Achievement of adequate pain relief after caesarean delivery is crucial because poorly controlled pain may interfere with mother–child bonding, early ambulation and hospital discharge. Severe acute pain after caesarean delivery is also a risk factor for the development of chronic pain and postpartum depression.1,2 Opioids administered neuraxially and systematically are commonly used for analgesia following caesarean delivery. However, they are associated with a high incidence of adverse effects, such as nausea, vomiting, pruritus and sedation. Thus, alternative strategies are needed to reduce the consumption of opioids and decrease opioid-related side-effects. Wound infiltration with local anaesthetics has been investigated as a potentially useful method for this purpose. However, previous studies investigating the use of this technique for postcaesarean delivery analgesia have shown conflicting results leading to a lack of consensus on its efficacy and benefits.
A previous Cochrane Review3 pooled the results of four studies and concluded that local anaesthetic wound infiltration in women undergoing caesarean delivery resulted in decreased 24-h opioid consumption (1.7 mg morphine equivalents’ reduction with wound infiltration compared with control), but did not reduce visual analogue pain scores. Since the publication of that review, we have identified 17 studies that also investigated local anaesthetic wound infiltration for postcaesarean delivery analgesia. Therefore, we performed this systematic review and meta-analysis to reappraise the literature regarding the efficacy of local anaesthetic wound infiltration for postoperative analgesia in parturients after caesarean delivery.
We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.6
Protocol and registration
The protocol for this meta-analysis was not registered in a public registry.
Eligibility criteria, information sources, search and study selection
We searched MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled trials (CENTRAL) for randomised controlled trials that assessed the efficacy of infusion techniques or single wound infiltration with a local anaesthetic for postcaesarean section analgesia. The term ‘caesarean section’ was combined with ‘wound infiltration’ and all of its variations (Appendix). The search was performed without any language restrictions. The date of the last computer search was December 2015. Additional studies were identified through the bibliographies of retrieved articles. We also searched clinicaltrials.gov to identify any unpublished studies. Abstracts, reviews, letters to the editors, retrospective studies and case reports were excluded.
Risk of bias in individual studies
The selected articles meeting the inclusion criteria were assessed separately by two reviewers (OA and UI) using the risk of bias assessment tool suggested by the Cochrane Collaboration.7 The criteria evaluated were selection bias (randomisation, sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data) and selective reporting bias. Each study was assessed in each parameter as low, unclear or high risk of bias. Any discrepancies were resolved by discussion with the third reviewer (AH).
Data collection process and data items
A data collection sheet was created and two reviewers (OA and UI) extracted data independently on: anaesthetic technique; number of patients included; primary outcome of the study; secondary outcomes of the study; pain scores at rest and on movement; opioid consumption; site of catheter placement; side-effects (nausea, vomiting and pruritus); duration of hospitalisation; need for rescue analgesia; and patient satisfaction. If data were reported in a graph, the authors were contacted. If the authors did not respond, the reviewers extracted the data from the graph using the WebPlotDigitizer software (Version 3.9, Ankit Rohatgi, Austin, Texas, USA).8 Any discrepancies in the extracted data were resolved by discussion with the third reviewer (AH).
Primary outcomes were pain intensity scores and opioid consumption at 24 h. Secondary outcomes were pain intensity scores at 6 and 48 h, opioid consumption at 6 and 48 h, duration of hospitalisation, side-effects, need for rescue analgesics and patient satisfaction. Visual analogue scale scores for pain intensity and patient satisfaction reported on a 0 to 100 scale were converted to a 0 to 10 point scale for analysis. If results were not reported at the time points specified in this analysis, those recorded closest to that time point were used instead. If an event rate was reported over multiple time intervals instead of the entire duration of the study, the highest recorded incidence was used for the analysis. Opioids were converted to morphine equivalents for analysis using a conversion factor of 3 : 1 for oral oxycodone,9 1 : 1 for i.v. oxycodone and ketobemidone10,11 and 10 : 1 for i.v. tramadol.12 If it was not clearly specified in the study whether intrathecal morphine (ITM) was used in the spinal anaesthetic, we made the assumption that ITM was not used.
