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A Review of Potential Adverse Effects of Long-term Opioid Therapy

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Relative frequency and take chances factors for long-term opioid therapy following surgery and trauma amongst adults: a systematic review protocol

  • Irina Kudrinathree  na1,
  • Hervé Tchala Vignon Zomahoun4,5,
  • Daniela Zieglersix,
  • Pierre Beaulieu2,vii,
  • Céline Charbonneauviii,
  • Jennifer Cogan2,ix,
  • Raoul Daoust10,
  • Marc O. Marteleleven,
  • Andrée Néron12,
  • Philippe Richebé2,xiii &
  • Hance Clarkexiv,fifteen

Systematic Reviews volume 7, Article number:97 (2018) Cite this article

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Abstruse

Background

When patients have been on opioid therapy for more than ninety days, more than than half of them continue using opioids years later. Knowing that long-term opioid consumption could atomic number 82 to harmful side effects including misuse, abuse, and habit, it is important to understand the risks of transitioning to prolonged opioid therapy to reduce its occurrence. Perioperative and trauma contexts are ideal models commonly used to report such transition. Long-term apply of opioids might be associated with transformation of acute pain to chronic, which might be an case of a risk cistron. The objectives of this knowledge synthesis are to examine the relative frequency and the adventure factors for transitioning to long-term opioid therapy amidst patients who have undergone a surgical procedure or experienced a trauma.

Methods

The proposed report methodology is based on Preferred ReportIng Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statements on the conduct of systematic review and meta-assay, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies, and the Cochrane Handbook for Systematic Review of Interventions. A systematic literature search will include multiple databases: Cochrane Central, EMBASE, MEDLINE, PsycINFO, CINHAL, PubMed, and the greyness literature. We will identify studies related to opioid use beyond acute/subacute hurting control afterward surgery or trauma. Two of the reviewers will screen all retrieved manufactures for eligibility and data extraction then critically assess all identified studies. We will compile a narrative synthesis of all results and deport a meta-analysis when feasible. As available data permits, we will perform a subgroup analysis of vulnerable populations.

Give-and-take

This systematic review will contribute to the prevention and harm reduction strategies associated with prescription opioids past identifying take chances factors leading to the unwarranted long-term opioid therapy. The identification of mutual risk factors for long-term opioid therapy will help to orient further research on pain management likewise equally offer key therapeutic targets for the development of strategies to prevent prolonged opioid apply.

Systematic review registration

This protocol was registered in PROSPERO on March 2, 2018; registration number CRD42012018089907.

Introduction

Opioid prescriptions accept significantly increased over the last two to three decades, especially in the The states and across Canada [i, 2]. Opioids remain amongst the most widely used analgesic medications in the treatment of chronic non-cancer pain (CNCP). Post-surgical pain management is a swell example of nearly systematic use of opioids as fourscore% of surgical patients are prescribed opioids [three]. Indeed, untreated postoperative pain could have detrimental consequences such as development of CNCP, deterioration of quality of life and poorer medical outcomes [iv]. It is non rare that opioid therapy is initiated without a articulate handling plan, and prescriptions are renewed when patients complain of persistent pain thus leading unintentionally to prolonged opioid therapy [five]. This practice has numerous societal implications since the storage of unused medications [6, seven], improper discarding practices of excess narcotic analgesics [8] and/or used medications (e.thou., fentanyl patches), and deficient inter-professional person communication (e.thou., family doctors and specialists) [9] could pose a public wellness threat. This may be complicated by diverse non-coordinated trials of opioids past unlike providers, some of which may exceed recovery time, in addition to the insufficient patient follow-upward and elevated caseload of many clinicians.

In this context, long-term opioid therapy refers to the use of prescription opioids that were initially intended to treat an acute pain condition and continued across the recovery phase [x], typically for more than 90 days.

The perioperative model offers an ideal context to study the transition from acute to chronic hurting [11] (pain that lasts for longer than expected, typically more than than three–6 months [12]) and astute to long-term opioid therapy [13, xiv]. When the onset of hurting and the date of initiation of opioid therapy are known, baseline measurements tin exist collected perioperatively to examine predisposing factors. The initial time-express utilization becomes prolonged for many patients; 27% of CNCP patients on opioid therapy (months to years post-obit their first prescription) were initially prescribed opioids following surgery [15]. Recent guidelines on the management of postoperative pain [16] recognize the demand for the round-the-clock analgesia over the first 24 h postoperatively and oft longer for major surgeries. The guidelines advocate for specific actions to facilitate hospital belch of patients on opioid therapy but recognize that in that location is insufficient noesis of how to perform a postoperative opioid taper [sixteen]. This lack of noesis nearly likely contributes to the unplanned evolution of prolonged opioid therapy. Considering that 2.5 million surgeries are performed yearly in Canada [17], thousands of these patients are potentially at risk for transition to prolonged and long-term opioid therapy.

