Abstract
Background: The opioid epidemic is one of the biggest public health crises of our time, and overprescribing of opioids after surgery has the potential to lead to long-term use. The purpose of this review was to identify and summarize the available evidence on interventions aimed at reducing opioid use after orthopedic surgery.
Methods: We searched CENTRAL, Embase and Medline from inception until August 2019 for studies comparing interventions aimed at reducing opioid use after orthopedic surgery to a control group. We recorded demographic data and data on intervention success, and recorded or calculated percent opioid reduction compared to control.
Results: We included 141 studies (20 963 patients) in the review, of which 113 (80.1%) were randomized controlled trials (RCTs), 6 (4.3%) were prospective cohort studies, 16 (11.4%) were retrospective cohort studies, 5 (3.6%) were case reports, and 1 (0.7%) was a case series. The majority of studies (95 [67.4%]) had a follow-up duration of 2 days or less. Interventions included the use of local anesthetics and/or nerve blocks (42 studies [29.8%]), nonsteroidal anti-inflammatory drugs (31 [22.0%]), neuropathic pain medications (9 [6.4%]) and multimodal analgesic combinations (25 [17.7%]. In 127 studies (90.1%), a significant decrease in postoperative opioid consumption compared to the control intervention was reported; the median opioid reduction in these studies was 39.7% (range 5%–100%). Despite these reductions in opioid use, the effect on pain scores and on incidence of adverse effects was inconsistent.
Conclusion: There is a large body of evidence from randomized trials showing the promise of a variety of interventions for reducing opioid use after orthopedic surgery. Rigorously designed RCTs are needed to determine the ideal interventions or combination of interventions for reducing opioid use, for the good of patients, medicine and society.
The conflict and tension between the intended good and unintended harms of opioids have been recognized within the medical context since the early 1900s.1 It is helpful to separate the harms broadly into 2 categories: short-term adverse effects, which are adverse drug effects experienced by the person using the drug, and long-term harms, which could be to the individual or to society (diversion). The immediate harms are considered under the term opioid-related adverse drug effects and they commonly include nausea/vomiting, sedation, itching, postoperative ileus and respiratory depression.2 Secondarily, they can lead to increased length of stay, opioid dependence, death and rising costs.3,4
The long-term harms of opioids are specifically responsible for the ongoing opioid epidemic in North America, as well as in other parts of the world.5 Over the past 20 years, opioid use disorder and opioid-related mortality have increased rapidly.6 In 2013, drug overdose surpassed motor vehicle crashes to become the leading cause of preventable death in the United States, with more than 42 000 opioid overdose deaths in 2016 alone.7,8 The number of opioid-related deaths has continued to rise, with an increase in deaths in Canada in 2017 of 30% from the previous year.7 These trends are matched by a marked increase in patient opioid prescriptions. In Canada, the defined daily dose per million population per day of opioids increased threefold between 2001–2003 and 2012–2014, from 10 209 to 30 540.7,8 This is second only to the US.7
In light of the current opioid epidemic, increased attention has been given to target areas to reduce opioid use and manage acute pain alternatively in the postoperative period. Owing to the substantial amount of pain after many orthopedic procedures, opioids have traditionally been used postoperatively in this field. There are many risks to consider when prescribing, which makes the issues at hand incredibly complex. Prescribing opioids peri- and postoperatively can trigger long-term use in people independent of opioid tolerance or previous use.9 A retrospective cohort study from Ontario showed increased risk of long-term opioid use after receiving a prescription for a short-stay surgery in 44% of 400 000 patients.9 In opioid-naive patients, a new opioid prescription after discharge from hospital increased the odds of long-term use 1 year later by 4.9 times (95% confidence interval 3.22–7.45).10 Two of the 3 surgical interventions that were associated with highest long-term opioid use were total knee arthroplasty (TKA) and total hip arthroplasty (THA).11 Other risks to consider include the possibility that the legal supply will be diverted to those with substance use disorder or people seeking illicit drugs.12,13 Studies repeatedly show that more than 50% of prescribed opioids go unused, and the majority are never disposed of safely.14
Managing pain is a key component of patient care. For opioid-reduction programs to be successful, they must recognize the challenges around pain, particularly in older patients and those with chronic pain, including the potential for persisting pain after surgery and, hence, the necessity of providing alternative analgesic modalities that depend less on opioids. Programs that aim to reduce opioid use substantially should not only focus on the physiologic management of pain, but also consider education initiatives on opioid use and assess for patients at high risk. To reduce dependency on opioids, pain should be managed with a multimodal analgesia regimen. This includes the use of pharmacologic modalities such as peripheral nerve blocks (PNBs) or local anesthetic infiltration (LAI), acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) in all patients, and the use of gabapentinoids and cannabinoids in suitable patients. Nonpharmacologic modalities that are considered as adjuncts include acupuncture, electrotherapy and transcutaneous electrical nerve stimulation.15–17 Evidence suggests that many of these modalities are underused.18,19
The goals of this scoping review were to 1) identify the current literature and level of evidence on reduction of opioid use after orthopedic surgery; 2) describe the interventions used; 3) summarize the results, noting the amount of opioid reduction and other postoperative outcomes; and 4) synthesize the results to highlight patterns seen with different interventions.