Summary measures, additional analyses and synthesis of results
For each outcome, we pooled all studies that used an infiltration technique. For the primary outcomes, we performed subgroup analyses according to infiltration method (single infiltration vs. infusion technique) and use of ITM (with ITM vs. without ITM). To evaluate heterogeneity within studies using infusion techniques, we investigated subgroups according to administration regimen (continuous infusion vs. intermittent boluses) and site of catheter placement (above vs. below the fascia). To evaluate heterogeneity within studies using single infiltration, we investigated the impact of the timing of single infiltration (before incision vs. end of procedure). A sensitivity analysis was performed for the primary outcomes excluding studies that had a high risk of bias for any of the domains assessed. Continuous data were summarised as mean difference with 95% confidence intervals (CIs). If the 95% CI included the value of 0, we considered the difference between wound infiltration and control not statistically significant. Dichotomous data were summarised as relative risk (RR) with 95% CI. If the 95% CI included a value of 1, we considered the difference not statistically significant. Analyses were performed using the Review Manager (RevMan, Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), comprehensive meta-analysis (Version 2, 2005) and R routine metacont (R package Meta). A random effects model was used. We considered heterogeneity to be present if I2 was greater than 50%. Forest plots were used to graphically present and evaluate treatment effects. Subgroups were compared using the Q-test.
Risk of bias across studies
We assessed for publication bias for the primary outcomes using funnel plots and Egger's test.13 In case of an asymmetrical funnel plot and statistically significant Egger test, we assessed for missing studies using the trim and fill method14 and examined the contour-enhanced funnel plots.15
A total of 96 studies were identified that fulfilled our initial search strategy. Twenty-one studies16–36 were included in the final analysis (Fig. 1). Eleven studies17,21,22,24,26,27,29,32–34,36 with 621 patients used an infusion technique (313 patients received local anaesthetic and 308 patients served as control) and 10 studies16,18–20,23,25,28,30,31,35 with 814 patients used single infiltration (428 patients received local anaesthetic and 386 patients served as controls). Spinal anaesthesia was used in 17 studies,16–18,20–29,33–36 whereas one study used epidural anaesthesia22 and five studies used general anaesthesia.19,25,30–32 ITM was used in four studies,17,20,24,28 and 18 studies did not use ITM.16,18,19,21–27,29–36 Seven studies16,20,21,24,26,29,35 used ropivacaine, eight studies17,22,23,27,28,31,33,34 used bupivacaine, four studies18,19,32,34 used levobupivacaine and two studies25,30 used lidocaine for the wound infiltration. In the studies using an infusion technique, six studies16,19–23 placed the catheter for infusion above the fascia and five studies below the fascia.24,27,32,34,36 Eight studies17,20–24,34,36 used continuous infusion and three studies21,27,33 intermittent bolusing. In studies using single infiltration, seven studies25–27,29,31,32,35 performed the infiltration at the end of the caesarean delivery and three studies25,28,30 performed the infiltration before incision. Two studies (NCT02264821, NCT02515422) were identified on clinicaltrials.gov which assessed the efficacy of continuous wound infusion for postcaesarean section analgesia that had been completed but have yet to be published.
The characteristics and the risk of bias of the included studies are shown in Tables 1 and 2 respectively.
Pain scores at 24 hours
Pain scores at rest at 24 h (Fig. 2) were reported in 18 studies (nine studies23–28,30,31,35 using single infiltration and nine studies19–24,33,34,36 using an infusion technique) and during movement (Fig. 3) in 11 studies (four studies16,19,28,35 using single infiltration and seven studies19,24,27,30,31,34,36 using an infusion technique). Pooled results showed a statistically significant reduction in pain scores at rest (mean difference −0.36, 95% CI, −0.58 to −0.14; I2 = 86%) and during movement (mean difference −0.61, 95% CI, −1.19 to −0.03; I2 = 92%) with local anaesthetic wound infiltration. Excluding one study that had high risk of bias34 did not change the conclusion about the pooled results. There was no evidence of publication bias for pain scores at rest or movement (P = 0.25 and 0.19 respectively).
