Opioid versus opioid-free analgesia after surgical discharge: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Excessive opioid prescribing after surgery has contributed to the current opioid crisis; however, the value of prescribing opioids at surgical discharge remains uncertain. We aimed to estimate the extent to which opioid prescribing after discharge affects self-reported pain intensity and adverse events in comparison with an opioid-free analgesic regimen. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, Scopus, AMED, Biosis, and CINAHL from Jan 1, 1990, until July 8, 2021. We included multidose randomised controlled trials comparing opioid versus opioid-free analgesia in patients aged 15 years or older, discharged after undergoing a surgical procedure according to the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity definition (minor, moderate, major, and major complex). We screened articles, extracted data, and assessed risk of bias (Cochrane's risk-of-bias tool for randomised trials) in duplicate. The primary outcomes of interest were self-reported pain intensity on day 1 after discharge (standardised to 0-10 cm visual analogue scale) and vomiting up to 30 days. Pain intensity at further timepoints, pain interference, other adverse events, risk of dissatisfaction, and health-care reutilisation were also assessed. We did random-effects meta-analyses and appraised evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluations scoring system. The review was registered with PROSPERO (ID CRD42020153050). FINDINGS: 47 trials (n=6607 patients) were included. 30 (64%) trials involved elective minor procedures (63% dental procedures) and 17 (36%) trials involved procedures of moderate extent (47% orthopaedic and 29% general surgery procedures). Compared with opioid-free analgesia, opioid prescribing did not reduce pain on the first day after discharge (weighted mean difference 0·01cm, 95% CI -0·26 to 0·27; moderate certainty) or at other postoperative timepoints (moderate-to-very-low certainty). Opioid prescribing was associated with increased risk of vomiting (relative risk 4·50, 95% CI 1·93 to 10·51; high certainty) and other adverse events, including nausea, constipation, dizziness, and drowsiness (high-to-moderate certainty). Opioids did not affect other outcomes. INTERPRETATION: Findings from this meta-analysis support that opioid prescribing at surgical discharge does not reduce pain intensity but does increase adverse events. Evidence relied on trials focused on elective surgeries of minor and moderate extent, suggesting that clinicians can consider prescribing opioid-free analgesia in these surgical settings. Data were largely derived from low-quality trials, and none involved patients having major or major-complex procedures. Given these limitations, there is a great need to advance the quality and scope of research in this field. FUNDING: The Canadian Institutes of Health Research.

Preventing opioid prescription after major surgery: a scoping review of opioid-free analgesia.

BACKGROUND: Excessive opioid prescribing after surgery has been recognised as a contributor to the current crisis of opioid addiction and overdose. Clinicians may potentially tackle this crisis by using opioid-free postoperative analgesia; however, the scientific literature addressing this approach is sparse and heterogeneous, thereby limiting robust conclusions. A scoping review was conducted to systematically map the extent, range, and nature of the literature addressing postoperative opioid-free analgesia. METHODS: Eight bibliographic databases were searched for studies addressing opioid-free analgesia after a major surgery. We extracted the study characteristics, including design, country, year, surgical procedure(s), and interventions. Results were organised thematically according to surgical specialty and targeted phase of recovery: in hospital (early recovery, ≤24 h after operation; intermediate recovery, >24 h) and post-discharge (late recovery). Reporting was according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for scoping reviews. RESULTS: We identified 424 studies addressing postoperative opioid-free analgesia. The number of studies conducted in countries where the opioid crisis is primarily focused was remarkably low (USA, n=11 [3%]; Canada, n=5 [1%]). Many RCTs compared opioid-free vs opioid analgesia during hospital stay (n=117), but few targeted analgesia post-discharge (n=8). Studies were predominantly focused on procedures in orthopaedic, general, and gynaecological/obstetric surgery. Limited attention has been directed towards non-pharmacological pain interventions. We did not identify knowledge synthesis studies (i.e. systematic reviews and meta-analyses) focused on the comparative effectiveness of opioid-free vs opioid analgesia. CONCLUSIONS: Opioids remain a mainstay analgesic for managing pain after surgery, but alternative analgesia strategies should not be overlooked. This scoping review indicates numerous opportunities for future research targeting opioid-free postoperative analgesia. REVIEW REGISTRATION: http://www.researchregistry.com; ID: reviewregistry576.