Methods
Protocol and registration
We conducted a scoping review of published literature on strategies to reduce opioid use in orthopedic surgery. The purpose of a scoping review is to map the current literature on a broad topic to identify gaps in the literature in order to plan future studies and to identify areas where there is enough information to conduct formal meta-analyses. This scoping review protocol was registered with the PROSPERO international prospective register of systematic reviews (CRD42020153418). The methodology of the review is in accordance with the PRISMA-ScR guidelines for scoping reviews.20
Literature search
We completed a comprehensive search of CENTRAL, Embase and Medline from database inception until August 2019 for studies aiming to eliminate or substantially reduce perioperative opioid use. Terms searched included common orthopedic interventions, analgesic options, alternative therapy options to manage acute pain and any phrases that suggest there has been a reduction in opioid use. We then performed an extensive manual search of reference lists from the included literature to seek any additional relevant studies. Our search strategy for each of the 3 databases is presented in Appendix 1 (available at www.canjsurg.ca/lookup/doi/10.1503/cjs.023620/tab-related-content).
Studies were included if at least 25% of the population were orthopedic surgery patients; they were original reports focused on perioperative and/or acute postoperative pain management (i.e., not chronic pain); the primary objective of the study was to reduce or eliminate perioperative or postoperative opioid use; and full-text articles were available. Studies were excluded if they were animal or preclinical studies, were in a language other than English, focused on cancer pain, focused exclusively on pediatric populations, or were opinion pieces, editorials or synthesis of literature, including reviews.
We managed references using Rayyan QCRI software (Qatar Computing Research Institute). Two reviewers (J.G., V.S.) independently screened titles identified by the literature search first and then all remaining abstracts. Any study that was distinctly irrelevant based on the eligibility criteria was excluded. At both the title and the abstract stage, a study was included if at least 1 of the 2 reviewers chose to include it. Full texts were obtained for all remaining studies when available. Both reviewers screened the remaining references independently. Any initial discrepancies at the full-text stage were resolved by discussion between the reviewers until agreement on inclusion or exclusion of the study in question was reached.
We extracted the data using a collaborative online spreadsheet (Google Sheets). The form included study characteristics (design, date, location, sample size, demographic characteristics and level of evidence), description of the population, intervention, comparator (if applicable) and relevant outcomes at final follow-up. The spreadsheet was piloted by 2 reviewers (J.G., V.S.) before data extraction. Each reviewer’s data were audited by the other reviewer using a random spot-check method.
Data analysis
As this was a scoping review, we presented our analysis and results in a descriptive fashion. We used frequencies and proportions for categoric data, and means and standard deviations, or median and range (depending on data distribution) for continuous data. We grouped studies based on type of orthopedic procedure: arthroplasty procedures (knee and/or hip), arthroscopy operations, spinal procedures and other peripheral limb procedures. We reported the category of opioid-sparing strategy used as pharmacologic or nonpharmacologic, and noted the type of interventions used within these categories as NSAIDs, acetaminophen derivatives, adjunct analgesic medications (gabapentinoids), PNBs, LAI, physical modalities, psychologic modalities and other. We noted the amount of opioid sparing or reduction as per the study reporting, including the dosage and duration of opioid therapy.
