Effectiveness of Interventions to Reduce Opioid Use After Orthopaedic Surgery: A Systematic Review of Randomised Controlled Trials
 

Despite increased awareness of the harms of opioids, persistent opioid use remains a global public health concern . Persistent opioid use is a major contributor to many opioid-related harms, including overdose , higher rates of dependence, addiction, cognitive impairment, and overall poor quality of life . There is limited evidence that opioid analgesics provide sufficient pain relief in the long term . A major contributor to persistent opioid use is the initial prescribing of opioids to patients for acute pain, such as postoperative pain, that then continues beyond the acute period . Opioids are commonly used in reducing postoperative pain . However, patients who take opioid analgesics after surgery are at an increased risk of immediate harms, such as postoperative nausea, vomiting, and bowel dysfunction, which can delay recovery times, placing burden on both patients and the healthcare system . Orthopaedic surgeries are one of the most common surgeries. Persistent opioid use after orthopaedic surgery is a challenge , especially in those who used opioids to manage their musculoskeletal complaints before surgery . Although previous systematic reviews  have identified potential interventions to reduce opioid use after orthopaedic surgery, they focused on specific interventions, such as educational interventions, or those implemented during the preoperative period. Investigating postoperative interventions is important because the focus during this period is on minimising patient discomfort, facilitating early mobilisation and recovery, and preventing acute pain developing into chronic pain while gradually reducing the need for analgesia . This review aims to investigate the effectiveness of any interventions aimed to reduce opioid use against any control in patients 1–3 months after orthopaedic surgery. Additionally, the review investigates the effects of these interventions on opioid use and clinical and safety outcomes up to 12 months after surgery. 

This systematic review was prospectively registered on PROSPERO (CRD42022357577)  and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020 (Fig. ) . Any protocol changes are listed in Appendix . Eligibility Criteria This review included randomised controlled trials that investigated any intervention(s) with an aim of reducing the dose of, or ceasing, opioid analgesics, taken by any route, targeted at adult patients, at the clinician or system level, implemented after orthopaedic surgery. Eligible studies were those that had recruited adults who had undergone any orthopaedic surgery. The scope of orthopaedic surgery for this review was adopted from previous studies  and comprised elective and non-elective surgical procedures performed to the musculoskeletal system. Participants may have received the intervention while in hospital and/or upon discharge from acute postoperative care (e.g. when the participants go home or to inpatient rehabilitation). There was no restriction on the type of intervention, which may include educational, pharmacological, alternative therapy (e.g. acupuncture), or biopsychosocial (e.g. mindfulness, meditation) interventions. There was no restriction on the control group, which could be usual care, no intervention, another active intervention, or placebo. We excluded studies that focused on patients receiving surgical treatment for cancer pain or palliative care or that focused on deprescribing methods involving opioid rotation or pharmacological substitution therapy. We also excluded studies that did not report the relevant outcome data (e.g., did not specify opioid dosage in morphine milligram equivalent [MME] or a form that could be converted to MME) or if they implemented interventions in the preoperative phase or during the operation. Data Sources and Searches MH and SM searched MEDLINE, Embase, PsycInfo, PEDro, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, http://www.who.int/ictrp/en/ ) databases from inception to 23 November 2023 with no language or publication restrictions. The search strategy was developed using the MEDLINE and Embase validated filters for the terms ‘randomised controlled trial’ and ‘deprescribing’ (defined as the systematic process of tapering or dose reducing aimed to achieve cessation) . Additional search filters included a combination of Medical Subject Headings and keywords for the terms ‘opioids’ and ‘surgery’ and were developed by the study team by investigating the filters used by similar reviews  with additional assistance from a librarian at The University of Sydney. The same search strategies were adapted and applied across all the databases. We also performed backwards citation tracking by screening the reference lists of included studies and relevant reviews. Forwards tracking was performed on Scopus and Web of Science for each included study. The full search strategies are detailed in Appendix 2. Study Selection Two independent reviewers (MH and SM) conducted the initial title and abstract screening from the list of references identified by the search. After discrepancies were resolved via discussion, the same reviewers conducted the full-text screening of each potentially eligible reference. If disagreements occurred, a third reviewer (CL) helped reach consensus. Outcomes Our primary outcome was the mean daily dose of opioid analgesic medications, measured in MMEs. Secondary outcomes were the number of patients who had ceased or reduced at least one opioid analgesic medication, pain intensity, disability, quality of life, the proportion of participants who reported adverse events or serious adverse events, and the proportion of participants who were taking medicines from the benzodiazepine and/or gabapentinoid drug classes. Follow-up times were classified as short term (< 1 month after randomisation), medium term (1–3 months after randomisation; primary time point), and long term (> 3–12 months after randomisation). The primary time point was determined based on the nature of acute pain that should resolve within 3 months and that opioid use is considered persistent beyond this time period. These outcomes were predetermined but not reported in the PROSPERO protocol. Data Extraction Two independent reviewers from a panel of seven (MH, MJ, SM, CL, DG, AW, and YL) used the pre-piloted, custom-designed, standardized data extraction forms to extract the data from eligible studies. The lead author (MH) met with each reviewer beforehand to explain the data extraction form and the process to ensure standardisation. Extracted data included bibliographical details (authors, title, year of publication, language, country of publication, and funding sources), study characteristics (setting, population, sample size, method of randomisation, concealment, and blinding), participant data (age, sex, diagnosis, surgery type, analgesic medications prescribed at baseline), data completeness (percentage of missing data, how missing data were handled), and outcomes (Sect. ). The data extraction forms were compared, and any differences were resolved via discussion or by a third reviewer as an arbitrator. Where necessary, we contacted the study authors for missing data or clarification. Risk of Bias The same reviewers who conducted the data extraction for each study independently assessed the risk of bias. The methods and criteria outlined in the original Cochrane 6-domain Risk of Bias Tool  and Cochrane Handbook for Systematic Reviews of Interventions were used to guide assessment and categorise the risk of bias as either low, high, or unclear. Reviewers compared their assessments and resolved any discrepancies through discussion or with the adjudication of a third reviewer. We considered a study as having an overall low risk of bias if it scored ‘low risk’ in at least four of the six items. This criterion was based on a previous Cochrane review . Certainty of Evidence The overall certainly of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)  approach, which determined the certainty of evidence based on risk of bias, inconsistency, indirectness, imprecision, and publication bias (Appendix 3). Data Synthesis and Analysis The flow of the studies was summarised in a study flow diagram following the PRISMA statement  (Fig. ). Study characteristics (setting, population, sample size, method of randomisation, concealment, and blinding) and participant characteristics (age, gender, surgery type) were reported descriptively. To facilitate analysis, studies were categorised according to the most common intervention types, which were multimodal analgesics , opioid analgesics, non-opioid analgesics, behavioural interventions, acupuncture/acupressure, cryotherapy, electrotherapy, and other therapies. Studies were then categorised according to whether the control group was placebo/no intervention/usual care or active control. Appendix 4 outlines the definitions of intervention and control categories. Data permitting, results were pooled in a meta-analysis using a random-effects model and displayed using forest plots. Heterogeneity was assessed by visual inspection of the forest plot (e.g. P values and overlapping confidence intervals [CIs]) and I 2 , following the recommended guide . Where heterogeneity between studies was considered substantial ( I 2 statistic value > 50%), or where outcomes could not be pooled because of a lack of comparability, we summarised the data narratively. Continuous outcomes were extracted as means and presented as the mean difference (MD) with the 95% CIs. Dichotomous outcomes are reported as the risk difference (RD; to account for when zero events were reported) as the effect measure with 95% CI. Where necessary, we converted any outcomes to a common scale (e.g. 0–100 for pain scores) to facilitate comparability. Opioid analgesic medicines were converted to MME dose to facilitate comparison and interpretability using the following formula: MME = total opioid dose per day (mg) × conversion factor . Data were analysed using the RevMan software . 

