Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors as adjuncts for postoperative pain management: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis to assess effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as adjuncts for postoperative pain management. METHODS: We searched seven databases and two trial registers from inception to February 2021 for RCTs that compared SSRIs or SNRIs with placebo or an active control for postoperative pain management. RESULTS: We included 24 RCTs with 2197 surgical patients (21 trials for SNRIs and three trials for SSRIs). Moderate-quality evidence found that, compared with placebo, SSRIs/SNRIs (majority SNRIs) significantly reduced postoperative pain within 6 h {weighted mean difference (WMD) -0.73 cm on a 10 cm VAS (95% confidence interval [CI]: -1.04 to -0.42)}, 12 h (-0.68 cm [-1.28 to -0.07]), 24 h (-0.68 cm [-1.16 to -0.20]), 48 h (-0.73 cm [-1.22 to -0.23]), 10 days to 1 month (-0.71 cm [-1.11 to -0.31]), 3 months (-0.64 cm [-1.05 to -0.22]), and 6 months (-0.95 cm [-1.64 to -0.25]), and opioid consumption within 24 h (WMD -12 mg [95% CI: -16 to -8]) and 48 h (-10 mg [-15 to -5]), and improved patient satisfaction (WMD 0.49 point on a 1-4 Likert scale [95% CI: 0.09 to 0.89]) without significant increase in adverse events. Selective serotonin reuptake inhibitors tended to be less effective despite non-significant subgroup effects. CONCLUSIONS: Serotonin-norepinephrine reuptake inhibitors as an adjunct to standard perioperative care probably provide small reduction in both acute and chronic postoperative pain and opioid consumption, and small improvement in patient satisfaction without increases in adverse events. The effects of SSRIs are inconclusive because of very limited evidence.

Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.

Benefits of Transversus Abdominis Plane Block on Postoperative Analgesia after Bariatric Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing bariatric surgery present unique analgesic challenges, including poorly controlled pain, increased prevalence of obstructive sleep apnea, and opioid-induced respiratory depression. The transversus abdominis plane (TAP) has been demonstrated to be a safe and effective component of multimodal analgesia for a variety of abdominal surgeries. OBJECTIVE: To determine the benefits of the TAP block on postoperative analgesia and recovery in patients undergoing bariatric surgery. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs) and non-randomized studies. METHODS: We conducted a comprehensive search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to April 2020 for studies using TAP block in bariatric surgeries and reporting postoperative pain, opioid consumption, and recovery-related outcomes. Primary outcomes included postoperative pain scores, opioid consumption, and recovery-related outcomes (e.g., length of stay, time to ambulation). Outcomes were pooled using random effects model and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Twenty-one studies (15 RCTs [n = 1410] and 6 nonrandomized studies [n = 1959]) were included. Among RCTs, the TAP block group required fewer opioid rescues (RR 0.28; 95% CI 0.18 to 0.42, P < 0.001) (moderate quality); reduced total opioid use over 24 hours (MD -8.33; 95% CI -14.78 to -1.89, P = 0.01); decreased time to ambulation (MD -1.12 hours; 95% CI -1.50 to -0.73, P < 0.001) (high quality); and had significantly lower pain scores at 6 hours (MD -1.52; 95% CI -1.90 to -1.13, P < 0.01) and 12 hours (MD -0.95; 95% CI -1.34 to -0.56, P < 0.001) on a 0-10 pain scale (moderate quality). No difference was observed for nausea and vomiting, or hospital length of stay. Meta-analyzed outcomes from observational studies supported these results, suggesting decreased postoperative pain and opioid consumption. LIMITATIONS: Studies varied with respect to type of surgery and components of comparator multimodal analgesia, likely contributing to heterogeneity. Subgroup analyses by type of comparator group were conducted to address these differences. We were unable to extract data from all trials included due to variability in outcomes reporting, such as non-opioid drugs for postoperative pain management or invalid dosages. Pain-related outcomes may be affected by operative differences leading to variation in visceral pain. Observational studies have their inherent limitations, such as confounding due to lack of participant randomization and intervention blinding, potentially affecting subjective outcomes, such as pain scores, as well as provider-dependent outcomes, such as hospital length of stay. Lastly, there was significant variation of TAP block technique across all studies. CONCLUSION: TAP block is an effective, safe modality that can be performed under anesthesia. It decreases pain, opioid use, and time to ambulation after bariatric surgeries and should be considered in multimodal analgesia for enhanced recovery in this high-risk surgical population.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. PURPOSE: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. STUDY SELECTION: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. DATA EXTRACTION: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). LIMITATIONS: Only English-language studies were included. The number of head-to-head comparisons was limited. CONCLUSION: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. PRIMARY FUNDING SOURCE: National Safety Council. (PROSPERO: CRD42018094412).