Results
The initial literature search yielded 20 309 studies; after removal of duplicates, this number was reduced to 14 121. Systematic screening and assessment of eligibility yielded 141 full-text articles that satisfied the criteria for inclusion (Figure 1).
Flow diagram showing study selection
Study quality
Of the 141 studies, 113 (80.1%) were randomized controlled trials (RCTs) (level I evidence), 6 (4.3%) were prospective cohort studies (level II evidence), 16 (11.3%) were retrospective cohort studies (level III evidence), 5 (3.5%) were case reports (level IV evidence), and 1 (0.7%) was a case series (level IV evidence).
Study characteristics
The 141 studies included in this review involved 20 963 patients (Table 1). The number of included patients per study ranged from 1 to 4046 (median 68). In the studies that reported gender, 9585/17 511 patients (54.7%) were female. The overall mean age was 57.8 (range 16–94) years. The length of follow-up ranged from 0.83 to 365 days, with 95 studies (67.4%) having 2 days or less of follow-up, 24 studies (17.0%) having 3–7 days of follow-up, and 12 studies (8.5%) having more than 7 days of follow-up.
Characteristics of included studies
There were 158 total intervention arms aimed at reducing opioid use, of which 145 (91.8%) were pharmacologic. The most commonly used pharmacologic interventions, either alone or in some combination, were PNB/LAI, acetaminophen, NSAIDs and additional analgesics (most commonly gabapentin). In 25 studies (17.7%), the use of a multimodal regimen (defined as the use of ≥ 2 analgesics) aimed at reducing opioid use was reported. Nonpharmacologic interventions included education (4 studies115,132,155,160), transcutaneous electrical nerve stimulation (3 studies69,112,126), transcranial direct current stimulation (2 studies24,97) and, in 1 study each, auricular acupressure, cryotherapy and millimetre wave therapy.33,48,49
Of the 141 studies, 139 (98.6%) (19 795 patients) included only patients who had orthopedic procedures. The most common procedures performed were lower limb total joint arthroplasty, with 38 studies (7124 patients) involving TKA, 25 studies (2346 patients) involving THA and 7 studies (730 patients) involving both, for a total of 70 studies (49.6%) examining pain control specifically after lower limb arthroplasty. The next most common surgical procedures were spinal surgery (29 studies [20.6%], 5013 patients) and arthroscopic surgery (15 studies [10.6%], 1160 patients). There were 27 studies on other surgical procedures, including fracture fixation.
In 127 studies (90.1%), a significant decrease in postoperative opioid consumption compared to the control intervention was reported; the median opioid reduction in these studies was 39.7% (range 5%–100%).
Procedures
Total knee arthroplasty
Among the 38 TKA studies, PNB/LAI was used in 15 (40%), NSAIDs were used in 5 (13%), a nonpharmacologic intervention was used in 4 (10%), and additional adjuvant analgesics were used in 5 (13%) (Table 1). Multimodal analgesia was used in 9 studies (24%).
A statistically significant reduction in opioid use compared to the control group was reported in 34 studies (90%) (Table 2). Percent opioid reduction ranged from 10% to 100% (median 37.8%). Twenty-three studies (60%) showed at least a 30% reduction in opioid use, and 12 (32%) showed more than a 50% reduction.
Major outcomes of included studies*
Of the 36 studies in which pain scores were reported, 26 (72%) showed significantly lower scores compared to the control intervention. Postoperative length of stay was reported in 5 studies, with all 5 showing significantly lower values compared to control. Mobilization was reported in 10 studies, of which 8 (80%) showed significant improvement compared to control. Patient satisfaction was reported in 2 studies,29,32 1 of which showed significantly higher satisfaction compared to control. The frequency of adverse events was reported in 17 studies, with 4 (24%) showing the intervention had a significantly positive effect; the remaining 13 studies (76%) showed no difference between the intervention and control groups.