Similar to the perioperative model, trauma is often associated with high intensity acute hurting, and more than than one-half of trauma patients are discharged from the hospital with an opioid prescription [10, 18]. Incidence of long-term opioid therapy following trauma may be high [nineteen,20,21,22]. For instance, 39% of workers who filed a bounty claim and who received an opioid prescription remained on opioid therapy ane year later [23]. Amongst patients with fractures, more than 40% and xxx% continue taking prescribed opioids 6 and 12 months post-fracture, respectively [19, 24].

Understanding how an initially time-limited opioid prescription turns into a long-term therapy is essential to optimize treatment and minimize potential damage associated with opioid therapy. To date, we accept found simply one narrative review on opioid consumption after surgery [25] that briefly discusses the incidence and take chances factors for long-term opioid therapy after surgery and emphasizes several strategies to facilitate opioid cessation. However, the authors omitted several relevant studies from this review [26,27,28]. There was no disquisitional appraisement of the literature or attempt to integrate results beyond the studies. This work does not examine the long-term opioid therapy in other contexts such as trauma. Lastly, considering the scientific search method is not reported, the review is subject to significant influence from the writers' opinions [29].

There is a famine of literature supporting effectiveness of long-term opioid therapy [30] and its potential negative consequences [31, 32]. As such, strategies promoting opioid-related harm reduction must target gamble factors for transitioning to long-term opioid therapy. This can only exist based on a strong understanding of how opioid therapy becomes prolonged in the commencement identify. A systematic review of the relative frequency of and the risk factors for long-term opioid therapy among populations for which opioids are oft used (e.g., fourscore% of surgical patients [3]) would generate such agreement. Due to the heterogeneity in the literature, information technology has been difficult to come to a specific conclusion. There is no consensus on what constitutes the most common risk and protective factors for the long-term utilise of opioids. The incidence of prolonged opioid use in different populations remains unknown [25]. Knowledge of what constitutes modifiable risk factors for unnecessary long-term opioid therapy is of vital importance to the prevention of secondary opioid damage. This systematic review seeks to contribute to the cognition of harm prevention; therefore, we present here details of the systematic review protocol.

Goals of systematic review

The ii master objectives of this systematic review are to:

  1. (1)

    Examine the relative frequency of prolonged and chronic opioid therapy

and

  1. (ii)

    Identify the adventure factors for transitioning to prolonged and chronic opioid therapy among developed patients who have experienced physical trauma requiring hospitalization and/or undergone surgery of any blazon within a hospital setting and who received an opioid prescription at discharge or within the 2 weeks post-obit infirmary belch.

Data will be examined separately for opioid-naive patients and patients on opioid therapy prior to surgery/trauma. If data permit, the relative frequency and risk factors volition exist examined in distinct populations (e.m., women, elderly, young adults, ethnic people, and individuals suffering from mental illness).

Methods

This protocol and its proposed methodology are based on Preferred ReportIng Systematic Reviews and Meta-Assay Protocols (PRISMA-P) statement [33] on the conduct of systematic review and meta-assay, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies [34], and the Cochrane Handbook for Systematic Review of Interventions [35]. The systematic review is composed of seven steps (see Fig. 1).

Fig. 1
figure 1

Steps of systematic review

Full size prototype

Operationalization of key constructs

  • Surgery refers to any minor or major operative or transmission procedure involving instrumental manipulation of the living human being tissues (performed past a surgeon [36] or a not-surgical specialty). Only surgeries typically performed in-infirmary (day surgery or inpatient surgery) will be included.

  • Trauma refers to an injury to the living tissue (eastward.chiliad., body wound) that is caused by an external agent (blunt force or penetrating) [37] or other physical stressors (east.g., falls, burns, and fractures) which may or may not require any further surgical intervention. Purely psychological traumas without a physical component will not exist considered for inclusion.

  • Opioids refer to a class of drugs targeting opioid receptors. Consistent with other systematic reviews, all opioid agonists/partial agonists will exist considered, administered using pure or mixed formulations, and all systemic routes of administration will be included (routes of assistants can change over fourth dimension).

  • Opioid therapy elapsing and frequency: categorization of opioid consumption will be based on a temporal definition (every bit opposed to dose-related). Nosotros will report the frequency of use as a number of prescriptions per considered period.

    • ○ Transient volition be divers as at to the lowest degree ane opioid prescription (prescribed, distributed, or reported) of whatever length within the first 44 days post discharge and at least 1 prescription of opioids between ane.5 and < 3 months (45 to 89 days) post infirmary discharge from the surgery/trauma.

