Int J Clin Exp Med 2015;8(6):10213-10224 www.ijcem.com /ISSN:1940-5901/IJCEM0011139
Review Article Local anaesthetic wound infiltration used for caesarean section pain relief: a meta-analysis Xiangnan Li1*, Miao Zhou2*, Xuan Shi3*, Haiqin Yang1, Yonghua Li1*, Jian Li1, Mei Yang1, Hongbin Yuan1 Department of Anesthesiology, Changzheng Hospital, The Second Military Medical University; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College; 3No. 12 branch of The Cadet Management Unit, Second Military Medical University, No 800 Xiang Yin Road, Shanghai. *Equal contributors and co-first authors. 1
Received June 7, 2015; Accepted June 11, 2015; Epub June 15, 2015; Published June 30, 2015 Abstract: Purpose: Local anaesthetic wound infiltration techniques were reported to reduce opiate requirements and pain scores in women undergoing caesarean section (CS). However, the results were conflicting. The primary aim of this meta-analysis was to assess whether local analgesia could reduce pain intensity when injected via wound catheters. Methods: A search of randomized clinical trials (RCTs) evaluating local analgesia in caesarean surgery in PubMed, EMBASE and the Cochrane database was performed. Cumulative morphine consumption and pain scores at rest at different time point after surgery were extracted and synthesized using random or fixed model for meta-analysis. Subgroup analysis was performed according to incision type and administration regimen. Results: Nine RCTs with a total of 512 patients were included. Cumulative morphine consumption was lower in LA group compared with placebo group in the first 12 h (SMD = -0.736, 95% CI (-1.105, -0.368)), 24 h (SMD = -0.378, 95% CI (-0.624, -0.132)) and 48 h after surgery (SMD = -0.913, 95% CI (-1.683 to -0.143)). Lower morphine consumption was observed in the first 6 h after surgery but the reduction failed to meet the common level of significance. Pain scores was significantly reducedat 12 h but not 6 h after surgery in the LA group compared with placebo group. At 24 h and 48 h after surgery, the pain sore was lower but the difference did not meet the common level of significance. Lower rate of post-operative nausea was observed in the LA group. Conclusions: Local anaesthetic wound infiltration can reduce morphine requirements and the rate of patients suffer nausea but not pain scores after caesarean section. Further procedure-specific RCTs were encouraged to confirm the efficacy of local anaesthetic wound infiltration techniques. Keywords: Local anaesthetic wound infiltration, caesarean section, meta-analysis
Introduction Caesarean section is the most widely performed obstetric procedure [1]. Postoperative pain is one of the greatest concerns during and after caesarean delivery [2]. Caesarean section commonly induces moderate to severe pain lasting 48 hours after surgery, and poor pain control in the post-operative period can lead to the failure to take care of the newborn soon after delivery, chronic pain syndromes and poor quality of life [3]. Currently, opioids are commonly used for relief of postoperative pain after caesarean section, either by intrathecal administration prior to section or postoperative parenteral administration [4]. But the usage of opioids are associated
with many undesirable side effects such as drowsiness, nausea and vomiting [5]. Thereafter, there are needs for alternative analgesic drugs to reduce the amount of opioids [6]. Local anesthetics (LA) are injected via catheters placed in surgical wounds for post-operative analgesia to provide analgesia by both single shoot and continuous infiltration. However, the use of local anaesthetic wound infiltration for alleviating post-operative pain has been studied in past decades with conflicting reports and scholars hold distinctly different views towards this issue [7, 8]. Two major endpoints to assess the efficacy of LA would infiltration are the decrease of opioids use and pain score relief. Some studies indicated that wound infusion with LA for post-caesarean section
