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Guideline Summary
Guideline Title
Canadian guideline for safe and effective use of opioids for chronic non-cancer pain.
Bibliographic Source(s)
National Opioid Use Guideline Group (NOUGG). Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part A: executive summary and background. Hamilton (Ontario): National Opioid Use Guideline Group (NOUGG); 2010 Apr 30. 38 p.

National Opioid Use Guideline Group (NOUGG). Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part B: recommendations for practice. Hamilton (Ontario): National Opioid Use Guideline Group (NOUGG); 2010 Apr 30. 126 p. [287 references]
Guideline Status

This is the current release of the guideline.

FDA Warning/Regulatory Alert

Note from the National Guideline Clearinghouse: This guideline references a drug(s) for which important revised regulatory and/or warning information has been released.

Drug Withdrawal

  • November 19, 2010 – Propoxyphene (Darvon, Darvocet) External Web Site Policy: The U.S. Food and Drug Administration notified healthcare professionals that Xanodyne Pharmaceuticals has agreed to withdraw propoxyphene, an opioid pain reliever used to treat mild to moderate pain, from the U.S. market at the request of the FDA, due to new data showing that the drug can cause serious toxicity to the heart, even when used at therapeutic doses.

Scope

Disease/Condition(s)

Chronic non-cancer pain

Guideline Category
Assessment of Therapeutic Effectiveness
Counseling
Diagnosis
Evaluation
Management
Risk Assessment
Screening
Treatment
Clinical Specialty
Anesthesiology
Family Practice
Geriatrics
Internal Medicine
Pharmacology
Physical Medicine and Rehabilitation
Intended Users
Advanced Practice Nurses
Dentists
Nurses
Pharmacists
Physician Assistants
Physicians
Psychologists/Non-physician Behavioral Health Clinicians
Substance Use Disorders Treatment Providers
Guideline Objective(s)

To assist physicians with decisions to initiate appropriate trials of opioid therapy for patients with chronic non-cancer pain, to monitor long-term opioid therapy, and to detect and respond appropriately to situations of opioid misuse including addiction

Target Population

Individuals with chronic non-cancer pain

Interventions and Practices Considered
  1. Documentation of patient's pain condition, medical condition, psychosocial history, psychiatric status, and substance use history
  2. Screening for risk of opioid addiction
  3. Urine drug screening
  4. Counseling patients on benefits and risks of opioid therapy
  5. Titrating benzodiazepines before initiating opioid therapy, especially in the elderly
  6. Conducting an opioid trial by starting with low doses and titrating slowly to optimal dose
  7. Consideration of safety and risk for misuse when conducting an opioid trial
  8. Monitoring long-term opioid therapy for effectiveness, adverse effects, complications, and aberrant drug-related behavior
  9. Assessment of ability to drive safely during long-term opioid therapy
  10. Communicating and clarifying roles of primary-care physicians and consultants during long-term opioid therapy
  11. Special considerations for opioid use in the elderly, adolescents, pregnant patients, and patients with psychiatric diagnoses
  12. Managing opioid misuse and addiction
Major Outcomes Considered
  • Prevalence and risk of opioid addiction
  • Sensitivity and specificity of risk assessment tests
  • Rates of opioid misuse
  • Incidence of opioid-related aberrant behaviors
  • Effectiveness of opioids
  • Required dosage
  • Pain relief and functional outcomes
  • Adverse events, toxicity, and complications of opioids
  • Rates of utilization of opioid therapy
  • Compliance in opioid use
  • Risk of overdose
  • Mortality

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Literature Search Methods

Development of this Canadian Guideline relied on the 2006 meta-analysis by Furlan et al. "Opioids for chronic non-cancer pain: a meta-analysis of effectiveness and side effects." In addition, three new literature searches were completed:

  • Search One: Search for randomized controlled trials published since May 2006 to update the Furlan meta-analysis.
  • Search Two: Search for additional literature (multiple designs) that answered questions about the treatment of chronic non-cancer pain (CNCP) with opioids and managing the patient with problematic opioid use.
  • Search Three: Search for additional literature (multiple designs) that answered questions about long-term outcomes of opioid use.

Description of Literature Search One

For details of the original Furlan meta-analysis search, see http://www.cmaj.ca/cgi/data/174/11/1589/DC1/1 External Web Site Policy and http://www.cmaj.ca/cgi/data/174/11/1589/DC1/10 External Web Site Policy.

