Epidural local anaesthetics versus opioid‐based analgesic regimens for postoperative gastrointestinal paralysis, vomiting and pain after abdominal surgery

Joanne Guay; Mina Nishimori; Sandra Kopp

doi:10.1002/14651858.CD001893.pub2

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Figure 1

Flow diagram. Study selection from the 2014 search. We reran the search in February 2016, and added 16 potential new studies of interest to the list of ‘Studies awaiting classification'. These studies will be incorporated into the formal review findings during the next review update. We also found one ongoing trial.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Meta‐regression of effects of the concentration of local anaesthetic used (mg/mL) after surgery on the standardized mean difference for return of gastrointestinal transit as measured by the time required to obtain first flatus. P value = 0.0008.

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Figure 5

Meta‐regression of the effects of mean age of participants included in the study on VAS scores at rest at 48 hours (P value = 0.0002). Older participants benefit more from an epidural containing a local anaesthetic for an abdominal surgery.

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Figure 6

Meta‐regression of the effects of mean age of participants included in the study on VAS scores on movement at 48 hours (P value = 0.002). Older participants benefit more from an epidural containing a local anaesthetic for an abdominal surgery.

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Analysis 1.1

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 1 Time to first flatus subgrouped by type of surgery.

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Analysis 1.2

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 2 Time to first faeces subgrouped according to duration of local anaesthetic administration.

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Analysis 1.3

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 3 Pain scores at rest at 6 to 8 hours after surgery subgrouped by type of surgery.

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Analysis 1.4

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 4 Pain scores on movement at 6 to 8 hours after surgery subgrouped by type of opioid in the control group.

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Analysis 1.5

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 5 Pain scores at rest at 24 hours subgrouped by type of opioid in the epidural.

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Analysis 1.6

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 6 Pain scores at rest at 24 hours subgrouped by opioid in the control group.

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Analysis 1.7

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 7 Pain scores on movement at 24 hours subgrouped by type of surgery.

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Analysis 1.8

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 8 Pain scores on movement at 24 hours subgrouped by type of opioid in the epidural.

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Analysis 1.9

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 9 Pain scores on movement at 24 hours subgrouped by type of opioids in the control group.

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Analysis 1.10

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 10 Pain scores at rest at 48 hours subgrouped by type of solution used.

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Analysis 1.11

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 11 Pain scores on movement at 48 hours subgrouped by type of solution in the epidural.

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Analysis 1.12

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 12 Pain scores at rest at 72 hours subgrouped by type of solution used.

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Analysis 1.13

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 13 Pain scores on movement at 72 hours subgrouped by type of solution used.

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Analysis 1.14

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 14 Vomiting.

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Analysis 1.15

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 15 Gastrointestinal tract anastomotic leak.

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Analysis 1.16

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 16 Length of stay in hospital subgrouped by type of surgery.

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Analysis 1.17

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 17 Length of stay in hospital subgrouped by surgical site for open surgery only.

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Analysis 1.18

Comparison 1 Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen, Outcome 18 Costs.

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Summary of findings for the main comparison. Epidural local anaesthetic compared with opioid‐based regimen for adults