Wound infiltration for pain relief and the Cochrane database covering the period from 1966 to November 2014. The search strategy included the following key words: “postoperative pain” OR “postoperative analgesia”, “local anesthetics”, “continuous” OR “infusion” OR “perfusion,” OR “irrigation” OR “instillation”, “Caesarean section”, “Caesarean delivery”. A manual search of the reference lists from selected articles was also carried out to further increase the number of publications with relevant data. Criteria for inclusion and exclusion The inclusion criteria were (a) randomized, controlled trials; (b) continuous infiltraFigure 1. A flow diagram of the studies identified and included is shown. RCT, tion by catheters or intermitrandomized-controlled trial. tent injections or continuous infusions with LA and postanalgesia was effective in reducing opioid conoperative pain after caesarean delivery. (c) sufficient published data for estimating, and (e) sumption [9-11]. On the contrary there are also article was either in English or Chinese. studies with similar design demonstrated no significant reduction in opioid requirements Exclusion criteria were studies that (a) did not [12]. However, most published studies indicathave a control group; (b) single injection of a LA ed there was not a significant improvement in through a wound catheter; (c) comparing LA reduced pain scores [13]. with other means of analgesia (for example, epidural analgesia); (d) without a proper control A previous meta-analysis summarized the group (an active substance or a combination results of 3 studies in applying LA infiltration of drugs); (e) intra- or extra-pleural catheters, to patients underwent Gynecological surgeries mediastinal catheters, intra-abdominal cathe[14], but the result was still gauge. As more ters for drug. Reviews and repeated literatures articles published, we intended to test the effiwere excluded. cacy of LA infiltration in patients underwent CS by comparing the cumulative opioid consumpIn the searching period, 73 records were includtion and the pain score from 4 h to 48 h after ed in the Pubmed and Embase. And 15 articles surgery. were found through hand search of the citations of included articles. Sixty-six articles Methods remained after removal of repeated literatures and article in other languages. We screened Publication search the remaining 66 articles and found that 40 of This meta-analysis was performed according to these studies focused on other means of drug the Preferred Reporting Items for Systematic delivery. In the remaining 23 studies for qualitative analysis, 12 articles were of a different Reviews and Meta-Analyses (PRISMA) guidestudy designs and excluded thereafter. One lines. A literature search was carried out includarticle failed to be eligible for quantitative syning the following databases: PubMed, EMBASE
10214
Int J Clin Exp Med 2015;8(6):10213-10224
Wound infiltration for pain relief Table 1. Characteristics of eligible studies No.
First Author
Cases OQS
Sites of placement
Method of injection
Intervention
NRS Score
Morphine consumption
LA drug
1
Trotter TN, et al. 1991
14+14
5
Over the fascia
Single injection
0.5% bupivacaine; Saline
NA
Lower consumption at 12 h and 24 h
Morphine
2
Fredman B, et al. 2000
25+25
5
Over the fascia
Intermittent
0.2% ropivacaine; Sterile water
Lower pain at 3, 4 and 5 h
Lower consumption during 0-6 h
Morphine
3
Givens VA, et al. 2002
20+16
5
Over the fascia
Continuous; Bolus 25 ml
0.25% bupivacaine; Saline
No difference
Lower consumption during 0-48 h
Morphine
Lavand’homme PM, et al. 2007 30+30
5
Over the fascia
Intermittent
0.2% ropivacaine; Saline
Lower pain 12 h
Lower consumption
Morphine
4 5
Mecklem DW, et al. 1995
35+35
5
Below the fascia; Beneath the rectus sheath
Intermittent
0.25% bupivacaine; Saline
Lower pain 18-24 h
Lower consumption during 0-4 h and 18-24 h
Morphine
6
Zohar, et al. 2006
30+30
5
Over the fascia
Intermittent
0.25% bupivacaine; Saline (+i.v. diclofenac)
No difference
Higher consumption
Morphine
7
Anthony AB, et al. 2008
50+50
5
All layers of abdominal wall and the peritoneum
Single injection
0.75% ropivacaine; Saline
8
Kainu JP, et al. 2012
22+20
5
Below the fascia
Intermittent; Bolus 20 ml
0.375% ropivacaine; Saline
No difference
Lower consumption 6, 9, 12 h
Oxycodone
9
Pavy T, et al. 2012
20+20
5
Over the fascia
Single injection
0.5% bupivacaine; Saline
No difference
NA
codeine phosphate +paracetomol
10
Reinikainen M, et al. 2014
33+34
5
Over the fascia
Continuous; Bolus 10 ml
0.75% ropivacaine; Saline
No difference
Lower consumption at first 6 h; but not 6-48 h.
