Effects of neuraxial blockade may be difficult to study using large randomized controlled trials: the PeriOperative Epidural Trial (POET) Pilot Study

Abstract

Background: 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.

Trial registration: ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817.

Trial registration: ClinicalTrials.gov NCT00221260 NCT00221260.

Figure 1. Flow of subjects through the PeriOperative Epidural Trial Pilot Study.

Figure 2. Box plots of duration of intraoperative anesthesia in hours and postoperative analgesia in days.

Blue denotes the epidural group; green denotes the IV group. Circles indicate individual data points, the horizontal bars denote the median durations, and the boxes denote the interquartile range.

Figure 3. Box plot of duration of hospital stay in days.

Blue denotes the epidural group; green denotes the IV group. Circles indicate individual data points, the horizontal bars denote the median durations, and the boxes denote the interquartile range.

Figure 4. Box plots of numeric rating scale scores for static pain by group and postoperative day.

The horizontal bars denote the median pain score, the boxes denote the interquartile range, the lower whiskers denote the lowest value lying within the first quartile subtract 1.5 times the interquartile range, the upper whiskers denote the highest value lying within the third quartile plus 1.5 times the interquartile range, and dots denote outliers.