Background

Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone.

Methods

Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml⁻¹ remifentanil with 0.05 μg kg⁻¹ h⁻¹ naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml⁻¹ remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery.

Results

The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups.

Conclusions

The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain.

Clinical trial registration

NCT02856087.

中文翻译：

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术中纳洛酮减少瑞芬太尼引起的术后痛觉过敏，但不减轻疼痛：一项随机对照试验

背景

术中使用大剂量瑞芬太尼可能会引起术后痛觉过敏。小剂量纳洛酮可以选择性逆转阿片类药物的某些不良反应，而不会影响镇痛作用。因此，我们假设与单独使用瑞芬太尼相比，术中使用大剂量瑞芬太尼联合小剂量纳洛酮可以减少术后痛觉过敏。

方法

根据术中作用部位瑞米芬太尼的浓度，在有或没有连续输注纳洛酮的情况下，将进行择期甲状腺手术的患者随机分为三组之一：4 ng ml ^-1雷米芬太尼与0.05μgkg ^-1 h ^-1纳洛酮高瑞芬太尼含纳洛酮组中分别为4或1 ng ml ^-1瑞芬太尼与安慰剂分别为高瑞芬太尼组或低瑞芬太尼组。我们在手术后24小时使用von Frey细丝测量了机械刺激的疼痛阈值（主要结局）和切口周围区域的痛觉过敏发生率。我们还测量了术后48小时的疼痛强度，止痛药消耗和不良事件。

结果

高瑞芬太尼组（n = 31）的以冯·弗雷数（中位数（四分位间距）表示）的疼痛阈值明显低于高瑞芬太尼联合纳洛酮（n = 30）和低瑞芬太尼（n = 30）组[3.63（3.22–3.84）vs 3.84（3.76-4.00）vs 3.80（3.69–4.08），P = 0.011]。高瑞芬太尼组的痛觉过敏发生率也高于其他组[21/31 vs 10/30 vs 9 /30 ，P = 0.005]。两组之间的术后疼痛强度，镇痛剂用量和不良反应相似。

结论

术中使用小剂量纳洛酮联合大剂量瑞芬太尼可减轻术后痛觉过敏，但不会减轻疼痛。

临床试验注册

NCT02856087。