Oxycodone
Lower pain during 15 min-24 h Lower consumption during 1-24 h
Pethidine
Table 2. Main Results of meta-analysis of cumulative morphine consumption and pain score Outcome
Time Span/Time epoch
No. of studies
No. of patients
Model
Morphine consumption Morphine consumption Morphine consumption Morphine consumption Pain Score Pain Score Pain Score Pain Score
0-6 hours 0-12 hours 0-24 hours 0-48 hours 4h 12 h 24 h 48 h
3 3 5 5 4 4 7 6
177 124 265 275 237 191 370 273
Random Fixed Random Random Random Random Fixed Random
No. 1 2 3 4 5 6 7 8
10215
Test of association Test of heterogeneity SMD (95% CI) P-value chi-squared P-value I2 -0.816 (-1.779, 0.148) 0.097 18.44
Review Article Local anaesthetic wound infiltration used for caesarean section pain relief: a meta-analysis Xiangnan Li1*, Miao Zhou2*, Xuan Shi3*, Haiqin Yang1, Yonghua Li1*, Jian Li1, Mei Yang1, Hongbin Yuan1 Department of Anesthesiology, Changzheng Hospital, The Second Military Medical University; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College; 3No. 12 branch of The Cadet Management Unit, Second Military Medical University, No 800 Xiang Yin Road, Shanghai. *Equal contributors and co-first authors. 1
Received June 7, 2015; Accepted June 11, 2015; Epub June 15, 2015; Published June 30, 2015 Abstract: Purpose: Local anaesthetic wound infiltration techniques were reported to reduce opiate requirements and pain scores in women undergoing caesarean section (CS). However, the results were conflicting. The primary aim of this meta-analysis was to assess whether local analgesia could reduce pain intensity when injected via wound catheters. Methods: A search of randomized clinical trials (RCTs) evaluating local analgesia in caesarean surgery in PubMed, EMBASE and the Cochrane database was performed. Cumulative morphine consumption and pain scores at rest at different time point after surgery were extracted and synthesized using random or fixed model for meta-analysis. Subgroup analysis was performed according to incision type and administration regimen. Results: Nine RCTs with a total of 512 patients were included. Cumulative morphine consumption was lower in LA group compared with placebo group in the first 12 h (SMD = -0.736, 95% CI (-1.105, -0.368)), 24 h (SMD = -0.378, 95% CI (-0.624, -0.132)) and 48 h after surgery (SMD = -0.913, 95% CI (-1.683 to -0.143)). Lower morphine consumption was observed in the first 6 h after surgery but the reduction failed to meet the common level of significance. Pain scores was significantly reducedat 12 h but not 6 h after surgery in the LA group compared with placebo group. At 24 h and 48 h after surgery, the pain sore was lower but the difference did not meet the common level of significance. Lower rate of post-operative nausea was observed in the LA group. Conclusions: Local anaesthetic wound infiltration can reduce morphine requirements and the rate of patients suffer nausea but not pain scores after caesarean section. Further procedure-specific RCTs were encouraged to confirm the efficacy of local anaesthetic wound infiltration techniques. Keywords: Local anaesthetic wound infiltration, caesarean section, meta-analysis
Introduction Caesarean section is the most widely performed obstetric procedure [1]. Postoperative pain is one of the greatest concerns during and after caesarean delivery [2]. Caesarean section commonly induces moderate to severe pain lasting 48 hours after surgery, and poor pain control in the post-operative period can lead to the failure to take care of the newborn soon after delivery, chronic pain syndromes and poor quality of life [3]. Currently, opioids are commonly used for relief of postoperative pain after caesarean section, either by intrathecal administration prior to section or postoperative parenteral administration [4]. But the usage of opioids are associated
with many undesirable side effects such as drowsiness, nausea and vomiting [5]. Thereafter, there are needs for alternative analgesic drugs to reduce the amount of opioids [6]. Local anesthetics (LA) are injected via catheters placed in surgical wounds for post-operative analgesia to provide analgesia by both single shoot and continuous infiltration. However, the use of local anaesthetic wound infiltration for alleviating post-operative pain has been studied in past decades with conflicting reports and scholars hold distinctly different views towards this issue [7, 8]. Two major endpoints to assess the efficacy of LA would infiltration are the decrease of opioids use and pain score relief. Some studies indicated that wound infusion with LA for post-caesarean section
