Regional Anaesthesia to Prevent Chronic Pain After Surgery
Regional Anaesthesia to Prevent Chronic Pain After Surgery
We give an overview of our search in Figure 1. Electronic searches were performed in February and March 2008, and updated between February and August 2010 and again between April and May 2012. Our electronic search retrieved 4481 references, 2047 in MEDLINE, 1185 in EMBASE, 991 in CENTRAL, 258 in CINAHL; we identified 1184 duplicates among them and excluded 4337 references as irrelevant or not RCTs in the screening process.
(Enlarge Image)
Figure 1.
Search diagram. The search diagram gives an overview of the search and selection process.
We performed a hand search and checked 2101 abstracts in the conference proceedings of the International Anesthesia Research Society and the European Society of Regional Anaesthesia for 2005–2007. Including links or references to relevant related articles, we found 372 references. Of a total of 2473 references, we excluded 2293 (+175 to be deemed duplicates) as irrelevant or not RCTs (Fig. 1). We included and reviewed manuscripts in several languages other than English, including Danish, Mandarin, Japanese, German, French, and Spanish. Three of the five studies included in our data synthesis were published in the non-English literature and hence were less accessible to most clinicians.
Among 144 full-text articles, we identified 23 studies for inclusion (Fig. 1). We identified six on-going trials listed in detail in the full review.
Included Studies. We identified 23 RCTs studying regional anaesthesia or local anaesthetics for the prevention of chronic pain after surgery. We present an abbreviated table of included studies ( Table 1 ) and reported details of the search, selection and on the methodological quality and other characteristics of the included studies elsewhere. We found five large on-going trials on regional anaesthesia for the prevention of chronic pain after surgery, plus one trial likely to report on PPP as a secondary outcome listed in the full review. We found many studies reporting outcomes only at 3 months or 12 weeks and will include these in the next review update possibly using a Bayesian approach to prevent the unit of analysis issues in pooling trials with repeated measures and data collected at disparate follow-ups.
Excluded Studies. We excluded no study for the lack of observer blinding alone. We considered the randomization inadequate in three trials. One of them would have also been excluded for failing on additional inclusion criteria.
We estimated that separate articles by the same author with identical participant numbers were reporting in fact on just one single trial and used these data sets only once. Despite our best efforts to reach the authors, we were not able to secure suitable or appropriate data for some studies.
Studies were clustered in broad categories (thoracotomy, limb amputation, breast surgery, laparotomy, and other). For thoracotomy the only regional technique studied was epidural anaesthesia. Two studies on breast cancer surgery used paravertebral blocks. In most other surgical subgroups, regional anaesthesia techniques varied (Table 1).
We pooled the data of 250 participants after thoracotomy and that of 89 women after breast cancer surgery with outcomes at 6 months. Only adults (>18 yr) were studied. Known risk factors for the development of persistent (chronic) pain were not reported, potentially introducing bias.
We summarized the risk of bias of included studies in Figure 2. We published a detailed table of risk of bias with justifications for our classifications elsewhere.
(Enlarge Image)
Figure 2.
Risk of bias graph. The review authors summarize their judgements about each study for each risk of bias category in the methodological summary figure. Detailed justifications are published elsewhere.
Randomization: Six studies did not detail the process of sequence generation. Study authors' responses provided additional unpublished information for some studies. Three studies were excluded for pseudo-randomization.
Allocation concealment: only eight studies described adequate concealment of allocation.
Blinding: effective blinding of patients and practitioners is difficult because many patients note the sensory effects of regional anaesthesia. Many authors made great efforts to blind participants, providers, and outcome assessors. No study was excluded for detection bias, and only outcome assessment blinding was a prerequisite for inclusion.
Incomplete outcome data: with the exception of six mostly recent studies, most studies did not adequately address incomplete outcome data.
Selective reporting: adverse outcomes were reported only anecdotally if at all in the included studies, raising concerns about selective reporting of unintended effects.
Thoracotomy. Our data synthesis (Fig. 1: forest plot) of 250 participants in three studies strongly favoured epidural anaesthesia for thoracotomy with an OR of 0.34 (95% CI 0.19–0.60) (P=0.0002). Excluding one study using cryotherapy as the control group did not alter the results. We found no evidence of between-study heterogeneity (I estimate of 0%).
