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Meta-Analysis
. 2016 Feb 12;2(2):CD009346.
doi: 10.1002/14651858.CD009346.pub2.

Pharmacological and non-pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults

Hemanshu Prabhakar  1 , Gyaninder Pal Singh, Zulfiqar Ali, Mani Kalaivani, Martha A Smith
Affiliations
Meta-Analysis

Pharmacological and non-pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults

Hemanshu Prabhakar et al. Cochrane Database Syst Rev. .

Abstract

Background: Rocuronium bromide is a routinely used muscle relaxant in anaesthetic practice. Its use, however, is associated with intense pain on injection. While it is well established that rocuronium bromide injection causes pain in awake patients, anaesthetized patients also tend to show withdrawal movements of the limbs when this muscle relaxant is administered. Various strategies, both pharmacological and non-pharmacological, have been studied to reduce the incidence and severity of pain on rocuronium bromide injection. We wanted to find out which of the existing modalities was best to reduce pain on rocuronium injection.

Objectives: The objectives of this review were to assess the ability of both pharmacological and non-pharmacological interventions to reduce or eliminate the pain that accompanies rocuronium bromide administration.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 7), MEDLINE via Ovid SP (1966 to July 2013) and EMBASE via Ovid SP (1980 to July 2013). We also searched specific websites. We reran the searches in February 2015 and will deal with the 11 studies of interest found through this search when we update the review.

Selection criteria: We included all randomized controlled trials (RCTs) that compared the use of any drug or a non-pharmacological method with control patients, or those receiving no treatment to reduce the severity of pain with rocuronium injection. Our primary outcome was pain on rocuronium bromide injection measured by a pain score assessment. Our secondary outcomes were rise in heart rate and blood pressure following administration of rocuronium and adverse events related to the interventions.

Data collection and analysis: We used the standardized methods for conducting a systematic review as described in the Cochrane Handbook for Systematic Reviews of Interventions. Two authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. We made all analyses on an intention-to-treat basis. We used a fixed-effect model where there was no evidence of significant heterogeneity between studies and a random-effects model if heterogeneity was likely.

Main results: We included 66 studies with 7840 participants in the review, though most analyses were based on data from fewer participants. In total there are 17 studies awaiting classification. No studies were at a low risk of bias. We noted substantial statistical and clinical heterogeneity between trials. Most of the studies reported the primary outcome pain as assessed by verbal response from participants in an awake state but some trials reported withdrawal of the injected limb as a proxy for pain after induction of anaesthesia in response to rocuronium administration. Few studies reported adverse events and no study reported heart rate and blood pressure changes after administration of rocuronium. Lidocaine was the most commonly studied intervention drug, used in 29 trials with 2256 participants. The risk ratio (RR) of pain on injection if given lidocaine compared to placebo was 0.23 (95% confidence interval (CI) 0.17 to 0.31; I² = 65%, low quality of evidence). The RR of pain on injection if fentanyl and remifentanil were given compared to placebo was 0.42 (95% CI 0.26 to 0.70; I² = 79%, low quality of evidence) and (RR 0.10, 95% CI 0.04 to 0.26; I² = 74%, low quality of evidence), respectively. Pain on injection of intervention drugs was reported with the use of lidocaine and acetaminophen in one study. Cough was reported with the use of fentanyl (one study), remifentanil (five studies, low quality evidence) and alfentanil (one study). Breath holding and chest tightness were reported with the use of remifentanil in two studies (very low quality evidence) and one study (very low quality evidence), respectively. The overall rate of complications was low.

Authors' conclusions: The evidence to suggest that the most commonly investigated pharmacological interventions reduce pain on injection of rocuronium is of low quality due to risk of bias and inconsistency. There is low or very low quality evidence for adverse events, due to risk of bias, inconsistency and imprecision of effect. We did not compare the various interventions with one another and so cannot comment on the superiority of one intervention over another. Complications were reported more often with use of opioids.

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Conflict of interest statement

Hemanshu Prabhakar: none known

Gyaninder Pal Singh: none known

Zulfiqar Ali: none known

Mani Kalaivani: none known

Martha Smith: none known

Figures

1
1
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
2
2
Funnel plot of comparison: lidocaine versus saline, outcome: pain
3
3
Study flow diagram
4
4
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Non‐pharmacological interventions versus placebo, Outcome 1 Pain.
2.1
2.1. Analysis
Comparison 2 Rocuronium admixtures, Outcome 1 Pain.
3.1
3.1. Analysis
Comparison 3 Opioids versus placebo, Outcome 1 Pain.
4.1
4.1. Analysis
Comparison 4 Anaesthetics versus placebo/control, Outcome 1 Pain.
5.1
5.1. Analysis
Comparison 5 Antiemetics versus placebo, Outcome 1 Pain.
6.1
6.1. Analysis
Comparison 6 Analgesics versus placebo, Outcome 1 Pain.
7.1
7.1. Analysis
Comparison 7 Antihistamines versus placebo, Outcome 1 Pain.
8.1
8.1. Analysis
Comparison 8 Miscellaneous drugs versus placebo, Outcome 1 Pain.
9.1
9.1. Analysis
Comparison 9 Adverse events, Outcome 1 Breath holding.
9.2
9.2. Analysis
Comparison 9 Adverse events, Outcome 2 Chest tightness.
9.3
9.3. Analysis
Comparison 9 Adverse events, Outcome 3 Cough.
9.4
9.4. Analysis
Comparison 9 Adverse events, Outcome 4 Pain on injection.
See this image and copyright information in PMC

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  • doi: 10.1002/14651858.CD009346

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References

References to studies included in this review

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Choi 2012 {published data only}
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Hwang 2004 {published data only}
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Jeon 2013 {published data only}
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Lee 2009a {published data only}
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References to other published versions of this review

Prabhakar 2011
    1. Prabhakar H, Singh GP, Ali Z, Kalaivani M. Pharmacological and non‐pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD009346] - DOI - PMC - PubMed

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