Wound infiltration for pain relief and the Cochrane database covering the period from 1966 to November 2014. The search strategy included the following key words: “postoperative pain” OR “postoperative analgesia”, “local anesthetics”, “continuous” OR “infusion” OR “perfusion,” OR “irrigation” OR “instillation”, “Caesarean section”, “Caesarean delivery”. A manual search of the reference lists from selected articles was also carried out to further increase the number of publications with relevant data. Criteria for inclusion and exclusion The inclusion criteria were (a) randomized, controlled trials; (b) continuous infiltraFigure 1. A flow diagram of the studies identified and included is shown. RCT, tion by catheters or intermitrandomized-controlled trial. tent injections or continuous infusions with LA and postanalgesia was effective in reducing opioid conoperative pain after caesarean delivery. (c) sufficient published data for estimating, and (e) sumption [9-11]. On the contrary there are also article was either in English or Chinese. studies with similar design demonstrated no significant reduction in opioid requirements Exclusion criteria were studies that (a) did not [12]. However, most published studies indicathave a control group; (b) single injection of a LA ed there was not a significant improvement in through a wound catheter; (c) comparing LA reduced pain scores [13]. with other means of analgesia (for example, epidural analgesia); (d) without a proper control A previous meta-analysis summarized the group (an active substance or a combination results of 3 studies in applying LA infiltration of drugs); (e) intra- or extra-pleural catheters, to patients underwent Gynecological surgeries mediastinal catheters, intra-abdominal cathe[14], but the result was still gauge. As more ters for drug. Reviews and repeated literatures articles published, we intended to test the effiwere excluded. cacy of LA infiltration in patients underwent CS by comparing the cumulative opioid consumpIn the searching period, 73 records were includtion and the pain score from 4 h to 48 h after ed in the Pubmed and Embase. And 15 articles surgery. were found through hand search of the citations of included articles. Sixty-six articles Methods remained after removal of repeated literatures and article in other languages. We screened Publication search the remaining 66 articles and found that 40 of This meta-analysis was performed according to these studies focused on other means of drug the Preferred Reporting Items for Systematic delivery. In the remaining 23 studies for qualitative analysis, 12 articles were of a different Reviews and Meta-Analyses (PRISMA) guidestudy designs and excluded thereafter. One lines. A literature search was carried out includarticle failed to be eligible for quantitative syning the following databases: PubMed, EMBASE
10214
Int J Clin Exp Med 2015;8(6):10213-10224
Wound infiltration for pain relief Table 1. Characteristics of eligible studies No.
First Author
Cases OQS
Sites of placement
Method of injection
Intervention
NRS Score
Morphine consumption
LA drug
1
Trotter TN, et al. 1991
14+14
5
Over the fascia
Single injection
0.5% bupivacaine; Saline
NA
Lower consumption at 12 h and 24 h
Morphine
2
Fredman B, et al. 2000
25+25
5
Over the fascia
Intermittent
0.2% ropivacaine; Sterile water
Lower pain at 3, 4 and 5 h
Lower consumption during 0-6 h
Morphine
3
Givens VA, et al. 2002
20+16
5
Over the fascia
Continuous; Bolus 25 ml
0.25% bupivacaine; Saline
No difference
Lower consumption during 0-48 h
Morphine
Lavand’homme PM, et al. 2007 30+30
5
Over the fascia
Intermittent
0.2% ropivacaine; Saline
Lower pain 12 h
Lower consumption
Morphine
4 5
Mecklem DW, et al. 1995
35+35
5
Below the fascia; Beneath the rectus sheath
Intermittent
0.25% bupivacaine; Saline
Lower pain 18-24 h
Lower consumption during 0-4 h and 18-24 h
Morphine
6
Zohar, et al. 2006
30+30
5
Over the fascia
Intermittent
0.25% bupivacaine; Saline (+i.v. diclofenac)
No difference
Higher consumption
Morphine
7
Anthony AB, et al. 2008
50+50
5
All layers of abdominal wall and the peritoneum
Single injection
0.75% ropivacaine; Saline
8
Kainu JP, et al. 2012
22+20
5
Below the fascia
Intermittent; Bolus 20 ml
0.375% ropivacaine; Saline
No difference
Lower consumption 6, 9, 12 h
Oxycodone
9
Pavy T, et al. 2012
20+20
5
Over the fascia
Single injection
0.5% bupivacaine; Saline
No difference
NA
codeine phosphate +paracetomol
10
Reinikainen M, et al. 2014
33+34
5
Over the fascia
Continuous; Bolus 10 ml
0.75% ropivacaine; Saline
No difference
Lower consumption at first 6 h; but not 6-48 h.
Oxycodone
Lower pain during 15 min-24 h Lower consumption during 1-24 h
Pethidine
Table 2. Main Results of meta-analysis of cumulative morphine consumption and pain score Outcome
Time Span/Time epoch
No. of studies
No. of patients
Model
Morphine consumption Morphine consumption Morphine consumption Morphine consumption Pain Score Pain Score Pain Score Pain Score
0-6 hours 0-12 hours 0-24 hours 0-48 hours 4h 12 h 24 h 48 h
3 3 5 5 4 4 7 6
177 124 265 275 237 191 370 273
Random Fixed Random Random Random Random Fixed Random
No. 1 2 3 4 5 6 7 8
10215
Test of association Test of heterogeneity SMD (95% CI) P-value chi-squared P-value I2 -0.816 (-1.779, 0.148) 0.097 18.44