Breast Surgery. Our analysis equally favoured paravertebral blocks for breast cancer surgery with an OR of 0.37 (95% CI 0.14–0.94) (P=0.04) based on two studies with 89 participants, when we excluded plastic surgery of the breast and a study with multimodal topical analgesia. Evidence synthesis including also these studies increased the confidence in the effect measure with an OR of 0.42 (95% CI 0.21–0.86) (P=0.02).
For the remaining subgroups and for the later follow-up intervals, the data were too sparse for evidence synthesis.
Limb Amputation. We did not pool two studies with 67 patients investigating the effect of regional anaesthesia after limb amputation on chronic pain (phantom limb pain) at 6 months. The small number of subjects and the high variance would have resulted in a very large CI; considerable heterogeneity was also suggested by an I estimate of 78%. The interpretation might have been controversial considering the exclusion of two studies in this subgroup for pseudo-randomization.
Laparotomy. We did not pool data from two studies with data at 6 months on 189 laparotomy patients as an I estimate of 90% suggested marked study heterogeneity. The positive study used adjuvants and comprehensive postoperative nociceptive block, while the inconclusive study used neither adjuvants nor any regional anaesthesia after operation. At 12 months, a single study favoured regional anaesthesia with an OR of 0.08 [95% CI 0.01–0.45].
Caesarean Section. We found two studies after Caesarean section (Pfannenstiel incision) including 414 participants, but abstained from pooling the data. One used continuous postoperative wound irrigation, the other used a single-shot instillation of local anaesthetic into the peritoneal pelvis. Orthodox evidence synthesis would be controversial in the light of this clinical heterogeneity of regional anaesthesia interventions.
Other Surgery. We found three single studies; all favoured regional anaesthesia. The OR was 0.01 [95% CI 0.00–0.09] for wound infiltration after iliac hernia repair. Continuous local infiltration reduced the risk of PPP after iliac crest bone graft harvesting with an OR of 0.22 [95% CI 0.03–1.42]. For single-shot local bupivacaine after vasectomy, the OR was 0.02 [95% CI 0.00–0.33].
Results
Search
We give an overview of our search in Figure 1. Electronic searches were performed in February and March 2008, and updated between February and August 2010 and again between April and May 2012. Our electronic search retrieved 4481 references, 2047 in MEDLINE, 1185 in EMBASE, 991 in CENTRAL, 258 in CINAHL; we identified 1184 duplicates among them and excluded 4337 references as irrelevant or not RCTs in the screening process.
(Enlarge Image)
Figure 1.
Search diagram. The search diagram gives an overview of the search and selection process.
We performed a hand search and checked 2101 abstracts in the conference proceedings of the International Anesthesia Research Society and the European Society of Regional Anaesthesia for 2005–2007. Including links or references to relevant related articles, we found 372 references. Of a total of 2473 references, we excluded 2293 (+175 to be deemed duplicates) as irrelevant or not RCTs (Fig. 1). We included and reviewed manuscripts in several languages other than English, including Danish, Mandarin, Japanese, German, French, and Spanish. Three of the five studies included in our data synthesis were published in the non-English literature and hence were less accessible to most clinicians.
Among 144 full-text articles, we identified 23 studies for inclusion (Fig. 1). We identified six on-going trials listed in detail in the full review.
Included Studies. We identified 23 RCTs studying regional anaesthesia or local anaesthetics for the prevention of chronic pain after surgery. We present an abbreviated table of included studies ( Table 1 ) and reported details of the search, selection and on the methodological quality and other characteristics of the included studies elsewhere. We found five large on-going trials on regional anaesthesia for the prevention of chronic pain after surgery, plus one trial likely to report on PPP as a secondary outcome listed in the full review. We found many studies reporting outcomes only at 3 months or 12 weeks and will include these in the next review update possibly using a Bayesian approach to prevent the unit of analysis issues in pooling trials with repeated measures and data collected at disparate follow-ups.
Excluded Studies. We excluded no study for the lack of observer blinding alone. We considered the randomization inadequate in three trials. One of them would have also been excluded for failing on additional inclusion criteria.