Epidural local anaesthetic compared with opioid‐based regimen for adults
Patient or population: adults Settings: Trials were performed in Australia (n = 4); Canada (n = 19); China (n = 6); Czech Republic (n = 1); Denmark (n = 8); Egypt (n = 3); Finland (n = 4); France (n = 5); Germany (n = 10); Greece (n = 2); India (n = 3); Israel (n = 2); Italy (n = 10); Japan (n = 1); Korea (n = 1); Lithuania (n = 1); Romania (n = 2); Russia (n = 1); Serbia (n = 1); Spain (n = 1); Sweden (n = 6); Switzerland (n = 2); The Netherlands (n = 1); Turkey (n = 8); United Kingdom (n = 6); United States of America (n = 17); and Uruguay (n = 1) Intervention: epidural local anaesthetic Comparison: opioid‐based regimen
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Opioid‐based regimen	Epidural local anaesthetic
Time required to observe first flatus		Mean time required to observe first flatus in the intervention groups was 1.28 standard deviations lower (1.71 to 0.86 lower)		1138 (22 studies)	⊕⊕⊕⊕ high^{a,b,c,d,e,f,g,h}	Effect size was proportionate to the concentration of local anaesthetic used Pooled reduction is equivalent to 17.5 hours
Time required to observe first faeces		Mean time required to observe first faeces in the intervention groups was 0.67 standard deviations lower (0.86 to 0.47 lower)		1559 (28 studies)	⊕⊕⊝⊝ low^{c,d,e,g,i,j,k,l}	Pooled reduction is equivalent to 22 hours
VAS scores on movement at 24 hours		Mean VAS scores on movement at 24 hours in the intervention groups was 0.85 standard deviations lower (1.04 to 0.67 lower)		2731 (35 studies)	⊕⊕⊕⊝ moderate^{a,b,c,d,e,f,g,l}	Pooled reduction is equivalent to 2.5 on a scale from 0 to 10
Vomiting during first 24 hours	Study population		RR 0.84 (0.57 to 1.23)	1154 (22 studies)	⊕⊕⊝⊝ low^{c,e,g,i,k,l,m,n}
	170 per 1000	143 per 1000 (97 to 210)
	Low
	50 per 1000	42 per 1000 (28 to 62)
	High
	250 per 1000	210 per 1000 (142 to 308)
Anastomotic leak	Study population		RR 0.74 (0.41 to 1.32)	848 (17 studies)	⊕⊕⊝⊝ low^{c,e,g,i,k,l,m,n}
	53 per 1000	39 per 1000 (22 to 70)
	Low
	30 per 1000	22 per 1000 (12 to 40)
	High
	100 per 1000	74 per 1000 (41 to 132)
Length of hospital stay		Mean length of hospital stay in the intervention groups was 0.20 standard deviations lower (0.35 to 0.04 lower)		2598 (30 studies)	⊕⊝⊝⊝ very low^{a,c,d,j,k,l,o,p}	Pooled reduction is equivalent to 1 day
The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: We are very uncertain about the estimate
^aAllocation concealment and/or blinding of outcome assessors rated as unclear or high risk for 75% or more of included studies for this outcome ^bWe did not downgrade the quality of evidence on the basis of inconsistency because a reasonable explanation was found for heterogeneity ^cDirect comparisons performed on the population of interest and not a surrogate marker ^dOptimal information size achieved ^eNo evidence of a publication bias, or applying a correction for the possibility of publication bias would not modify the conclusion ^fLarge effect size (SMD≥ 0.8) ^gNo evidence of confounding factors to justify upgrading ^hEffect size was proportionate to the local anaesthetic concentration ⁱ50% or more of included studies were rated as unclear or high risk for allocation concealment and/or blinding of outcome assessors ^jWe downgraded the level of evidence on inconsistency owing to a moderate amount of heterogeneity ^kNo evidence of a large effect ^lNo evidence of a dose‐response effect ^mNo heterogeneity or heterogeneity less than 25% ⁿOptimal information size not achieved ^oCorrecting for the possibility of publication bias would modify the conclusion ^pLength of hospital stay may not adequately reflect readiness for discharge, as actual discharge may be delayed for various reasons

Summary of findings for the main comparison. Epidural local anaesthetic compared with opioid‐based regimen for adults

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Comparison 1. Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Time to first flatus subgrouped by type of surgery Show forest plot	22	1138	Std. Mean Difference (Random, 95% CI)	‐1.28 [‐1.71, ‐0.86]

1.1 Gynaecology	3	122	Std. Mean Difference (Random, 95% CI)	‐1.24 [‐1.86, ‐0.62]
1.2 Cholecystectomy	1	27	Std. Mean Difference (Random, 95% CI)	‐0.15 [‐0.91, 0.61]
1.3 Gastrointestinal surgery	14	690	Std. Mean Difference (Random, 95% CI)	‐1.34 [‐1.82, ‐0.86]
1.4 Urology	1	40	Std. Mean Difference (Random, 95% CI)	‐0.83 [‐1.48, ‐0.17]
1.5 Vascular surgery	1	34	Std. Mean Difference (Random, 95% CI)	‐12.86 [‐15.98, ‐9.73]
1.6 Various	2	225	Std. Mean Difference (Random, 95% CI)	‐0.03 [‐0.29, 0.23]
2 Time to first faeces subgrouped according to duration of local anaesthetic administration Show forest plot	28	1559	Std. Mean Difference (Random, 95% CI)	‐0.67 [‐0.86, ‐0.47]

