Randomized controlled trial of gabapentin as an adjunct to perioperative analgesia in total hip arthroplasty patients.

PURPOSE: Gabapentin was investigated as a single-dose adjunct to morphine for postoperative pain management. The primary objective was to determine if gabapentin given preoperatively and for two days postoperatively as part of multimodal analgesia would decrease postoperative morphine consumption in patients undergoing primary total hip arthroplasty (THA). METHODS: The study group included 102 patients aged 19-90 years who were undergoing primary THA in a single joint with no contraindications to the study medications, no chronic pain syndrome, and no chronic opioid use. Intervention group patients (n = 48) received gabapentin 600 mg po preoperatively and 200 mg postoperatively on the day of surgery. They were continued on gabapentin at 200 mg three times daily for two days. Control group patients (n = 54) received placebo in a similar fashion. Preoperatively, all patients were given 30 mg of ketorolac intravenously and acetaminophen 1000 mg po. Postoperatively, they received intravenous patient-controlled analgesia with morphine, along with ketorolac 15 mg iv and acetaminophen 1000 mg po every six hours. RESULTS: The primary outcome was mean (SD) postoperative morphine consumption at 72 hr which was 55.8 (39.2) mg in the gabapentin groups vs 60.7 (37.2) mg for the control group (mean difference, -4.91 mg, 95% confidence intervals [CI]: -21.2 to 11.35; P = 0.550). There were no significant differences between the groups regarding secondary outcomes: pain scores, side effects, range of motion. Patient satisfaction on day 3 was more favourable in the placebo group. Length of hospitalization was marginally shorter in the placebo group. CONCLUSIONS: This trial indicated that gabapentin treatment had no clinically important reduction in postoperative morphine consumption at 72 hr in patients undergoing THA. Multimodal analgesia may account for the similar primary and secondary outcomes found in the groups. This trial was registered at ClinicalTrials.gov, number: NCT01307202.

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

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.

Empirical comparison of four baseline covariate adjustment methods in analysis of continuous outcomes in randomized controlled trials.

BACKGROUND: Although seemingly straightforward, the statistical comparison of a continuous variable in a randomized controlled trial that has both a pre- and posttreatment score presents an interesting challenge for trialists. We present here empirical application of four statistical methods (posttreatment scores with analysis of variance, analysis of covariance, change in scores, and percent change in scores), using data from a randomized controlled trial of postoperative pain in patients following total joint arthroplasty (the Morphine COnsumption in Joint Replacement Patients, With and Without GaBapentin Treatment, a RandomIzed ControlLEd Study [MOBILE] trials). METHODS: Analysis of covariance (ANCOVA) was used to adjust for baseline measures and to provide an unbiased estimate of the mean group difference of the 1-year postoperative knee flexion scores in knee arthroplasty patients. Robustness tests were done by comparing ANCOVA with three comparative methods: the posttreatment scores, change in scores, and percentage change from baseline. RESULTS: All four methods showed similar direction of effect; however, ANCOVA (-3.9; 95% confidence interval [CI]: -9.5, 1.6; P=0.15) and the posttreatment score (-4.3; 95% CI: -9.8, 1.2; P=0.12) method provided the highest precision of estimate compared with the change score (-3.0; 95% CI: -9.9, 3.8; P=0.38) and percent change (-0.019; 95% CI: -0.087, 0.050; P=0.58). CONCLUSION: ANCOVA, through both simulation and empirical studies, provides the best statistical estimation for analyzing continuous outcomes requiring covariate adjustment. Our empirical findings support the use of ANCOVA as an optimal method in both design and analysis of trials with a continuous primary outcome.

Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial.

PURPOSE: This study assessed whether gabapentin given preoperatively and for two days postoperatively (in addition to patient-controlled analgesia [PCA] morphine, acetaminophen, and ketorolac) is effective in reducing morphine requirements and moderating pain scores when compared with placebo for primary total knee arthroplasty. METHODS: This single-centre double-blind randomized controlled trial was undertaken in patients who underwent primary total knee arthroplasty. All subjects received acetaminophen 1,000 mg and ketorolac 15 mg po preoperatively. Postoperatively, subjects received PCA morphine, acetaminophen 1,000 mg every six hours, and ketorolac 15 mg po every six hours. Subjects received either gabapentin 600 mg po preoperatively followed by 200 mg po every eight hours for two days or matching placebo. The primary outcome was cumulative morphine consumption at 72 hr following surgery. Secondary outcome measures included pain scores and patient satisfaction. RESULTS: There were 52 subjects in the gabapentin group and 49 subjects in the placebo group. The average cumulative morphine consumption at 72 hr postoperatively was 66.3 mg in the gabapentin group and 72.5 mg in the placebo group (difference -6.2 mg; 95% confidence interval -29.1 to 16.8 mg; P = 0.59). Mean pain scores at rest, with passive movement, or with weight bearing were similar in both groups at corresponding time periods for the first three days following surgery. In addition, mean patient satisfaction scores and hospital length of stay were similar in the two groups. CONCLUSION: Gabapentin 600 mg po given preoperatively followed by 200 mg po every eight hours for two days has no effect on postoperative morphine consumption, pain scores, patient satisfaction, or length of hospital stay. This trial is registered at ClinicalTrials.gov NCT01307202.