The following bibliographic data sources were used to update the review to July 2009:

  • Cochrane Central Register of Controlled Trials (CENTRAL) 2009
  • MEDLINE (OVID) from 2005 to July 2009 (same strategy as the 2006 review)
  • EMBASE from 2005 to July 2009 (same strategy as the 2006 review)
  • Reference lists of retrieved articles
  • Articles forwarded by the National Advisory Panel

Search strategies for MEDLINE and EMBASE are available (see Appendix A-4 of the original guideline document). A research librarian ran the electronic searches and coordinated the data entry into Reference Manager® 11, removing all duplicates.

Relevance Screening for Search One

Three College of Physicians and Surgeons of Ontario (CPSO) research associates independently reviewed the titles and abstracts using the following criteria: 1) not a letter, editorial, or short commentary (usually less than three pages in length); 2) focus of the article is not dealing with surgical pain, 3) article is not dealing with cancer pain, 4) population studied had chronic non-cancer pain, and 5) focus is on opioids. Studies that passed the relevance screen were forwarded to the Research Group for inclusion/exclusion criteria screening.

Inclusion/Exclusion Screening for Search One

Text of full articles was obtained for studies that passed the relevance screening. Two Research Group members independently reviewed these studies and applied inclusion/exclusion criteria as described in section 10.1.2 of Part A of the original guideline document. For Search One, two reviewers reviewed selected titles, abstracts, and full texts and determined the articles for inclusion. If consensus could not be achieved, a third reviewer was consulted. On some occasions, authors of the randomized trials were contacted to obtain more details that were not reported in the publication.

Description of Literature Search Two and Search Three

Search Two was conducted to find articles that could be useful in drafting the recommendations on the treatment of CNCP with opioids and managing the patient with problematic opioid use. Search Three was conducted to understand the effects of prolonged opioid use. These searches were not limited to randomized controlled trials. (See Appendices A-5 and A-4 of the original guideline document.)

The following bibliographic data sources were used:

  • CENTRAL 2009
  • MEDLINE (OVID) from 1950 to July 2009
  • EMBASE from 1982 to July 2009
  • Reference lists of retrieved articles
  • Articles forwarded by the National Advisory Panel

Relevance Screen for Search Two and Search Three

A CPSO research associate independently reviewed the titles and abstracts using the following criteria: 1) not a letter, editorial, or short commentary (usually less than three pages in length), 2) population studied has chronic non-cancer pain, 3) focus on opioids, and 4) focus on addiction.

Inclusion/Exclusion Screen for Search Two and Search Three

From the titles and abstracts that passed the relevance screen, text of full articles was obtained, and two out of four Research Group members applied inclusion criteria described in section 10.2.2 in Part A of the original guideline document. For Searches Two and Three, four reviewers worked in pairs to select articles for inclusion. When in doubt, a third reviewer from the other pair was consulted.

Additional Strategies for Search Two and Search Three

All included and excluded studies from Search One were also evaluated by two reviewers against the list of useful topics developed for inclusion of studies in the Searches Two and Three.

Number of Source Documents

184 studies met inclusion criteria.

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Canadian Task Force on Preventive Health Care (CTFPHC) Evidence Grading System

I. Evidence from randomized controlled trials.

II – 1. Evidence from controlled trial(s) without randomization.

II – 2. Evidence from cohort or case-control analytic studies, preferably from more than one centre or research group.

II – 3. Evidence from comparisons between times or places with or without the intervention; dramatic results from uncontrolled studies could be included here.

III. Opinions of respected authorities, based on clinical experience; descriptive studies or reports of expert committees.

Methods Used to Analyze the Evidence
Meta-Analysis
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

The Research Group provided methodological and clinical expertise in the area of chronic pain and addiction medicine. They summarized evidence from the selected studies.

Methodological Quality Screen for Search One

Two Research Group members completed an independent appraisal of methodological quality on studies admitted after inclusion/exclusion screening. Where needed, they reached consensus through discussion. Reviewers were not blinded with respect to authors, institution, and journal because they were familiar with the literature. In cases of disagreement, a third reviewer was consulted. Each study was scored from 0 to 5 with the instrument developed by Jadad and colleagues. The instrument includes three questions about randomization methods, double-blinding, and number of withdrawals. Studies scoring 3, 4, or 5 were considered to be of high quality; scoring 0, 1, or 2, of low quality. Study scores were recorded in a Microsoft Excel® spreadsheet (see Appendix B-13 in the original guideline document).

