Take-Home Naloxone in the Emergency Department
Date First Published:
February 21, 2022
Last Updated:
June 28, 2022
Report by:
Sinead Davies, Foundation Year 2 Doctor (University Hospital of Wales)
Search checked by:
Nicholas Manville, University Hospital of Wales
Three-Part Question:
In [Emergency Department (ED) patients presenting with opiate overdose], is [the distribution of Take-Home Naloxone (THN)] effective in [reducing opioid related deaths]?
Clinical Scenario:
A 31-year-old woman presents at the Emergency Department by ambulance following a heroin overdose. She requires naloxone for opioid-reversal. She has made a full recovery and is ready for discharge.
Search Strategy:
Medline 1966-31/8/21 using PubMed interface.
Search Details:
[Opioid overdose] AND [Take home naloxone] AND [emergency department]
Outcome:
62 papers were found in Medline of which 53 were irrelevant and a further 1 of insufficient quality. A further 5 relevant papers were found by scanning the references of relevant papers.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Association of take-home naloxone and opioid overdose reversals performed by patients in an opioid treatment program Katzman JG, et al 2020 United States | 395 participants >18 years enrolled at an Addiction and Substance Abuse Opioid Treatment Program, with a positive history of opioid use disorder treated with opioid replacement. | Retrospective cohort study (2b) | To measure the association of take-home naloxone with overdose reversals performed by patients with opioid use disorder within enrolled in an opioid treatment program. | 18% of participants performed 14 OD reversals in the community using take home naloxone | •tAll participants were already receiving opioid replacement •tData collected in outpatient setting rather than the Emergency Department •tNo comparison with patients not receiving take-home naloxone as this was not deemed ethical |
| Peer navigation and take-home naloxone for opioid overdose emergency department patients: Preliminary patient outcomes Samuels EA, et al 2018 United States | 151 participants: ED patients discharged after non-fatal opioid overdose in the six months after implementation of an ED naloxone distribution and recovery coach consultation program | Observational retrospective cohort study (2b) |
To measure the effect of THN and recovery coach consultation program on initiation of medication for opioid use disorder, repeat ED visits for opioid overdose, and all-cause mortality. | All-cause mortality was 6.7% (95%CI 2.5, 16.7) for patients receiving usual care after opioid overdose and 3.8 [0.5,23.8] for patients receiving THN. No statistically significant difference. | •tNumber of participants did not reach desired effect size •tSelection bias may have impacted participant treatment group assignment (was determined by provider and patient discretion) |
| A systematic review of opioid overdose interventions delivered within emergency departments Chen Y, et al 2020 Australia | Using PRISMA guidelines, four databases (Medline; Embase; Scopus; PsycINFO) were searched for peer reviewed articles on ED based interventions to prevent opioid overdose | Systematic review based on observational cohort studies and RCTs (2a) |
To examine the feasibility of ED-based delivery of opioid overdose prevention interventions | 7/13 studies focused on provision of take-home naloxone and overdose education describing the successful delivery of THN by ED staff and barriers to delivery | •tExamined feasibility of providing THN in an ED setting rather than the effectiveness of THN in reducing opioid overdose deaths |
| The emergency department as an opportunity for naloxone distribution Gunn AH, et al. 2018 United States | Using PRISMA guidelines, six databases were searched for peer-reviewed journals using a combination of ED and naloxone terminology | Systematic review based on observational cohort studies and RCTs (2a) | To review the literature relating to THN and ED, in order to assess whether ED is a potential setting for THN distribution.To review the literature relating to THN and ED, in order to assess whether ED is a potential setting for THN distribution. | Available evidence is limited. ED distribution of THN has the potential for harm reduction, but barriers include burden on workflow and physician resistance. | •tPoor follow-up in many studies due to the social and economic factors of patient population •tSmall sample size- highlights need for future research •tMeta-analysis not possible due to heterogeneity of interventions and analysis. |
| Opioid education and nasal naloxone rescue kits in the emergency department Dwyer K, et al 2015 United States | 359 patients who had received overdose education (n=359) or overdose education plus intranasal THN (N=59) in the Emergency Department | Observational retrospective cohort study (2b) | To evaluate the feasibility of an ED-based overdose prevention program | No significant differences in behaviour in a witnessed overdose between the overdose education (OE) + THN and OE-only groups. In the OE+ THN group, 16% (6/37) reported using their kit to successfully reverse a witnessed overdose | •tOnly a small percentage of study members were given naloxone as an intervention •tFollow up was poor via telephone consultation •tSome of the OE group received THN from other sources (other than ED) |