This review included randomised controlled trials that investigated any intervention(s) with an aim of reducing the dose of, or ceasing, opioid analgesics, taken by any route, targeted at adult patients, at the clinician or system level, implemented after orthopaedic surgery. Eligible studies were those that had recruited adults who had undergone any orthopaedic surgery. The scope of orthopaedic surgery for this review was adopted from previous studies  and comprised elective and non-elective surgical procedures performed to the musculoskeletal system. Participants may have received the intervention while in hospital and/or upon discharge from acute postoperative care (e.g. when the participants go home or to inpatient rehabilitation). There was no restriction on the type of intervention, which may include educational, pharmacological, alternative therapy (e.g. acupuncture), or biopsychosocial (e.g. mindfulness, meditation) interventions. There was no restriction on the control group, which could be usual care, no intervention, another active intervention, or placebo. We excluded studies that focused on patients receiving surgical treatment for cancer pain or palliative care or that focused on deprescribing methods involving opioid rotation or pharmacological substitution therapy. We also excluded studies that did not report the relevant outcome data (e.g., did not specify opioid dosage in morphine milligram equivalent [MME] or a form that could be converted to MME) or if they implemented interventions in the preoperative phase or during the operation. 

MH and SM searched MEDLINE, Embase, PsycInfo, PEDro, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, http://www.who.int/ictrp/en/ ) databases from inception to 23 November 2023 with no language or publication restrictions. The search strategy was developed using the MEDLINE and Embase validated filters for the terms ‘randomised controlled trial’ and ‘deprescribing’ (defined as the systematic process of tapering or dose reducing aimed to achieve cessation) . Additional search filters included a combination of Medical Subject Headings and keywords for the terms ‘opioids’ and ‘surgery’ and were developed by the study team by investigating the filters used by similar reviews  with additional assistance from a librarian at The University of Sydney. The same search strategies were adapted and applied across all the databases. We also performed backwards citation tracking by screening the reference lists of included studies and relevant reviews. Forwards tracking was performed on Scopus and Web of Science for each included study. The full search strategies are detailed in Appendix 2. 

Two independent reviewers (MH and SM) conducted the initial title and abstract screening from the list of references identified by the search. After discrepancies were resolved via discussion, the same reviewers conducted the full-text screening of each potentially eligible reference. If disagreements occurred, a third reviewer (CL) helped reach consensus. 

Our primary outcome was the mean daily dose of opioid analgesic medications, measured in MMEs. Secondary outcomes were the number of patients who had ceased or reduced at least one opioid analgesic medication, pain intensity, disability, quality of life, the proportion of participants who reported adverse events or serious adverse events, and the proportion of participants who were taking medicines from the benzodiazepine and/or gabapentinoid drug classes. Follow-up times were classified as short term (< 1 month after randomisation), medium term (1–3 months after randomisation; primary time point), and long term (> 3–12 months after randomisation). The primary time point was determined based on the nature of acute pain that should resolve within 3 months and that opioid use is considered persistent beyond this time period. These outcomes were predetermined but not reported in the PROSPERO protocol. 

Two independent reviewers from a panel of seven (MH, MJ, SM, CL, DG, AW, and YL) used the pre-piloted, custom-designed, standardized data extraction forms to extract the data from eligible studies. The lead author (MH) met with each reviewer beforehand to explain the data extraction form and the process to ensure standardisation. Extracted data included bibliographical details (authors, title, year of publication, language, country of publication, and funding sources), study characteristics (setting, population, sample size, method of randomisation, concealment, and blinding), participant data (age, sex, diagnosis, surgery type, analgesic medications prescribed at baseline), data completeness (percentage of missing data, how missing data were handled), and outcomes (Sect. ). The data extraction forms were compared, and any differences were resolved via discussion or by a third reviewer as an arbitrator. Where necessary, we contacted the study authors for missing data or clarification. 

The same reviewers who conducted the data extraction for each study independently assessed the risk of bias. The methods and criteria outlined in the original Cochrane 6-domain Risk of Bias Tool  and Cochrane Handbook for Systematic Reviews of Interventions were used to guide assessment and categorise the risk of bias as either low, high, or unclear. Reviewers compared their assessments and resolved any discrepancies through discussion or with the adjudication of a third reviewer. We considered a study as having an overall low risk of bias if it scored ‘low risk’ in at least four of the six items. This criterion was based on a previous Cochrane review . 

The overall certainly of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)  approach, which determined the certainty of evidence based on risk of bias, inconsistency, indirectness, imprecision, and publication bias (Appendix 3). 