Data Extraction and Synthesis for Search One

Research Group members extracted the data from the high quality studies using Microsoft Excel®. Meta-analyses and meta-regression were conducted using Comprehensive Meta-Analysis© software, with calculations of effect sizes for pain relief and functional outcomes (see section 10.1.4 of Part A of the original guideline document for details on effect sizes).

For side effects, all meta-analyses were done using RevMan 52 using risk differences. Statistical heterogeneity was tested by Q test (chi-square) reported as I2 (higher values indicate higher heterogeneity).

All meta-analyses were conducted using a random effects model. Sub-groups were decided a priori to assess the variations in effect sizes. Clinical significance of side effects was considered when the incidence was 10% or higher in the opioid or reference group.

The evidence-grading system was adapted from the Canadian Task Force on Preventive Health Care (see the "Rating Scheme for Strength of Evidence" field).

Methodological Quality Screen for Searches Two and Three

Observational studies were not assessed for methodological quality due to lack of resources to fund experts in epidemiological methods necessary to complete the more complex and subjective review required.

Limitations

The literature searches for observational studies used broad terms and might have missed relevant studies. Of the 184 studies used to support the recommendations, only 62 were randomized trials; the remaining were observational studies. Given that the quality of the observational studies was not formally assessed, the grading system of the Canadian Task Force on Preventive Health Care (CTFPHC) was adapted.

Methods Used to Formulate the Recommendations
Expert Consensus (Delphi)
Description of Methods Used to Formulate the Recommendations

Canadian Guideline Inception

Canadian medical regulatory authorities (MRAs) created the National Opioid Use Guideline Group (NOUGG) to oversee the development and implementation of a guideline for safe and effective opioid use for chronic non-cancer pain (CNCP). NOUGG is a unique collaboration of MRAs with the active support and/or representation from all provincial Colleges, Yukon Medical Council, Government of Nunavut, and the Federation of Medical Regulatory Authorities of Canada (FMRAC). Two NOUGG co-chairs convened monthly meetings to facilitate and oversee the development and implementation.

Players Involved in Development

Three groups were involved in developing the Canadian Guideline: NOUGG, the Research Group, and the National Advisory Panel (NAP).

National Opioid Use Guideline Group

NOUGG is a task-specific group convened with the assistance and support of FMRAC. It was formed in November 2007 with support and/or representation from all provincial medical regulatory authorities and subsequently the Medical Council of Yukon and the Government of Nunavut. NOUGG's role was to oversee the development and implementation of a guideline. The regulatory bodies and FMRAC appointed the Group members, and two co-chairs were selected.

Research Group

The Research group comprised six members: a physician/epidemiologist, four physician-researchers, and a research librarian. It was responsible for the literature review, quality appraisal, evidence summary, and the first draft of recommendations for practice. Two physician-researchers were previous members of the College of Physicians and Surgeons of Ontario task force responsible for the predecessor guideline, "Evidence-based Recommendations for Medical Management of Chronic Non-Malignant Pain." The physician/epidemiologist, research librarian, and one physician-researcher were secured from the Institute for Work & Health, which has a systematic review program of research that includes the Cochrane Back Review Group. NOUGG approached Institute for Work & Health, and they agreed to contribute their expertise to oversee the systematic review process from literature search to data extraction.

National Advisory Panel

The NAP is a group of 49 individuals from across Canada who were invited in September 2008 to participate in the Canadian Guideline development. They were identified by NOUGG members, using common selection criteria to ensure the group included a wide cross-section of medical expertise, patient perspectives, other healthcare providers, and geographic representation. NAP's role was to review draft materials prepared by the Research Group and, using an electronic, blinded Modified Delphi technique, reach consensus on recommendations for practice. In addition, NAP members provided extensive narrative comment that was organized by theme and used in iterative revision.

Recommendation Development Process

The Research Group provided methodological and clinical expertise in the area of chronic pain and addiction medicine. They summarized evidence from the studies and drafted 49 initial recommendations that each included a discussion and related evidence. An iterative course of action ensued, using a Modified Delphi technique with the NAP, to produce final recommendations. NAP member identities were blind to the Research Group and each other until the last round of review.

NAP received material via email and responded using an on-line survey tool to rate their opinion on relevance, feasibility, clarity, and their degree of agreement with each recommendation. They also provided open-ended narrative comments. See section 11 of Part A of the original guideline document for details on the NAP Consultation process.

Consensus was defined as 80% of NAP members supporting a recommendation. Recommendations that did not receive this level of consensus were revised using feedback provided by NAP and re-rated in the next round. With each round of review, each NAP member received a complete transcript of all written comments made by NAP in the previous round.

