The effectiveness and safety of intranasal naloxone for the treatment of heroin overdose with a view to peer distribution
Creators: name: Kerr, Debra
Publisher: name: Monash University
Year: 2017
Subjects: Uncategorized

description: BACKGROUND Heroin overdose is a major cause of death in some countries. Overdose deaths are preventable; with modifiable risk factors including injecting alone, concomitant drug and alcohol use and reduced tolerance after periods of abstinence. In addition, fatalities may be prevented by timely treatment with naloxone, an opiate antagonist. In the community setting, paramedics routinely administer naloxone for suspected opioid overdose. Traditionally, naloxone has been administered via the intramuscular (IM) and intravenous (IV) routes. Drug administration by these routes is problematic to the person administering the drug in a population at higher risk of infection with blood-borne viruses (BBV) because of the risks associated with needlestick injury. Peers witness most overdoses. If fatal, death typically occurs several hours after heroin injection. Naloxone distribution programs have been introduced successfully in some regions to facilitate peer-administered treatment for heroin overdose. Concerns have been raised regarding such programs including incompetent drug administration and unsafe disposal of needles. Administration of naloxone by the intranasal (IN) route to victims of suspected heroin overdose is a novel approach, with recognised advantages including ease of administration and elimination of cross-transmission of infectious disease. In addition, an aerosol spray has advantages for ‘take-home’ distribution. However, evidence to date has been limited to one randomised controlled trial (RCT), co-ordinated by the candidate, and several observational studies. These studies have been limited by small samples and inadequate preparation of naloxone for IN administration. Further well designed research is needed to confirm safety and effectiveness. OBJECTIVES The research reported in this thesis examined: 1. The effectiveness and safety of concentrated IN naloxone compared to IM naloxone for treatment by paramedics of suspected opiate overdose in the prehospital setting; 2. Reported overdose response by current injecting drug users (IDU) during overdose events and compared this to previous research; explored attitudes and willingness of IDUs regarding naloxone distribution for peer administration after heroin overdose; and assessed preferred mode of administration (IV, IM, IN) for peer administration of naloxone. RANDOMISED CONTROLLED TRIAL – INTRANASAL NALOXONE A RCT was performed in the prehospital setting to measure the effectiveness of concentrated IN naloxone in comparison to IM naloxone. One hundred and seventy-two patients treated for suspected opiate overdose were randomised to receive IM (2mg in 5 mL, Min-I-Jet prefilled syringe) or IN (2mg in 1mL) naloxone. The primary outcome measured was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Rates of response within 10 minutes were similar: IN naloxone (60/83, 72%) compared with IM naloxone (69/89, 78%) (Odds Ratio (OR) = 0.8, 95% CI 0.3 to 1.5). No clinically important difference was observed in mean response time (Difference = 0.1 minutes, 95% CI –1.3 to 1.5). However, supplementary naloxone was administered to fewer patients who received IM naloxone (IN: 15/83, 18.1%; IM: 4/89, 4.5%) (OR = 4.8, 95% CI 1.4 to 16.3). PEER RESPONSE TO HEROIN OVERDOSE Data regarding first-aid response to heroin overdose, attitudes of IDUs about peer naloxone treatment after heroin overdose and preferences for mode of administration were collected by survey. Ninety-nine current injecting heroin users who presented to needle syringe exchange programs (NSP) during 2007 were recruited. The findings confirm that heroin overdose is a common occurrence for IDU with 61% reporting a prior overdose event, and 84% reporting having witnessed an overdose in the past. An improvement in response to witnessed heroin overdose was observed in our study, with increased rates of ambulance notification (76% vs 10-56%) and expired air resuscitation (EAR) (44% vs 9-31%) in comparison to previous Australian studies. The large majority of the sample reported positive attitudes towards naloxone distribution (good to very good idea: 89%) and 92% said they were willing to participate in a related training program. Some participants raised concerns about peer administration including the competence of IDUs to administer naloxone in an emergency, victim response on wakening and legal implications. Most (74%) indicated a preference for IN administration in comparison to other administration methods (21%), which was unrelated to any key variable (e.g. age, sex, treatment status). CONCLUSION Concentrated IN naloxone successfully reversed heroin overdose for a high proportion of patients. These results support the administration of IN naloxone by paramedics as first-line treatment for heroin overdose. Heroin users often witness peer overdose and can respond with appropriate life-saving measures including ambulance notification, EAR and correct positioning. In addition, there appears to be strong support amongst Australian IDU for naloxone distribution. IN spray is the preferred route of administration for peer reversal.