In subgroup analysis, pain scores at rest were reduced with single infiltration but not with an infusion technique (Fig. 2). However, the reduction with single infiltration, while statistically significant, is very small and probably clinically irrelevant. Pain scores with movement were not reduced with either single infiltration or an infusion technique (Fig. 3), but with pain scores on movement with an infusion technique, the CIs were wide, including a clinically relevant reduction in pain scores, suggesting that our data are insufficient to reach a conclusion about this outcome. There were no significant differences between the infiltration methods for pain scores at rest (P = 0.15) or with movement (P = 0.38).
In 16 studies16,18,21–26,29–36 local anaesthetic wound infiltration was compared with control in patients who did not receive ITM, whereas in two studies,20,28 all patients received ITM. Pain scores at rest were reduced in both subgroups (Table 3), with no significant differences between the subgroups (P = 0.10).
When accounting for the timing of the single infiltration, pain scores at rest, but not on movement, were reduced with infiltration performed both prior to incision and at the end of the caesarean delivery (Table 3). There were no statistically significant differences between the subgroups for pain scores at rest (P = 0.10) or on movement (P = 0.25).
Continuous infusion vs. intermittent bolus
Pain scores at rest and during movement were reduced by continuous infusion but not with intermittent boluses (Table 3). There was a significant difference between the subgroups for pain scores at rest (P = 0.008) in favour of the continuous infusion technique but no significant difference between the infusion methods for pain scores on movement (P = 0.13).
Location of catheter placement
In the nine studies using an infusion technique and reporting pain scores, five studies21,22,26,29,33 placed the catheter above the fascia and four studies24,32,34,36 placed the catheter below the fascia. Pain scores at rest and movement were only reduced with catheter placement below the fascia (Table 3). There was a significant difference in pain scores at rest (P < 0.0001) and during movement (P = 0.03) between groups in favour of catheter placement below the fascia.
Opioid consumption at 24 hours
Opioid consumption at 24 h (Fig. 4) was reported in 13 studies (five studies16,18,19,31,35 using single infiltration and eight studies17,22,24,26,29,32,34,36 using an infusion technique). Pooled results showed a statistically significant reduction in opioid consumption with local anaesthetic wound infiltration (mean difference −9.69 mg morphine equivalent, 95% CI, −14.85 to −4.52; I2 = 96%). Excluding one study that had high risk of bias34 did not change the conclusion about the pooled results. The Egger's test (P = 0.003) indicated funnel plot asymmetry. The trim and fill method suggested that there was one missing study, with an adjusted pooled result of −10.44 mg morphine equivalent, 95% CI, −15.48 to −5.40 for 24-h opioid consumption. Examination of the contour-enhanced funnel plot (Fig. 5) indicates that the missing study lies in the area of statistical significance of 0.1 < P < 0.05, suggesting that the asymmetry might be because of a small study effect rather than publication bias.
In subgroup analysis, opioid consumption at 24 h was reduced by both single infiltration and an infusion technique (Fig. 4), with no significant differences between the infiltration methods (P = 0.77).
In subgroup analysis, opioid consumption at 24 h was decreased in patients who did not receive ITM. No statistically significant difference was seen in patients who received ITM (Table 3). There was a significant difference between the subgroups with regards to 24-h opioid consumption with significantly greater opioid sparing in patients who did not receive ITM (P = 0.002).
Of the eight studies using an infusion technique and reporting opioid consumption at 24 h, four studies17,22,26,29 placed the catheter above the fascia and four studies24,32,34,36 placed the catheter below the fascia. Morphine consumption was significantly reduced in studies placing the infusion catheter below the fascia, but no definitive conclusions could be drawn regarding the pooled results for studies where the catheter was placed above the fascia because of the wide CIs of the pooled results (Table 3). There were no statistically significant differences between subgroups (P = 0.31).