    • ○ Prolonged opioid therapy will be defined as at least i prescription (prescribed, distributed, or reported) inside the commencement 44 days post discharge, at least one prescription of opioids between 1.five and iii months post hospital discharge and at to the lowest degree one prescription of opioids of any length betwixt 3 and 6 months post hospital discharge from the surgery/trauma, irrespective of the dose.

    • ○ Chronic opioid therapy volition be defined equally at least one opioid prescription (prescribed, distributed or reported) of whatsoever length more than than half-dozen months post hospital belch post-obit surgery/trauma in addition to coming together criteria for prolonged opioid therapy.

These definitions are based on time-to-cessation [38] of opioids following surgery. Long-term opioid therapy is used in this article to comprehend both prolonged and chronic opioid apply (a generic term describing opioid consumption that exceeds xc days following infirmary belch post-event).

  • Daily dosing: in that location is no consensus on definitions of lower versus high-dose therapy [39]. Fifty-fifty morphine equivalence daily doses (MEDD) between 20 and fifty mg are associated with increased risk of overdose and death [40]. When information are available, we volition convert reported daily doses for long-term opioid therapy into their respective MEDD. Daily opioid consumption volition be reported equally follows:

    • ○ Low dose defined equally a total daily dose less than 50 MEDD

    • ○ Moderate dose defined every bit a total daily dose betwixt 50 and 90 MEDD

    • ○ High dose defined every bit a total daily dose above ninety MEDD

  • Type of opioid use will be defined as episodic or continuous

    • ○ Episodic use is opioid consumption > 3 months with total days of opioid supply < 120, and total number of prescriptions filled < 10

    • ○ Continuous apply is opioid consumption > 3 months with ≥120 days of opioid supply and ≥ 10 total number of prescriptions filled [5, 41, 42].

  • Preoperative and pre-trauma opioid use condition: patients volition be classified equally preoperative or pre-trauma opioid users if they have received opioid supplies more than one month before surgery or trauma. Patients who received opioids only in the days before surgery (30 days or less) will be considered equally opioid naive given that opioids are ofttimes prescribed to patients before surgery for postoperative pain control.

Eligibility criteria

Eligibility criteria are defined based on the PICOS (Participants, Intervention/Exposition, Control, Outcomes, and Report pattern) approach [43]. Study pick will be based on the criteria outlined below.

Participants

Inclusion criteria

Studies will exist included if they meet the following criteria: adults (≥ 18 years old), surgery (minor/major performed at the hospital) and/or physical trauma/injury (requiring hospitalization) and requiring opioid-based analgesia of whatever duration post-infirmary belch (at least one opioid prescription filled at discharge or within ii weeks of infirmary discharge). Consistent with other reviews, in case of mixed populations (e.one thousand., a study that has included some cancer patients within their sample) for which information cannot exist obtained by authors, studies with ≥ 75% of patients coming together the inclusion criteria will be accepted [41]. Purely psychological traumas without a physical component will non be considered for inclusion. Methadone and buprenorphine are almost never starting time-line analgesic agents; however, they will be included if time for initiation and analgesic purpose are clearly identified in a report. Since the principles of pediatric analgesia rely on differing therapeutic criteria [44, 45], only adults are included in this review.

Exclusion criteria

Studies will exist excluded if whatsoever of the post-obit conditions apply: study participants suffering from cancer pain, requiring end-of-life intendance, with addiction substitution/maintenance therapy, with lack of consideration for presence/absence of opioid therapy pre-surgery/trauma, and having undergone another surgical process or experienced another trauma during the study follow-upwards period. Studies in which a fourth dimension frame for opioid initiation and handling duration cannot be identified volition be excluded. In cases where studies examine only the 3-month outcomes with no mention of opioid intake betwixt discharge and follow-upward, these studies will be included if information is available to decide that the opioid prescription at 3 months is taken because of the indexed result. Given that opioid-naive patients and patients on opioid therapy earlier surgery or trauma will exist examined separately, studies with mixed populations that do non allow for subgroup analyses and the examination of incidence and risk factors separately (eastward.g., for opioid-naive patients and preoperative/pre-trauma opioid users) will be excluded.

Exposure

Exposure will consist of having received at least 1 opioid prescription inside 2 weeks post-obit hospital belch post-event.

Comparison

Comparing, when applicable, would consist of comparison the presence/absenteeism or degree of risk factors between patients who developed long-term opioid therapy vs. those who discontinued opioids in the astute phase.