Evaluation of New Tests and Interventions for Prostate Cancer Management: A Systematic Review.

Background: Inaccurate risk classification and the burden of unnecessary biopsies are a challenge due to the limited ability of current risk assessment tools and modalities to diagnose prostate cancer (PCa) and distinguish indolent from aggressive disease. This systematic review assesses newly developed tests and interventions with high evidence of clinical utility that might be adopted in clinical practice during PCa management before initial and repeat biopsy, after positive biopsy, and after radical treatment. Methods: The Cochrane, Embase, MEDLINE, and Web of Science databases were searched for studies pertaining to the clinical utility of PCa diagnostic tests. Outcomes of interest were (1) a measure of the percentage of altered decision-making, (2) decrease in number of unnecessary biopsies, (3) decrease or increase in treatment intensity, and (4) risk reclassification after test results. Results: The search yielded 2,940 articles, of which 46 met the inclusion criteria. We found clinical utility evidence on the Prostate Health Index (PHI), 4Kscore test, MRI, OncotypeDX, Decipher test, Prolaris, ConfirmMDx, Progensa PCA3, NADiA ProsVue, and ProMark. No evidence was identified for Prostarix, ProstaVysion, Prostate Core Mitomic Test, and Mi-Prostate Score. The interventions demonstrated their clinical utility in terms of change in treatment recommendations, decrease/increase in interventional treatment, decrease in biopsy, and risk reclassification. At diagnosis after a positive biopsy, ProMark, OncotypeDX, Prolaris, and MRI guided the use of active surveillance. Use of NADiA ProsVue, Decipher, and Prolaris aided in the decision to add adjuvant therapy post-prostatectomy. PHI, 4Kscore, and MRI used prior initial and repeat biopsies, and ConfirmMDx and Progensa PCA3 used prior repeat biopsies to improve prediction of biopsy outcome, allowing a decrease in unnecessary biopsies. Conclusions: This systematic review suggests that implementation of these tests in clinical practice could effectuate personalized treatment of PCa. Further clinical and economic evaluation studies of long-term PCa outcomes are warranted to provide further guidance.

Opioid versus opioid-free analgesia after surgical discharge: protocol for a systematic review and meta-analysis.

INTRODUCTION: Excessive prescribing after surgery has contributed to a public health crisis of opioid addiction and overdose in North America. However, the value of prescribing opioids to manage postoperative pain after surgical discharge remains unclear. We propose a systematic review and meta-analysis to assess the extent to which opioid analgesia impact postoperative pain intensity and adverse events in comparison to opioid-free analgesia in patients discharged after surgery. METHODS AND ANALYSIS: Major electronic databases (MEDLINE, Embase, Cochrane Library, Scopus, AMED, BIOSIS, CINAHL and PsycINFO) will be searched for multi-dose randomised-trials examining the comparative effectiveness of opioid versus opioid-free analgesia after surgical discharge. Studies published from January 1990 to July 2019 will be targeted, with no language restrictions. The search will be re-run before manuscript submission to include most recent literature. We will consider studies involving patients undergoing minor and major surgery. Teams of reviewers will, independently and in duplicate, assess eligibility, extract data and evaluate risk of bias. Our main outcomes of interest are pain intensity and postoperative vomiting. Study results will be pooled using random effects models. When trials report outcomes for a common domain (eg, pain intensity) using different scales, we will convert effect sizes to a common standard metric (eg, Visual Analogue Scale). Minimally important clinical differences reported in previous literature will be considered when interpreting results. Subgroup analyses defined a priori will be conducted to explore heterogeneity. Risk of bias will be assessed according to the Cochrane Collaboration's Risk of Bias Tool 2.0. The quality of evidence for all outcomes will be evaluated using the GRADE rating system. ETHICS AND DISSEMINATION: Ethical approval is not required since this is a systematic review of published studies. Our results will be published in a peer-reviewed journal and presented at relevant conferences. Further knowledge dissemination will be sought via public and patient organisations focussed on pain and opioid-related harms.