The flow of the studies was summarised in a study flow diagram following the PRISMA statement  (Fig. ). Study characteristics (setting, population, sample size, method of randomisation, concealment, and blinding) and participant characteristics (age, gender, surgery type) were reported descriptively. To facilitate analysis, studies were categorised according to the most common intervention types, which were multimodal analgesics , opioid analgesics, non-opioid analgesics, behavioural interventions, acupuncture/acupressure, cryotherapy, electrotherapy, and other therapies. Studies were then categorised according to whether the control group was placebo/no intervention/usual care or active control. Appendix 4 outlines the definitions of intervention and control categories. Data permitting, results were pooled in a meta-analysis using a random-effects model and displayed using forest plots. Heterogeneity was assessed by visual inspection of the forest plot (e.g. P values and overlapping confidence intervals [CIs]) and I 2 , following the recommended guide . Where heterogeneity between studies was considered substantial ( I 2 statistic value > 50%), or where outcomes could not be pooled because of a lack of comparability, we summarised the data narratively. Continuous outcomes were extracted as means and presented as the mean difference (MD) with the 95% CIs. Dichotomous outcomes are reported as the risk difference (RD; to account for when zero events were reported) as the effect measure with 95% CI. Where necessary, we converted any outcomes to a common scale (e.g. 0–100 for pain scores) to facilitate comparability. Opioid analgesic medicines were converted to MME dose to facilitate comparison and interpretability using the following formula: MME = total opioid dose per day (mg) × conversion factor . Data were analysed using the RevMan software . 

