Local anesthetics and regional anesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children: A Cochrane systematic review and meta-analysis update

Abstract

Background: Regional anesthesia may mitigate the risk of persistent postoperative pain (PPP). This Cochrane review, published originally in 2012, was updated in 2017.

Methods: We updated our search of Cochrane CENTRAL, PubMed, EMBASE and CINAHL to December 2017. Only RCTs investigating local anesthetics (by any route) or regional anesthesia versus any combination of systemic (opioid or non-opioid) analgesia in adults or children, reporting any pain outcomes beyond three months were included. Data were extracted independently by at least two authors, who also appraised methodological quality with Cochrane 'Risk of bias' assessment and pooled data in surgical subgroups. We pooled studies across different follow-up intervals. As summary statistic, we reported the odds ratio (OR) with 95% confidence intervals and calculated the number needed to benefit (NNTB). We considered classical, Bayesian alternatives to our evidence synthesis. We explored heterogeneity and methodological bias.

Results: 40 new and seven ongoing studies, identified in this update, brought the total included RCTs to 63. We were only able to synthesize data from 39 studies enrolling 3027 participants in a balanced design. Evidence synthesis favored regional anesthesia for thoracotomy (OR 0.52 [0.32 to 0.84], moderate-quality evidence), breast cancer surgery (OR 0.43 [0.28 to 0.68], low-quality evidence), and cesarean section (OR 0.46, [0.28 to 0.78], moderate-quality evidence). Evidence synthesis favored continuous infusion of local anesthetic after breast cancer surgery (OR 0.24 [0.08 to 0.69], moderate-quality evidence), but was inconclusive after iliac crest bone graft harvesting (OR 0.20, [0.04 to 1.09], low-quality evidence).

Conclusions: Regional anesthesia reduces the risk of PPP. Small study size, performance, null, and attrition bias considerably weakened our conclusions. We cannot extrapolate to other interventions or to children.

Keywords: Anesthesia; Chronic pain/prevention & control; Conduction; Meta-analysis.

Figure 1:. Quorum flow diagram

The process of reference search and selection is detailed in this Quorum flow diagram, depicting the study flow. Among the 469 articles evaluated in full text, 79 were excluded and listed in the Supple Table 3 of Characteristics of Excluded Studies with details as to why they were excluded. Of the 63 included randomized trials, we were able to include 39 in our inclusive analysis. For the remaining 24 trials, only a single study was found for the surgical intervention investigated, study data were unavailable, or data could not be pooled for other reasons (reported in our Cochrane Review)[29]. We enumerate every single included study for which the data could not be pooled in a meta-analysis in Suppl. Table 4: Study data not included in meta-analysis.

Figure 2. Risk of bias graph

Figure 3 summarizes the risk of bias graphically across all included studies based on the review authors’ judgements about selection, performance, detection and attrition bias, as well as selective reporting and Null bias. A comprehensive risk of bias tables, published in our Cochrane Review, provides detail at the study level and support for the judgement in tabular form[29].

Figure 3. Forest plot thoracotomy

In this forest plot, each of the seven randomized trials investigating regional anesthesia for the prevention of prevention of persistent postoperative pain after thoracotomy is depicted as a small blue square. Their sizes correspond to the number of study participants with bars on either side indicating the confidence in the effect estimate. The midline indicates no effect, with studies on the left favoring regional anesthesia. The diamond below reflects the pooled estimate favoring regional anesthesia with an odds ratio of 0.52 and a 95% confidence interval ranging from 0.32 to 0.84. The use of epidural anesthesia may mitigate the risk of persistent pain after thoracotomy in one patient out of every six treated.

Figure 4. Forest plot breast surgery

18 studies investigating the effect of regional anesthesia for the prevention of persistent pain after breast surgery are grouped by intervention and shown on this forest plot. Each study is shown by a small blue square. The number of study participants and the confidence in the effect estimate are reflected in the size of the square and the lateral bars, respectively. Studies favoring regional anesthesia fall on the left of the midline of no effect. The pooled effect estimates are shown for each subgroup and for all studies as black diamonds. Pooling all studies results favors regional anesthesia (odds ratio 0.43; 95% CI [0.28, 0.68]). The number needed to benefit for paravertebral block for breast cancer surgery is about seven.