Total hip arthroplasty
Among the 25 THA studies, PNB/LAI was used in 8 (32%), NSAIDs were used in 6 (24%), a nonpharmacologic intervention was used in 1 (4%),69 and additional adjuvant analgesics were used in 5 (21%). Multimodal analgesia was used in 5 studies (21%).
Twenty-four studies (96%) showed a statistically significant reduction in opioid use compared to control. Percent opioid reduction ranged from 15% to 100% (median 40.3%). Eighteen studies (72%) showed at least a 30% reduction in opioid use, and 6 studies (24%) showed more than a 50% reduction.
Pain scores were reported in 20 studies, 13 (65%) of which showed significantly lower scores compared to the control intervention. Postoperative length of stay was reported in 3 studies,77,80,83 all of which showed significantly lower values compared to control. Of the 2 studies in which mobilization was reported,62,80 1 showed significant improvement compared to control.80 Patient satisfaction was reported in 2 studies;59,75 both showed significantly higher satisfaction compared to control. The frequency of adverse events was reported in 16 studies, 6 (38%) of which showed a significantly lower incidence compared to control.
Total knee and total hip arthroplasty
Among the 7 studies in patients underwent THA or TKA, the intervention consisted of PNB/LAI in 1 (14%),87 NSAIDs in 3 (43%),86,88,89 acetaminophen in 1 (14%),90 additional adjuvant analgesics in 1 (14%)85 and multimodal analgesia in 1 (14%).84 Six studies (86%) showed a statistically significant reduction in opioid use compared to control. Percent opioid reduction ranged from 23.4% to 89.3% (median 36.3%). Four studies (57%) showed at least a 30% reduction in opioid use, and 2 studies (29%) showed more than a 50% reduction.
Pain scores were reported in 4 studies, all of which showed a significant decrease. The frequency of adverse events was reported by 4 studies; all 4 indicated that the intervention had no impact on the frequency of adverse events.
Arthroscopy
Among the 15 arthroscopy studies, PNB/LAI was used in 5 (33%), NSAIDs were used in 4 (27%), a nonpharmacologic intervention was used in 2 (13%),126,132 gabapentinoids were used in 3 (20%),120,128,129 and additional adjuvant analgesics were used in 1 (7%).
Fourteen studies (93%) showed a statistically significant reduction in opioid use compared to control. Percent opioid reduction ranged from 14% to 89% (median 40.6%). Nine studies (60%) showed a reduction in opioid use of at least 30%, and 5 studies (33%) showed a reduction of more than 50%.
Pain scores were reported in 11 studies, of which 9 (82%) showed significantly lower scores compared to the control intervention. The 1 study121 in which postoperative length of stay was reported indicated significantly lower values compared to control. Patient satisfaction was reported in 1 study,125 which showed that the intervention had a significantly positive effect. The frequency of adverse events was reported in 7 studies, 1 (14%) of which showed a significantly lower incidence compared to control.
Spinal surgery
Among the 29 spinal surgery studies, the intervention consisted of PNB/LAI in 4 (14%), NSAIDs in 6 (21%), acetaminophen in 2 (7%),99,117 a nonpharmacologic intervention in 3 (10%),97,112,115 gabapentinoids in 3 (10%)94,105,110 and additional adjuvant analgesics in 4 (14%). Multimodal analgesia was used in 7 studies (24%).
A statistically significant reduction in opioid use compared to control was reported in 27 studies (93%). Percent opioid reduction ranged from 8.5% to 100% (median 35.3%). Of the 29 studies, 19 (66%) showed at least a 30% reduction in opioid use, and 9 (31%) showed more than a 50% reduction.