Outcomes

Objective 1

Frequency of opioid use, daily dosing, and type of opioid utilise at dissimilar fourth dimension points (45 days, 90 days, 6 months, and 12 months post-obit hospital discharge postal service event) volition be reported for each blazon of surgery and trauma. At that place must be an show of electric current opioid use (i.e., opioid prescription filled within that time window) at the pre-determined cut-off points for transient, prolonged, and chronic opioid therapy and no menses greater than 90 days without opioid consumption at any signal since hospital belch [46]. This data will have been sourced from the medico-administrative databases or medical charts, or patient self-report information.

Objective two

In the identification of biopsychosocial take chances and protective factors for long-term opioid therapy mail-discharge, three types of risk factors will be assessed related to (1) patients, (2) health care providers, and (iii) wellness care system. Data sources for patient factors will include validated self-report questionnaires as well as medical charts/medico-authoritative databases. Data sources for wellness care providers and wellness intendance organisation factors will include medical charts, md-authoritative databases, and clinical/health care systems.

Study design

Inclusion

The post-obit study designs volition exist included: experimental designs (randomized controlled trial, quasi-experimental designs), observational studies (cross-sectional, accomplice, example-control, example series), and mixed methods studies.

Exclusion

We will exclude editorials and commentaries. Studies with a follow-up period shorter than 1.5 months following hospital discharge post-event will be excluded.

Limits

Language: Merely manufactures published in English or French will be considered.

Publication status and publication year: Articles published since 1998 or in printing will be considered for inclusion. This cut-off was chosen given that it follows the first consensus argument by the American Academy of Pain Medicine and the American Pain Club on the use of opioids in the treatment of chronic non-cancer pain [47] leading to significant do change in the employ of opioids for CNCP management.

Information sources

The following four literature categories volition be searched:

  1. ane.

    Databases: The post-obit databases will exist searched by a professional person report librarian (DZ) and reviewed past 2 independent librarians: MEDLINE (1998–), PubMed (1998–), CINAHL (1998–), PsycINFO (1998–), EMB Review (1998–), EMBASE (1998-), Cochrane Database of Systematic Reviews, and Cochrane Cardinal Register of Controlled Trials.

  2. 2.

    Reference lists of identified studies and whatsoever relevant review manufactures institute will exist screened;

  3. three.

    Additional manual search of relevant journals peculiarly for trauma given the variety of key words used for indexing (Trauma and Acute Intendance, Register of Emergency Medicine, Emergency Medicine International, European Journal of Trauma & Emergency Surgery);

  4. 4.

    Grey literature (Google scholar, Pro Quest Dissertation and Theses; published reports).

The search bibliography will also be circulated to all study authors who accept expertise in the domain.

A focused search for distinct populations (elderly, women, young adults, indigenous people, and individuals suffering from mental illness) volition also be performed using Google Scholar. To conduct this specific search, we will add key terms (e.1000., Ethnic) to the search strategy in Google Scholar and compare the manufactures retrieved to those found in the original search. We will continue until 10 pages with the maximum number of articles take been reviewed or until saturation signal has been reached (when Google Scholar does not identify any articles not previously included), whichever happens first.

Search strategy

The search strategy was elaborated past our information expert (librarian) (DZ) and our field experts (GP, IK) and reviewed by a 2d independent librarian. We have reviewed central words, MeSH terms, and search strategies used in relevant original studies and literature reviews. We program to behave the search for the relevant studies based on the following terms and derived terminology from the iv pre-identified conceptual groups: (1) opioid (including synonyms, generic, and brand names of medications); (ii) surgery or trauma (including names of specific weather typically not indexed nether these terms, e.g., knee arthroplasty, fracture, and burn down); (three) transient/prolonged/long-term/frequency/prevalence/incidence or hazard factors. The complete search strategy for MEDLINE database is presented in the Appendix. These search terms volition be adapted for each of the databases to be considered. For each of the databases, controlled vocabulary (MeSH, EMTREE, and others), and gratuitous-text searching will be used. A transmission search of the bibliographies of each of the original studies and relevant reviews included volition be conducted by GP and research assistants to identify other potential relevant references.

Study records

Data management

All search results will exist merged using the EndNote software, and indistinguishable records will exist removed. The written report selection process volition be performed using the software DistillerSR (DistillerSR, Bear witness Partners, Ottawa, Canada). Titles and abstracts will be independently screened for eligibility past ii reviewers. Reviewers will include GP, IK, and experienced research assistants. The full text of potentially relevant reports volition exist further analyzed for eligibility. Disagreements volition exist resolved by consensus and if needed, past requesting the opinion of the tertiary reviewer. To ensure consistency across reviewers, a review of selection procedure volition exist performed after ten% of the identified articles take been reviewed. Levels of inter-rater agreement [48] (kappa statistics) will be documented.

