Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. The aim of this secondary analysis of two previous trials was to follow up with patients who had received a single intraoperative dose of either methadone or traditional opioids for complex spine or cardiac surgical procedures. Methods Preplanned analyses of long-term outcomes were conducted for spinal surgery patients randomized to receive 0.2 mg/kg methadone at the start of surgery or 2 mg hydromorphone at surgical closure, and for cardiac surgery patients randomized to receive 0.3 mg/kg methadone or 12 μg/kg fentanyl intraoperatively. A pain questionnaire assessing the weekly frequency (the primary outcome) and intensity of pain was mailed to subjects 1, 3, 6, and 12 months after surgery. Ordinal data were compared with the Mann–Whitney U test, and nominal data were compared using the chi-square test or Fisher exact probability test. The criterion for rejection of the null hypothesis was P < 0.01. Results Three months after surgery, patients randomized to receive methadone for spine procedures reported the weekly frequency of chronic pain was less (median score 0 on a 0 to 4 scale [less than once a week] vs. 3 [daily] in the hydromorphone group, P = 0.004). Patients randomized to receive methadone for cardiac surgery reported the frequency of postsurgical pain was less at 1 month (median score 0) than it was in patients randomized to receive fentanyl (median score 2 [twice per week], P = 0.004). Conclusions Analgesic benefits of a single dose of intraoperative methadone were observed during the first 3 months after spinal surgery (but not at 6 and 12 months), and during the first month after cardiac surgery, when the intensity and frequency of pain were the greatest.

Background Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone. Methods In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg−1 · h−1 infusion [no bolus] intraoperatively and then 0.1 mg · kg−1 · h−1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days. Results Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups. Conclusions Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND: Patients undergoing thoracoscopic procedures may be at high-risk for incomplete neuromuscular recovery and associated complications. The aim of this clinical investigation was to assess the incidence of postoperative residual neuromuscular blockade in adult thoracic surgical patients administered neostigmine or sugammadex when optimal dosing and reversal strategies for these agents were used. The effect of choice of reversal agent on hypoxemic events and signs and symptoms of muscle weakness were also determined. Additionally, operative conditions in each group were graded by surgeons performing the procedures. METHODS: Two hundred patients undergoing thoracoscopic surgical procedures were enrolled in this nonrandomized controlled trial. One hundred consecutive patients maintained at moderate levels of neuromuscular blockade were reversed with neostigmine (neostigmine group) followed by 100 consecutive patients given sugammadex to antagonize deeper levels of neuromuscular blockade (sugammadex group). Anesthetic and neuromuscular management were standardized. Surgeons rated operative conditions at the conclusion of the procedure on a 4-point scale (grade 1 = excellent to grade 4 = poor). Train-of-four ratios were measured immediately before extubation and at PACU admission (primary outcomes). Postoperatively, patients were assessed for adverse respiratory events and 11 signs and 16 symptoms of muscle weakness. RESULTS: The 2 groups were similar in intraoperative management characteristics. The percentage of patients with residual neuromuscular blockade, defined as a normalized train-of-four ratio <0.9, was significantly greater in the neostigmine group than the sugammadex group at both tracheal extubation (80% vs 6%, respectively, P < .0001) and PACU admission (61% vs 1%, respectively, P < .0001). Patients in the neostigmine group had less optimal operative conditions (median score 2 [good] versus 1 [excellent] in the sugammadex group; P < .0001), and more symptoms of muscle weakness were present in these subjects (median number [interquartile range] 4 [1–8] vs 1 [0–2] in the sugammadex group, P < .0001). No differences between groups in adverse airway events were observed. CONCLUSIONS: Despite the application of strategies documented to reduce the risk of residual neuromuscular blockade, a high percentage of thoracoscopic patients whose neuromuscular blockade was reversed with neostigmine were admitted to the PACU with clinical evidence of residual paralysis. In contrast, muscle weakness was rarely observed in patients whose neuromuscular blockade was antagonized with sugammadex.