most patients and a limited risk of needle stick exposures [11]. Two additional studies [12], [17]—a randomized control trial and a retrospective case review—both conclude that IN naloxone was effective, but time to onset was prolonged from IV and intramuscular naloxone.

The intent of this study was to investigate whether IN naloxone was noninferior compared to IV naloxone in increasing respiratory rates (RRs) and mental status in patients presenting with suspected opioid overdose in the prehospital setting. Our primary outcome measures were changes in Glasgow Coma Scale (GCS) and unassisted RRs after administration of IN and IV naloxone. We also attempt to demonstrate that GCS is correlated with RR in opioid overdose.

We hypothesize that in patients presenting with opioid overdoses, IN naloxone will be noninferior to IV naloxone in increasing RR and GCS.

Section snippets

Design

The study is a retrospective cohort conducted by chart review.

Setting

The study was conducted at a university-based level I trauma center in an urban setting. The EMS system contain 6 advanced life support (ALS) units that perform 6920 ALS treats per year within a context of approximately 30 000 dispatches per year (including basic life support units). Only ALS may administer naloxone in our study's site. All ALS personnel received training in IN and IV naloxone administration during paramedic class,

Characteristics of study subjects

From a database of advanced life support emergency medical calls, 344 patients received naloxone. These patients were assessed for eligibility for enrollment in the study. Patients excluded from the study were 23 in cardiac arrest, 8 intubated before naloxone administration, and 3 sedated before naloxone administration. An additional 33 patients were excluded due to missing data on PCRs. Of these 33 patients, 11 (3 IN, 8 IV) were confirmed acute opioid intoxications. The data points missing

Discussion

Among subjects with confirmed opioid overdoses, IN naloxone is as effective as IV naloxone at reversing the central nervous system-depressing effects caused by opioids. Subjects were compared by route of naloxone administration, using RR and GCS score as indicators of opioid intoxication. In addition to having similar baseline characteristics, both the IV and IN groups had significant increases in RR and GCS score. Furthermore, the data shows both IV and IN naloxone significantly increases both

References (24)

  • NgaiS.H. et al.

    Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action

    Anesthesiology

    (1976)
  • EvansJ.M. et al.

    Degree and duration of reversal by naloxone of effects of morphine in conscious subjects

    Br Med J

    (1974)
  • Cited by (0)

    This study received no grants or financial support. It has not been presented at any meeting.

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