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence. RESULTS: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%). CONCLUSIONS: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.

Management of acute musculoskeletal pain (excluding low back pain): protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: Acute, non-low back-related musculoskeletal pain is common and associated with significant socioeconomic costs. No review has evaluated all interventional studies for acute musculoskeletal pain, which limits attempts to make inferences regarding the relative effectiveness of treatments. METHODS AND ANALYSIS: We will conduct a systematic review of all randomised controlled trials evaluating therapies for acute musculoskeletal pain (excluding low back pain). We will identify eligible, English-language, trials by a systematic search of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, Physiotherapy Evidence Database (PEDro) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to February 2018. Eligible trials will: (1) enrol patients presenting with acute, non-low back-related musculoskeletal pain (duration of pain ≤4 weeks), and (2) randomise patients to alternative interventions or an intervention and a placebo/sham arm. Fractures will be considered ineligible, unless they are non-surgical and therapy is directed at pain relief. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. Disagreements will be resolved through discussion to achieve consensus. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence supporting treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effect meta-analysis to establish the effectiveness of therapeutic interventions on patient-important outcomes; and (2) multiple treatment comparison meta-analysis to assess the relative effects of treatments. We will use a priori hypotheses to explain heterogeneity between studies. We will use STATA V.14.2 for all analyses. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. The results of this systematic review will be disseminated through publication in a peer-reviewed journal, conference presentations and will inform a clinical practice guideline. PROSPERO REGISTRATION NUMBER: CRD42018094412.

Attitudes Toward and Management of Fibromyalgia: A National Survey of Canadian Rheumatologists and Critical Appraisal of Guidelines.

BACKGROUND: Canadian rheumatologists' attitudes toward and management of fibromyalgia remain uncertain. OBJECTIVE: The aim of this study was to explore management strategies and attitudes of Canadian rheumatologists toward fibromyalgia and concordance with guideline recommendations. METHODS: We administered a 17-item cross-sectional survey to Canadian rheumatologists and explored the concordance between respondents' management practices with the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia. RESULTS: Among 331 Canadian rheumatologists who were approached, 140 returned the survey for a 42% response rate. The majority felt that fibromyalgia was a useful clinical diagnosis (110/138 [80%]) but was divided as to whether fibromyalgia was objectively defined (75/138 [54%]) or a psychosocial condition (42/138 [30%]) or could result in an inability to work (37/138 [27%]). Contrary to guideline recommendations, most (82/134 [61%]) endorsed that tender points were useful for diagnosis. Half endorsed potentially refusing consultations with fibromyalgia patients, and only 42% (59/139) agreed that there were effective therapies for this syndrome. Consistent with the guideline, most respondents managed fibromyalgia with education, exercise therapy, antidepressants, and nonnarcotic analgesics (≥89% for all); however, fewer than half agreed that any of these modalities were effective (endorsement ranged from 9% to 47%). Assessment of the 2012 guideline revealed a number of important limitations. CONCLUSIONS: Canadian rheumatologists largely do not provide primary care for fibromyalgia. Most adhere to guideline recommendations for management of fibromyalgia, but few endorse these interventions as effective. Further research, including updating of the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia, is required to inform this disconnect.