While participation rates declined as the Modified Delphi progressed, the portion of NAP members involved remained high throughout, as summarized in Table A-10.3.1 in the original guideline document. A drop in the last two rounds could have been due to Panel fatigue, or related to the H1N1 pandemic occurring in Canada at the time. Consensus on recommendations resulted after four rounds of electronic review and rating, culminating with a final telephone and web-assisted meeting.

Recommendation Grading

The evidence-grading system was adapted from the Canadian Task Force on Preventive Health Care (CTFPHC) (Woolf 1990). A single recommendation statement can be supported by one, two, or three different grades of evidence (see the "Rating Scheme for the Strength of Recommendations" field).

Each recommendation includes a key word, recommendation statement, discussion, and evidence summary. References may be provided in both the discussion and evidence summary. There are two types of references used: those that 1) provide direct or indirect support for the recommendation statement and 2) provide contextual information.

If a reference is supported directly, the recommendation statement was graded consistent with the study design of that reference, i.e., "A" or "B." If a reference supported indirectly, the recommendation statement was graded to reflect the primary source driving the recommendation.

  • Example 1: A randomized controlled trial (RCT) informed the recommendation but the recommendation is graded "B" or "C" (rather than "A") — this is because the recommendation statement is not directly extracted from the main hypothesis of the RCT.
  • Example 2: References are graded "B" in the evidence summary, but the recommendation statement is graded "C" — this is because expert opinion from NAP was the predominant driver of the recommendation statement, even though some of the recommendation's concepts were backed by the studies mentioned in the evidence summary.
  • Example 3: A reference conflicts with the recommendation, and the recommendation statement is graded "C" — this reflects NAP expert opinion assessing the evidence as weak or not generalizable.

Limitations

The Canadian Guideline is constrained by the paucity of evidence to support most of the topics where recommendations for practice were considered necessary and relevant. This required a heavy reliance on the opinion and expertise of the NAP to develop recommendations.

Rating Scheme for the Strength of the Recommendations

Canadian Guideline Recommendation Grading

Grade A: Recommendations are supported by evidence from randomized controlled trials.

Grade B: Recommendations are supported by:

  • Evidence from controlled trial(s) without randomization, or
  • Evidence from cohort or case-control analytic studies, preferably from more than one centre or research group, or
  • Evidence from comparisons between times or places with or without the intervention; dramatic results in uncontrolled experiments could be included here.

Grade C: Recommendations are supported by consensus opinion of the National Advisory Panel.

Cost Analysis

Published cost analyses were reviewed.

Method of Guideline Validation
Comparison with Guidelines from Other Groups
Peer Review
Description of Method of Guideline Validation

National Advisory Panel (NAP) Review

The NAP is a group of 49 individuals from across Canada who were invited in September 2008 to participate in the Canadian Guideline development. NAP members provided extensive narrative comment that was organized by theme and used in iterative revision. See Section A-11 of the original guideline document for a more detailed explanation of the NAP review process.

Comparison with Other Guidelines

There are numerous other clinical practice guidelines that address the management of chronic non-cancer pain (CNCP) with opioids. In preparation for developing the Canadian Guideline, searches in MEDLINE and www.guideline.gov External Web Site Policy up to February 2009 were conducted with 15 relevant guidelines selected for a detailed evaluation. This evaluation determined that most guidelines were either focused on a specific health problem (fibromyalgia, neuropathic pain, osteoarthritis, low-back pain) or were out-of-date.

Three current guidelines are similar to the Canadian Guideline in terms of scope, population, development, sponsorship, recommendations, and presentation.

When work began on the Canadian Guideline, only one of these was published — the American Society of Interventional Pain Physicians guideline, originally published in 2006 (Trescot 2006) and updated in 2008 (Trescot 2008): however, the target audience was interventional pain specialists.

In 2009, when the Canadian Guideline development was well underway, two other similar guidelines were published. The guideline of the American Pain Society/American Academy of Pain Medicine (Chou 2009) has additional recommendations not included in the Canadian Guideline: treatment of breakthrough pain, management of side effects, selection of short-acting versus long-acting preparations, special issues with methadone, and awareness of state laws. The Utah Department of Health guideline (Utah Department of Health 2009) is in fact a compilation of recommendations from six other guidelines on the management of CNCP with opioids. There are no major discrepancies between the Utah and the Canadian Guideline.

Recommendations

Major Recommendations

Grades of recommendation (A-C) are defined at the end of the "Major Recommendations" field.

