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KSR Number: KSRA13614

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain

  • Cochrane Database Syst Rev 2017, 2, CD011419, 10.1002/14651858.CD011419.pub2
  • Full report

Risk of Bias Assessment

Overall summary: Low risk of bias in the review

Bottom Line

The evidence suggested that liposomal bupivacaine appeared to reduce postoperative pain when compared to placebo at the site of surgery. The findings were likely to be reliable. Furthermore, large randomised controlled trials on the role of liposomal bupivacaine in this area were needed to support the current findings.

Risk of Bias Assessment

Overall summary Low risk of bias in the review

Low

All domains were considered at low concern.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably yes
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Low

Details of Review

Number of studies 9
Number of participants 1,377
Last search date January 2016
Review type Intervention
Objective To determine the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain.
Population Participants (18 years of age and older) undergoing elective surgery at any surgical site, without restriction on any co-morbidities.
Interventions Single dose of liposomal bupivacaine.
Comparator Placebo or other types of analgesia delivered systemically, via local infiltration, perineural injection, or epidural or subarachnoid (spinal) routes.
Outcome Primary outcomes: pain intensity assessed on a 100 mm visual analogue scale (VAS) over the initial 72 hours following surgery, at rest or with activity and serious adverse events (incidence of cardiac events and incidence of wound complications within 30 days of surgery).

Secondary outcomes: mean pain score, at rest or with activity, assessed on a 100 mm VAS at 12, 24, 48, 72 and 96 hours following surgery, time to first postoperative opioid dose over the initial 72 hours, total postoperative opioid consumption over the first 72 hours, percentage of participants who did not require postoperative opioids over the initial 72 hours, health economics assessed using a recognised health economic technique, incidence of adverse events within 30 days of surgery and patient-reported outcomes using validated outcome scores at any time point following surgery.
Study design Prospective randomised and quasi-randomised controlled trials, double-blind, placebo or active-controlled clinical trials.

Results

One study observed a reduction in mean cumulative pain score at the end of the operation to 72 hours in the liposomal bupivacaine intervention group 60.7 points lower when compared to the placebo control group 202.5 points.

Two studies reported a longer time to first postoperative opioid dose with the liposomal bupivacaine group 7. 2 and 14.3 hours when compared to the placebo control group 4.3 and 1.2 hours. Moreover, a reduction in the mean cumulative parenteral morphine equivalent dose over the first 72 hours in liposomal bupivacaine (6.8 mg) compared to the placebo group (29.1 mg).

One study reported a significantly higher proportion of participants who did not require postoperative opioids over the initial 72 hours with liposomal bupivacaine (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.94), Whereas, another study found no difference (RR 0.99, 95% CI 0.95 to 1.03).

No studies reported data on mean pain score at 12, 24, 48, 72 and 96 hours following surgery (numeric rating scale zero to 10). Additionally, two studies reported no drug-related serious adverse events and no study withdrawals due to drug-related adverse events. Whereas, the majority of studies reported nausea, constipation and vomiting as the most common adverse events within 30 days of surgery.

Full Risk of Bias Assessment

The research objective was clearly stated and appropriate inclusion criteria were defined. No restriction was reported based on study characteristics and sources of information.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Probably yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Probably yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? Yes
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Yes
Concerns regarding specification of study eligibility criteria Low

CENTRAL, MEDLINE, MEDLINE In-Process, EMBASE, ISI Web of Science were searched to retrieve all relevant studies. A search was done through the meta-Register of controlled trials (mRCT), Clinicaltrials.gov and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) for ongoing trials. Additionally, the reference lists of retrieved articles were scanned and authors were contacted. The full search strategy was provided and found to be appropriate. The search was not restricted based on date, publication format, or language. Two review authors were independently involved in the study selection process and disagreements were resolved by consensus with input from the senior author.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Yes
2.2 Were methods additional to database searching used to identify relevant reports? Yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Probably yes
2.4 Were restrictions based on date, publication format, or language appropriate? Probably yes
2.5 Were efforts made to minimise error in selection of studies? Yes
Concerns regarding methods used to identify and/or select studies Low

Two authors extracted data independently and in pretested, standardised, electronic data collection forms and disagreements were resolved through discussion or by consulting a third review author. Sufficient study characteristics appeared to have been extracted to allow interpretation of the results. The study results were appropriately collected for the synthesis. Two review authors independently assessed methodological quality of the included studies using appropriate criteria.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably yes
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Yes
3.5 Were efforts made to minimise error in risk of bias assessment? Yes
Concerns regarding methods used to collect data and appraise studies Low

The synthesis included all relevant trials and was appropriate. A narrative synthesis was performed to summarise the findings. Quality of the individual trials was considered in the synthesis of findings.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably yes
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably yes
4.4 Was between-study variation minimal or addressed in the synthesis? Probably yes
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? Probably yes
Concerns regarding synthesis and findings Low

Keywords

  • Anesthetics, Local
  • Bupivacaine
  • Pain, Postoperative