Selection process

A research assistant will obtain the full text of all relevant publications and further analyze the data against the defined eligibility criteria. Two reviewers will exist assigned to each publication, and input from the tertiary reviewer volition exist solicited in case of disagreement. The following information volition be recorded in this modified Effective Practice and Organisation of Care (EPOC) course: surname of first author, year of beginning report, engagement course completed, names of reviewers extracting data, report title, type of publication, funding source, conflicts of interests, and report characteristics (study blazon, participant, intervention types, and outcomes).

A manual search using authors' names volition be conducted to place unmarried studies that accept been published more than once. The review authors volition not be blinded to journal titles and study authors of institutions.

Data extraction and reporting

For the data extraction of selected studies, we volition adapt the Cochrane EPOC Data Brainchild Form and Information Extraction Instructions [49]). Data extraction will exist washed inside the DistillerSR software. For the specific needs of this systematic review, GP and the research assistant will pilot the adapted EPOC course with instructions on 10 randomly chosen studies to refine and finalize information technology.

Information extraction will be independently done by GP and research administration using the adjusted recording form. The data extraction form sections are designed to excerpt data concerning all aspects of each study, including population and study characteristics, methods used to mensurate exposition and issue characteristics, results on association measures of involvement, and results applicability. Authors will exist contacted as needed to obtain missing information.

Patient data will be organized into the broad categories of risk factors like to those for chronic postoperative pain [11], namely sociodemographic, psychosocial, and medical/surgical/trauma characteristics. Health care professional person take chances factors will be categorized into sociodemographic, psychosocial, and professional (e.thousand., experience, type of profession, and prescribing practices). Lastly, health intendance system take a chance factors will be categorized into infrastructure (e.k., proximity of pharmacies and access to health care professional) and economic (e.g., percent of reimbursement of opioid prescription costs).

Data items and outcomes

Objective 1: relative frequency of opioid therapy

Primary outcome

The primary outcome will be the relative frequency of long-term opioid therapy (≥ xc days) post-obit hospital discharge post trauma and/or mail service surgery. This will be reported as a proportion of patients on opioid therapy out of the full number of eligible patients (refer to the section "Operationalization of fundamental constructs" for more details).

Secondary outcomes

Secondary outcomes will examine the relative frequency of opioid therapy at different stages post-obit infirmary discharge (transient, prolonged, and chronic utilize periods). Relative frequencies will exist examined based on preoperative/pre-trauma opioid status and if data permits based on small vs. major surgeries [50].

Objective 2: risk and protective factors for long-term opioid therapy

3 types of run a risk factors volition exist assessed (patients, wellness care providers, and health care system).

Chief issue

Identification of biopsychosocial risk and protective factors for long-term opioid therapy mail service-discharge (≥ 90 days).

Secondary outcomes

In identification of biopsychosocial risk and protective factors at the different stages post-obit hospital belch, some literature suggests that the risk factors for the development (3-month status) vs. maintenance (12-month status) of postoperative pain are not the same (due east.g., [51]). As such, as data permits, this review will examine risk factors for prolonged opioid use separately from chronic opioid use, the latter allowing for run a risk factors measured 3 months later infirmary belch to exist examined.

Risk of bias in private studies

Two from the v reviewers (GP, IK, research administration) will review each included commodity separately to assess the risk of bias for each outcome of interest. In example of disagreement, a word will have place to achieve consensus; otherwise, a third reviewer volition appraise the study. Dissimilar assessment tools will exist used depending on each report design: the Effective Public Wellness Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies for cohort studies and case-control studies [52], the EPOC Hazard of Bias Tool for RCT [53], the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies [54], and Mixed Methods Appraisal Tool for Systematic Mixed Studies Reviews [55]. 8 categories (option, written report design, confounders, blinding, data drove methods, withdrawals/drop-outs, integrity of delivered intervention, analyses) will be assessed using 21 items. The EPHPP tool has a good inter- and intra-rater reliability [52, 56] and is one of the top tools for disquisitional appraisal in systematic reviews [57]. Source of report funding (eastward.g., sponsored by pharmaceutical companies or not) will also be examined.

Synthesis

Data synthesis process

First, results of the study selection process volition exist described using a PRISMA Flowchart [58], and the statistic of inter-rater agreement (kappa) [48] will be reported. Second, we will perform a qualitative description of the population, the studies included, the risk factors identified, and the upshot characteristics using unproblematic frequency counts and a narrative approach. Third, only the studies in which data on risk factors and the outcomes of interest are bachelor to estimate the relative frequency and effect size volition be included in the meta-analysis.