Cluster 1: Deciding to Initiate Opioid Therapy

R01 Before initiating opioid therapy, ensure comprehensive documentation of the patient's pain condition, general medical condition, and psychosocial history (Grade C), psychiatric status, and substance use history (Grade B).

R02 Before initiating opioid therapy, consider using a screening tool to determine the patient's risk for opioid addiction (Grade B).

R03 When using urine drug screening (UDS) to establish a baseline measure of risk or to monitor compliance, be aware of benefits and limitations, appropriate test ordering and interpretation, and have a plan to use results (Grade C).

R04 Before initiating opioid therapy, consider the evidence related to effectiveness in patients with chronic non-cancer pain (Grade A).

R05 Before initiating opioid therapy, ensure informed consent by explaining potential benefits, adverse effects, complications and risks (Grade B). A treatment agreement may be helpful, particularly for patients not well known to the physician or at higher risk for opioid misuse (Grade C).

R06 For patients taking benzodiazepines, particularly for elderly patients, consider a trial of tapering (Grade B). If a trial of tapering is not indicated or is unsuccessful, opioids should be titrated more slowly and at lower doses (Grade C).

Cluster 2: Conducting an Opioid Trial

R07 During dosage titration in a trial of opioid therapy, advise the patient to avoid driving a motor vehicle until a stable dosage is established and it is certain the opioid does not cause sedation (Grade C); and when taking opioids with alcohol, benzodiazepines, or other sedating drugs (Grade B).

R08 During an opioid trial, select the most appropriate opioid for trial therapy using a stepped approach, and consider safety (Grade C).

R09 When conducting a trial of opioid therapy, start with a low dosage, increase dosage gradually and monitor opioid effectiveness until optimal dose is attained (Grade C).

R10 Chronic non-cancer pain (CNCP) can be managed effectively in most patients with dosages at or below 200 mg/day of morphine or equivalent (Grade A). Consideration of a higher dosage requires careful reassessment of the pain and of risk for misuse, and frequent monitoring with evidence of improved patient outcomes (Grade C).

R11 When initiating a trial of opioid therapy for patients at higher risk for misuse, prescribe only for well-defined somatic or neuropathic pain conditions (Grade A), start with lower doses and titrate in small-dose increments (Grade B), and monitor closely for signs of aberrant drug-related behaviors (Grade C).

Cluster 3: Monitoring Long-Term Opioid Therapy (LTOT)

R12 When monitoring a patient on long-term therapy, ask about and observe for opioid effectiveness, adverse effects or medical complications, and aberrant drug-related behaviours (Grade C).

R13 For patients experiencing unacceptable adverse effects or insufficient opioid effectiveness from one particular opioid, try prescribing a different opioid or discontinuing therapy (Grade B).

R14 When assessing safety to drive in patients on LTOT, consider factors that could impair cognition and psychomotor ability, such as a consistently severe pain rating, disordered sleep, and concomitant medications that increase sedation (Grade C).

R15 For patients receiving opioids for a prolonged period who may not have had an appropriate trial of therapy, take steps to ensure that long-term therapy is warranted and dose is optimal (Grade C).

R16 When referring patients for consultation, communicate and clarify roles and expectations between primary-care physicians and consultants for continuity of care and for effective and safe use of opioids (Grade C).

Cluster 4: Treating Specific Populations with Long-Term Opioid Therapy

R17 Opioid therapy for elderly patients can be safe and effective (Grade B) with appropriate precautions, including lower starting doses, slower titration, longer dosing interval, more frequent monitoring, and tapering of benzodiazepines (Grade C).

R18 Opioids present hazards for adolescents (Grade B). A trial of opioid therapy may be considered for adolescent patients with well-defined somatic or neuropathic pain conditions when non-opioid alternatives have failed, risk of opioid misuse is assessed as low, close monitoring is available, and consultation, if feasible, is included in the treatment plan (Grade C).

R19 Pregnant patients taking long-term opioid therapy should be tapered to the lowest effective dose slowly enough to avoid withdrawal symptoms, and then therapy should be discontinued if possible (Grade B).

R20 Patients with a psychiatric diagnosis are at greater risk for adverse effects from opioid treatment. Usually in these patients, opioids should be reserved for well-defined somatic or neuropathic pain conditions. Titrate more slowly and monitor closely; seek consultation where feasible (Grade B).