| Impacts of an opioid overdose prevention intervention delivered subsequent to acute care Banta-Green CJ, et al 2019 United States | 219 patients abusing opiates were identified by reviewing electronic medical records | Randomised control trial (low quality- <80% follow up) (2b) | Primary outcome to identify time to first opioid overdose-related event resulting in medical attention or death, using competing risks survival analysis | No significant difference in overdose events between intervention (behavioural intervention + THN) and comparison group (sub-hazard ratio: 0.83; 95%CI 0.49-1.40) | •tNull findings may be related to poor housing security, drug use, unemployment and acute health care issues. •tLimited by sample size and challenge of study recruitment |
| Effectiveness of Scotland’s National Naloxone Programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison Bird S, et al 2016 United Kingdom | Data from the National Records of Scotland, including all opioid-related deaths in people who had been either released from prison or discharged from hospital in the 4 weeks previously, comparing 2006-10 with 2011-13. | Observational retrospective cohort study (2b) |
The study measured the effectiveness of take-home naloxone in reducing number of opioid-related deaths. Cost effectiveness was assessed by prescription costs against life-years gained per opioid-related death everted. | 2006-10 19% of Scotland’s opioid-related deaths had been released from prison or discharged from hospital in 4 weeks prior vs only 14.9% in 2011-13 (p=0.003). | •tThis study has a main focus on recent inmates and not necessarily applicable to the general population •tThere is no specification as to whether naloxone kits were distributed in ED or community |
| Emergency department naloxone rescue kits dispensing and patient follow-up Kaucher K, et al 2018 United States | 106 patients presenting with opioid overdose were followed up by phone >30 days after initial ED visit | Case series study (4) | Evaluating number of THN kits used, enrolment in opioid-replacement for opioid dependence and return visits to ED for overdose | 26% (n = 27) self-reported an opiate overdose, after receiving their THN, which required an ED visit (median = 1 overdose [range 1–4]). | •tInability to compare with patients who did not receive take-home naloxone •tRisk of selection bias of patients receiving THN •tFocuses on repeat ED visits as outcome rather than opioid-overdose deaths. |
| Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria Mcdonald R and Strang J 2016 United Kingdom | PubMed, MEDLINE and psych INFO were searched for peer review publications (randomized or observational). No relevant randomized studies available. | Systematic review based on observational cohort studies (2a) | To study the association between THN provision and the number of naloxone administrations, overdose reversals and adverse events. | 2249 successful overdose reversals [96.3%; 95%CI=95.5, 97.1], among 2336 THN administrations. This indicates a strong association between THN programmes and overdose survival. | •tReview is not specific to the ED environment- review concludes that THN distribution to ‘at-risk users’ should be introduced for community-based prevention •tPossible selection bias- 50% of studies relied on spontaneous follow-up with THN programme i.e. participants being asked to report back on naloxone usage when collecting a naloxone refill |
| Harm Reduction Database Wales: Drug related mortality Public Health Wales 2020 United Kingdom | Annual report 2019/2020 of drug related mortality in Wales | Outcomes research (2c) | Report measuring prevalence of THN use and number of opioid-related deaths in Wales 2013-20. | THN used in 2855 opioid drug poisoning events since April 2013. Fatal opioid poisoning was reported in 1.3% (n=37) of events where THN was used. | •tReport not specific to ED environment •t15% records in 2019/2020 have no recorded outcome of opioid overdoses |
| Opioid overdose rates and imple- mentation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis Walley AY, Xuan Z, Hackman HH, et al 2013 United States | Data from the 19 communities within Massachusetts with >4 opioid-related fatal poisonings from each year from 2004-6. | Observational cohort study (2b) | To evaluate impact of overdose education and nasal naloxone distribution on mortality from opiate overdoses in Massachusetts. | OEND programs trained 2912 people who reported 327 rescues. Community-year strata with 1-100 enrolments per 100000 population (adjusted ratio 0.73, 95%CI =0.57-0.91). Significantly reduced adjusted rate ratios compared to communities with no implementation of THN programs | •tCommunity setting rather than ED •tTrue population of opioid users in each community was not known •tOpioid overdose fatalities may have been mis-clarified •tOverdoses were likely under-reported as description of overdose rescue events were limited to those reported back to the program |
| Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom Langham S, et al 2018 United Kingdom | Markov model (based on Coffin and Sullivan model) used to evaluate cost-effectiveness of intramuscular naloxone, with the expectation that it reaches 30% of UK heroin users | Analysis based on clinically sensible costs or alternatives with limited reviews of the evidence (2b) |