Data synthesis reporting

If effect sizes are available or calculable in two or more studies for a specific outcome, a meta-assay will be conducted using the software Review Director [59]. For continuous outcomes, nosotros will employ standardized mean difference (SMD) with 95% CI, and for dichotomous outcomes, we will use the relative risk (RR) with 95% CI. Adding and/or transformation of consequence sizes into RR or SMD will be done when possible. When issue sizes cannot exist calculated or when merely one effect size is available for an event, we volition report the results of this issue every bit a narrative synthesis. Due to the predictable heterogeneity of the information, we will use a random-effects model to puddle the effect size of the adventure factor for each upshot [60]. Only the adjusted issue sizes will be considered in this model. Nosotros will besides calculate Higgins' I 2 statistic, i.e., the per centum of variability in the outcome size estimates due to the heterogeneity [61]. The chi-squared test will be used to test the heterogeneity [61, 62]. Moreover, the potential heterogeneity (i.e., I 2 ≥ 50%) volition be explored using subgroup analyses based on studies, participants, and exposure characteristics mentioned above.

If sufficient information are available to examine RR and gamble factors for long-term opioid therapy amidst individuals with low socioeconomic status, women, youth, ethnic people, and individuals with a diagnosed mental disease, we volition summarize and synthesize the data in a narrative fashion.

Meta-biases

For clinical trials published after 2005, reporting bias will be assessed past determining whether a protocol for the selected articles was published prior to data collection. We will besides assess the publication bias for each outcome by visually examining funnel plots when more than than ten studies are included in the meta-assay [35]. Finally, we plan to perform the following sensitivity analyses in guild to assess the robustness of our results on each consequence of involvement: (i) nosotros volition explore the individual influence of each study by sequentially removing i at the time from the pooled effect size interpretation, (2) we will repeat the pooled effect size estimation by including only studies with depression risk of bias, and (3) as we anticipate that misreckoning variables may vary depending on which studies are included, we will approximate the pooled crude effect size for each outcome using crude effect sizes (non-adjusted) merely. Results of these analyses will be compared with the initial pooled effect sizes in society to appraise the impact of the confounding variables.

Confidence in cumulative evidence

For each effect, we volition assess the quality of cumulative evidence with the Grading of Recommendations Assessment, Development and Evaluation (Grade) [63] to reduce the misinterpretation of the results of the review. This tool is based on v criteria such every bit the adventure of bias in each individual study, the indirectness of the prove, the heterogeneity of the data, the imprecision of the effect size estimates, and the risk of publication bias. The quality of evidence will be rated high, moderate, low, or very low. Equally mentioned previously, we volition as well examine the take a chance of bias associated with a funding source.

Discussion

The outcomes of this systematic review will directly inform health care policies and could potentially change the clinical practise of multiple wellness professionals who are involved in the initial prescriptions of opioids (e.g., anesthesiologists, surgeons, emergency physicians, obstetricians, and physiatrists). The results of this review will modify approach to prolonged and chronic opioid therapy among the providers involved in the renewal and discontinuation of opioid therapy (e.thou., pharmacists, primary care physicians, orthopedic surgeons, and psychiatrists), and those practicing at the primary, perioperative and trauma (post-acute treatment decision) care levels. The agreement of the underlying risks for long-term opioid therapy will ultimately contribute to the cost-effect optimization of the patient monitoring processes in the days/weeks following the initiation of opioid therapy. The synthesis data will inform clinical algorithms and help to develop appropriate risk prevention programs.

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Acknowledgements

Caroline Sauvé, librarian at the Department of Information science of the Hôtel Dieu, Center hospitalier de fifty'Université de Montréal has contributed to the elaboration of the search strategy in MEDLINE.

Funding

This systematic review is funded and sponsored by the Canadian Institutes of Health Research Operating Grant: Opioid Crunch Knowledge Synthesis # 397974. Through funding, peer review process reviewers have provided comments that were incorporated into this manuscript. The written report team has received in-kind contribution from the "Health and Social Services Systems, Knowledge Translation and Implementation" component of the Quebec SPOR-Support Unit.

Amendments

If amendments are needed to this protocol as we motion forward with the review, we will provide the date of each amendment as well as a description and rationale of each change fabricated when publishing the review.