Cluster 5: Managing Opioid Misuse and Addiction in CNCP Patients

R21 For patients with CNCP who are addicted to opioids, three treatment options should be considered: methadone or buprenorphine treatment (Grade A), structured opioid therapy (Grade B), or abstinence-based treatment (Grade C). Consultation or shared care, where available, can assist in selecting and implementing the best treatment option (Grade C).

R22 To reduce prescription fraud, physicians should take precautions when issuing prescriptions and work collaboratively with pharmacists (Grade C).

R23 Be prepared with an approach for dealing with patients who disagree with their opioid prescription or exhibit unacceptable behaviour (Grade C).

R24 Acute or urgent health care facilities should develop policies to provide guidance on prescribing opioids for chronic pain to avoid contributing to opioid misuse or diversion (Grade C).

Definitions:

Canadian Guideline Recommendation Grading

Grade A: Recommendations are supported by evidence from randomized controlled trials.

Grade B: Recommendations are supported by:

  • Evidence from controlled trial(s) without randomization, or
  • Evidence from cohort or case-control analytic studies, preferably from more than one centre or research group, or
  • Evidence from comparisons between times or places with or without the intervention; dramatic results in uncontrolled experiments could be included here.

Grade C: Recommendations are supported by consensus opinion of the National Advisory Panel.

Clinical Algorithm(s)

The original guideline document contains a "Recommendations Roadmap" clinical algorithm.

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Safe and effective use of opioids for chronic non-cancer pain

Potential Harms
  • The most common adverse effects of opioids include nausea, constipation, somnolence/drowsiness, dizziness/vertigo, dry-skin/itching/pruritus, and vomiting. The data for these adverse effects shown in Table B-5.1 in the original guideline document are from randomized trials, excluding enrichment design trials, and results show a clinically important difference (Diff>10%) and are statistically significant (P<0.05).
  • Adverse effects where the difference was not clinically important (Diff <10%) and/or not statistically significant (P≥0.05) include dry-mouth, headache, sexual dysfunction, hot flushes, loss of appetite, abdominal pain, fatigue, sleeplessness/insomnia, sweating, blurred vision/confusion, muscle contractions, diarrhea, ataxia, edema, difficulty urinating, restless legs, application site reaction, heartburn, anxiety, weakness.
  • Information about medical complications associated with long-term opioid therapy (LTOT) is reported in nonrandomized trials (randomized controlled trials are short-term: 3 months). There is no evidence regarding the frequency of medical complications, the relationship between length of time on opioids and occurrence of medical complications, or whether the complications are permanent or transient. Patients should be informed about potential long-term use medical complications such as neuroendocrine (hypogonadism and amenorrhea), sleep apnea (central sleep apnea or worsening of obstructive sleep apnea), and opioid-induced hyperalgesia. See Table B-5.2 and notes, the Discussion, and the Summary of Peer-Reviewed Evidence for recommendation 5 in Part B of the original guideline document for additional details on medical complications associated with LTOT.
  • There is evidence that benzodiazepines increase opioid toxicity and risk of overdose. See the Discussion and the Summary of Peer-Reviewed Evidence for recommendation 6 in Part B of the original guideline document for additional detail.
  • Patients who undergo a significant increase in the dose of narcotic experience significant cognitive impairment. In a population receiving both narcotics and benzodiazepines, the cognitive impairment noted was found to be more likely due to benzodiazepines than to narcotics. See the Discussion and the Summary of Peer-Reviewed Evidence for recommendation 7 in Part B of the original guideline document for additional detail.
  • Safety issues for specific agents (see Table B-8.2 and the Supporting Evidence for recommendation 8 in Part B of the original guideline document for additional detail):
    • Morphine can cause toxicity in patients with renal dysfunction.
    • There is evidence that oxycodone and hydromorphone have a higher abuse liability than other opioids. This is based on phase-2 studies, patient surveys, and studies of treatment programs.
    • Fentanyl can cause significant cognitive impairment in non-tolerant opioid patients. Fentanyl has contributed to numerous overdose deaths. Chronic non-cancer pain (CNCP) patients on codeine are at risk for overdose when switched to fentanyl.
    • Methadone has been associated with numerous overdose deaths in pain patients.
    • Repeated parenteral doses of meperidine are associated with adverse neurological events.
    • Acetaminophen (in acetaminophen-opioid combinations) is a common cause of hepatotoxicity; risk increases with alcohol use.
    • Controlled release opioids are available in high-dose formulations which increase their risk of abuse and overdose.
  • Physicians' prescriptions are a significant source of abused opioids. See the Summary of Peer-Reviewed Evidence for recommendation 11 in the original guideline document for discussion of the risk of opioid misuse.
  • Several pharmacokinetic factors put the elderly at higher risk for opioid overdose than younger patients, including lower serum binding, lower stroke volume (slows liver metabolism), and greater sensitivity to the psychoactive and respiratory effects of opioids.
  • A high proportion of elderly patients on opioids are also on benzodiazepines and other psychotropic medications, increasing the risk of sedation. See the Discussion and the Summary of Peer-Reviewed Evidence for recommendation 17 in Part B of the original guideline document for additional detail.
  • Non-medical use of opioids is common among adolescents, and may be a risk factor for future opioid addiction. See the Discussion and the Summary of Peer-Reviewed Evidence for recommendation 18 for additional detail.
  • Opioid use during pregnancy (see Summary of Peer-Reviewed Evidence for recommendation 19 in the original guideline document for additional details):
    • There is evidence that regular, scheduled opioid use for CNCP during pregnancy is associated with a neonatal abstinence syndrome.
    • Codeine use in breast-feeding women has been associated with fatal opioid toxicity in the neonate.
    • Pregnant women addicted to opioids have improved obstetrical and neonatal outcomes when on methadone treatment.
  • Increased risks with co-morbid psychiatric conditions (see Summary of Peer-Reviewed Evidence for recommendation 20 in the original guideline document for additional detail):
    • Patients on chronic opioid therapy have a higher prevalence of depression and other psychiatric conditions than the general population.
    • Patients on LTOT who have psychiatric disorders are more at risk for substance misuse and dependence than patients on LTOT without psychiatric disorders.
    • Patients on LTOT are at higher risk for completed suicide.