Characteristics of Included Studies The search yielded 17,471 records, of which 39 were eligible for inclusion (Fig. ). The reasons for exclusion at full-text review are reported in Appendix 5. The included studies investigated 4054 adult participants (1858 males and 2196 females) with a mean age range of 30–75 years and a mean sample size of 103 participants. All included studies were published in English, and 56.4% ( n = 22 studies) were from the USA. The studies investigated a variety of orthopaedic surgeries, with the most common being knee arthroplasty (14 studies ) and hip arthroplasty (eight studies ). Most studies only reported short-term data (i.e. < 1 month after randomisation), and no studies reported outcomes in the long term (> 3 months after randomisation). A summary of study characteristics is provided below and in Appendix 6. Risk of Bias In total, 21 studies  had an overall low risk of bias (Fig. ), and most scored well in random sequence generation. A total of 18 studies had a high risk of bias, and eight studies had not blinded participants or study personnel, six had not blinded outcome assessors, seven displayed selective outcome reporting, and five had high levels of attrition or missing data. Interventions Included studies investigated multimodal analgesics (seven studies ), opioid analgesics (three studies ), non-opioid analgesics (eight studies ), behavioural interventions (three studies ), acupressure or acupuncture (four studies ), cryotherapy (five studies ), electrotherapy (six studies ), and other therapies (five studies ). In total, 28 studies  compared their intervention with a placebo/no intervention or usual care control, and 14  compared an intervention with an active control, for example, a cryotherapy treatment at a lower temperature  or nurse-administered versus patient-controlled analgesia . Further details on the intervention and control groups for each study are outlined in Appendix 6. Outcomes Additional pooled and unpooled data (mean scores, CIs, and GRADE scores) are provided in Appendix 7, and meta-analysis results are provided in Appendix 8. Primary Outcome The mean daily opioid dose was reported by all 39 studies. Meta-analyses results are shown in Figs. and . Multimodal Analgesics Versus Placebo/No Intervention/Usual Care Four studies  compared multimodal analgesics with placebo/no intervention/usual care. Statistical heterogeneity was high, so data could not be pooled, although the mean daily dose was lower across all multimodal analgesic groups than for placebo/no intervention/usual care in both the medium and short term. Multimodal Analgesics Versus Active Control Three studies  compared multimodal analgesic interventions and active control (included a standard or traditional opioid regimen). One study  (containing two separate comparisons) reported data in the medium term showing a lower daily dose in the intervention group but could not be pooled because of a lack of data. Multimodal analgesics resulted in lower mean daily doses than active control in the short term (MD − 4.34 MME [95% CI − 6.77 to − 1.90], two studies , I 2 = 0%, GRADE = low). Opioid Analgesics Versus Placebo/No Intervention/Usual Care No studies compared opioid analgesics with a placebo/no intervention/usual care control. Opioid Analgesics Versus Active Control Three studies  compared opioid analgesics and active control (minimal vs standard opioid dosage regimens). Statistical heterogeneity was high, so data could not be pooled, but no between-group differences in the mean daily dose were found in the medium or short term. Non-opioid Analgesics Versus Placebo/No Intervention/Usual Care Five studies  compared non-opioid analgesics with placebo/no intervention/usual care. No studies reported the mean daily opioid dose in the medium term. Clinical and statistical heterogeneity were high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower in the non-opioid intervention groups than with placebo/no intervention/usual care. Non-opioid Analgesics Versus Active Control Four studies  compared non-opioid analgesics with active control. Clinical and statistical heterogeneity was high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower with the non-opioid intervention than with the active control. Acupuncture/Acupressure Versus Placebo/No Intervention/Usual Care Four studies  compared acupuncture/acupressure with placebo/no intervention/usual care, one of which  (containing two separate comparisons) reported no between-group differences in the mean daily opioid dose in the medium term (MD − 1.36 MME [95% CI − 4.35–1.63], one study , I 2 = 0%, GRADE = low). In the short term, data could not be pooled for the three included studies . However, no between-group differences were found across these studies. Acupuncture/Acupressure Versus Active Control No studies compared acupuncture/acupressure interventions with active control. Electrotherapy Versus Placebo/No Intervention/Usual Care Six studies  compared electrotherapy with placebo/no intervention/usual care. As no measure of variance was provided, data could not be pooled for four studies , but no between-group differences were found in the medium term. Two studies  reported data in the short term (MD 0.00 MME [95% CI − 0.00–0.00), I 2 = 0%, GRADE = moderate), but no between-group differences were found. Electrotherapy Versus Active Control No studies compared electrotherapy interventions with active control. Cryotherapy Versus Placebo/No Intervention/Usual Care Three studies  compared cryotherapy with placebo/no intervention/usual care, although all studies could not be pooled. There were no between-group differences in two studies in the medium term, but the mean daily dose in the short term was lower with cryotherapy than with placebo/no intervention/usual care. Cryotherapy Versus Active Control Two studies , which could not be pooled, compared cryotherapy with active control and reported that the mean daily dose was lower in the intervention group than with active control in the short term. In these studies, active control was cryotherapy at a different regimen from the intervention group (generally higher temperature [17–21 °C] in active control and lower temperature [11–12 °C] in the intervention). Behavioural Interventions Versus Placebo/No Intervention/Usual Care No studies reported the mean daily opioid dose in the medium term. One study  compared mobile messaging with placebo/no intervention/usual care in the short term and reported a lower dose in the intervention group. Behavioural Interventions Versus Active Control Two studies  compared behavioural interventions with active control, but no between-group differences were found in one study investigating a physical copy of an opioid prescription versus an automatically filled prescription . The other study (nurse-administered analgesia vs patient-controlled analgesia)  reported a lower dose in the control group in the short term. Other Therapies Versus Placebo/No Intervention/Usual Care Five studies  compared the intervention with placebo/no intervention/usual care. There were no significant between-group differences in the medium term (MD 0.32 MME [95% CI − 1.41–2.04], two studies , I 2 = 0%, GRADE = moderate). Clinical and statistical heterogeneity was high, so short-term data could not be pooled; however, no between-group differences were found in any study. Other Therapies Versus Active Control One study  compared the intervention with active control and found no between-group differences in the medium term but a slightly lower dose in the intervention group (cannabis) than with active control (essential oils) in the short term. Number of Participants Who Reduced or Ceased Using Opioid Analgesics Seven studies  reported on the number of participants who ceased their opioid medications. Data on two comparisons within one study of multimodal analgesia versus placebo/no intervention/usual care  found no difference between groups at all time points (RD 0.09 [95% CI − 0.04–0.23], I 2 = 13%, GRADE = moderate). All other studies could not be pooled because of high statistical heterogeneity. Overall, most studies found no differences between groups, except for one cryotherapy versus placebo/no intervention/usual care study  and one study of multimodal analgesia (combination of ketorolac and meloxicam) versus active control (traditional opioid pain protocol) , both of which favoured the intervention groups. Pain Pain intensity was reported by 34 studies . In total, 17 studies compared placebo/no intervention/usual care with multimodal analgesia , acupuncture/acupressure , electrotherapy , cryotherapy , and other therapies . There was no significant difference in pain intensity between all other therapies and placebo/no intervention/usual care in the medium term (MD 2.46 [95% CI − 4.37–9.29], two studies , I 2 = 0%, GRADE = moderate) or the short term (MD − 1.28 [95% CI − 8.39–5.83], two studies , I 2 = 0%, GRADE = low). Statistical and clinical heterogeneity was high, so other comparisons could not be pooled; however, no between-group differences were found in the medium or short term. Ten studies compared active control against multimodal analgesia , opioid analgesia , non-opioid , electrotherapy , and other therapies . Statistical and clinical heterogeneity was high, so pain scores could not be pooled for most studies. All studies found no between-group differences in the short term, except two non-opioid studies , which reported a lower pain score in the intervention group (ibuprofen  or standard bupivacaine ) than with active control (standard opioid-only regimen) (MD 2.23 [95% CI − 2.58–7.04], two studies , I 2 = 0%, GRADE = moderate). Cryotherapy was no better than active control (cryotherapy at an alternative temperature) (MD 2.93 [95% CI − 4.95–10.45], two studies , I 2 = 0%, GRADE = low) in the medium term. Additionally, a lower pain intensity was found in the active control groups (patient-controlled analgesia and general patient information) than with the behavioural interventions (nurse-administered analgesia or a physical copy of opioid prescription) in the short term. Disability Disability was reported by six studies . One study investigating other therapies  (cannabis) versus placebo/no intervention/usual care found no between-group differences (RD − 1.53 [95% CI − 6.05–3.00], I 2 = 0%, GRADE = moderate) in the medium term. Three studies comparing acupuncture/acupressure , electrotherapy , and cryotherapy  versus placebo/no intervention/usual care could not be pooled. Although a slightly lower disability score was found in the acupuncture/acupressure intervention in the short term, no between-group differences were found between other comparisons . Single studies found no between-group differences for cryotherapy (at 10 °C) versus active control (cryotherapy at 21 °C)  or other therapies (cannabis) versus active control (essential oils)  in the medium term, and an opioid analgesic (genotype-guided opioid dosing) versus active control (usual postoperative opioid dosing)  in the short term. Quality of Life Quality of life was reported by five studies  comparing other therapies , acupuncture/acupressure , electrotherapy , or cryotherapy  with placebo/no intervention/usual care in the medium or short term, or a cryotherapy  or other therapies  (cannabis) versus active control in the medium term. None of the comparisons showed a between-group difference. Adverse Events and Serious Adverse Events In total, 17 studies  reported the number of participants who experienced adverse events, and 16 studies  reported the number of participants who experienced serious adverse events. The number of adverse and serious adverse events was not significant across any intervention versus placebo/no intervention/usual care. Where meta-analysis was possible, no intervention had an increased risk of adverse events or serious adverse events. The most frequent adverse events reported across studies were common analgesia-related side effects such as nausea, drowsiness, and dizziness. Most studies reported zero serious adverse events. There were also no between-group differences in the number of (serious) adverse events between any intervention versus active control. Number of Participants Who were Taking Medications from the Benzodiazepine or Gabapentinoid Drug Classes Only three studies  reported on the number of participants taking gabapentin at the short-term time point. Heterogeneity was high and reporting unclear, so these data could not be pooled, but no study found between-group differences. 

The search yielded 17,471 records, of which 39 were eligible for inclusion (Fig. ). The reasons for exclusion at full-text review are reported in Appendix 5. The included studies investigated 4054 adult participants (1858 males and 2196 females) with a mean age range of 30–75 years and a mean sample size of 103 participants. All included studies were published in English, and 56.4% ( n = 22 studies) were from the USA. The studies investigated a variety of orthopaedic surgeries, with the most common being knee arthroplasty (14 studies ) and hip arthroplasty (eight studies ). Most studies only reported short-term data (i.e. < 1 month after randomisation), and no studies reported outcomes in the long term (> 3 months after randomisation). A summary of study characteristics is provided below and in Appendix 6. 

In total, 21 studies  had an overall low risk of bias (Fig. ), and most scored well in random sequence generation. A total of 18 studies had a high risk of bias, and eight studies had not blinded participants or study personnel, six had not blinded outcome assessors, seven displayed selective outcome reporting, and five had high levels of attrition or missing data. 

