title: Single dose intra-articular morphine for pain control after knee arthroscopy.
abstract: BACKGROUND
  Knee arthroscopy is a common procedure and is associated with postoperative pain. Intra-articular (IA) injection of morphine for pain control has been widely studied, but its analgesic effect after knee arthroscopy is uncertain.
  
  
  OBJECTIVE
  To evaluate the relative effects on pain relief and adverse events of IA morphine given for pain control after knee arthroscopy compared with placebo, other analgesics (local anaesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), other opioids) and other routes of morphine administration.
  
  
  METHODS
  We searched CENTRAL (The Cochrane Library Issue 4, 2015), MEDLINE via Ovid (January 1966 to May 2015), EMBASE via Ovid (January 1988 to May 2015), and the reference lists of included articles. We also searched the metaRegister of controlled trials, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials.
  
  
  METHODS
  We identified all the randomised, double-blind controlled trials that compared single dose IA morphine with other interventions for the treatment of postoperative pain after knee arthroscopy. We excluded studies with fewer than 10 participants in each group, using spinal or epidural anaesthesia, or assessing the analgesic effect of IA morphine on chronic pain.
  
  
  METHODS
  Two authors independently assessed the quality of each trial and extracted information on pain intensity, supplementary analgesics consumption and adverse events. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables.
  
  
  RESULTS
  We included 28 small, low quality studies (29 reports) involving 2564 participants. Of 20 studies (21 reports) comparing morphine with placebo, nine studies with adequate data were included in the meta-analysis. Overall, the risk of bias was unclear. Overall, the quality of the evidence assessed using GRADE was low to very low, downgraded primarily due to risk of bias, small study size, and imprecision.No statistical difference was found between 1 mg IA morphine and placebo in pain intensity (visual analogue scale (VAS)) at early phase (zero to two hours) (mean difference (MD) -0.50, 95% CI -1.15 to 0.14; participants = 297; studies = 7; low quality evidence), medium phase (two to six hours) (MD -0.47, 95% CI -1.09 to 0.14; participants = 297; studies = 7; low quality evidence) and late phase (six to 30 hours) (MD -0.88, 95% CI -1.81 to 0.04; participants = 297; studies = 7; low quality evidence). No significant difference was found between 1 mg and 2 mg morphine for pain intensity at early phase (MD -0.56, 95% CI -1.93 to 0.81; participants = 105; studies = 2; low quality evidence), while 4 mg/5 mg morphine provided better analgesia than 1 mg morphine at late phase (MD 0.67, 95% CI 0.08 to 1.25; participants = 97; studies = 3; low quality evidence). IA morphine was not better than local anaesthetic agents at early phase (MD 1.43, 95% CI 0.49 to 2.37; participants = 248; studies = 5; low quality evidence), NSAIDs at early phase (MD 0.95, 95% CI -0.95 to 2.85; participants = 80; studies = 2; very low quality evidence), sufentanil, fentanyl or pethidine for pain intensity. IA morphine was similar to intramuscular (IM) morphine for pain intensity at early phase (MD 0.21, 95% CI -0.48 to 0.90; participants = 72; studies = 2; very low quality evidence).Meta-analysis indicated that there was no difference between IA morphine and placebo or bupivacaine in time to first analgesic request. Eleven out of 20 studies comparing morphine with placebo reported adverse events and no statistical difference was obtained regarding the incidence of adverse events (risk ratio (RR) 1.09, 95% CI 0.51 to 2.36; participants = 314; studies = 8; low quality evidence). Seven of 28 studies reported participants' withdrawal. There were not enough data for withdrawals to be able to perform meta-analysis.
  
  
  CONCLUSIONS
  We have not found high quality evidence that 1 mg IA morphine is better than placebo at reducing pain intensity at early, medium or late phases. No statistical difference was reported between IA morphine and placebo regarding the incidence of adverse events. The relative effects of 1 mg morphine when compared with IA bupivacaine, NSAIDs, sufentanil, fentanyl and pethidine are uncertain. The quality of the evidence is limited by high risk of bias and small size of the included studies, which might bias the results. More high quality studies are needed to get more conclusive results.
authors.affiliation: Department of Anaesthesiology, Changzheng Hospital, The Second Military Medical University, No 415, Feng Yang Road, Shanghai, Shanghai, China, 200003.
authors.forename: Zui
authors.initials: Z
authors.lastname: Zou
authors.forename: Mao Mao
authors.initials: MM
authors.lastname: An
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.forename: Xiao Y
authors.initials: XY
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Guan J
authors.initials: GJ
authors.lastname: Liu
authors.forename: Xue Y
authors.initials: XY
authors.lastname: Shi
mesh_terms: D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001182:Arthroscopy / Q000009:adverse effects*; D004333:Drug Administration Routes; D006801:Humans; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000601:surgery*; D009020:Morphine / Q000008:administration & dosage*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009020:Morphine