Reanalysis of morphine consumption from two randomized controlled trials of gabapentin using longitudinal statistical methods

Abstract

Shiyuan Zhang,1 James Paul,2 Manyat Nantha-Aree,2 Norman Buckley,2 Uswa Shahzad,2 Ji Cheng,2 Justin DeBeer,5 Mitchell Winemaker,5 David Wismer,5 Dinshaw Punthakee,5 Victoria Avram,5 Lehana Thabane1–4 1Department of Clinical Epidemiology and Biostatistics, McMaster University, 2Department of Anesthesia, McMaster University, 3Biostatistics Unit/Centre for Evaluation of Medicines, St Joseph’s Healthcare-Hamilton, 4Population Health Research Institute, Hamilton Health Science/McMaster University, 5Department of Surgery, Division of Orthopaedics, McMaster University, Hamilton, ON, Canada Background: Postoperative pain management in total joint replacement surgery remains ineffective in up to 50% of patients and has an overwhelming impact in terms of patient well-being and health care burden. We present here an empirical analysis of two randomized controlled trials assessing whether addition of gabapentin to a multimodal perioperative analgesia regimen can reduce morphine consumption or improve analgesia for patients following total joint arthroplasty (the MOBILE trials). Methods: Morphine consumption, measured for four time periods in patients undergoing total hip or total knee arthroplasty, was analyzed using a linear mixed-effects model to provide a longitudinal estimate of the treatment effect. Repeated-measures analysis of variance and generalized estimating equations were used in a sensitivity analysis to compare the robustness of the methods. Results: There was no statistically significant difference in morphine consumption between the treatment group and a control group (mean effect size estimate 1.0, 95% confidence interval −4.7, 6.7, P=0.73). The results remained robust across different longitudinal methods. Conclusion: The results of the current reanalysis of morphine consumption align with those of the MOBILE trials. Gabapentin did not significantly reduce morphine consumption in patients undergoing major replacement surgeries. The results remain consistent across longitudinal methods. More work in the area of postoperative pain is required to provide adequate management for this patient population. Keywords: postoperative morphine consumption, randomized controlled trials, gabapentin, reanalysis