Included studies investigated multimodal analgesics (seven studies ), opioid analgesics (three studies ), non-opioid analgesics (eight studies ), behavioural interventions (three studies ), acupressure or acupuncture (four studies ), cryotherapy (five studies ), electrotherapy (six studies ), and other therapies (five studies ). In total, 28 studies  compared their intervention with a placebo/no intervention or usual care control, and 14  compared an intervention with an active control, for example, a cryotherapy treatment at a lower temperature  or nurse-administered versus patient-controlled analgesia . Further details on the intervention and control groups for each study are outlined in Appendix 6. 

Additional pooled and unpooled data (mean scores, CIs, and GRADE scores) are provided in Appendix 7, and meta-analysis results are provided in Appendix 8. Primary Outcome The mean daily opioid dose was reported by all 39 studies. Meta-analyses results are shown in Figs. and . Multimodal Analgesics Versus Placebo/No Intervention/Usual Care Four studies  compared multimodal analgesics with placebo/no intervention/usual care. Statistical heterogeneity was high, so data could not be pooled, although the mean daily dose was lower across all multimodal analgesic groups than for placebo/no intervention/usual care in both the medium and short term. Multimodal Analgesics Versus Active Control Three studies  compared multimodal analgesic interventions and active control (included a standard or traditional opioid regimen). One study  (containing two separate comparisons) reported data in the medium term showing a lower daily dose in the intervention group but could not be pooled because of a lack of data. Multimodal analgesics resulted in lower mean daily doses than active control in the short term (MD − 4.34 MME [95% CI − 6.77 to − 1.90], two studies , I 2 = 0%, GRADE = low). Opioid Analgesics Versus Placebo/No Intervention/Usual Care No studies compared opioid analgesics with a placebo/no intervention/usual care control. Opioid Analgesics Versus Active Control Three studies  compared opioid analgesics and active control (minimal vs standard opioid dosage regimens). Statistical heterogeneity was high, so data could not be pooled, but no between-group differences in the mean daily dose were found in the medium or short term. Non-opioid Analgesics Versus Placebo/No Intervention/Usual Care Five studies  compared non-opioid analgesics with placebo/no intervention/usual care. No studies reported the mean daily opioid dose in the medium term. Clinical and statistical heterogeneity were high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower in the non-opioid intervention groups than with placebo/no intervention/usual care. Non-opioid Analgesics Versus Active Control Four studies  compared non-opioid analgesics with active control. Clinical and statistical heterogeneity was high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower with the non-opioid intervention than with the active control. Acupuncture/Acupressure Versus Placebo/No Intervention/Usual Care Four studies  compared acupuncture/acupressure with placebo/no intervention/usual care, one of which  (containing two separate comparisons) reported no between-group differences in the mean daily opioid dose in the medium term (MD − 1.36 MME [95% CI − 4.35–1.63], one study , I 2 = 0%, GRADE = low). In the short term, data could not be pooled for the three included studies . However, no between-group differences were found across these studies. Acupuncture/Acupressure Versus Active Control No studies compared acupuncture/acupressure interventions with active control. Electrotherapy Versus Placebo/No Intervention/Usual Care Six studies  compared electrotherapy with placebo/no intervention/usual care. As no measure of variance was provided, data could not be pooled for four studies , but no between-group differences were found in the medium term. Two studies  reported data in the short term (MD 0.00 MME [95% CI − 0.00–0.00), I 2 = 0%, GRADE = moderate), but no between-group differences were found. Electrotherapy Versus Active Control No studies compared electrotherapy interventions with active control. Cryotherapy Versus Placebo/No Intervention/Usual Care Three studies  compared cryotherapy with placebo/no intervention/usual care, although all studies could not be pooled. There were no between-group differences in two studies in the medium term, but the mean daily dose in the short term was lower with cryotherapy than with placebo/no intervention/usual care. Cryotherapy Versus Active Control Two studies , which could not be pooled, compared cryotherapy with active control and reported that the mean daily dose was lower in the intervention group than with active control in the short term. In these studies, active control was cryotherapy at a different regimen from the intervention group (generally higher temperature [17–21 °C] in active control and lower temperature [11–12 °C] in the intervention). Behavioural Interventions Versus Placebo/No Intervention/Usual Care No studies reported the mean daily opioid dose in the medium term. One study  compared mobile messaging with placebo/no intervention/usual care in the short term and reported a lower dose in the intervention group. Behavioural Interventions Versus Active Control Two studies  compared behavioural interventions with active control, but no between-group differences were found in one study investigating a physical copy of an opioid prescription versus an automatically filled prescription . The other study (nurse-administered analgesia vs patient-controlled analgesia)  reported a lower dose in the control group in the short term. Other Therapies Versus Placebo/No Intervention/Usual Care Five studies  compared the intervention with placebo/no intervention/usual care. There were no significant between-group differences in the medium term (MD 0.32 MME [95% CI − 1.41–2.04], two studies , I 2 = 0%, GRADE = moderate). Clinical and statistical heterogeneity was high, so short-term data could not be pooled; however, no between-group differences were found in any study. Other Therapies Versus Active Control One study  compared the intervention with active control and found no between-group differences in the medium term but a slightly lower dose in the intervention group (cannabis) than with active control (essential oils) in the short term. Number of Participants Who Reduced or Ceased Using Opioid Analgesics Seven studies  reported on the number of participants who ceased their opioid medications. Data on two comparisons within one study of multimodal analgesia versus placebo/no intervention/usual care  found no difference between groups at all time points (RD 0.09 [95% CI − 0.04–0.23], I 2 = 13%, GRADE = moderate). All other studies could not be pooled because of high statistical heterogeneity. Overall, most studies found no differences between groups, except for one cryotherapy versus placebo/no intervention/usual care study  and one study of multimodal analgesia (combination of ketorolac and meloxicam) versus active control (traditional opioid pain protocol) , both of which favoured the intervention groups. Pain Pain intensity was reported by 34 studies . In total, 17 studies compared placebo/no intervention/usual care with multimodal analgesia , acupuncture/acupressure , electrotherapy , cryotherapy , and other therapies . There was no significant difference in pain intensity between all other therapies and placebo/no intervention/usual care in the medium term (MD 2.46 [95% CI − 4.37–9.29], two studies , I 2 = 0%, GRADE = moderate) or the short term (MD − 1.28 [95% CI − 8.39–5.83], two studies , I 2 = 0%, GRADE = low). Statistical and clinical heterogeneity was high, so other comparisons could not be pooled; however, no between-group differences were found in the medium or short term. Ten studies compared active control against multimodal analgesia , opioid analgesia , non-opioid , electrotherapy , and other therapies . Statistical and clinical heterogeneity was high, so pain scores could not be pooled for most studies. All studies found no between-group differences in the short term, except two non-opioid studies , which reported a lower pain score in the intervention group (ibuprofen  or standard bupivacaine ) than with active control (standard opioid-only regimen) (MD 2.23 [95% CI − 2.58–7.04], two studies , I 2 = 0%, GRADE = moderate). Cryotherapy was no better than active control (cryotherapy at an alternative temperature) (MD 2.93 [95% CI − 4.95–10.45], two studies , I 2 = 0%, GRADE = low) in the medium term. Additionally, a lower pain intensity was found in the active control groups (patient-controlled analgesia and general patient information) than with the behavioural interventions (nurse-administered analgesia or a physical copy of opioid prescription) in the short term. Disability Disability was reported by six studies . One study investigating other therapies  (cannabis) versus placebo/no intervention/usual care found no between-group differences (RD − 1.53 [95% CI − 6.05–3.00], I 2 = 0%, GRADE = moderate) in the medium term. Three studies comparing acupuncture/acupressure , electrotherapy , and cryotherapy  versus placebo/no intervention/usual care could not be pooled. Although a slightly lower disability score was found in the acupuncture/acupressure intervention in the short term, no between-group differences were found between other comparisons . Single studies found no between-group differences for cryotherapy (at 10 °C) versus active control (cryotherapy at 21 °C)  or other therapies (cannabis) versus active control (essential oils)  in the medium term, and an opioid analgesic (genotype-guided opioid dosing) versus active control (usual postoperative opioid dosing)  in the short term. Quality of Life Quality of life was reported by five studies  comparing other therapies , acupuncture/acupressure , electrotherapy , or cryotherapy  with placebo/no intervention/usual care in the medium or short term, or a cryotherapy  or other therapies  (cannabis) versus active control in the medium term. None of the comparisons showed a between-group difference. Adverse Events and Serious Adverse Events In total, 17 studies  reported the number of participants who experienced adverse events, and 16 studies  reported the number of participants who experienced serious adverse events. The number of adverse and serious adverse events was not significant across any intervention versus placebo/no intervention/usual care. Where meta-analysis was possible, no intervention had an increased risk of adverse events or serious adverse events. The most frequent adverse events reported across studies were common analgesia-related side effects such as nausea, drowsiness, and dizziness. Most studies reported zero serious adverse events. There were also no between-group differences in the number of (serious) adverse events between any intervention versus active control. Number of Participants Who were Taking Medications from the Benzodiazepine or Gabapentinoid Drug Classes Only three studies  reported on the number of participants taking gabapentin at the short-term time point. Heterogeneity was high and reporting unclear, so these data could not be pooled, but no study found between-group differences. 

