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Meta-Analysis
. 2024 May 1;165(5):972-982.
doi: 10.1097/j.pain.0000000000003119. Epub 2023 Nov 30.

Remifentanil-induced hyperalgesia in healthy volunteers: a systematic review and meta-analysis of randomized controlled trials

Cinzia Dello Russo  1   2 , Valeria Di Franco  3 , Elisabetta Tabolacci  4 , Natalia Cappoli  1 , Pierluigi Navarra  1 , Liliana Sollazzi  3   5 , Francesca Rapido  6   7 , Paola Aceto  3   5
Affiliations
Meta-Analysis

Remifentanil-induced hyperalgesia in healthy volunteers: a systematic review and meta-analysis of randomized controlled trials

Cinzia Dello Russo et al. Pain. .

Abstract

Recent literature suggests that the withdrawal of remifentanil (RF) infusion can be associated with hyperalgesia in clinical and nonclinical settings. We performed a systematic review and a meta-analysis of randomized controlled trials with cross-over design, to assess the effect of discontinuing RF infusion on pain intensity and areas of hyperalgesia and allodynia in healthy volunteers. Nine studies were included. The intervention treatment consisted in RF infusion that was compared with placebo (saline solution). The primary outcome was pain intensity assessment at 30 ± 15 minutes after RF or placebo discontinuation, assessed by any pain scale and using any quantitative sensory testing. Moreover, postwithdrawal pain scores were compared with baseline scores in each treatment. Secondary outcomes included the areas (% of basal values) of hyperalgesia and allodynia. Subjects during RF treatment reported higher pain scores after discontinuation than during treatment with placebo [standardized mean difference (SMD): 0.50, 95% confidence interval (CI): 0.03-0.97; P = 0.04, I 2 = 71%]. A significant decrease in pain scores, compared with baseline values, was found in the placebo treatment (SMD: -0.87, 95% CI: -1.61 to -0.13; P = 0.02, I 2 = 87%), but not in the RF treatment (SMD: -0.28, 95% CI: -1.18 to 0.62; P = 0.54, I 2 = 91%). The area of hyperalgesia was larger after RF withdrawal (SMD: 0.55; 95% CI: 0.27-0.84; P = 0.001; I 2 = 0%). The area of allodynia did not vary between treatments. These findings suggest that the withdrawal of RF induces a mild but nonclinically relevant degree of hyperalgesia in HVs, likely linked to a reduced pain threshold.

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Conflict of interest statement

V.D.F. is an employee of Angelini Pharma since April 2023. The other authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram of the study selection process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2.
Figure 2.
Forest plots reporting pain intensity after remifentanil withdrawal (A), pain score change (postinfusion vs preinfusion) in placebo treatment (B), pain score change (postinfusion vs preinfusion) in remifentanil treatment (C), area (expressed as % of basal value) of hyperalgesia (D), and allodynia (E) after remifentanil withdrawal. The effect size is calculated as standardized mean difference (SMD) and corresponding 95% confidence interval (95% CI). Data suggest higher pain score in RF treatment (A) and stability of pain intensity in the postinfusion vs preinfusion analysis in the RF treatment (C). RF, remifentanil.
Figure 3.
Figure 3.
Review authors' judgment of each of the risk-of-bias items across the included studies evaluated using the Cochrane Risk of Bias 2 tool (Rob 2).
Figure 4.
Figure 4.
Certainty of evidence assessment for the randomised controlled trials with cross-over design included in the meta-analysis.
See this image and copyright information in PMC

References

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