Opioid use disorder (OUD) is a potentially chronic, relapsing condition associated with a great degree of morbidity and mortality.1 Although appropriate treatment can lead to sustained remission and improved quality of life, OUD continues to be a considerable public health concern, highlighted by the increasing number of opioid-related fatalities across Canada and the United States.2,3 In Canada, OUD is at the forefront of the opioid epidemic, which has claimed more than 8000 lives between January 2016 and March 2018, of which 94% were accidental or unintentional apparent opioid-related deaths.4
Canadian studies have shown that people with OUD are more likely to seek care at emergency departments (EDs) than primary care settings due to the inaccessibility of primary care services, psychosocial factors, stigma, and the presence of multimorbidity.5–9 The number of opioid-related hospital visits in Ontario spiked from 1858 in 2003 to 4427 in 2016.5 Consequently, opioids became the drug responsible for the second greatest use of hospital resources after alcohol, with hospital costs for opioid-related admissions increasing by 61% from approximately $9 million in 2006 to almost $15 million in 2011.5 But despite increases in the number of patients with OUD presenting with opioid-related emergencies at hospitals,10 hospital-based interventions for OUD remain uncommon in Canada and the United States.11,12 Few EDs or hospitals provide opioid agonist therapy (OAT), even in patients presenting with life-threatening conditions, such as opioid overdose or infectious endocarditis.13 In sum, a large proportion of hospitals do not have a prescribed standard of care to manage patients presenting with OUD and its complications.
Responses to the opioid crisis have included increasing access to naloxone kits,14 listing OAT on provincial drug formularies,15 developing new “best practice” opioid prescribing standards,1,16,17 and promoting rapid access to addiction medicine services.18,19 The recent Canadian Medical Association guidelines have recommended opioid agonist treatment with buprenorphine–naloxone as the preferred first-line treatment (over methadone) for OUD, and have supported the use of a stepped, integrated, and patient-centred approach.1 Unfortunately, numerous barriers, such as suboptimal addictions training for physicians, OAT prescribing barriers, and pervasive stigma toward addictions,20–23 have slowed the uptake of evidence-based addictions services in many community centres, and this has been shown to be an independent risk factor for injection drug use initiation and opioid overdose death.24
As individuals with OUD are more likely to receive health services from the ED and acute hospitalizations,5,25,26 it makes logical sense for there to be a move toward improving the quality of hospital-based services. Hospitalization represents a golden opportunity to connect patients who have OUD with evidence-based treatments.27 During an admission, patients with OUD have the potential to access multidisciplinary care from physicians, nurses, pharmacists, social workers, therapists, educators, and other allied health professionals.28 Initiation of OAT and addictions services in hospital has been shown to increase the likelihood of follow-up with addictions care in the community.29
Although there have been many prior community-based opioid guidelines, which often emphasize the importance of opioid stewardship, chronic pain management, and harm-reduction strategies,30,31 few have explored the role, value, or effectiveness of hospital-based interventions. The complex health and social issues surrounding hospitalization of patients with OUD require a comprehensive, compassionate, and evidence-based response, and a synthesis of evidence-based interventions are urgently needed in this setting.
To inform the development of evidence-based approaches, we conducted a scoping review and synthesis of hospital-based interventions for individuals with OUD. Specifically, our aim was to answer the following research questions:
- What hospital-based interventions have been used for OUD?
- What is the effectiveness of such interventions on OUD-related morbidity and mortality?
- What interventions require further research?
- What barriers prevent the effective implementation of such interventions in the context of the opioid epidemic?
Protocol and registration
Our protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Scoping-Reviews Extension.32,33 Adherence is outlined in the methodological checklist (Supplementary Appendix 1, Supplemental Digital Content 1, http://links.lww.com/CJA/A4). The final protocol was registered prospectively with the Open Science Framework on October 7, 2018 (https://osf.io/3z8tw/).
To be included in the review, papers needed to measure or focus on specific hospital-based interventions for aspects of care regarding individuals with OUD (or dependence or abuse). Peer-reviewed journal papers were included if they were written in English, involved human participants, and described a measure for intervention outcome. Quantitative, qualitative, and mixed-method studies were included in order to consider different aspects and types of interventions.
Papers were excluded if they did not fit into the conceptual framework of the study, were community or outpatient-based, did not include opioid-specific content, or were not interventional in nature. Review papers discussing theories or approaches to addictions care in hospital were excluded unless they included tangible measures of treatment outcomes.
