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IA injection of morphine + bupivacaine vs. morphine alone for analgesia after arthroscopy

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IA injection of morphine + bupivacaine vs. morphine alone for analgesia after arthroscopy

Vol: 5| Issue: 1| Number:73| ISSN#: 2564-2537
Study Type:Meta-analysis/Systematic Review
OE Level Evidence:1
Journal Level of Evidence:1

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

PLoS One. 2015 Oct 16;10(10):e0140512

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13 randomized controlled trials were included in this systematic review and meta-analysis to determine the safety and efficacy of a single intra-articular injection of morphine + bupivacaine compared to morphine alone in managing pain after knee arthroscopy. Pooled analysis found combined treatment to significantly lower pain in the immediate postoperative period (0-2 hours) and significantly increase the time to first request for rescue analgesia compared to morphine alone. No significant differences in pain intensity from 2-48 hours or in the number of patients requiring rescue analgesia was observed between groups. Qualitative analysis found adverse events to be similar between treatment groups.

Publication Funding Details +
Non-Industry funded
The National Natural Science Foundation of China
None disclosed

Risk of Bias


Reporting Criteria


Fragility Index


Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.




Accessing Data


Analysing Data





Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

Knee arthroscopy is a procedure often accompanied by moderate-to-severe postoperative pain, making pain management an important consideration for patient recovery and decreased length of hospital stay. Intra-articular (IA) injections of local anaesthetic and analgesics have gained popularity given their practical application. Two common treatments with different mechanisms of action include morphine and bupivacaine. While both have proven effective in IA injection, their onset and duration of action vary. A combination of these two drugs may provide an earlier onset and longer duration of analgesia. However, previous studies have shown conflicting evidence regarding the efficacy of combination treatment over morphine alone, indicating a need for the present systematic review and meta-analysis.

What was the principal research question?

How safe and efficacious is a single-dose intra-articular injection of morphine plus bupivacaine in comparison to morphine alone in managing pain up to 48 hours after knee arthroscopy?

Study Characteristics -
Data Source:
An electronic database search was conducted using MEDLINE/PubMed, the Cochrane Central Register Trials (CENTRAL) and Embase, for English studies up to August 10, 2014. Reference lists of selected articles and recent reviews were additionally searched.
Index Terms:
Search terms included: "arthroscopy", "arthroscopic", "arthroscope", "anterior cruciate ligament", "bupivacaine", "morphine", "randomized controlled trial".
Study Selection:
Two independent reviewers assessed articles for adherence to inclusion criteria, and disagreements were resolved by consensus or judgement by a third reviewer. Inclusion criteria were randomized controlled trials (RCTs) on patients undergoing knee arthroscopy, with experimental groups receiving a combination of IA morphine and bupivacaine, control group receiving morphine only, and both groups not given other analgesics (13 RCT's [564 patients] included, 11 utilized in quantitative analysis).
Data Extraction:
Two independent reviewers extracted data using a standardized form. Postoperative pain intensity measured on a visual analogue scale (VAS) was the primary outcome. Secondary outcomes included time to first rescue medication, number of patients requiring supplementary analgesia, and adverse reactions.
Data Synthesis:
Review Manager 5.2 was used for meta-analyses. Continuous outcomes were reported as weighted mean difference (WMD) and dichotomous outcomes as relative risk (RR), both with corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the Q and I2 statistics with a p value>0.05 and an I2 > 50% indicating statistical heterogeneity. A random effects model was used in the case of significant heterogeneity, otherwise a fixed effect model was used for meta-analyses. Sensitivity analyses were conducted, publication bias was assessed using the Begg's test and funnel plots, and study quality was assessed by 2 independent reviewers using the Modified Oxford Scale.

What were the important findings?

  • During the immediate post-operative period (0-2h), the combined treatment group showed a significantly lower postoperative pain intensity compared with the morphine group (9 studies; 305 patients; WMD: -1.16 [95% CI -2.01, -0.31]; p=0.007; I2=82%)
  • During the early post-operative (2-6h) and late post-operative (6-48h) periods, no significant difference in pain intensity was observed between groups (Early: 8 studies; 237 patients; WMD: -0.36 [95% CI -1.13, 0.41]; p=0.35; I2=67% | Late: 8 studies; 257 patients; WMD: 0.32 [95% CI -0.32, 0.95]; p=0.33; I2=61%)
  • Time to first analgesic request was significantly greater in the combined treatment group compared with the morphine group (4 studies; 216 patients; WMD: 2.05 [95% CI 0.19, 3.92]; p=0.03; I2=95%)
  • No significant difference was observed between groups in the number of patients requiring supplementary analgesia (6 studies; 146 patients; RR: 0.78 [95% CI 0.57, 1.05]; p=0.10; I2=0%)
  • Sensitivity analyses confirmed all quantitative results except for difference in time to first analgesic request, which became insignificant between groups when studies that used epinephrine in the intervention treatment were removed (WMD: 2.20 [95% CI 0.01, 4.40]; p=0.05; I2=97%)
  • Adverse events were reported in 7 of 13 studies: 2 studies observed urinary retention, nausea and vomiting with no significant differences between groups, 4 studies found no adverse effects in either group

What should I remember most?

Following knee arthroscopy, a combined intra-articular injection of morphine and bupivacaine significantly lowered immediate (0-2 hours) postoperative pain intensity and increased time to first request for rescue analgesia compared to morphine alone. Sensitivity analysis removing studies which used epinephrine resulted in a nonsignificant between group difference in time to first analgesic request. No significant differences were observed between groups in terms of pain intensity during the early and late post-operative period (2-48 hours) or number of patients requiring rescue analgesia. Qualitative analysis found no significant difference in adverse events between groups.

How will this affect the care of my patients?

Results suggest that for patients undergoing knee arthroscopy, administration of a single intra-articular injection of morphine plus bupivacaine provides better immediate pain relief and extended time until first analgesic request as compared to an injection of morphine alone, with no difference in adverse events. Further high-quality RCTs with homogeneous reporting methods and longer follow-up periods are required to effectively assess adverse events through pooled analysis.

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