de Oliveira Filho Getúlio Rodrigues, Kammer Raquel Spilere, Dos Santos Heloísa de Cássia
Department of Surgery, Federal University of Santa Catarina, Campus Universitário, Rua Professora Maria Flora Pausewang, s/n°, Trindade, 88036-800 Florianópolis, SC, Brazil.
J Clin Anesth. 2020 Aug;63:109785. doi: 10.1016/j.jclinane.2020.109785. Epub 2020 Mar 14.
Duloxetine administered during the acute perioperative period has been associated with lesser postoperative pain and analgesic consumption.
The study aimed to quantify the pooled effects of duloxetine on postoperative pain, analgesic consumption, and side-effects in the first 48 postoperative (PO) hours.
Systematic review with meta-analysis.
Postoperative pain management.
Adult patients undergoing elective surgery. Search strategy and study selection. Medline, Cochrane, EMBASE, CENTRAL, and Web of Science were searched without language restrictions for prospective, parallel randomized controlled trials comparing duloxetine to placebo for the management of postoperative pain in adult patients.
Pain scores (11-point scales), opioid consumption (i.v. morphine equivalents), and frequency of side-effects were compared between duloxetine and placebo. Effect sizes were summarized as mean differences (MD), standardized mean differences (SMD) or risk ratios (RR) with the respective 95% confidence intervals (95% CI). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were used to classify the quality of evidence.
Thirteen studies were included. Duloxetine decreased pain at 24 h (MD = -0.66 points; 95% CI = -1.14 to -0.19 points; SMD = -0.59; 95% CI = -1.06 to -0.12; p = 0.01; I2 = 88%), and at 48 PO hours (MD = -0.90 points; 95% CI = -1.54 to -0.26 points; SMD = -0.66; 95% CI = -0.94 to -0.38; p = 0.01; I2 = 93%); and opioid consumption at 24 PO hours (MD = -8.21 mg; 95% CI = -13.32 mg to -3.10 mg; SMD = -2.17; 95% CI = -3.10 to -1.24; p < 0.001; I2 = 95%), and at 48 PO hours (MD = 7.71 mg; 95% CI = -13.86 mg to -1.56 mg; SMD = -2.13; 95% CI = -3.51 to -0.75; p = 0.02; I2 = 97%). Duloxetine did not affect the prevalence of postoperative nausea and/or vomiting (PONV) pruritus, headache or dizziness. High inter-study heterogeneity and within-study bias resulted in very-low quality of evidence for the primary outcomes.
Although statistically significant effects of duloxetine were found on postoperative pain and opioid consumption during the first 48 postoperative hours, the effect sizes were below the expected minimal clinically relevant differences. Also, high risk-of-bias and inter-study heterogeneity caused the very-low quality of evidence (GRADE). We conclude that the currently available evidence does not support the clinical use of duloxetine for the management of acute postoperative pain.
围手术期急性阶段使用度洛西汀与术后疼痛减轻及镇痛药用量减少有关。
本研究旨在量化度洛西汀在术后48小时内对术后疼痛、镇痛药用量及副作用的综合影响。
系统评价与荟萃分析。
术后疼痛管理。
接受择期手术的成年患者。检索策略与研究选择。对Medline、Cochrane、EMBASE、CENTRAL和科学网进行检索，无语言限制，以查找将度洛西汀与安慰剂比较用于成年患者术后疼痛管理的前瞻性、平行随机对照试验。
比较度洛西汀与安慰剂之间的疼痛评分（11分制）、阿片类药物用量（静脉注射吗啡当量）及副作用发生频率。效应量汇总为平均差（MD）、标准化平均差（SMD）或风险比（RR）及各自的95%置信区间（95%CI）。采用推荐分级的评估、制定和评价（GRADE）标准对证据质量进行分类。
纳入13项研究。度洛西汀在术后24小时减轻疼痛（MD = -0.66分；95%CI = -1.14至-0.19分；SMD = -0.59；95%CI = -1.06至-0.12；p = 0.01；I² = 88%），在术后48小时也减轻疼痛（MD = -0.90分；95%CI = -1.54至-0.26分；SMD = -0.66；95%CI = -0.94至-0.38；p = 0.01；I² = 93%）；在术后24小时减少阿片类药物用量（MD = -8.21mg；95%CI = -13.32mg至-3.10mg；SMD = -2.17；95%CI = -3.10至-1.24；p < 0.001；I² = 95%），在术后48小时同样减少用量（MD = 7.71mg；95%CI = -13.86mg至-1.56mg；SMD = -2.13；95%CI = -3.51至-0.75；p = 0.02；I² = 97%）。度洛西汀不影响术后恶心和/或呕吐（PONV）、瘙痒、头痛或头晕的发生率。研究间高度异质性和研究内偏倚导致主要结局的证据质量极低。
尽管度洛西汀在术后48小时内对术后疼痛和阿片类药物用量有统计学上的显著影响，但效应量低于预期的最小临床相关差异。此外，高偏倚风险和研究间异质性导致证据质量极低（GRADE）。我们得出结论，目前可得的证据不支持度洛西汀用于急性术后疼痛管理的临床应用。