The scoping review search strategy was developed in corroboration with an experienced health sciences research librarian (Ms Sandra Halliday) and further refined through team discussion in order to reduce the risk of missing relevant studies. A combination of the following keywords and subject headings were used in the preliminary search: “opioid use disorder,” “intervention,” and “hospital.” This preliminary strategy was conducted in Ovid MEDLINE followed by an analysis of citations to identify additional relevant keywords and subject headings. Preliminary searching in Ovid MEDLINE indicated approximately 200 results.
To identify potentially relevant documents, the following 5 bibliographic databases were searched from inception to September 26, 2018: Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. The final search results were exported into the Zotero citation manager,34 and duplicates were removed using Zotero's built-in duplicate citation removal function. The reference lists of full-text articles were screened for potentially eligible studies. Because we aimed to identify evidence-based interventions and given the large number of records identified in our preliminary search, we did not include the grey literature, such as theses and conference proceedings.
The final search strategy for the databases can be found in Supplementary Appendix 2, Supplemental Digital Content 2, http://links.lww.com/CJA/A5.
Selection of sources of evidence
Nonduplicate citations were imported into the Covidence review manager.35 To increase consistency, all reviewers screened the same publications, discussed the results and amended the screening and data extraction criteria before beginning screening for this review. Independently, reviewers evaluated the titles, abstracts and then full text of all publications identified by our searches for potentially relevant publications. Retrieved studies were coded (include or exclude) by each reviewer using the Covidence review interface; the coder initials, coding responses, and reasons for exclusion were noted. Once this initial review was completed, the first author reviewed the responses including reasons for exclusion; records where there was disagreement among reviewers were reviewed in detail and resolved by consensus. Following the selection of articles to be included, reviewers met to review the titles and abstracts to inform logical categories of interventions and refine the data to be extracted.
Data collection process
Among the selected articles, information on the intervention, effectiveness, and contextual and operational factors were into customized forms within Covidence and are include in Supplementary Appendix 3, Supplemental Digital Content 3, http://links.lww.com/CJA/A6.
The data that were extracted included citation, study location, number of subjects and characteristics, study design, type of intervention, important contextual and operational factors related to implementation of the intervention, measured outcomes, estimates of effect, and potential bias. These data items are similar to that used in prior reviews of the efficacy of interventions for preventing and treating opioid overdose.36 The categories shown in Table 1 were refined following the review of selected articles as described above.
Risk of bias in individual studies
The quality of the eligible studies was appraised using Cochrane's Risk of Bias Tool,37 which assesses the methodological quality of interventional studies on the basis of 7 domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. Each domain is rated as low, high, or unclear risk of bias.
Synthesis of results
We grouped the studies by the types of intervention they analyzed, and summarized the type of settings, populations, and study designs for each group, along with the measures used and broad findings. Where we identified a systematic or other review, we counted the number of studies included in the review that potentially met our inclusion criteria and noted how many studies had been missed by our search. Summary statistics (such as number of studies investigating the particular intervention and distribution of study types) were tabulated, as was evidence of effectiveness (risk ratios, 95% confidence interval) where relevant.
The scoping review strategy resulted in 354 records (Fig. 1). A total of 6 duplicates and 194 nonpertinent or nonappropriate references were deleted, resulting in 154 potentially relevant articles. Twenty-two studies (14.3%) met inclusion criteria.
The characteristics for the 22 included studies are presented across Tables 1–4. The studies were published between 1975 and 2017, with 5 (22.7%) published before 2000. In 2006, the number of papers published increased and the yearly rate remained steady since then. These papers appeared in 20 different journals. In total, 10 (45%) were randomized controlled trials, while the remaining 12 (55%) employed cohort designs. The majority of studies were from the USA (n = 9), Russia (n = 2), and Australia (n = 2). Studies were conducted in a variety of hospital settings: specialized addictions units (n = 8), EDs (n = 4), and general hospitals (n = 10).
With the exception of 2 studies reporting outcomes in newborns admitted for the management of neonatal abstinence syndrome (NAS),38,39 the remaining 20 studies involved adult participants with an established diagnosis of OUD, confirmed by the Diagnostic and Statistical Manual of Mental Disorders.40,41 Six studies focused exclusively on adult participants with heroin dependence, while the remaining 16 included individuals with any opioid dependence (illicit or prescription). The study sample included a total of 3604 individuals.
Risk of bias within studies
Using the Cochrane Risk of Bias Tool, we found that the majority of studies were of average quality (Supplementary Appendix 4, Supplemental Digital Content 4, http://links.lww.com/CJA/A7) (Figs. 2 and 3).