2.1 Epidural local anaesthetic administered during surgery only	1	30	Std. Mean Difference (Random, 95% CI)	0.03 [‐0.68, 0.75]
2.2 Epidural local anaesthetic administered postoperatively for < 48 hours	8	363	Std. Mean Difference (Random, 95% CI)	‐0.57 [‐1.06, ‐0.07]
2.3 Epidural local anaesthetic administered for ≥ 48 hours after surgery	19	1166	Std. Mean Difference (Random, 95% CI)	‐0.73 [‐0.93, ‐0.53]
3 Pain scores at rest at 6 to 8 hours after surgery subgrouped by type of surgery Show forest plot	20	947	Std. Mean Difference (Random, 95% CI)	‐0.84 [‐1.08, ‐0.61]

3.1 Cholecystectomy	1	16	Std. Mean Difference (Random, 95% CI)	0.33 [‐0.65, 1.32]
3.2 Gastrointestinal surgery	8	387	Std. Mean Difference (Random, 95% CI)	‐0.74 [‐1.06, ‐0.42]
3.3 Gynaecology	2	68	Std. Mean Difference (Random, 95% CI)	‐0.76 [‐1.70, 0.18]
3.4 Urology	4	136	Std. Mean Difference (Random, 95% CI)	‐1.16 [‐1.66, ‐0.67]
3.5 Vascular surgery	2	154	Std. Mean Difference (Random, 95% CI)	‐0.63 [‐1.00, ‐0.26]
3.6 Various	4	186	Std. Mean Difference (Random, 95% CI)	‐1.24 [‐2.18, ‐0.29]
4 Pain scores on movement at 6 to 8 hours after surgery subgrouped by type of opioid in the control group Show forest plot	13	617	Std. Mean Difference (Random, 95% CI)	‐1.05 [‐1.52, ‐0.58]

4.1 Epidural LA compared with IV or epidural fentanyl	3	119	Std. Mean Difference (Random, 95% CI)	‐1.15 [‐3.91, 1.61]
4.2 Epidural LA compared with IT (De Pietri 2006) or IV (all others) morphine	8	387	Std. Mean Difference (Random, 95% CI)	‐0.93 [‐1.28, ‐0.59]
4.3 Epidural LA with opioids compared with IV piritramide	1	19	Std. Mean Difference (Random, 95% CI)	‐0.62 [‐1.54, 0.30]
4.4 Epidural LA alone compared with epidural sufentanil	1	67	Std. Mean Difference (Random, 95% CI)	‐0.95 [‐1.78, ‐0.12]
4.5 Epidural LA with opioids compared with IV tramadol	1	25	Std. Mean Difference (Random, 95% CI)	‐2.19 [‐3.18, ‐1.20]
5 Pain scores at rest at 24 hours subgrouped by type of opioid in the epidural Show forest plot	46	3085	Std. Mean Difference (Random, 95% CI)	‐0.62 [‐0.82, ‐0.43]

5.1 Local anaesthetic only	13	414	Std. Mean Difference (Random, 95% CI)	‐0.16 [‐0.70, 0.38]
5.2 Epidural local anaesthetic with the addition of meperidine	1	59	Std. Mean Difference (Random, 95% CI)	‐0.11 [‐0.65, 0.44]
5.3 Epidural local anaesthetic with the addition of morphine	12	634	Std. Mean Difference (Random, 95% CI)	‐1.32 [‐1.87, ‐0.78]
5.4 Epidural local anaesthetic with the addition of fentanyl	18	891	Std. Mean Difference (Random, 95% CI)	‐0.55 [‐0.77, ‐0.33]
5.5 Epidural local anaesthetic with the addition of sufentanil	4	199	Std. Mean Difference (Random, 95% CI)	‐0.61 [‐0.94, ‐0.29]
5.6 Epidural with different solutions	1	888	Std. Mean Difference (Random, 95% CI)	‐0.29 [‐0.42, ‐0.15]
6 Pain scores at rest at 24 hours subgrouped by opioid in the control group Show forest plot	42	2066	Std. Mean Difference (Random, 95% CI)	‐0.69 [‐0.91, ‐0.47]

