N-甲基-D-天冬氨酸拮抗剂和类固醇预防胸腔镜手术后持续性疼痛：一项随机对照、析因设计、国际多中心试验

N-Methyl-D-Aspartate Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicenter Pilot Trial.

作者信息

Shanthanna Harsha, Turan Alparslan, Vincent Jessica, Saab Remie, Shargall Yaron, O'Hare Turlough, Davis Kimberly, Fonguh Sylvanus, Balasubramaniam Kumar, Paul James, Gilron Ian, Kehlet Henrik, Sessler Daniel I, Bhandari Mohit, Thabane Lehana, Devereaux P J

机构信息

Department of Anesthesia, McMaster University, Hamilton, ON, Canada.

Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA.

出版信息

J Pain Res. 2020 Feb 12;13:377-387. doi: 10.2147/JPR.S237058. eCollection 2020.

DOI:10.2147/JPR.S237058

PMID:32104059

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7024793/

Abstract

PURPOSE

We conducted a feasibility 2×2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph's Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥90% of eligible patients; and 3) >90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes.

METHODS

Using computerized randomization, patients were allocated to one of four groups: NMDA active with steroid placebo; NMDA placebo with steroid active; both NMDA and steroid active; both NMDA and steroid placebo. Patients, health providers, and data analysts were blinded to allocation. Patients were followed for 3 months after randomization.

RESULTS

The trial was initiated in May 2017 at Hamilton and, after subsequent regulatory and ethics approval, in April 2018 at Cleveland. The trial had to be stopped after only 1 month of recruitment in Cleveland because the packaged study medications (memantine) expired and we were unable to procure the dosage required. Among 41 eligible patients, 27 (66%) were randomized. The recruitment rate/week was 0.63, 95% confidence interval (CI): 0.47-0.79 in Hamilton; and 1, 95% CI: 0.83-1.17 in Cleveland. Follow-up was complete for all 24 patients (100%) in Hamilton, and 3 of 4 patients in Cleveland. In total, only 4 patients (15%), and 2 patients (7%) had persistent pain at rest and with movement, respectively. There were no significant differences between groups for other outcomes.

CONCLUSION

The trial had to be stopped prematurely due to non-availability of study medications. Trial feasibility objectives of recruiting 90% of eligible patients and recruiting at least one patient/week per site were not met. Consideration for protocol changes will be necessary for the full trial.

TRIAL REGISTRATION

NCT02950233.

摘要

目的

我们在加拿大汉密尔顿的圣约瑟夫医院和美国克利夫兰的克利夫兰诊所，对接受选择性电视辅助胸腔镜肺叶切除术的患者进行了一项可行性2×2析因试验，比较N-甲基-D-天冬氨酸（NMDA）拮抗剂（静脉注射氯胺酮和口服美金刚）与安慰剂，以及静脉注射类固醇与安慰剂的效果。我们的可行性目标是：1）每周招募率；2）招募≥90%的符合条件的患者；3）随访率>90%。次要目标是持续性术后疼痛（PPSP）的发生率和强度以及其他临床和安全性结果。

方法

采用计算机随机分组，将患者分配到四组之一：NMDA活性药物加类固醇安慰剂；NMDA安慰剂加类固醇活性药物；NMDA和类固醇均为活性药物；NMDA和类固醇均为安慰剂。患者、医疗服务提供者和数据分析人员对分组情况不知情。随机分组后对患者进行3个月的随访。

结果

该试验于2017年5月在汉密尔顿启动，在随后获得监管和伦理批准后，于2018年4月在克利夫兰启动。由于包装好的研究药物（美金刚）过期且我们无法获取所需剂量，该试验在克利夫兰仅招募了1个月后就不得不停止。在41名符合条件的患者中，27名（66%）被随机分组。汉密尔顿的每周招募率为0.63，95%置信区间（CI）：0.47 - 0.79；克利夫兰的每周招募率为1，95%CI：0.83 - 1.17。汉密尔顿的所有24名患者（100%）和克利夫兰的4名患者中的3名完成了随访。总共只有4名患者（15%）和2名患者（7%）分别在休息和活动时有持续性疼痛。各治疗组在其他结果方面无显著差异。