Overview of findings
The hospital-based care for individuals with OUD was described as medically and psychosocially complicated across all studies. Individuals with OUD were frequently described as having multiple psychiatric and medical comorbidities, including HIV, hepatitis B or C, depression, chronic pain, anxiety, and metabolic disorders. Due to the diverse patient population, multiple types of measures and interventions were utilized. All included studies used at least 1 objective measure of intervention efficacy, including length of hospital stay, opioid-free status (via self-report or urine drug screen), retention, and/or engagement with outpatient treatment following hospital discharge, completion of inpatient treatment (vs premature discharge and going against medical advice), and cost savings analyses. A few different screening instruments were also utilized, such as the Addictions Severity Index42 and the Maudsley Addiction Profile.43 Study interventions were organized into 4 broad categories: detoxification programs (n = 7), relapse prevention programs using (n = 11), maternal–perinatal programs (n = 2), and combination programs (n = 2).
The 7 studies of inpatient opioid detoxification programs looked at a broad selection of different detoxification strategies involving rapid detoxification under general anaesthesia (RDGA) (n = 2), clonidine (n = 3), methadone (n = 3), naltrexone (n = 1), or buprenorphine (n = 1). Overall, these programs were associated with several positive outcomes. One study44 found that referral to a specialized inpatient detoxification ward was associated with greater rates of completion of inpatient detoxification (75% vs 43%) and higher opioid-free status in follow-up (79% vs 31%) than referral to a general psychiatric ward for medication-assisted opioid detoxification.
The 2 RDGA studies45,46 found that there was a considerably higher percentage of abstinence in the RDGA group after 1, 2, and 3 months of follow-up; however, there was no difference at 6 and 12 months.
In the study comparing methadone to buprenorphine for medication-assisted opioid detoxification,47 there was a significantly greater rate of completion of detoxification in the buprenorphine group (89%) than the methadone group (78%).
Relapse prevention programs
There were 11 studies measuring the efficacy of hospital-based relapse prevention programs for individuals with OUD. Overall, all studies indicated that the use of OAT as a maintenance strategy improved retention in treatment and reduced the use of illicit opioids. These studies looked at a variety of different strategies, including psychosocial interventions (n = 3), methadone maintenance (n = 1), naltrexone maintenance (n = 4), buprenorphine maintenance (n = 2), and stereotactic ablation of the nucleus accumbens (n = 1).
The nonmedication interventions included personalized nursing follow-up, an intensive biopsychosocial ED diversion program, and the use of individualized care-plans for high-frequency users of the ED.25,48,49 Collectively, these 3 programs found that there was a significant reduction in the amount of illicit opioid use and per-patient hospital costs.
Initiation of methadone50 and buprenorphine–maintenance26,51 in hospital was associated with improved rates of abstinence and engagement with outpatient addictions follow-up. Specifically, ED-initiated buprenorphine treatment versus brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services.
The 4 studies utilizing injectable extended-release naltrexone studies52–55 were inconsistent: while there was some evidence of improved retention in treatment, there were also some serious concerns raised about naltrexone-related adverse effects, such as cardiac arrhythmias and severe opioid withdrawal.
Finally, the 1 study56 exploring the utility of neurosurgical ablation of the nucleus accumbens—which was described by the authors as the theoretic locus of opioid addiction—was associated with an abstinence rate of 53.8% over 4 years of follow-up; however, there were several long-term neuropsychiatric sequelae reported.
There were 2 studies38,39 of infants with NAS, which found support for rooming-in (the practice followed in hospitals and nursing homes where the baby's crib is kept by the side of the mother's bed) and a higher dose morphine protocol (0.06 vs 0.04 mg/kg/dose); in both studies, the experimental intervention (rooming-in, high-dose morphine) led to an average reduction in the duration of stay and duration of treatment by 7 days.
Two studies57,58 found that combining detoxification and prevention programs led to improved retention in treatment and rates of abstinence from illicit opioids. For example, participants who were maintained on buprenorphine after detoxification from illicit opioids were more likely to enter outpatient treatment than those who did not continue maintenance therapy (73.8% vs 13.8%, P < 0.001).
This scoping review identified 22 intervention studies measuring the effectiveness of hospital-based detoxification, relapse prevention, maternal–perinatal, and combination programs for individuals with OUD. Detoxification programs involved RDGA, clonidine, methadone, naltrexone, or buprenorphine. Relapse prevention programs used psychosocial interventions, methadone maintenance, naltrexone maintenance, buprenorphine maintenance, or stereotactic ablation of the nucleus accumbens. Although studies were heterogeneous in the types of outcomes they examined, the interventions were all found to be fairly effective and feasible.