6.1 Epidural local anaesthetic compared with fentanyl	4	144	Std. Mean Difference (Random, 95% CI)	‐1.11 [‐3.18, 0.96]
6.2 Epidural local anaesthetic compared with ketobemidone	1	40	Std. Mean Difference (Random, 95% CI)	‐1.23 [‐1.91, ‐0.56]
6.3 Epidural local anaesthetic compared with piritramide	1	19	Std. Mean Difference (Random, 95% CI)	0.14 [‐0.76, 1.04]
6.4 Epidural local anaesthetic compared with meperidine	3	219	Std. Mean Difference (Random, 95% CI)	‐0.86 [‐1.73, 0.00]
6.5 Epidural local anaesthetic compared with sufentanil	1	67	Std. Mean Difference (Random, 95% CI)	0.44 [‐0.08, 0.95]
6.6 Epidural local anaesthetic compared with tramadol	2	65	Std. Mean Difference (Random, 95% CI)	‐1.09 [‐3.30, 1.12]
6.7 Epidural local anaesthetic compared with morphine	30	1435	Std. Mean Difference (Random, 95% CI)	‐0.64 [‐0.87, ‐0.41]
6.8 Epidural local anaesthetic compared with buprenorphine	2	77	Std. Mean Difference (Random, 95% CI)	‐1.05 [‐1.52, ‐0.57]
7 Pain scores on movement at 24 hours subgrouped by type of surgery Show forest plot	35	2731	Std. Mean Difference (Random, 95% CI)	‐0.85 [‐1.04, ‐0.67]

7.1 Gastrointestinal surgery	18	864	Std. Mean Difference (Random, 95% CI)	‐1.12 [‐1.43, ‐0.80]
7.2 Cholecystectomy	1	31	Std. Mean Difference (Random, 95% CI)	‐0.89 [‐1.62, ‐0.15]
7.3 Gynaecological surgery	2	144	Std. Mean Difference (Random, 95% CI)	‐0.20 [‐0.88, 0.48]
7.4 Urological surgery	4	136	Std. Mean Difference (Random, 95% CI)	‐0.66 [‐1.71, 0.40]
7.5 Vascular surgery	1	40	Std. Mean Difference (Random, 95% CI)	‐1.70 [‐2.43, ‐0.98]
7.6 Various surgeries	10	1516	Std. Mean Difference (Random, 95% CI)	‐0.61 [‐0.81, ‐0.41]
8 Pain scores on movement at 24 hours subgrouped by type of opioid in the epidural Show forest plot	34	1843	Std. Mean Difference (Random, 95% CI)	‐0.88 [‐1.09, ‐0.66]

8.1 Local anaesthetic alone	6	234	Std. Mean Difference (Random, 95% CI)	‐0.38 [‐0.93, 0.17]
8.2 Epidural meperidine	1	59	Std. Mean Difference (Random, 95% CI)	0.31 [‐0.24, 0.86]
8.3 Epidural fentanyl	16	756	Std. Mean Difference (Random, 95% CI)	‐0.95 [‐1.20, ‐0.69]
8.4 Epidural sufentanil	3	129	Std. Mean Difference (Random, 95% CI)	‐0.77 [‐1.14, ‐0.41]
8.5 Epidural morphine	10	665	Std. Mean Difference (Random, 95% CI)	‐1.19 [‐1.69, ‐0.69]
9 Pain scores on movement at 24 hours subgrouped by type of opioids in the control group Show forest plot	33	1796	Std. Mean Difference (Random, 95% CI)	‐0.90 [‐1.15, ‐0.66]

9.1 Compared with IV or epidural fentanyl	4	128	Std. Mean Difference (Random, 95% CI)	‐0.83 [‐3.13, 1.47]
9.2 Compared with sufentanil	1	67	Std. Mean Difference (Random, 95% CI)	‐0.10 [‐0.91, 0.70]
9.3 Compared with meperidine	3	219	Std. Mean Difference (Random, 95% CI)	‐0.64 [‐1.57, 0.29]
9.4 Compared with piritramide	1	19	Std. Mean Difference (Random, 95% CI)	‐0.78 [‐1.72, 0.15]
9.5 Compared with morphine	23	1249	Std. Mean Difference (Random, 95% CI)	‐0.87 [‐1.05, ‐0.69]
9.6 Compared with oxycodone	1	58	Std. Mean Difference (Random, 95% CI)	‐0.80 [‐1.33, ‐0.26]
9.7 Compared with tramadol	1	25	Std. Mean Difference (Random, 95% CI)	‐3.14 [‐4.31, ‐1.97]
9.8 Compared to buprenorphine	1	31	Std. Mean Difference (Random, 95% CI)	‐0.77 [‐1.50, ‐0.04]
10 Pain scores at rest at 48 hours subgrouped by type of solution used Show forest plot	30	2466	Std. Mean Difference (Random, 95% CI)	‐0.47 [‐0.71, ‐0.24]

10.1 Local anaesthetic alone	7	256	Std. Mean Difference (Random, 95% CI)	0.38 [‐0.49, 1.25]
10.2 Local anaesthetic with an opioid	24	2210	Std. Mean Difference (Random, 95% CI)	‐0.66 [‐0.89, ‐0.43]
11 Pain scores on movement at 48 hours subgrouped by type of solution in the epidural Show forest plot	27	2398	Std. Mean Difference (Random, 95% CI)	‐0.85 [‐1.10, ‐0.60]