Pain scores at rest at 6 h and 48 h were reported in 14 studies (eight studies16,18,20,23,25,30,31,35 using single infiltration and six studies21,29,32–34,36 using an infusion technique) and nine studies (four studies18,20,25,28 using single infiltration and five studies22,24,26,29,34 using an infusion technique) respectively. Pain scores on movement at 6 and 48 h were reported in 10 studies (four studies16,19,23,35 using single infiltration and six studies21,29,32–34,36 using an infusion technique) and four studies (one study28 using single infiltration and three studies26,29,34 using an infusion technique) respectively. Pooled results showed a statistically significant reduction in pain scores at 6 h at rest (mean difference −1.09, 95% CI, −1.65 to −0.53, I2 = 98%) and during movement (mean difference −1.25, 95% CI, −2.24 to −0.25, I2 = 96%) with local anaesthetic wound infiltration. No statistically significant reduction was seen with pain scores at 48 h at rest (mean difference −0.08, 95% CI, −0.27 to 0.11, I2 = 27%) or on movement (mean difference −0.63, 95% CI, −0.08 to 1.00, I2 = 77%).
Opioid consumption at 6 and 48 h was reported in four studies (one study using single infiltration31 and three studies using an infusion technique21,29,33 and seven studies (one study20 using single infiltration and six studies using an infusion technique17,22,24,26,27,29) respectively. Pooled results showed a statistically significant reduction in opioid consumption at 48 h with local anaesthetic wound infiltration (mean difference −8.88 mg ME, 95% CI, −16.34 to −1.43, I2 = 93%). No statistically significant reduction was seen at 6 h, but the CIs were wide, preventing us drawing any definitive conclusions (mean difference −3.14 mg morphine equivalents, 95% CI, −10.75 to 3.48, I2 = 95%).
Incidences of nausea, vomiting and pruritus were investigated in 11,16,18,20,23,24,27–29,32,33,36 eight16,18–20,23,27,32,34 and five studies,16,19,24,27,28 respectively. Pooled results showed no statistically significant reduction in nausea (RR 0.75, 95% CI, 0.50 to 1.13, I2 = 51%), vomiting (RR 0.72, 95% CI, 0.48 to 1.08, I2 = 0%) or pruritus (RR 0.69, 95% CI, 0.48 to 1.00, I2 = 0%). However, the 95% CIs of these pooled results were wide and include clinically relevant reductions in those side-effects, suggesting that the data were insufficient to reach a conclusion about those outcomes.
Need for rescue analgesia
A need for rescue analgesia was reported in six studies.17,18,21,25,30,33 Pooled results showed no statistically significant reduction in the need for rescue analgesia with infiltration techniques (RR 0.88, 95% CI, 0.60 to 1.30, I2 = 90%).
Duration of hospitalisation
Duration of hospitalisation was reported in four studies20,21,30,33 with pooled results showing no statistically significant difference between the groups (mean difference – 0.05 days; 95% CI, −0.10 to 0.01; I2 = 0%).
Patient satisfaction scores were reported on a 0 to 10 point scale in two studies.24,29 Pooled results showed no difference between the groups (mean difference 0.27; 95% CI, −0.17 to 0.70; I2 = 0%). Two studies21,31 reported patient satisfaction as excellent, good, satisfactory or poor. Pooling the excellent and good results showed no statistically significant difference (RR 1.24; 95% CI, 0.64 to 2.41; I2 = 85%) between the groups, but the CIs are wide suggesting that the data are insufficient to reach a conclusion.
This systematic review and meta-analysis suggests that local anaesthetic wound infiltration might be an effective adjunct modality for improving postcaesarean section analgesia. Indirect comparisons from subgroup analysis suggested that wound infusion with catheter placement below the fascia is associated with improved analgesia compared with administration above the fascia. In women who do not receive ITM, wound infiltration with local anaesthesia provides an opioid-sparing effect, but there was very limited data available for patients receiving ITM.
