The Outcomes of Opioid Education and Naloxone Distribution (OEND) Services in Cases of Naloxone Reversed Overdose
Authors: Kelsey Melgaard, PD3, University of Minnesota College of Pharmacy
Heather Blue, PharmD, University of Minnesota College of Pharmacy
Correspondence: Kelsey Melgaard
901 Boulder Drive Apt 214
Duluth, MN, 55811
(218) 849-5393
PHAR 6782
9/17/17
Word Count: 2,635
Abstract: The opioid epidemic is making a world-wide impact with an increasing number of overdose deaths since 2000. A literature review was conducted, looking at the outcomes of OEND services in the rates of successful reversals, implied reduced mortality, and a reduction in emergency department visits related to opioid use. Multiple studies have sited that a majority of cases receiving naloxone due to OEND services have successfully reversed overdose significantly. Some studies also suggest that these reversals have also reduced mortality of opioid use and led to fewer emergency department visits related to opioid use. These results appear to have positive impacts and implications on communities that have incorporated OEND services, but there is still more research that needs to be done.
Introduction:
In the United States, drug overdose deaths have at least doubled between 1999 and 2015; in 2013, 37% were associated with prescription opioids and 19% were associated with heroin, both of which are preventable with naloxone 1. Minnesota is one of many states that is currently being impacted by the opioid epidemic as the death rates due to overdose have been climbing since 2000 2. In 2015, Minnesota had 216 deaths due to opioid pain reliever overdoses and 114 deaths due to heroin overdose 2; these all could have been potentially preventable with access to the opioid antagonist, naloxone. Naloxone provided through opioid overdose education and naloxone distribution (OEND) programs reduce the opioid overdose death rates through training of patients and bystanders to respond to an overdose 3. OEND programs can be implemented through emergency departments, clinics, or community resources in order to increase opioid overdose awareness and provide patients with substance use disorders with a life saving medication. Even though naloxone doesn't help to overcome the addiction directly, it may be the tool to change a person’s life realizing that they might not be as lucky next time and giving them the hope to seek treatment. Overdose prevention strategies such as OEND programs may also lead to reductions in drug use for injected drug users 4. Patient education on substance use disorders, may lead to reduced opioid use and consideration of treatment options. This could be due to efforts to reduce the stigma associated with naloxone and substance use in order to allow them openly speak with health professionals about recovery through OEND programs. Even though naloxone access is increasing due to pharmacists being able to dispense naloxone without a physician’s prescription, it is still an ethical controversy between both public health professionals, healthcare professionals, and the communities impacted by substance use disorders. This stigma associated with naloxone and substance use disorders is felt worldwide in developed countries as drug addiction was ranked the most strongly stigmatized overall in a cross-cultural study with 18 countries 5. Pharmacists are currently allowed to prescribe naloxone in Minnesota under collaborative practice agreements (CPA) or other protocol, but these are limiting in multiple aspects; the pharmacist prescribing either has to seek out their own CPA, or be included in a store or company-wide CPA, and insurance coverage 6. These barriers can be overcome by following Minnesota Board of Pharmacy protocols that have already been put into place to develop a CPA and connecting patients with payment assistance programs. However, pharmacists are in a unique position and may not realize how large of an impact naloxone can have on patients that overdose, hopefully empowering them to seek care for treatment rather than face the risk of overdose again. Although naloxone itself does not treat addiction, opioid related deaths are preventable with naloxone distribution and accessibility to all patients that may be at risk of overdose or encounter an overdose.
Methods:
A literature search was conducted using OVID Medline (May 2014 to April 2017), and and PubMed (2001-August 2017). These databases were searched using the keywords “OEND,” “naloxone” OR “Narcan,” and “outcome,” using AND in order to combine search terms. Keywords were linked to MeSH (Medical Subject Headings) terms in OVID Medline and searched as free text in PubMed. The website, clinicaltrials.gov was searched for similar studies that were currently ongoing on unpublished. Reference lists of studies included were reviewed in supplementation of the methodical search methods.
Studies were included if they reported patient outcomes of OEND programs. Studies were excluded if they only described the implementation of OEND programs rather than outcomes of educating laypersons. Articles were also included through scanning references of applicable articles that were selected for use in analysis. Data for analysis, including study design, population, interventions, outcomes, and any other relevant information, was extracted from each study by the chief investigator. The Oxford Centre of Evidence-Based Methods (OCEBM) Levels of Evidence tool was used to assess the quality of the evidence of each study 7.
Table 1: Results of Search Strategy and Study Selection
Studies Reporting Outcomes of Opioid Education and Naloxone Distribution
All 6 studies included in this review published efficacy outcomes ranging from success of naloxone rescue, rate of overdose death following release from prison or hospital discharge, or a decrease in the number of opioid related ED visits. The overall results indicate an overarching positive impact of successful naloxone rescues. Only one study was able to suggest a reduction in mortality through the use of OEND. Details of each study are expanded on below.