Contraindications

Contraindications

Morphine is contraindicated in renal insufficiency.

Qualifying Statements

Qualifying Statements
  • While every effort has been made to ensure the accuracy of the contents at the time of publication, the National Opioid Use Guideline Group (NOUGG) does not give any guarantee as to the accuracy of the information contained nor accept any liability, with respect to loss, damage, injury or expense arising from any errors or omissions in the contents of this work. Reference throughout the document to specific pharmaceutical products as examples does not imply endorsement of any of these products.
  • The Canadian Guideline is intended to assist physicians with decisions to initiate appropriate trials of opioid therapy for patients with chronic non-cancer pain (CNCP), to monitor long-term opioid therapy, and to detect and respond appropriately to situations of opioid misuse including addiction. It was not designed to serve as a standard of care nor as a training manual.
  • Limitations of the Canadian Guideline:
    • The Canadian Guideline is constrained by the paucity of evidence to support most of the topics where recommendations for practice were considered necessary and relevant. This required a heavy reliance on the opinion and expertise of the National Advisory Panel to develop recommendations. The literature searches for observational studies used broad terms and might have missed relevant studies.
    • Functional outcomes studied were predominantly "activity of daily living" and "quality of life" — other important outcomes such as return to work, productivity, and cognitive impairment were rarely reported. Potential long-term complications of opioid use (hypogonadism, opioid-induced hyperalgesia, addiction) cannot be ruled out even if the recommendations are strictly followed.
    • The guideline addresses only one modality for managing CNCP — opioid therapy, and it does not discuss or provide guidance about selecting other options.
    • An attempt was made to maintain national perspective but the National Advisory Panel pointed out numerous instances where recommendations were dependent on access to resources not available in all parts of Canada (e.g., access to pain or addiction specialists, multi-disciplinary pain management teams, prescription monitoring databases).
    • In spite of its narrow focus, the Canadian Guideline is a lengthy and detailed document, and will need to be translated into feasible and practical tools for day-to-day use by busy practitioners. Screening tools, e.g., the Opioid Risk Tool, are only valid when the patient's reporting is accurate.
    • The group overseeing guideline development (the National Opioid Use Guideline Group) represents medical regulatory authorities, and this could create concern that the Canadian Guideline will be used as a standard of practice rather than for its intended purpose as advice to assist physicians.

Implementation of the Guideline

Description of Implementation Strategy

Implementation to Practice

From its inception, the National Opioid Use Guideline Group (NOUGG) viewed developing the guideline as only the first step, and articulated an additional goal: Develop and implement a knowledge transfer strategy that ensures the guideline moves into practice as a useful decision-making tool for physicians treating patients with chronic non-cancer pain.