Our findings of decreased opioid consumption at 24 h with local anaesthetic wound infiltration are similar to the results of the earlier Cochrane review,3 although the reduction of 1.7 mg morphine equivalents reported in the Cochrane review was significantly lower than the 9.7 mg we found in our analysis, which translates to a 23% opioid-sparing effect. However, our findings of decreased pain scores at 6 and 24 h are in contrast to the previous review. There have been several studies investigating the efficacy of wound infiltration for postcaesarean delivery analgesia published after the Cochrane review. Therefore, this difference in results can be explained by the larger number of studies included in our analysis. However, our findings show only a small decrease in pain scores that might not be clinically relevant. Furthermore, the opioid-sparing effect associated with wound infiltration was not associated with a reduction in opioid-related side-effects.
Transversus abdominis plane (TAP) block has also been investigated as a potential technique to optimise pain relief after caesarean delivery. Three previous studies37–39 compared the analgesic efficacy of TAP block with local anaesthetic wound infiltration. One study39 reported improved analgesia in patients receiving TAP block, but a second study38 found no significant differences in analgesia between the two groups. However, another study37 was terminated prematurely because of the occurrence of generalised seizures in a patient who received TAP block and, thus, was underpowered to detect any significant difference between continuous wound infiltration and TAP block.
Our findings support previous evidence suggesting that the efficacy of local anaesthetic techniques on postcaesarean delivery analgesia is impacted on by the use or no use of ITM. We found that local anaesthetic wound infiltration reduced opioid consumption at 24 h in patients who did not receive ITM but not in those who received ITM, with statistically significant differences between the two subgroups. This agrees with findings of a previous meta-analysis by Mishriky et al.,4 who concluded that TAP block might be an effective modality for reducing pain scores and opioid consumption only in patients who do not receive ITM.4 However, in a study conducted by Kainu et al.24 comparing the efficacy of continuous wound infusion with ITM for postcaesarean delivery analgesia, the use of ITM reduced opioid consumption by 46% in the first 24 h when compared with ropivacaine wound infusion. This also agrees with findings suggesting that ITM provides improved analgesia compared with TAP blocks.4 Postoperative pain after caesarean delivery is multifactorial, with a visceral component because of uterine and abdominal manipulation and a somatic component arising from the wound.40,41 Local anaesthetic techniques such as TAP block and wound infiltration affect only the somatic component. In patients who did not receive ITM, blocking the somatic afferents with local anaesthetic wound infiltration improved post-caesarean delivery analgesia and reduced opioid consumption. Therefore this technique might be particularly valuable in patients receiving general anaesthesia or in situations where neuraxial opioids are not used, but further studies are needed to investigate its use in those circumstances. It is important to remember that only one study reported opioid consumption with local anaesthetic wound infiltration in patients who received ITM, and the results of this indirect comparison in the subgroup analysis should be interpreted with caution in the context of this limitation.
The use of NSAIDs alone or in addition to a local anaesthetic for wound infiltration is an emerging technique for postcaesarean delivery analgesia. Lavand’homme et al.26 investigated the analgesic effects of continuous wound infusion using diclofenac compared with local anaesthetic alone and a control group receiving systemic diclofenac following caesarean delivery. Carvalho et al.42 investigated the effects of administering a low dose of ketorolac or hydromorphone with local anaesthetic wound infusion compared with the local anaesthetic alone. These studies suggest that continuous infusion of NSAIDs into the surgical wound provides improved analgesia compared with systemic NSAIDs or local infiltration with local anaesthetic alone and reduces inflammatory mediators in wound exudate. More studies are needed to further investigate this potentially promising technique for improving postcaesarean delivery analgesia.
Our indirect comparison in the subgroup analysis also suggests that local anaesthetic infusion below the fascia has better analgesic efficacy compared with infusion above the fascia. This is in agreement with a study by Rackelboom et al.5 which demonstrated that continuous administration of combined NSAID and local anaesthetic below the fascia was more effective than above the fascia, leading to a significant reduction in pain scores and 40% less morphine consumption in the first 48 h.