The mean daily opioid dose was reported by all 39 studies. Meta-analyses results are shown in Figs. and . Multimodal Analgesics Versus Placebo/No Intervention/Usual Care Four studies  compared multimodal analgesics with placebo/no intervention/usual care. Statistical heterogeneity was high, so data could not be pooled, although the mean daily dose was lower across all multimodal analgesic groups than for placebo/no intervention/usual care in both the medium and short term. Multimodal Analgesics Versus Active Control Three studies  compared multimodal analgesic interventions and active control (included a standard or traditional opioid regimen). One study  (containing two separate comparisons) reported data in the medium term showing a lower daily dose in the intervention group but could not be pooled because of a lack of data. Multimodal analgesics resulted in lower mean daily doses than active control in the short term (MD − 4.34 MME [95% CI − 6.77 to − 1.90], two studies , I 2 = 0%, GRADE = low). Opioid Analgesics Versus Placebo/No Intervention/Usual Care No studies compared opioid analgesics with a placebo/no intervention/usual care control. Opioid Analgesics Versus Active Control Three studies  compared opioid analgesics and active control (minimal vs standard opioid dosage regimens). Statistical heterogeneity was high, so data could not be pooled, but no between-group differences in the mean daily dose were found in the medium or short term. Non-opioid Analgesics Versus Placebo/No Intervention/Usual Care Five studies  compared non-opioid analgesics with placebo/no intervention/usual care. No studies reported the mean daily opioid dose in the medium term. Clinical and statistical heterogeneity were high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower in the non-opioid intervention groups than with placebo/no intervention/usual care. Non-opioid Analgesics Versus Active Control Four studies  compared non-opioid analgesics with active control. Clinical and statistical heterogeneity was high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower with the non-opioid intervention than with the active control. Acupuncture/Acupressure Versus Placebo/No Intervention/Usual Care Four studies  compared acupuncture/acupressure with placebo/no intervention/usual care, one of which  (containing two separate comparisons) reported no between-group differences in the mean daily opioid dose in the medium term (MD − 1.36 MME [95% CI − 4.35–1.63], one study , I 2 = 0%, GRADE = low). In the short term, data could not be pooled for the three included studies . However, no between-group differences were found across these studies. Acupuncture/Acupressure Versus Active Control No studies compared acupuncture/acupressure interventions with active control. Electrotherapy Versus Placebo/No Intervention/Usual Care Six studies  compared electrotherapy with placebo/no intervention/usual care. As no measure of variance was provided, data could not be pooled for four studies , but no between-group differences were found in the medium term. Two studies  reported data in the short term (MD 0.00 MME [95% CI − 0.00–0.00), I 2 = 0%, GRADE = moderate), but no between-group differences were found. Electrotherapy Versus Active Control No studies compared electrotherapy interventions with active control. Cryotherapy Versus Placebo/No Intervention/Usual Care Three studies  compared cryotherapy with placebo/no intervention/usual care, although all studies could not be pooled. There were no between-group differences in two studies in the medium term, but the mean daily dose in the short term was lower with cryotherapy than with placebo/no intervention/usual care. Cryotherapy Versus Active Control Two studies , which could not be pooled, compared cryotherapy with active control and reported that the mean daily dose was lower in the intervention group than with active control in the short term. In these studies, active control was cryotherapy at a different regimen from the intervention group (generally higher temperature [17–21 °C] in active control and lower temperature [11–12 °C] in the intervention). Behavioural Interventions Versus Placebo/No Intervention/Usual Care No studies reported the mean daily opioid dose in the medium term. One study  compared mobile messaging with placebo/no intervention/usual care in the short term and reported a lower dose in the intervention group. Behavioural Interventions Versus Active Control Two studies  compared behavioural interventions with active control, but no between-group differences were found in one study investigating a physical copy of an opioid prescription versus an automatically filled prescription . The other study (nurse-administered analgesia vs patient-controlled analgesia)  reported a lower dose in the control group in the short term. Other Therapies Versus Placebo/No Intervention/Usual Care Five studies  compared the intervention with placebo/no intervention/usual care. There were no significant between-group differences in the medium term (MD 0.32 MME [95% CI − 1.41–2.04], two studies , I 2 = 0%, GRADE = moderate). Clinical and statistical heterogeneity was high, so short-term data could not be pooled; however, no between-group differences were found in any study. Other Therapies Versus Active Control One study  compared the intervention with active control and found no between-group differences in the medium term but a slightly lower dose in the intervention group (cannabis) than with active control (essential oils) in the short term. 