11.1 Local anaesthetic alone	4	184	Std. Mean Difference (Random, 95% CI)	‐0.56 [‐1.71, 0.58]
11.2 Local anaesthetic with an opioid	23	2214	Std. Mean Difference (Random, 95% CI)	‐0.88 [‐1.13, ‐0.63]
12 Pain scores at rest at 72 hours subgrouped by type of solution used Show forest plot	15	1821	Std. Mean Difference (Random, 95% CI)	‐0.56 [‐0.88, ‐0.24]

12.1 Local anaesthetic alone	4	146	Std. Mean Difference (Random, 95% CI)	‐0.00 [‐0.34, 0.34]
12.2 Local anaesthetic plus opioids	12	1675	Std. Mean Difference (Random, 95% CI)	‐0.77 [‐1.16, ‐0.39]
13 Pain scores on movement at 72 hours subgrouped by type of solution used Show forest plot	15	1873	Std. Mean Difference (Random, 95% CI)	‐0.69 [‐0.99, ‐0.39]

13.1 Local anaesthetic alone	3	135	Std. Mean Difference (Random, 95% CI)	‐0.03 [‐0.38, 0.32]
13.2 Local anaesthetic with an opioid	12	1738	Std. Mean Difference (Random, 95% CI)	‐0.87 [‐1.22, ‐0.51]
14 Vomiting Show forest plot	22	1154	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.57, 1.23]

14.1 Gynaecological	4	223	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.06, 1.29]
14.2 Gastrointestinal	12	512	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.48, 1.32]
14.3 Various	6	419	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.44, 2.35]
15 Gastrointestinal tract anastomotic leak Show forest plot	17	848	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.41, 1.32]

16 Length of stay in hospital subgrouped by type of surgery Show forest plot	34	2774	Std. Mean Difference (Random, 95% CI)	‐0.13 [‐0.29, 0.02]

16.1 Cholecystectomy	1	20	Std. Mean Difference (Random, 95% CI)	‐0.5 [‐1.38, 0.38]
16.2 Gynaecological surgery	2	62	Std. Mean Difference (Random, 95% CI)	0.07 [‐0.43, 0.57]
16.3 Gastrointestinal surgery	18	936	Std. Mean Difference (Random, 95% CI)	‐0.11 [‐0.34, 0.12]
16.4 Urological surgery	4	141	Std. Mean Difference (Random, 95% CI)	‐0.52 [‐0.85, ‐0.18]
16.5 Vascular surgery	5	336	Std. Mean Difference (Random, 95% CI)	‐0.26 [‐0.65, 0.13]
16.6 Various surgeries	4	1279	Std. Mean Difference (Random, 95% CI)	0.16 [‐0.25, 0.57]
17 Length of stay in hospital subgrouped by surgical site for open surgery only Show forest plot	30	2598	Std. Mean Difference (Random, 95% CI)	‐0.20 [‐0.35, ‐0.04]

17.1 Open vascular surgery	5	336	Std. Mean Difference (Random, 95% CI)	‐0.26 [‐0.65, 0.13]
17.2 Open urological surgery	4	141	Std. Mean Difference (Random, 95% CI)	‐0.51 [‐0.85, ‐0.18]
17.3 Open cholecystectomy	1	20	Std. Mean Difference (Random, 95% CI)	‐0.50 [‐1.39, 0.39]
17.4 Open gynaecological surgery	2	62	Std. Mean Difference (Random, 95% CI)	0.07 [‐0.43, 0.57]
17.5 Open gastrointestinal surgery	14	760	Std. Mean Difference (Random, 95% CI)	‐0.24 [‐0.47, ‐0.01]
17.6 Open various surgeries	4	1279	Std. Mean Difference (Random, 95% CI)	0.15 [‐0.26, 0.57]
18 Costs Show forest plot	3		Std. Mean Difference (Random, 95% CI)	Subtotals only

18.1 Costs related to pain therapy only	1	62	Std. Mean Difference (Random, 95% CI)	19.96 [19.57, 20.34]
18.2 Hospital costs	2	103	Std. Mean Difference (Random, 95% CI)	0.17 [‐0.22, 0.55]

Comparison 1. Epidural with a local anaesthetic with or without opioids compared with opioid‐based regimen

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