Bird et al. 8 looked into evaluating the effectiveness of reducing mortality rates due to opioid overdose following release from prison as their primary outcome, and adding discharge from a hospital as their secondary outcome. This study analyzed data prior to and following implementation of the National Naloxone Policy (NNP) offering naloxone-on-release in all of Scotland’s prisons. The implementation of the policy was in response to the increased rate of opioid related deaths during the first four weeks following release from a prison; this was thought to be due to decreased tolerance to opioids after limited to no access within prison, and likely chances of using again following prison if they used before coming to prison. Prisoners were offered opioid overdose response training and naloxone upon release. From 2011-2013, nearly 12,000 naloxone kits were distributed to those being released from prison. Upon analysis of data, it was found that the opioid related deaths were significantly reduced from 9.8% (2006-2010) to 6.3% (2011-2013), by a proportion of 36% during the first 3 years of implementation. With analysis of secondary outcomes, 19% of opioid related deaths were in persons either released from prison or discharged from a hospital in the previous four weeks between 2006-2010; this was significantly decreased to 14.9% of opioid related deaths between 2011-2013, resulting in a 22% reduced proportion before and after NNP implementation.
Coffin et al. 9 looked into coprescription of naloxone for patients prescribed long term opioid therapy. Providers and support staff were trained on the logistics of who should be prescribed naloxone and how to go about doing that. Chart reviews were completed to register patients qualifying for long term opioid use, and ED visits were coded as ‘opioid-related’ for data analysis. In total, 1985 adult patients qualified for data analysis, and 38.2% of these patients were coprescribed naloxone with their opioids. In terms of MEQ daily doses, it wasn’t until at least 201 mg MEQ was reached for at least half of patients to receive naloxone prescriptions; current Centers for Disease Control guidelines for opioid prescribing suggest consideration of naloxone when MEQ is above 50 mg 14. In the nonrandomized cohort that received naloxone, there were 47% fewer and 63% opioid-related ED visits following coprescription during the first 6 months and 1 year, respectively, compared to those that did not receive naloxone.
Doyon et al. 10 analyzed the incorporation of poison center services within Maryland’s statewide opioid education and naloxone distribution (OEND) program. The poison center conducted retrospective case reviews of all reported OEND trained bystander administered naloxone during the first 16 months of the OEND program. In total 78 cases of naloxone administered by bystanders were analyzed. Of the bystander-administered naloxone to overdose victims, 85.1% were given naloxone for abused opioid use, 4.1% were intervening on an attempted overdose suicide, and 10.8% had an unknown specific reason for giving naloxone. 50% of the victims were exposed exclusively to heroin, 25% were exclusively exposed to prescription opioids, 7.8% had an unknown primary drug exposure, and the remaining 17.2% were exposed to a combination of illicit or prescription drugs. In total, the outcomes resulted in a 75.6% success of reversal with only 7.7% of victims experiencing a naloxone-precipitated withdrawal. 89% of all the reports came from OEND trained law enforcement.
Lankenau et al. 11 followed injection drug uses enrolled in and OEND program, evaluating retrospective responses and outcomes of the program. Injection drug users were qualified to enroll in the study if they self-reported using injection drugs within the past 30 days, hand having witnessed an overdose since training and in the past 12 months. 60% of the OEND participants were male. The OEND program included teaching them how to respond to an overdose and deliver naloxone if they witness an overdose. The intervention resulted in an intervention attempt on 30 witnessed overdoses with a 97% known recovery rate either on the scene or at a hospital. One overdose victim had an unknown outcome after seeking emergency medical care for the victim.
Leece et al. 12 described the Prevent Overdose in Toronto (POINT) community-based OEND program and provides an evaluation of the outcomes from the first two years of the program. Clients of the program were 52.4% male, a mean age of 38.3 years and a range of 14-69 years. Of the clients, 69.3% are self-reported current opioid users, 22.7% are past opioid users, and 8.1% have not used opioids. In the first two years of the program, 662 clients were trained in POINT and provided with a naloxone kit. Of the naloxone kits given out, 67 clients used them plus a client’s bystander used one, totaling 10% utilization. Naloxone kit refills were provided to 75 clients on 156 occasions. In total 98 naloxone administrations were reported with 98% success, with 1 unknown outcome and 1 death.