Pain scores were reported in 25 studies, of which 13 (52%) showed significantly lower scores compared to the control intervention. Of the 2 studies in which postoperative length of stay was reported,93,95 1 showed significantly lower values compared to control. Mobilization was reported in 1 study,114 which showed a significant improvement compared to control. Patient satisfaction was reported in 2 studies,98,103 with 1 showing significantly higher satisfaction compared to control.98 The frequency of adverse events was reported in 15 studies, of which 3 (20%) indicated that the intervention had a significant improvement on the incidence of adverse events; the remaining studies showed no difference between the intervention and control groups.
Other orthopedic surgery
Among the 27 studies on other surgical procedures, PNB/LAI was used in 7 (26%), NSAIDs in 7 (26%), acetaminophen in 3 (11%),137,148,159 a nonpharmacologic intervention in 2 (7%)155,160 and additional adjuvant analgesics in 5 (18%). Multimodal analgesia was used in 3 studies (11%).151,154,156
Twenty-four studies (89%) showed a statistically significant opioid reduction compared to control. Percent opioid reduction ranged from 3% to 100% (median 40%). A reduction in opioid use of at least 30% was reported in 20 studies (74%), and a reduction in opioid use of more than 50% was reported in 9 studies (33%).
Pain scores were reported in 20 studies, with 10 (50%) showing significantly lower scores compared to the control intervention. Both studies148,156 in which postoperative length of stay was reported indicated significantly lower values compared to control. The frequency of adverse events was reported in 16 studies, with 3 (19%) showing significantly lower values compared to control; in the remaining studies, no difference was observed between the intervention and control groups.
Discussion
Our review was a comprehensive review of the literature on reduction in opioid use after orthopedic surgery. It was conducted systematically with rigorous methodology, as outlined in the PRISMA extension for scoping reviews.20 Although a majority (81.6%) of the included studies showed a reduction in opioid consumption of at least 25%, the reduction was not associated with a simultaneous positive effect on pain scores or the incidence of adverse events.
A majority (67.4%) of studies included a follow-up duration of 2 days or less, with only 8.5% having a followup duration of more than 7 days. This is a major drawback when one is trying to infer the potential for limiting persistent opioid use after orthopedic surgery.
Even among studies that reported a significant decrease in opioid use, a reduction in opioid-related adverse drug effects was reported or observed inconsistently. This may be a result of the particular type of intervention, as well as its potential to affect pain directly and its relative effect on adverse effects. For example, the use of gabapentin, although associated with decreased opioid use, has been shown to be associated with substantial sedation and risk of adverse effects on its own.162
Opioid sparing is most possible with the use of a multimodal approach rather than a single, nonopioid substitute; however, this approach continues to be underused or applied inconsistently.163–166 In our review, multimodal analgesia was used in less than 25% of studies within each procedure type.
It is also relevant to note that postsurgical pain can be influenced by many patient- and procedure-dependent factors. In addition, studies have shown significant variation in pain-resolution patterns,167–170 and analgesic consumption is dynamic and changes with time.171
An important factor not reported in many studies is the use of preoperative screening based on known risk factors for long-term opioid use after surgery, including male sex, age more than 50 years, prior opioid use, alcohol abuse and mental illness.11,172,173 As well, the use of benzodiazepines or antidepressants preoperatively has been found to be associated with a higher risk of long-term opioid use postoperatively.11,174 Future trials should consider screening protocols to evaluate risk in potential patients.175,176 One step toward this has been preoperative screening and referral to pain specialists for patients with preoperative long-term opioid use.114,177
The context of opioid use in hospital and its effect on long-term opioid use is still unclear. Although studies have shown a reduction in inpatient opioid consumption, especially with implementation of Enhanced Recovery After Surgery pathways,178,179 there is no evidence to suggest that limiting intraoperative administration of opioids influences the risk of long-term opioid use postoperatively.180–182 The most direct contributor to long-term opioid use identified in the literature is inappropriate physician prescribing.11,171,183 An observational study showed that opioids are prescribed postoperatively to 98.3% of patients in North America, compared to 70.2% of patients in Europe, although the mean worst pain scores were higher in North American patients than in patients from Europe (7.4/10 v. 5.4/10).184 Yet although opioid prescribing has been identified as the problem, it seems that very few investigators have incorporated this factor in their interventions. In a scoping review of opioid-free analgesia after major surgery, Fiore and colleagues185 observed that a majority of RCTs compared opioid-free strategies only during the hospital stay, and only 7 targeted postdischarge analgesia.