Missing and Duplicate Data
We estimated that separate articles by the same author with identical participant numbers were reporting in fact on just one single trial and used these data sets only once. Despite our best efforts to reach the authors, we were not able to secure suitable or appropriate data for some studies.
Regional Techniques and Surgical Interventions
Studies were clustered in broad categories (thoracotomy, limb amputation, breast surgery, laparotomy, and other). For thoracotomy the only regional technique studied was epidural anaesthesia. Two studies on breast cancer surgery used paravertebral blocks. In most other surgical subgroups, regional anaesthesia techniques varied (Table 1).
We pooled the data of 250 participants after thoracotomy and that of 89 women after breast cancer surgery with outcomes at 6 months. Only adults (>18 yr) were studied. Known risk factors for the development of persistent (chronic) pain were not reported, potentially introducing bias.
Methodological Quality
We summarized the risk of bias of included studies in Figure 2. We published a detailed table of risk of bias with justifications for our classifications elsewhere.
(Enlarge Image)
Figure 2.
Risk of bias graph. The review authors summarize their judgements about each study for each risk of bias category in the methodological summary figure. Detailed justifications are published elsewhere.
Randomization: Six studies did not detail the process of sequence generation. Study authors' responses provided additional unpublished information for some studies. Three studies were excluded for pseudo-randomization.
Allocation concealment: only eight studies described adequate concealment of allocation.
Blinding: effective blinding of patients and practitioners is difficult because many patients note the sensory effects of regional anaesthesia. Many authors made great efforts to blind participants, providers, and outcome assessors. No study was excluded for detection bias, and only outcome assessment blinding was a prerequisite for inclusion.
Incomplete outcome data: with the exception of six mostly recent studies, most studies did not adequately address incomplete outcome data.
Selective reporting: adverse outcomes were reported only anecdotally if at all in the included studies, raising concerns about selective reporting of unintended effects.
Effect of the Intervention
Thoracotomy. Our data synthesis (Fig. 1: forest plot) of 250 participants in three studies strongly favoured epidural anaesthesia for thoracotomy with an OR of 0.34 (95% CI 0.19–0.60) (P=0.0002). Excluding one study using cryotherapy as the control group did not alter the results. We found no evidence of between-study heterogeneity (I estimate of 0%).
Breast Surgery. Our analysis equally favoured paravertebral blocks for breast cancer surgery with an OR of 0.37 (95% CI 0.14–0.94) (P=0.04) based on two studies with 89 participants, when we excluded plastic surgery of the breast and a study with multimodal topical analgesia. Evidence synthesis including also these studies increased the confidence in the effect measure with an OR of 0.42 (95% CI 0.21–0.86) (P=0.02).
For the remaining subgroups and for the later follow-up intervals, the data were too sparse for evidence synthesis.
Limb Amputation. We did not pool two studies with 67 patients investigating the effect of regional anaesthesia after limb amputation on chronic pain (phantom limb pain) at 6 months. The small number of subjects and the high variance would have resulted in a very large CI; considerable heterogeneity was also suggested by an I estimate of 78%. The interpretation might have been controversial considering the exclusion of two studies in this subgroup for pseudo-randomization.
Laparotomy. We did not pool data from two studies with data at 6 months on 189 laparotomy patients as an I estimate of 90% suggested marked study heterogeneity. The positive study used adjuvants and comprehensive postoperative nociceptive block, while the inconclusive study used neither adjuvants nor any regional anaesthesia after operation. At 12 months, a single study favoured regional anaesthesia with an OR of 0.08 [95% CI 0.01–0.45].
Caesarean Section. We found two studies after Caesarean section (Pfannenstiel incision) including 414 participants, but abstained from pooling the data. One used continuous postoperative wound irrigation, the other used a single-shot instillation of local anaesthetic into the peritoneal pelvis. Orthodox evidence synthesis would be controversial in the light of this clinical heterogeneity of regional anaesthesia interventions.
Other Surgery. We found three single studies; all favoured regional anaesthesia. The OR was 0.01 [95% CI 0.00–0.09] for wound infiltration after iliac hernia repair. Continuous local infiltration reduced the risk of PPP after iliac crest bone graft harvesting with an OR of 0.22 [95% CI 0.03–1.42]. For single-shot local bupivacaine after vasectomy, the OR was 0.02 [95% CI 0.00–0.33].
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