Choi Peter T, Beattie W Scott, Bryson Gregory L, Paul James E, Yang Homer
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS One. 2009;4(2):e4644. doi: 10.1371/journal.pone.0004644. Epub 2009 Feb 27.
Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada.
METHODOLOGY/PRINCIPAL FINDINGS: After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were > or = 45 years old, had an expected hospital stay > or = 48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group) and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group) and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5+/-0.3 (mean+/-SEM) subjects per week per centre; 112/494 (22.7%) eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5%) of 49 subjects in the epidural group crossed over to the IV group; seven (14.3%) were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8%) of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0%) of 101 subjects were successfully followed up until 30 days after their surgery.
CONCLUSION/SIGNIFICANCE: Of the criteria we defined for the feasibility of a full-scale trial, only the follow-up target was met. The other feasibility outcomes did not meet our preset criteria for success. The results suggest that a large multicentre trial may not be a feasible design to study the perioperative effects of neuraxial blockade.
ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817.
早期随机对照试验表明，神经轴阻滞可能降低非心胸外科手术后的心肺并发症，但近期规模更大的试验尚无定论。我们开展了一项试点研究，以评估在加拿大进行大规模多中心随机对照试验的可行性。
方法/主要发现：经参与机构的研究伦理委员会批准后，招募年龄≥45岁、预期住院时间≥48小时、正在接受适合硬膜外镇痛的非心胸外科手术、符合六项风险标准之一且无神经轴阻滞禁忌证的受试者。在获得知情同意后，将受试者随机分配至联合硬膜外镇痛组（硬膜外组）和神经轴麻醉组（可联合或不联合全身麻醉），或静脉阿片类镇痛组（静脉组）和全身麻醉组。主要结局指标为招募率以及招募的符合条件患者的百分比、交叉率和完全随访率。可行性目标为预先设定。由一个盲法独立委员会判定次要临床结局。受试者在住院期间每天接受随访，术后30天也进行随访。分析采用意向性分析。在15个月的时间里，每个中心每周的招募率为0.5±0.3（均值±标准误）名受试者；在加拿大的四家三级护理教学医院中，112/494（22.7%）名符合条件的受试者被招募。硬膜外组49名受试者中有13名（26.5%）交叉至静脉组；其中7名（14.3%）是由于镇痛失败或不足或硬膜外镇痛并发症。静脉组中的受试者51名中有5名（9.8%）交叉至硬膜外组，但均不是由于镇痛不足或并发症。101名受试者中有98名（97.0%）在术后30天成功完成随访。
结论/意义：在我们为全面试验可行性定义的标准中，仅达到了随访目标。其他可行性结局未达到我们预设的成功标准。结果表明，大规模多中心试验可能并非研究神经轴阻滞围手术期效应的可行设计。
ClinicalTrials.gov NCT 0221260；Controlled-Trials.com ISRCTN 35629817。