Four studies  compared multimodal analgesics with placebo/no intervention/usual care. Statistical heterogeneity was high, so data could not be pooled, although the mean daily dose was lower across all multimodal analgesic groups than for placebo/no intervention/usual care in both the medium and short term. 

Three studies  compared multimodal analgesic interventions and active control (included a standard or traditional opioid regimen). One study  (containing two separate comparisons) reported data in the medium term showing a lower daily dose in the intervention group but could not be pooled because of a lack of data. Multimodal analgesics resulted in lower mean daily doses than active control in the short term (MD − 4.34 MME [95% CI − 6.77 to − 1.90], two studies , I 2 = 0%, GRADE = low). 

No studies compared opioid analgesics with a placebo/no intervention/usual care control. 

Three studies  compared opioid analgesics and active control (minimal vs standard opioid dosage regimens). Statistical heterogeneity was high, so data could not be pooled, but no between-group differences in the mean daily dose were found in the medium or short term. 

Five studies  compared non-opioid analgesics with placebo/no intervention/usual care. No studies reported the mean daily opioid dose in the medium term. Clinical and statistical heterogeneity were high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower in the non-opioid intervention groups than with placebo/no intervention/usual care. 

Four studies  compared non-opioid analgesics with active control. Clinical and statistical heterogeneity was high, so short-term data could not be pooled, but all studies found that the mean daily dose was lower with the non-opioid intervention than with the active control. 

Four studies  compared acupuncture/acupressure with placebo/no intervention/usual care, one of which  (containing two separate comparisons) reported no between-group differences in the mean daily opioid dose in the medium term (MD − 1.36 MME [95% CI − 4.35–1.63], one study , I 2 = 0%, GRADE = low). In the short term, data could not be pooled for the three included studies . However, no between-group differences were found across these studies. 

No studies compared acupuncture/acupressure interventions with active control. 

Six studies  compared electrotherapy with placebo/no intervention/usual care. As no measure of variance was provided, data could not be pooled for four studies , but no between-group differences were found in the medium term. Two studies  reported data in the short term (MD 0.00 MME [95% CI − 0.00–0.00), I 2 = 0%, GRADE = moderate), but no between-group differences were found. 

No studies compared electrotherapy interventions with active control. 

Three studies  compared cryotherapy with placebo/no intervention/usual care, although all studies could not be pooled. There were no between-group differences in two studies in the medium term, but the mean daily dose in the short term was lower with cryotherapy than with placebo/no intervention/usual care. 

Two studies , which could not be pooled, compared cryotherapy with active control and reported that the mean daily dose was lower in the intervention group than with active control in the short term. In these studies, active control was cryotherapy at a different regimen from the intervention group (generally higher temperature [17–21 °C] in active control and lower temperature [11–12 °C] in the intervention). 

No studies reported the mean daily opioid dose in the medium term. One study  compared mobile messaging with placebo/no intervention/usual care in the short term and reported a lower dose in the intervention group. 

Two studies  compared behavioural interventions with active control, but no between-group differences were found in one study investigating a physical copy of an opioid prescription versus an automatically filled prescription . The other study (nurse-administered analgesia vs patient-controlled analgesia)  reported a lower dose in the control group in the short term. 

Five studies  compared the intervention with placebo/no intervention/usual care. There were no significant between-group differences in the medium term (MD 0.32 MME [95% CI − 1.41–2.04], two studies , I 2 = 0%, GRADE = moderate). Clinical and statistical heterogeneity was high, so short-term data could not be pooled; however, no between-group differences were found in any study. 

One study  compared the intervention with active control and found no between-group differences in the medium term but a slightly lower dose in the intervention group (cannabis) than with active control (essential oils) in the short term. 

Seven studies  reported on the number of participants who ceased their opioid medications. Data on two comparisons within one study of multimodal analgesia versus placebo/no intervention/usual care  found no difference between groups at all time points (RD 0.09 [95% CI − 0.04–0.23], I 2 = 13%, GRADE = moderate). All other studies could not be pooled because of high statistical heterogeneity. Overall, most studies found no differences between groups, except for one cryotherapy versus placebo/no intervention/usual care study  and one study of multimodal analgesia (combination of ketorolac and meloxicam) versus active control (traditional opioid pain protocol) , both of which favoured the intervention groups. 

Pain intensity was reported by 34 studies . In total, 17 studies compared placebo/no intervention/usual care with multimodal analgesia , acupuncture/acupressure , electrotherapy , cryotherapy , and other therapies . There was no significant difference in pain intensity between all other therapies and placebo/no intervention/usual care in the medium term (MD 2.46 [95% CI − 4.37–9.29], two studies , I 2 = 0%, GRADE = moderate) or the short term (MD − 1.28 [95% CI − 8.39–5.83], two studies , I 2 = 0%, GRADE = low). Statistical and clinical heterogeneity was high, so other comparisons could not be pooled; however, no between-group differences were found in the medium or short term. Ten studies compared active control against multimodal analgesia , opioid analgesia , non-opioid , electrotherapy , and other therapies . Statistical and clinical heterogeneity was high, so pain scores could not be pooled for most studies. All studies found no between-group differences in the short term, except two non-opioid studies , which reported a lower pain score in the intervention group (ibuprofen  or standard bupivacaine ) than with active control (standard opioid-only regimen) (MD 2.23 [95% CI − 2.58–7.04], two studies , I 2 = 0%, GRADE = moderate). Cryotherapy was no better than active control (cryotherapy at an alternative temperature) (MD 2.93 [95% CI − 4.95–10.45], two studies , I 2 = 0%, GRADE = low) in the medium term. Additionally, a lower pain intensity was found in the active control groups (patient-controlled analgesia and general patient information) than with the behavioural interventions (nurse-administered analgesia or a physical copy of opioid prescription) in the short term. 