In view of these challenges, education as a nonpharmacologic tool to reduce opioid consumption and alleviate pain may play an important role. However, in the present review, an educational intervention was used in only 4 studies (2.8%); all showed significant reduction in opioid use, ranging from 22.1% to 54.5%. Notably, these studies involved education in many different forms, whether for prescribers115,160 or patients.132 Bohl and colleagues116 investigated the use of a multimodal analgesia protocol that included preoperative counselling in addition to a variety of different classes of analgesic medications pre-, intra- and postoperatively. Similarly, Ali and colleagues114 used an Enhanced Recovery After Surgery protocol involving preoperative education and screening for long-term opioid use, as well as multimodal perioperative analgesia. Both studies showed significant positive effects on opioid consumption. A recent systematic review of institutional interventions such as education, counselling and prescribing guidelines showed that, on the patient side, educational programs were most effective, and on the provider side, the use of prescribing guidelines was most effective.186 Although there is scant evidence available on these types of interventions, with only 13 studies being included in that systematic review, there is reason to believe that these institutional strategies will be crucial in tackling this complex problem.
Somewhat unexpectedly, the majority (80.1%) of studies that included evidence on reducing opioid consumption after orthopedic surgery in the present review were randomized studies. This not only suggests the importance of this problem in this surgical specialty, but also identifies opportunities for synthesis of available information in the form of appropriate meta-analyses and network meta-analyses to investigate the relative merits and effect size of opioid reduction with individual interventions or combination of interventions.16,187,188
Future trials should also consider methodologic issues in surgical trials looking at opioid reduction. Measuring opioid use, for either relative increase or decrease, in postsurgical trials can be challenging: apart from the weak correlation between pain intensity and opioid use, there may also be issues of sedation accompanying adjuvant analgesics.189,190 Ideally, there should be some integrated measure of pain intensity and analgesic (opioid) demand.191
Limitations
One limitation of this review is the inclusion of all levels of evidence instead of only evidence from RCTs. As well, much of the data gathered were reported simply in terms of whether or not there was improvement, with many studies reporting little quantitative data. However, the purpose of this scoping review was to identify literature and general results, with the goal of directing areas for future research, as well as guiding the development of study protocols incorporating a variety of both pharmacologic and nonpharmacologic interventions. Included studies were relatively small, with a median sample of 68 participants, and relatively short, with a median follow-up duration of 2 days. Last, there was a wide variety of procedures with varying levels of postoperative pain represented in the included studies.
Conclusion
This scoping review showed that there is a large body of evidence, much of it from randomized trials, that shows the promise of both pharmacologic and nonpharmacologic interventions in the goal of reduction of opioid use after orthopedic surgery. However, rigorously designed RCTs incorporating evidence-based pharmacologic and nonpharmacologic interventions in a multimodal regimen are needed to evaluate the goal of reducing opioid use, for the good of patients, medicine and society.
Footnotes
Contributors: J. Gormley, D. Tushinski and K. Madden designed the study. K. Gouveia, S. Sakha, V. Stewart, U. Emmanuel and M. Shehata acquired the data, which V. Stewart and H. Shanthanna analyzed. J. Gormley, K. Gouveia, S. Sakha, V. Stewart, U. Emmanuel, M. Shehata and K. Madden wrote the manuscript, which D. Tushinski and H. Shanthanna critically revised. All authors gave final approval of the article to be published.
Competing interests: Kim Madden reports research support from the Research Institute of St. Joe’s Hamilton, the Canadian Institutes of Health Research, BioTalent Canada and McMaster University, outside the submitted work. She has participated on a data safety monitoring board at the University of Calgary. She is an associate editor for Clinical Orthopaedics and Related Research and Pilot and Feasibility Studies, and sits on the Equity, Diversity and Inclusion Committee of the Society for Clinical Trials. No other competing interests were declared.
- Accepted January 7, 2022.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
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