Review question / objective

What is the effectiveness of strategies and interventions to manage acute pain in patients who are identified as having a tolerance to or dependence on opioids?

The objective of the review is to establish the effectiveness of pharmacological and non-pharmacological strategies and interventions to manage acute pain in patients who are identified as having a tolerance to or dependence on opioids.

Background

The effective management of pain is a top priority for all patients and health care providers. It is one of the most common reasons patients seek assistance, so it is vital that the assessment and treatment of pain is effective and efficient, regardless of the patient's history.1 Inadequate treatment of pain can lead to a detrimental outcome and may also result in unnecessary suffering of the patient. In addition it can also be a cost burden on health care systems.2 In recent times a greater focus has been placed on pain as a health issue.3 In particular, the effectiveness of managing patients with pain has been complicated by the escalation of opioid prescriptions. Throughout history, opioids have been a common analgesic used for managing pain. Opioids are derived from opium; this includes morphine which is in its natural form. Oxycodone and hydromorphone for example are semisynthetic derivatives, whereas fentanyl and methadone are totally synthetic opioids.4 The main action of opioids is to cause analgesia by binding to opioid receptors (mu [[mu]], delta [[delta]], kappa [[kappa]] and opioid receptor-like) within the body. including the brain and spinal cord.5 They can cause severe side effects to people who receive them, such as sedation, respiratory depression, constipation, nausea and vomiting. Some of these side effects may be more severe than others.

Management and assessment of acute pain become more challenging when patients present to health care facilities with opioid tolerance, which may include dependence, addiction or misuse of opioids.6 In the absence of effective pain management, the patients may manifest aggression and frustration and may feel judged because of their tolerance and that their treatment is inappropriate.6 It is important to consider the various terms used for this patient group, including dependence, tolerance and addiction of opioids.7 "Tolerance is a physiological adaptation to the presence of a drug in the body such that increased doses are required to produce the pharmacological effects."1(p658) Dependence is also a physiological adaptation in response to the ongoing presence of certain drugs but is distinct in that signs of withdrawal will be present when the drug is significantly reduced or stopped.1 A patient may also be considered dependent if they satisfy the following characteristics8-10 :

* Require a dose of opioid to relieve or prevent symptoms of withdrawal

* Take the substance in increasing amounts over a lengthened period

* Unable to control the use of the substance

* Have associated cravings

* Display decreased psychosocial function

* Continued use despite risk to the patients' health.

Drug addiction is a disorder in which there is both a compulsion to take a drug to excess and loss of control to limit that intake.11 Macintyre and Schug argue that tolerance and dependence occur due to the natural progression of repeated exposure to certain medications and that this process does not indicate the person has an addiction.9 Savage et al. also agree by suggesting that dependence and tolerance occur due to the continual presence of medications in the patient's body.1 It is postulated that dependence can occur without addiction and often this is the case.9 Many patients, particularly those who suffer from chronic pain, may develop a physical dependence or tolerance to opioids but have no craving or compulsive behavior that would indicate an addiction.1 In 1964 the World Health Organization (WHO) ceased using the term "drug addiction". Instead they introduced the term "drug dependence". This was then updated in 1998 to "dependence syndrome".1 This illustrates the concerns about the historical inappropriate use of these terms, particularly "addiction". Although the primary focus of this review is in patients with opioid tolerance, the terms "dependence" and "addiction" will also be used in the search terms.

Tolerance to opioids is characterized by patients having higher than expected pain scores resulting in the patient requiring a frequent increase in dose to gain comfort.12 In recent times, the number of patients presenting to health care facilities with tolerance to opioids has increased significantly.13 Thus effective treatment of patients with acute pain becomes more challenging for clinicians.

