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.

Objectives

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.

Search 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.

Selection criteria

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.

Data collection and analysis

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.

Main 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.

Authors' 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.

Author(s)

Zui Zou, Mao Mao An, Qun Xie, Xiaoyan Y Chen, Hao Zhang, Guan J Liu, Xue Y Shi

Abstract

Plain language summary

Morphine injections for pain relief after knee arthroscopy

Background

Knee arthroscopy is a surgical procedure on the knee. The surgery is minimally invasive, which means that only a small cut (incision) is needed. An examination, and sometimes treatment, of damage is performed using an arthroscope, which is inserted into the joint through the small incision. Knee arthroscopy is used to assess or treat many orthopaedic (musculoskeletal) conditions, and patients may have pain after surgery. Morphine injected directly into the knee (intra‐articular morphine) to relieve pain has been widely studied, but we do not know how well it works.

Key results and quality of the evidence

In May 2015, this review identified 28 small, low quality studies involving 2564 participants looking at intra‐articular morphine for pain relief after knee arthroscopy. From 9/20 studies we did not find evidence that intra‐articular morphine given at a dose of 1 mg was better than placebo for pain relief. From the limited evidence available we were unable to determine how intra‐articular morphine compared with morphine injected into the muscle (intra‐muscular morphine). There was also low quality evidence for the effects of 1 mg intra‐articular morphine compared with intra‐articular bupivacaine, non‐steroidal anti‐inflammatory drugs (NSAIDs), sufentanil, fentanyl and pethidine, so we were unsure which worked best. We were unable to determine how similar the rates of side effects such as nausea and vomiting were between intra‐articular morphine and placebo. Overall, the quality of the evidence was low.

Future research should focus on finding effective analgesics for knee arthroscopy.

Author(s)

Zui Zou, Mao Mao An, Qun Xie, Xiaoyan Y Chen, Hao Zhang, Guan J Liu, Xue Y Shi

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

This review did not find 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.

Implications for research 

Though many trials in this area have been conducted, the quality of reporting in these trials is disappointing. Most of the included studies were of small size, so likely to introduce bias and make the conclusions less robust. Some of the studies did not set a primary end point or calculate sample size. Most studies were published at least ten years before we ran our search. Data from the studies were insufficient to show whether IA morphine is beneficial or not.

New standards for clinical trials are now in place, which aim to make clinical trials more strict and precise. Several previous systematic reviews reached different conclusions to this review, but high quality trials with at least 200 participants in each arm are needed to get a more conclusive result of the efficacy and safety of single dose intra‐articular morphine for post‐operative pain after knee arthroscopy. Future trials should focus on quality of reporting, for example by specifying the randomisation process and attempting to conceal allocation of participants to study groups. Better reporting of adverse events and withdrawal is required to fully evaluate the safety of morphine. The incidence of adverse events and their severity should be clearly reported in the trials.

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