Walley et al. 13 reports on an evaluation of the impacts of an OEND program in Massachusetts with an analysis of opioid related deaths from overdose and acute care utilization. This is done through an interrupted time series analysis of 19 communities in Massachusetts that are impacted by a high burden of opioid overdose. The population of these communities makes up approximately 30% of the entire state’s population. The communities are compared between a high level, low level, and no OEND implementation within communities. There was a total of 2912 OEND trained potential bystanders with 327 reported naloxone rescues. The overall results suggest a 98% success was of naloxone rescue attempts reported by OEND-trained bystanders. Of the naloxone rescue attempts that were not successful, those people received emergency medical care and survived.
Discussion and Conclusions:
The results of these studies have important implications and considerations for public health agencies and the whole healthcare team. The overall considerations indicate that access to naloxone kits are helpful for bystander intervention in an opioid overdose, however current access to OEND services may not be widespread enough to have a clear conclusion about the mortality reducing benefits of naloxone. It is also clear that more research should be done in these areas in order to have a better understanding of the implications, how to access and provide services to the high risk populations, and how to improve safe opioid use when other treatment options have failed.
As described by Bird et al., a modest 20% reduction of opioid related deaths could be expected through implementation of an efficient OEND program for prisoners being released. One limitation of this study was inclusion of hospital discharge opioid related death outcomes, even though the current NNP in Scotland has very little impact on hospital practice, other than recommended naloxone prescribing for at risk patients. Bird et al. also noted a goal of NNP was to have at least ten times as many naloxone kits available to at risk people than the number of opioid related deaths, and this threshold was not achieved; had this been achieved, perhaps the proportional reduction of opioid related deaths could have been even higher.
As noted in Coffin et al. coprescription habits were varied between clinics and providers involved in the study. Certain populations including older patients and black patients were less likely to receive naloxone in this study than other demographics, so additional education and protocols may help to reduce these differences. Next, it cannot be definitely inferred that naloxone caused fewer ED visits because this was an observational study, and verification that patient’s filled their naloxone prescription could not be confirmed. It is possible that having an opioid and naloxone conversation during a visit may alter the patient’s opioid use habits in itself. This study also did not collect data or analyze successful opioid reversals reported by patients like most of the the other studies in this review. Although there are some limitations, this study demonstrated that naloxone coprescribing may reduce the number of opioid-related ED visits, suggesting that the risk of opioid overdose can also be reduced in this way.
Doyon et al. reported that a significant number of bystander administered naloxone cases were left unreported to the poison center because there was no active monitoring of OEND trained participants. There were also significant delays in calling in reports, leading to cases being lost to follow up and reduction in toxicology tests that could be done. This study resulted in an overall response rate of 75.6%, suggesting that naloxone is a necessary intervention for bystanders to help while waiting for emergency care. It also confirmed the importance of making sure multiple doses of naloxone are available, with re-administration being required in 25.6% of cases. This also suggested that calling 911 is still very important because ICU admission rate was 30% for prescription opioid users and 16% for heroin users. The difference in ICU admission rate may be due to prolonged release and elimination of some prescription preparations of opioids with extended release delivery systems or topical delivery systems, or common use of multiple drugs that could contribute to the toxicity..
As discussed in Lankenau et al. OEND training of bystanders can save the lives of overdose victims while they are waiting on further help and direction from emergency medical professionals. The OEND program taught the SCARE ME technique including identifying an overdose, calling 911, provide rescue breathing, evaluate, deliver naloxone, and staying with the victim for aftercare. Approximately 50% of cases sought help from 911, while reasons for not calling 911 included fear of arrest or other fears associated with authority. Overall, this study emphasized the importance of getting naloxone into the populations at significantly higher risk of opioid overdose than the general populations, such as injection drug users, and supporting “Good Samaritan” laws so all are protected from trouble with the law when medical emergencies arise.
As mentioned in Leece et al. individuals at high risk of opioid overdose participated in the OEND and were able to respond to overdose events and report the results back to the POINT program. This indicates that the POINT program is reaching the individuals that are at the highest risks of opioid overdose. A couple findings that were found in this study include that many overdose events happen in private residencies, strengthening the importance of not using opioids when alone and making sure others know how to administer naloxone if needed. POINT clients also noted barriers of calling 911 following an overdose including the fear of police involvement. The overall support of the program between staff and clients is overall positive.
As interpreted by Walley et al. this studies suggests that OEND can be an effective intervention for potential bystanders of opioid overdose to reduce mortality. The communities that had low or high enrollment in OEND programs saw a significantly lower rate of opioid related overdose deaths during this study. Although this study saw no difference in the number of ED visits between any of the groups, this OEND intervention among many others encourage people to still seek emergency medical care following an overdose to ensure the patient does not slip back into overdose if in the presence of long-acting opioids. Overall, OEND programs should be tailored to the needs of the communities they will serve in order to have the highest effectiveness the program can provide.
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