Local and regional anaesthesia at the time of surgery to prevent longer-term persistent pain after surgery

Review question

We set out to determine if the use of local anaesthetics (numbing medicine) at the time of surgery reduces the risk of having pain that persists for three months and more after surgery. The comparison was with pain killers alone, such as opioids and non-steroidal anti-inflammatory drugs.

Background

Pain that persists long after surgery is called persistent postoperative pain (PPP), and is not uncommon. Tissue damage and nerve injury can change pain pathways and sensibility to pain so that pain persists for months. A person may also feel pain more intensely or with a stimulus that normally is not perceived as pain. These changes can be permanent. Applying local anaesthetics close to nerves, bundles of nerves, or nerve roots in the central nervous system, as with an epidural, can interrupt the conduction of pain impulses from the surgical site to the central nervous system. Effective treatment of acute pain may prevent PPP. Wound infiltration uses a specially designed tube with multiple holes that is placed inside the wound to deliver the local anaesthetic.

Study characteristics

The evidence is current to December 2016. We found 63 randomized controlled trials (RCTs) with participants undergoing open chest, heart, breast, abdominal, vascular, gynaecological and other surgery, but not orthopaedic surgery. RCTs are studies where people are allocated by chance to one or the other of different treatments being studied. The studies included only adults, and were mostly conducted in Europe and North America, with some from China, Egypt and Brazil. The types of surgery included surgery with a high event rate of persistent pain after surgery, such as breast surgery, limb amputation and opening the chest, and surgery with a lower risk but high numbers of procedures, such as caesarean section.

We were able to pool results from 41 RCTs enrolling a total of 3143 participants for our inclusive analysis. Follow-up was for 1331 participants at three months, 1443 participants at six months, 326 participants at 12 months, and 43 participants at 20 or more months after surgery. The RCTs did not report surgical and anaesthetic complications consistently and little information was available on these. The studies were mostly funded by the institutions conducting the studies.

Key results

Regional anaesthesia reduced the number of people who experienced persistent pain after undergoing non-orthopaedic surgery. For open chest surgery, giving an epidural halved the odds of a person having persistent postoperative pain at three to 18 months after surgery (7 RCTs, 499 participants, moderate-quality evidence). Seven people needed to be treated in this way for one to benefit.

For the prevention of persistent pain three to 12 months after breast cancer surgery, seven people needed regional anaesthesia for one to benefit (18 RCTs, 1297 participants, low-quality evidence). Infusion of local anaesthetic into a vein was shown to reduce the risk of persistent pain three to six months after breast surgery (2 RCTs, 97 participants, moderate-quality evidence), with three people needing to be treated for one to benefit. Regional anaesthesia reduced the odds by more than half of a woman experiencing persistent pain after caesarean section (4 RCTs, 551 participants, moderate-quality evidence). The number of women treated for one to benefit was 19.

Continuous local anaesthetic infusion of the site where bone tissue was obtained from the hip bone did not clearly reduce the number of people with persistent pain at three to 55 months (3 RCTs, 123 participants, low-quality evidence).

We could not synthesize evidence for limb amputation, hernia repair, cardiac or abdominal surgery because of differences in how treatment was given or how results were reported.

Quality of the evidence

We found consistent evidence supporting the use of regional anaesthesia in adults to prevent persistent pain after a number of types of surgery. However, we observed variations in the effect sizes, and at different times after surgery. Some studies could not be blinded to the treatment received and our results are affected by the small number of studies and participants, and the loss to follow-up of participants over time. The evidence was therefore of low or moderate quality.

Authors' conclusions: 

We conclude that there is moderate-quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section. There is low-quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery. There is moderate evidence that intravenous infusion of local anaesthetics may reduce the risk of developing PPP three to six months after breast cancer surgery.

Our conclusions are considerably weakened by the small size and number of studies, by performance bias, null bias, attrition and missing data. Larger, high-quality studies, including children, are needed. We caution that except for breast surgery, our evidence synthesis is based on only a few small studies. On a cautionary note, we cannot extend our conclusions to other surgical interventions or regional anaesthesia techniques, for example we cannot conclude that paravertebral block reduces the risk of PPP after thoracotomy. There are seven ongoing studies and 12 studies awaiting classification that may change the conclusions of the current review once they are published and incorporated.

Read the full abstract...
Background: 

Regional anaesthesia may reduce the rate of persistent postoperative pain (PPP), a frequent and debilitating condition. This review was originally published in 2012 and updated in 2017.

Objectives: 

To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery.

Search strategy: 

We searched CENTRAL, MEDLINE, and Embase to December 2016 without any language restriction. We used a combination of free text search and controlled vocabulary search. We limited results to randomized controlled trials (RCTs). We updated this search in December 2017, but these results have not yet been incorporated in the review. We conducted a handsearch in reference lists of included studies, review articles and conference abstracts. We searched the PROSPERO systematic review registry for related systematic reviews.

Selection criteria: 

We included RCTs comparing local or regional anaesthesia versus conventional analgesia with a pain outcome beyond three months after elective, non-orthopaedic surgery.

Data collection and analysis: 

At least two review authors independently assessed trial quality and extracted data and adverse events. We contacted study authors for additional information. We presented outcomes as pooled odds ratios (OR) with 95% confidence intervals (95% CI), based on random-effects models (inverse variance method). We analysed studies separately by surgical intervention, but pooled outcomes reported at different follow-up intervals. We compared our results to Bayesian and classical (frequentist) models. We investigated heterogeneity. We assessed the quality of evidence with GRADE.

Main results: 

In this updated review, we identified 40 new RCTs and seven ongoing studies. In total, we included 63 RCTs in the review, but we were only able to synthesize data on regional anaesthesia for the prevention of PPP beyond three months after surgery from 41 studies, enrolling a total of 3143 participants in our inclusive analysis.

Evidence synthesis of seven RCTs favoured epidural anaesthesia for thoracotomy, suggesting the odds of having PPP three to 18 months following an epidural for thoracotomy were 0.52 compared to not having an epidural (OR 0.52 (95% CI 0.32 to 0.84, 499 participants, moderate-quality evidence). Simlarly, evidence synthesis of 18 RCTs favoured regional anaesthesia for the prevention of persistent pain three to 12 months after breast cancer surgery with an OR of 0.43 (95% CI 0.28 to 0.68, 1297 participants, low-quality evidence). Pooling data at three to 8 months after surgery from four RCTs favoured regional anaesthesia after caesarean section with an OR of 0.46, (95% CI 0.28 to 0.78; 551 participants, moderate-quality evidence). Evidence synthesis of three RCTs investigating continuous infusion with local anaesthetic for the prevention of PPP three to 55 months after iliac crest bone graft harvesting (ICBG) was inconclusive (OR 0.20, 95% CI 0.04 to 1.09; 123 participants, low-quality evidence). However, evidence synthesis of two RCTs also favoured the infusion of intravenous local anaesthetics for the prevention of PPP three to six months after breast cancer surgery with an OR of 0.24 (95% CI 0.08 to 0.69, 97 participants, moderate-quality evidence).

We did not synthesize evidence for the surgical subgroups of limb amputation, hernia repair, cardiac surgery and laparotomy. We could not pool evidence for adverse effects because the included studies did not examine them systematically, and reported them sparsely. Clinical heterogeneity, attrition and sparse outcome data hampered evidence synthesis. High risk of bias from missing data and lack of blinding across a number of included studies reduced our confidence in the findings. Thus results must be interpreted with caution.

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