An effective implementation plan would ensure that clinicians can easily apply the recommendations in demanding day-to-day practice environments. NOUGG created the National Faculty to guide and assist with moving the recommendations to practice. Individuals were selected from across the country, based on matching one or more of the following criteria:

  • Involvement in physician, inter-professional, or patient education
  • Focus/interest in the topic of chronic pain and opioid use for chronic non-cancer pain (CNCP)
  • Contribution of relevant materials, teaching resources, or expertise (e.g., continuing professional development, knowledge transfer, guideline implementation)
  • Connection to some knowledge-to-practice infrastructure, and
  • Canadian Guideline "ambassador" potential

At the June 2009 inaugural meeting, participants (representing nine provinces, one territory, and eight national associations) agreed on a set of goals:

  1. Define targeted outcomes for implementation to promote safe and effective use of opioids for CNCP
  2. Develop an implementation strategy considering multiple audiences
  3. Contribute to creating a funding plan for implementing to practice, and
  4. Define strategies to evaluate impact of the Canadian Guideline

The Michael G. DeGroote National Pain Centre (along with ongoing responsibility for the Canadian Guideline) will coordinate continuing activities initiated by the National Faculty to ensure the Canadian Guideline improves practice and patient outcomes.

Implementation Tools
Chart Documentation/Checklists/Forms
Clinical Algorithm
Foreign Language Translations
Patient Resources
Resources
Tool Kits
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Living with Illness
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness
Safety

Identifying Information and Availability

Bibliographic Source(s)
National Opioid Use Guideline Group (NOUGG). Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part A: executive summary and background. Hamilton (Ontario): National Opioid Use Guideline Group (NOUGG); 2010 Apr 30. 38 p.

National Opioid Use Guideline Group (NOUGG). Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part B: recommendations for practice. Hamilton (Ontario): National Opioid Use Guideline Group (NOUGG); 2010 Apr 30. 126 p. [287 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Apr 30
Guideline Developer(s)
National Opioid Use Guideline Group - Independent Expert Panel
Guideline Developer Comment

National Opioid Use Guideline Group (NOUGG) members: Federation of Medical Regulatory Authorities of Canada, College of Physicians & Surgeons of British Columbia, College of Physicians & Surgeons of Alberta, College of Physicians and Surgeons of Saskatchewan, College of Physicians & Surgeons of Manitoba, College of Physicians and Surgeons of Ontario, Collège des médecins du Québec, College of Physicians and Surgeons of New Brunswick, College of Physicians and Surgeons of Nova Scotia, College of Physicians and Surgeons of Prince Edward Island, College of Physicians and Surgeons of Newfoundland and Labrador, Government of Nunavut, Yukon Medical Council

Source(s) of Funding

All funding to support the development of the Canadian Guideline was provided by Canadian medical regulatory authorities and the Federation of Medical Regulatory Authorities of Canada. The Canadian Institute of Health Research (CIHR) provided a one-time grant to support two meetings of the National Faculty who are focused on implementation. The project received no funding from commercial organizations.

Guideline Committee

National Opioid Use Guideline Group (NOUGG), the Research Group, and the National Advisory Panel (NAP)

Composition of Group That Authored the Guideline

Research Group Members: Dr. Andrea Furlan, Dr. Meldon Kahan, Dr. Angela Mailis-Gagnon, Ms Emma Irvin, Dr. Luis Chaparro, Dr. Anita Srivastava

Financial Disclosures/Conflicts of Interest

See Appendix A-7 of the original guideline document for a copy of the competing interest disclosure form and Appendix A-2 of the original guideline document for Research Group members and their declared competing interests. See Appendix A-3 of the original guideline document for National Advisory Panel members and their declared competing interests.

Guideline Status

This is the current release of the guideline.

Guideline Availability
Availability of Companion Documents

The following are available:

In addition, a variety of tools, including tools for assessing alcohol and other substance abuse (CAGE questionnaire) or opioid risk, a sample opioid medication agreement, an example for documenting opioid therapy, the Brief Pain Inventory, the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-P) and Current Opioid Misuse Measure (COMM), information on opioid tapering, and benzodiazepine tapering, are available in the appendices of the original guideline document External Web Site Policy.

Patient Resources

Appendix B-4 in the original guideline document External Web Site Policy contains opioid information for patients.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC Status

This NGC summary was completed by ECRI Institute on May 4, 2012. The information was verified by the guideline developer on June 5, 2012. This summary was updated by ECRI Institute on October 28, 2013 following the U.S. Food and Drug Administration advisory on Acetaminophen.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Disclaimer

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The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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