Writer information

Author notes

  1. Yard. Gabrielle Pagé and Irina Kudrina contributed equally to this work.

Affiliations

  1. Centre de recherche du Centre hospitalier de fifty'Université de Montréal (CRCHUM), Tour Saint-Antoine S01-112, 850 rue St-Denis, Montreal, QC, H2X 0A9, Canada

    M. Gabrielle Pagé

  2. Section of Anesthesiology and Hurting Medicine, Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, local S-712, C.P. 6128, Succ. Heart-ville, Montréal, QC, H3C 3J7, Canada

    M. Gabrielle Pagé, Pierre Beaulieu, Jennifer Cogan & Philippe Richebé

  3. Section of Family unit Medicine, Kinesthesia of Medicine, McGill University, 5858 Ch de la Côte des Neiges, Montreal, QC, H3S 1Z1, Canada

    Irina Kudrina

  4. Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Pavillon Ferdinand-Vandry, 1050 ave de la Médecine, local 2431, Québec, QC, G1V 0A6, Canada

    Hervé Tchala Vignon Zomahoun

  5. Health and Social Services Systems, Cognition Translation and Implementation Component of the Quebec SPOR-SUPPORT Unit, Pavillon Landry-Poulin, 2525, Chemin de la Canardiere, Quebec, QC, G1J 0A4, Canada

    Hervé Tchala Vignon Zomahoun

  6. Section of Informatics, Hotel Dieu, 3840 Saint-Urbain Pavillon Olier 4e étage porte two-428, Montreal, QC, H2W 1T8, Canada

    Daniela Ziegler

  7. Anesthesiology Section, Heart hospitalier de 50'Université de Montréal, 1051 rue Sanguinet, Montreal, QC, H2X 0C1, Canada

    Pierre Beaulieu

  8. Association Québécoise de la douleur chronique (AQDC), bureau 403, 2030 boul. Pie-Ix, Montreal, QC, H1V 2C8, Canada

    Céline Charbonneau

  9. Department of Anesthesiology, Montreal Heart Found, 5000 Bélanger, Montreal, QC, H1T 1C8, Canada

    Jennifer Cogan

  10. Emergency medicine, Hôpital du Sacré-Coeur de Montréal, 5400 Boul. Gouin Ouest, Montreal, QC, H4J 1C5, Canada

    Raoul Daoust

  11. Kinesthesia of Dentistry, McGill University, 2001 Avenue McGill College, |500, Montreal, QC, H3A 1G1, Canada

    Marc O. Martel

  12. Clinique de la douleur, Département de pharmacie, Centre hospitalier de l'Université de Montréal, 5e, Pav C – C0550, 1051 rue Sanguinet, Montreal, QC, H2X 0C1, Canada

    Andrée Néron

  13. Section of Anesthesiology, Hôpital Maisonneuve-Rosemont, 5415 Assumption Blvd, Montreal, QC, H1T 2M4, Canada

    Philippe Richebé

  14. Department of Anesthesia and Hurting Management, Toronto General Infirmary, University Health Network, 200 Elizabeth St 3EN-464, Toronto, ON, M5G 2C4, Canada

    Hance Clarke

  15. Transitional Pain Service, Toronto General Infirmary, University Wellness Network, 200 Elizabeth St 3EN-464, Toronto, ON, M5G 2C4, Canada

    Hance Clarke

Contributions

All study authors contributed intellectually to the evolution of the nowadays protocol. GP and IK wrote the manuscript. All authors reviewed and approved the final version of this manuscript. GP is the report guarantor.

Corresponding author

Correspondence to M. Gabrielle Pagé.

Ideals declarations

Ideals approving and consent to participate

Ethics approval is not required for systematic reviews.

Consent for publication

Not applicable.

Competing interests

The authors declare that they accept no competing interests.

Publisher'southward Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Appendix

Appendix

Search Strategy

Database: Ovid MEDLINE® in-process and other not-indexed citations, Ovid MEDLINE®, 1946 to present.