To assess the cost effectiveness of distributing THN kits to adults at risk of opioid overdose, compared to no naloxone distribution | The model predicts that distribution of IM naloxone decreases overdose deaths by 6.6%. This would prevent 2500 deaths in a population of 200000 heroin users with a cost effective QALY of £899. | •tNot specific to an ED environment •tOnly focusing on IM naloxone and not intranasal naloxone •tModel uses data based on non-RCT studies. |
| Take-home naloxone rescue kits following heroin overdose in the emergency department to present opioid overdose-related repeat emergency department visits, hospitalisation and death Papp J et al 2019 United States | 18-89 years with a diagnosis of heroin overdose treated in the ED | Retrospective cohort study (2b) | To measure repeat opioid overdose-elated ED visits, hospitalisation and death at 0-3 months and 3-6 months following opioid overdose | No difference in mortality at 3 or 6 months was detected, p=0.15 and 0.36 respectively | •tNumber of participants did not reach desired effect size •tOverall mortality from heroin overdose increased during study period due to more lethal street-drugs made available •tParticipants may have obtained naloxone kit outside county in which the study took place |
Author Commentary:
The studies are not of the best quality. The majority of available studies on this topic are retrospective cohort studies rather than randomised control trials, likely due to difficulty in gaining ethical approval. Sample sizes are often too small to produce statistically significant results, largely attributable to poor follow up in a high-risk target population.
Estimating overdose mortality relating to THN distribution is further complicated by the following factors. Firstly, the majority of evidence currently available is based on the United States healthcare system and may not be generalizable to the British system. In addition, results may be confounded by a concurrent education programme, which is often delivered at the point of dispensing THN to opiate-users. The kits are also usually used on, or by, an individual other than the receiver of the prescription.
If we were to remove ‘ED’ from the search criteria, there is greater evidence available to suggest the benefit of dispensing THN kits within the local community. Thus, a reasonable alternative is for ED staff to liaise with, and signposting to, local drug and housing services, rather than providing THN directly from the emergency department. This encourages ongoing access to support and education for opioid-users in the community after discharge.
Estimating overdose mortality relating to THN distribution is further complicated by the following factors. Firstly, the majority of evidence currently available is based on the United States healthcare system and may not be generalizable to the British system. In addition, results may be confounded by a concurrent education programme, which is often delivered at the point of dispensing THN to opiate-users. The kits are also usually used on, or by, an individual other than the receiver of the prescription.
If we were to remove ‘ED’ from the search criteria, there is greater evidence available to suggest the benefit of dispensing THN kits within the local community. Thus, a reasonable alternative is for ED staff to liaise with, and signposting to, local drug and housing services, rather than providing THN directly from the emergency department. This encourages ongoing access to support and education for opioid-users in the community after discharge.
Bottom Line:
There is no current statistically significant evidence to demonstrate that take home-naloxone prescribed by the Emergency Department reduces overdose deaths. Instead, a focus on encouraging access to take-home naloxone in the local community may be more beneficial.
References:
- Katzman JG, et al. Association of take-home naloxone and opioid overdose reversals performed by patients in an opioid treatment program
- Samuels EA, et al. Peer navigation and take-home naloxone for opioid overdose emergency department patients: Preliminary patient outcomes
- Chen Y, et al. A systematic review of opioid overdose interventions delivered within emergency departments
- Gunn AH, et al.. The emergency department as an opportunity for naloxone distribution
- Dwyer K, et al. Opioid education and nasal naloxone rescue kits in the emergency department
- Banta-Green CJ, et al. Impacts of an opioid overdose prevention intervention delivered subsequent to acute care
- Bird S, et al. Effectiveness of Scotland’s National Naloxone Programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison
- Kaucher K, et al. Emergency department naloxone rescue kits dispensing and patient follow-up
- Mcdonald R and Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria
- Public Health Wales. Harm Reduction Database Wales: Drug related mortality
- Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and imple- mentation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis
- Langham S, et al. Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom
- Papp J et al. Take-home naloxone rescue kits following heroin overdose in the emergency department to present opioid overdose-related repeat emergency department visits, hospitalisation and death