The findings of our study demonstrate that there is a high degree of congruence between the effectiveness of interventions initiated in the community and hospital.36 Certain strategies, such as initiating OAT in hospital or in the ED, were shown to reduce the proportion of patients that leave hospital against medical advice. Overall, initiating hospital-based treatment for OUD was shown to improve patient retention in treatment and improve multiple dimensions of addictions care in the community, which supports previous findings.29
While our study identified a host of evidence-based interventions for hospitalized patients with OUD, access to some of these interventions is not yet widely available. However, there is some evidence that access is improving for certain types of interventions. Injectable naltrexone is now available in Canada through special authorization from Health Canada.59 Thus, while provincial formularies may still present barriers to coverage, providers are able to prescribe naltrexone outside of research settings; however, it is primarily used for the treatment of alcohol use disorder.
Historically, infants born to mothers with OUD have been excluded from OUD reviews; however, the 2 relevant studies identified by our review suggest that there are significant healthcare resource utilization benefits associated with rooming-in for infants at risk of NAS.
For patients with OUD who require hospitalization, comorbidity is the rule rather than the exception. As such, a hospitalization for an individual with an OUD often requires the concurrent management of multiple medical and psychiatric comorbidities, which frequently requires concomitant input from multiple subspecialties.30 Some studies estimate that over 50% of all hospitalized patients have 1 or more substance use disorders,60–65 which emphasizes the need for improved addictions and opioid-specific training for medical students, physicians, and allied health practitioners.20
Although our review did not specifically address chronic pain, it is a highly prevalent comorbidity in individuals with OUD, and is one of the primary drivers of the opioid epidemic.10,66 Both acute and chronic pain can be particularly frustrating for patients with OUD and their physicians, who are often undertrained in evidence-based pain management.66,67 As access to chronic pain specialists is limited in the community, this may represent yet another reason to optimize existing resources for patients with OUD while they are in the hospital.67
In a similar vein, discharge from hospital provides yet another key opportunity for intervention, and a critical point in the transition of care for patients with OUD.68 As opioid tolerance is lost quickly following cessation of opioids, patients with OUD who undergo forced withdrawal following admission to a hospital are at increased risk of overdose with resumption of opioid consumption. Physicians and allied health providers should engage patients in discussion regarding long-term addiction treatment options and harm-reduction strategies at discharge and should ensure appropriate follow-up is arranged. Interdisciplinary collaboration with organizations dedicated to addictions education, such as MetaPhi based out of Women's College Hospital in Toronto, may represent an efficient mode of rapidly addressing knowledge deficits around addictions.69 Fortifying addictions training opportunities in medical school, residency, and fellowship programs will also support the acquisition of key skills and expertise in the next generation of physicians, who may live to see the fall of the opioid epidemic.20,70–72
Our study, however, is not without limitations. As a scoping review, the quality of our review is limited by the quality of its component studies. As we excluded grey literature, this may have reduced the potential yield of our search strategy. Certain established interventions for patients with OUD were excluded because these studies were not hospital-based—thus, our approach may have been overly restrictive in this sense. In addition, given that we did not exclude nonrandomized studies, our findings are especially heterogenous, which precluded meta-analysis.
Individuals with OUD are frequent users of the hospital, and as such, this review of hospital-based interventions for such individuals has identified that there are a number of effective detoxification, prevention, and combination programs that can lead to significant improvements in their care. Although the management of individuals with OUD is fairly complex and frequently involves multimodal treatment and multidisciplinary approaches, there are many effective strategies that can reduce morbidity and mortality in this population. The use of medications (such as naltrexone, methadone, buprenorphine, medication-assisted detoxification) and psychosocial interventions are cost-effective strategies that can improve engagement in long-term outpatient addictions care and reduce hospital length of stay. Thus, hospitalization of patients with OUD represents a critical opportunity to intervene in the lives of those who struggle with a significant chronic illness.
We would like to thank Ms Sandra Halliday, Research Librarian at Bracken Health Sciences Library at Queen's University, Kingston, ON, Canada. We would also like to thank Dr. Heather Stuart and Dr. Susan Brogly for providing inspiration for this review.
No funding was received for this project.
Data statement: Data available online. DOI:10.13140/RG.2.2.12705.86881.
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addictive; behaviour; buprenorphine; continuity of patient care; length of stay; methadone; opiate substitution treatment; opioid-related disorders; outcome assessment (health care); secondary prevention; Mots clés; Buprénorphine; Comportement; dépendance; Continuité des soins aux patients; Durée du séjour; Évaluation des résultats (soins de santé); Méthadone; Prévention secondaire; Traitement de substitution aux opiacés; Troubles liés aux opioïdes
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