Acute pain is classified by duration and etiology. A pain that lasts for a short time and generally occurs following a surgical procedure or trauma or even occurs from a specific condition is referred to as acute pain. Chronic pain however is characterized by prolonged duration beyond the expected healing time, with no apparent reason.14,15 Chronic pain is difficult to treat and assess. As this review will focus on the patient's acute pain, and not chronic pain that is escalating, it is important to have clear classifications of the types of pain. In some instances, patients may experience an onset of new acute pain (trauma or surgery, for example) in addition to their existing chronic pain.

Optimal treatment for acute pain is severely compromised in patients who have been taking opioids for a prolonged period.12 Use of illicit opioids of uncertain potency or use of recreational opioid drugs adds to this complexity, making titration of opioids given for acute pain relief to a therapeutic level challenging and often hard to achieve.16,17 Patients are often highly anxious in these situations because of previous experiences in hospital settings where their pain was mismanaged or where they felt that their pain relief was not adequate.10 Managing acute pain appropriately and effectively improves patient outcomes, decreases hospital admission times and is easier to provide when opioid tolerance, dependence or addiction is recognized and managed early in the patient's admission.18 It is often thought that the focus of the management of these patients should be on promoting adequate analgesia, preventing withdrawal syndromes and assisting with other psychosocial issues that the patient may or may not have.12

Initiating support early on in the patient's admission from specialist teams like acute pain services (APS) or drug and alcohol rehabilitation units (DARU) may enable the clinicians to optimize the pain treatment plan. Both of these services are used to provide specialist advice for clinicians for complex cases such as the opioid tolerant patient. The first APS was implemented in 1988 in Seattle in the United States of America (USA) which resulted in the development of guidelines for managing acute pain. Subsequently in the early 1990s these guidelines were implemented in Australia, the United Kingdom (UK) and the rest of the USA.19

An initial search of the literature for this review highlighted the issue of patients being treated inadequately through under dosing or even under estimation of the severity of the pain.10 Different opioids act on different receptors, hence the efficacy of opioids and side effects may vary depending on which receptors are activated.4 It is important to recognize that opioids are not the only treatment options available to patients suffering acute pain. Multi modal approaches using non-opioid medications are used frequently and are common methods for treating pain. In addition to non-opioid medications, non-pharmacological treatment options such as relaxation, massage and thermal therapy are commonly used as alternate and adjunctive therapies in controlling pain.20 These intervention methods will be considered for inclusion in the review.

Effective treatment outcomes of pain are usually determined by the level of comfort and function. Assessment of acute pain is made relatively easy with tools such as the numerical rating scale (NRS), the visual analogue scale (VAS) and the verbal categorical rating scale (VRS).21 Another method to measure and determine whether analgesia is adequate is by using the functional activity score (FAS). The following criteria are used as a subjective measure of analgesia effectiveness based on the patient's ability to deep breathe, cough and participate in daily living activities:

* A - no limitation of activity due to pain

* B - mild limitation

* C - severe limitation.12

Giving opioids to the extent of rendering the patient unable to function but have no or minimal pain is not therapeutic and should not be the aim.22 Functional activity scores and the ability of the patient to care for themselves, to deep breathe and cough are often used to identify sufficient analgesia.23 The maintenance of careful awareness and monitoring is essential to "balance the need for effective analgesia with patient safety".3(p46) For this reason the review will not include studies where patients are identified as palliative.

Palliative care can be described as "the care of patients with active, progressive, advanced disease where the prognosis is short and the focus of care is the quality of life".24(p. 8) The analgesic treatment, methods and aims of treating palliative patients vary greatly to those of patients who have acute pain. This may not be the aim or outcome of palliative analgesia.

A preliminary literature search was conducted using PubMed, Cumulative Index for Allied Health Library (CINAHL), Cochrane Library and the JBI Database of Systematic Reviews and Implementation Reports. No systematic reviews were identified in relation to effective pain management in opioid tolerant and/or opioid dependent patients and the challenges faced with this group.