1 Thoracic Surgery/
2 Surgery Department, Hospital/
three Gynecologic Surgical Procedures/
4 Convalescent Surgical Procedures/
v Surgical Procedures, Operative/
half-dozen Cardiovascular Surgical Procedures/
7 Digestive Organization Surgical Procedures/
8 Elective Surgical Procedures/
9 Endocrine Surgical Procedures/
10 Minor Surgical Procedures/
eleven Neurosurgical Procedures/
12 Obstetric Surgical Procedures/
13 Ophthalmologic Surgical Procedures/
14 Orthopedic Procedures/
15 Otorhinolaryngologic Surgical Procedures/
xvi Perioperative Intendance/
17 Reconstructive Surgical Procedures/
18 Thoracic Surgical Procedures/
19 Cardiovascular Arrangement/su [Surgery]
20 Bariatric Surgery/
21 "Wounds and Injuries"/
22 Intestinal Injuries/
23 Amputation, Traumatic/
24 Arm Injuries/
25 Back Injuries/
26 BURNS/
27 Common cold Injury/
28 Contrecoup Injury/
29 Trounce Injuries/
30 Electrical Injuries/
31 Fractures, Bone/
32 Hand Injuries/
33 Hip Injuries/
34 Joint Dislocations/
35 Leg Injuries/
36 Neck Injuries/
37 Occupational Injuries/
38 Shoulder Injuries/
39 Soft Tissue Injuries/
xl "Sprains and Strains"/
41 Tendon Injuries/
42 Thoracic Injuries/
43 Peripheral Nerve Injuries/
44 Vascular System Injuries/
45 War-Related Injuries/
46 Wounds, Nonpenetrating/
47 Wounds, Penetrating/
48 POSTOPERATIVE CARE/ or POSTOPERATIVE Catamenia/ or Pain, Postoperative/
49 (injur* or surger* or surgical or traum* or arthroplast* or accident* or fracture* or dislocation*).tw,sh,kw,kf,oa.
l or/1-49
51 exp Analgesics, Opioid/
52 exp CODEINE/
53 exp MORPHINE/
54 CODEINE/
55 FENTANYL/
56 HYDROCODONE/
57 HYDROMORPHONE/
58 MEPERIDINE/
59 OXYCODONE/
60 exp NARCOTICS/
61 BUPRENORPHINE/
62 BUPRENORPHINE, NALOXONE DRUG COMBINATION/
63 METHADONE/
64 OXYCODONE/
65 OXYMORPHONE/
66 PENTAZOCINE/
67 TRAMADOL/
68 LEVORPHANOL/
69 (actiq or adolonta or amadol or analgesic* or anpec or ardinex or asimadolin* or astramorph or avinza or biodalgic or bpethidine or buprenorphine or carfentanil or codeine or codinovo or contramal or demerol or dicodid or dihydrocodeinone or dihydrohydroxycodeinone or dihydromorphinone or dihydrone or dilaudid or dinarkon or dolantin or dolargan or dolcontral or dolosal or dolsin or dur?gesic or dur?morph or epimorph or eucodal or exalgo or fentanest or fentanyl or fentora or fortral or hycodan or hycon or hydrocodeinonebitartrate or hydrocodone or hydrocodone* or hydromorphon or hydromorphone or hydroxyacetanilide or hydroxycodeinon or hysingla or isocodeine or isonipecain or jutadol or kadian or l dromoran or laudacon or levodroman or levodromoran or levo-dromoran or levorphan or levorphanol or lexir or lidol or lorcet or lortab or lydol or meperidine hydrochloride or methadone or morfin or morfine or morphia or morphin or morphine or morphinium or morphium or ms contin or n methylmorphine or narcotic or n-methylmorphine or nobligan or norco or numorphan or operidine or opiate or opioid* or opso or oramorph sr or oripavine or oxecta or oxiconum or oxycodeinon or oxycodone or oxycone or oxycontin or oxymorphone or palladone or pancodine or pentazocine or percocet or pethidine or phentanyl or prontofort or propoxyphene or robidone or roxicet or roxicodone or skenan or sublimaze or takadol or talwin or thebaine or theocodin or theradol or tiral or topalgic or tradol or tradolpuren or tradonal or tralgiol or trama or tramadin or tramadoc or tramadol or tramadolhameln or tramadolor or tramadorsch or tramadura or tramagetic or tramagit or tramake or tramal or tramex or tramundin or trasedal or ultram or vicodin or zamudol or zohydro or zumalgic or zydol or zytram).tw,sh,kw,kf,oa,nm.
70 or/51-70
71 ((chronic* or persistent or long-term or "long term" or prolonged or continu*) adj2 (user* or "use" or usage or pattern or consumption or therap* or event or effects)).tw,sh,kw,kf,oa.
72 PREVALENCE/
73 INCIDENCE/
74 Hazard Assessment/
75 Take a chance Factors/
76 ("long term" or prolonged or chronic*).tw,sh,kw,kf,oa.
77 ("risk factors" and ("long term" or prolonged or chronic*)).tw,sh,kw,kf,oa.
78 76 and 77
79 or/72-75
80 78 or 79 or eighty
81 50 and 71 and 81
82 limit 82 to twelvemonth="1998 -Current"
83 animals/
84 humans/
85 84 not (84 and 85)
86 83 not 86

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Pagé, One thousand., Kudrina, I., Zomahoun, H. et al. Relative frequency and take a chance factors for long-term opioid therapy following surgery and trauma amid adults: a systematic review protocol. Syst Rev 7, 97 (2018). https://doi.org/ten.1186/s13643-018-0760-three

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  • DOI : https://doi.org/10.1186/s13643-018-0760-3

Keywords

  • Systematic review protocol
  • Surgery
  • Trauma
  • Opioids
  • Take chances factors
  • Prolonged therapy
  • Long-term use

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