Disability was reported by six studies . One study investigating other therapies  (cannabis) versus placebo/no intervention/usual care found no between-group differences (RD − 1.53 [95% CI − 6.05–3.00], I 2 = 0%, GRADE = moderate) in the medium term. Three studies comparing acupuncture/acupressure , electrotherapy , and cryotherapy  versus placebo/no intervention/usual care could not be pooled. Although a slightly lower disability score was found in the acupuncture/acupressure intervention in the short term, no between-group differences were found between other comparisons . Single studies found no between-group differences for cryotherapy (at 10 °C) versus active control (cryotherapy at 21 °C)  or other therapies (cannabis) versus active control (essential oils)  in the medium term, and an opioid analgesic (genotype-guided opioid dosing) versus active control (usual postoperative opioid dosing)  in the short term. 

Quality of life was reported by five studies  comparing other therapies , acupuncture/acupressure , electrotherapy , or cryotherapy  with placebo/no intervention/usual care in the medium or short term, or a cryotherapy  or other therapies  (cannabis) versus active control in the medium term. None of the comparisons showed a between-group difference. 

In total, 17 studies  reported the number of participants who experienced adverse events, and 16 studies  reported the number of participants who experienced serious adverse events. The number of adverse and serious adverse events was not significant across any intervention versus placebo/no intervention/usual care. Where meta-analysis was possible, no intervention had an increased risk of adverse events or serious adverse events. The most frequent adverse events reported across studies were common analgesia-related side effects such as nausea, drowsiness, and dizziness. Most studies reported zero serious adverse events. There were also no between-group differences in the number of (serious) adverse events between any intervention versus active control. 

Only three studies  reported on the number of participants taking gabapentin at the short-term time point. Heterogeneity was high and reporting unclear, so these data could not be pooled, but no study found between-group differences. 

This review investigated interventions aiming to reduce the use of opioid analgesics after orthopaedic surgery and found 39 studies covering a wide range of pharmacological and non-pharmacological interventions. At the medium-term time point (1–3 months after randomisation) results based on individual studies found that multimodal analgesic interventions were more effective at reducing opioid use than were placebo/no intervention/usual care or active control. However, studies found that non-pharmacological interventions compared with placebo/no intervention/usual care, or opioid analgesic interventions compared with active control, were not effective at reducing opioid use in the medium term. At the short-term time point (< 30 days), multimodal analgesia, non-opioid analgesia, and cryotherapy interventions reduced opioid use when compared with placebo/no intervention/usual care or active control, based on either low-certainty evidence or individual studies. Opioid analgesia and non-pharmacological interventions were not effective compared with placebo/no intervention/usual care or active control in the short term. Additionally, no difference was found for most interventions compared with placebo/no intervention/usual care or active control in all secondary and safety outcomes at the medium- and short-term time points. No studies measured long-term outcomes. Similar to this review, other studies  have also found multimodal or non-opioid analgesia interventions to be more effective in decreasing opioid consumption in the general postoperative period than placebo, no intervention, or active control. This is because the perioperative use of non-steroidal anti-inflammatories (NSAIDs) or paracetamol in addition to opioids provides an additive, if not synergistic, analgesic effect, thus reducing opioid consumption when compared with opioids alone . Therefore, the use of multimodal or non-opioid medications has been framed as ‘opioid-sparing’ analgesia and become part of the postoperative standard of care to reduce the risk of persistent opioid use . In addition, this review found moderate-certainty evidence that non-opioid analgesics such as NSAIDs or paracetamol, in addition to opioids, may result in greater pain reduction than opioids alone in the short term. This finding is similar to those of other studies looking at interventions to reduce opioid use in chronic pain settings, where various opioid-reduction interventions are also not associated with an increase in pain levels . This further supports evidence that opioid-reduction interventions can provide sufficient pain relief while reducing the risks of harm from opioids . The primary time point for this review was the medium-term postoperative period (1–3 months after randomisation), which was determined based on the nature of acute pain that should resolve within 3 months and that opioid use is considered persistent beyond this time . Most studies included in this review reported their outcomes within the short term (< 1 month), and studies reporting outcomes in the long term (> 90 days) were scarce. Additionally, half of the surgeries investigated in this review were total knee and total hip arthroplasty, which are characterised by significant pain and rehabilitation . Different orthopaedic surgeries can vary in pain severity and length of recovery and therefore may require different opioid-reduction strategies. With all these factors in mind, future randomised controlled trials can investigate long-term outcomes of various interventions such as those investigated in this review and include different types of orthopaedic surgeries to determine whether a short-term decrease in opioid use continues into long-term opioid cessation . Additionally, although evidence has found that preoperative opioid consumption is one of the greatest predictors of persistent opioid use after surgery, this review did not investigate whether patients who had prior use of opioids or were opioid naïve before their surgery would require different deprescribing interventions. This could be another direction for future research. A main strength of this review was that, to our knowledge, it is the first to investigate a wide variety of interventions to reduce opioid use after orthopaedic surgery, implemented specifically in the postoperative period. However, the diversity of studies in this review was also a limitation because of the low number of studies within each comparison and high statistical or clinical heterogeneity. This often meant that data from most studies could not be pooled. The low certainty of evidence was also impacted by small sample sizes and the risk of bias due to blinding, incomplete outcome data, and selective reporting. Overall, this indicates clinical uncertainty about what interventions are effective at reducing opioid use after orthopaedic surgery. 

This review found, from single studies, that multimodal analgesic interventions resulted in reduced opioid use compared with placebo/no intervention/usual care or active control in the medium term. However, the high statistical and clinical heterogeneity and low quality of evidence means it remains uncertain which interventions are effective in reducing opioid use after orthopaedic surgery. 

Below is the link to the electronic supplementary material. Supplementary file1 (DOCX 65 KB) Supplementary file2 (DOCX 828 KB) 