The aim of this systematic review is therefore to identify, appraise and synthesize the available evidence to determine if there are effective methods for treating acute pain in patients who are identified as tolerant to opioids. It is expected that these treatment methods not only provide adequate analgesia with minimal adverse side effects, but also does not escalate their existing opioid use.

Inclusion criteria

Types of participants

This review will consider studies that include patients over the age of 18 years who have presented to a hospital or health care facility requiring management for acute pain, and are identified within the studies as having a dependence or tolerance to opioids. This includes but is not limited to patients with a history of:

* Dependence or tolerance of opioids

* Recreational opioid use

* Substance addiction

* Opioid replacement therapy.

Patients may have a history of chronic pain or cancer pain; however the pain being treated must also be classified as new in diagnosis and not an increase of pre-existing pain. Patients who are classified as palliative will be excluded from the systematic review.

Types of intervention(s)

This review will consider studies that focus on interventions and strategies aimed at effectively managing acute pain in opioid tolerant patients. Interventions and strategies may include but are not limited to:

* Types/combinations of analgesia which may include: morphine, semisynthetic derivatives such as oxycodone and hydromorphone and totally synthetic derivatives such as fentanyl and methadone. Combinations of opioids and non-opioids; non-opioids will also be considered

* Patient controlled analgesia (PCA)

* Non-pharmaceutical methods of analgesia such as massage, exercise, relaxation techniques and thermal therapy

* Acute pain services

* Drug and alcohol rehabilitation services.

Interventions will be compared with standard acute care management practices.

Types of outcomes

This systematic review will look at studies that evaluate outcomes including but not limited to the following:

Primary outcomes

* Pain scores

- Numerical rating scales (NRS)

- Visual analogue scales (VRS)

* Functional assessment score

- Functional activity score (FAS).

Secondary outcomes

* Signs of withdrawal during treatment of their acute pain

- o Sweating, abdominal cramping, increase in pain above the expected level

* Length of stay.

Types of studies

The review will consider both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental studies, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion. The quantitative component of the review will also consider descriptive epidemiological study designs including case series, individual case reports and descriptive cross sectional studies for inclusion.

In the absence of research studies, other text such as opinion papers and reports will be considered. The textual component of the review will consider expert opinion, discussion papers, position papers and other text.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken, followed by an analysis of the text words contained in the title and abstract and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference lists of all identified reports and articles will be searched for additional studies. Only studies published in English will be considered for inclusion in this review, as there are no resources for translation of non-English language papers. Studies from 1988 will be included due to the recognition and implementation of APS and guideline development surrounding acute pain from this time.

The databases to be searched include:

PubMed

CINAHL

Scopus

EMBASE

Cochrane Central Register of Controlled Trials

ISI Current Contents.

The search for unpublished studies will include:

Index to Thesis

ProQuest Dissertations and Theses: Health and Medicine

Google Scholar.

Initial keywords to be used will be:

acute pain, effective management, opioid tolerant, opioid dependent, addiction, chronic pain, non- cancer pain, dependence syndrome, drug dependence.

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review, using the standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Textual papers selected for retrieval will be assessed by two independent reviewers for authenticity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Narrative, Opinion and Text Assessment and Review Instrument (JBI-NOTARI) (Appendix I).

Data extraction

Data will be extracted using the JBI-MAStARI data extraction instruments, the JBI-MAStARI data extraction form for systematic review of experimental/observational studies (Appendix II). In the event of missing data, the authors of this systematic review will endeavor to contact the author(s) of the paper in question to seek clarification.

Textual data will be extracted from papers included in the review using the standardized data extraction tool from JBI-NOTARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.

Data synthesis

Where possible, quantitative research study results will be pooled in statistical meta-analysis using review manager software JBI-MAStARI software. Where possible, sub group analysis will be performed on heterogeneous groups such as different population groups or models of care. Odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed using the standard Chi-square. Where statistical pooling is not possible the findings will be presented in narrative form.

Conflicts of interest

The authors declare that there are no conflicts of interest.

References