We found no statistically significant differences between single infiltration and infusion techniques in our primary endpoints of pain scores and opioid consumption at 24 h. Performing single infiltration of local anaesthetic might be simpler, cheaper and less taxing than infusion methods. However, it is important to remember that our conclusions from this subgroup analysis are based on an indirect comparison, and that there are no studies to date that have directly compared the two techniques.
This systemic review has several limitations. The number of studies included in the review is small, particularly those assessing the use of wound infiltration in patients receiving ITM. There were differences among the studies in the anaesthetic technique used and in the approaches to performing wound infiltration, such as the local anaesthetic agent used, dose, site of catheter placement and duration of wound infiltration, resulting in significant heterogeneity in many of the outcomes that we examined. We attempted to address this heterogeneity by performing a number of subgroup analyses to assess separately the impact of various factors on outcomes, but as the number of studies was small, it was not possible to perform a meta-regression to simultaneously assess the impact of potential confounders. Furthermore, results from these analyses should be regarded as observational in nature, may be biased and limited by the small number of studies included in some of the subgroups, and should therefore be interpreted with caution.7 The Egger's test indicated funnel plot asymmetry that might suggest the possibility of publication bias for the endpoint of opioid consumption at 24 h. Tests of publication bias must be interpreted with caution in the presence of a small number of studies such as in our meta-analysis.43 Furthermore, there are other reasons for funnel plot asymmetry44 and examination of the contour-enhanced funnel plot suggests that reasons other than publication bias, such as small study effect, might be responsible for this asymmetry.
This review identified some areas for future research. More studies are needed to assess the efficacy of local anaesthetic wound infiltration in patients receiving ITM in the context of a multimodal analgesic regimen, as this is the standard of care in most institutions. Large studies with adequate power are also needed to investigate the efficacy of different dosing regimens of local anaesthetics for wound infiltration. Although some studies have investigated wound infiltration with other adjuvants,26,39 more studies are needed to investigate specifically the efficacy of NSAID infiltration for postcaesarean delivery analgesia. Studies are also needed to compare directly the analgesic efficacy of single infiltration and infusion techniques.
In conclusion, this systematic review and meta-analysis suggests that local anaesthetic wound infiltration provides a postoperative opioid-sparing effect but was associated with only a small reduction in pain scores and no statistically significant reduction in opioid-related side-effects. The value of this technique in patients receiving ITM remains less clear and should be investigated in future studies.
Acknowledgements relating to this article
Assistance with the study: we would like to thank Mary Cooter for her assistance in producing the contour-enhanced funnel plot.
Financial support and sponsorship: none.
Conflicts of interest: none.
Presentation: this study was presented, in part, at the meeting of the Society of Obstetric Anesthesia and Perinatology, Colorado Springs, Colorado, May 2015, USA.
Appendix MeSH terms
‘Cesarean Section’ [MeSH] OR ‘c-section’[tiab] OR ‘c-sections’ [tiab] OR ‘pregnancy’ [MeSH] OR ‘pregnancy’ [tiab] OR ‘cesarean’ [tiab] OR ‘cesareans’ [tiab] OR ‘abdominal delivery’ [tiab] OR ‘abdominal deliveries’ [tiab] OR ‘caesarean’[tiab] OR ‘caesareans’[tiab]
‘Abdomen/innervation’[Mesh] OR ‘wound infiltration’ [tiab] OR ‘wound infusion’[tiab] OR ‘wound instillation’ [tiab] OR ‘skin infiltration’ [tiab] OR ‘skin infusion’ [tiab] OR ‘subcutaneous instillation’ [tiab] OR ‘subcutaneous infusion’ [tiab] OR ‘subcutaneous infiltration’ [tiab] OR ‘site infiltration’[tiab] OR ‘site infusion’ [tiab] OR ((‘incision site’[tiab] OR ‘incision-site’[tiab]) AND ‘injection’[tiab]) OR ‘wound irrigation’[tiab] OR ‘intraincisional injection’[tiab] OR ‘intermittent instillation’[tiab]
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