Context:Dexmedetomidine is being increasingly used in nerve blocks. However, there are only a few dose determination studies.Aims:To compare two doses of dexmedetomidine, in femoral nerve block, for postoperative analgesia after total knee arthroplasty (TKA).Settings and Design:A prospective, randomized, controlled trial was conducted in the Department of Anesthesia at AIIMS, a Tertiary Care Hospital.Materials and Methods:Sixty American Society of Anesthesiologists I–II patients undergoing TKA under subarachnoid block were randomized to three Groups A, B, and C. Control Group A received 20 ml (0.25%) of bupivacaine in femoral nerve block. Groups B and C received 1 and 2 μg/kg dexmedetomidine along with bupivacaine for the block, respectively. Outcomes measured were analgesic efficacy measured in terms of visual analog scale (VAS) score at rest and passive motion, duration of postoperative analgesia, and postoperative morphine consumption. Adverse effects of dexmedetomidine were also studied.Statistical Analysis Used:All qualitative data were analyzed using Chi-square test and VAS scores using Kruskal–Wallis test. Comparison of patient-controlled analgesia (PCA) morphine consumption and time to first use of PCA were done using ANOVA followed by Least Significant Difference test. A P < 0.05 was considered statistically significant.Results:The VAS score at rest was significantly lower in Group C compared to Groups A and B (P < 0.05). There was no difference in VAS score at motion between Groups B and C. The mean duration of analgesia was significantly longer in Group C (6.66 h) compared to Groups A (4.55 h) and B (5.70 h). Postoperative mean morphine consumption was significantly lower in Group C (22.85 mg) compared to Group A (32.15 mg) but was comparable to Group B (27.05 mg). There was no significant difference in adverse effects between the groups.Conclusion:The use of dexmedetomidine at 2 μg/kg dose in femoral nerve block is superior to 1 μg/kg for providing analgesia after TKA, although its role in facilitating early ambulation needs further evaluation.

BACKGROUND: Intraoperative methadone, a long-acting opioid, is increasingly used for postoperative analgesia, although the optimal methadone dosing strategy in children is still unknown. The use of a single large dose of intraoperative methadone is controversial due to inconsistent reductions in total opioid use in children and adverse effects. We recently demonstrated that small, repeated doses of methadone intraoperatively and postoperatively provided sustained analgesia and reduced opioid use without respiratory depression. The aim of this study was to characterize pharmacokinetics, efficacy, and safety of a multiple small-dose methadone strategy. METHODS: Adolescents undergoing posterior spinal fusion (PSF) for idiopathic scoliosis or pectus excavatum (PE) repair received methadone intraoperatively (0.1 mg/kg, maximum 5 mg) and postoperatively every 12 hours for 3–5 doses in a multimodal analgesic protocol. Blood samples were collected up to 72 hours postoperatively and analyzed for R-methadone and S-methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) metabolites, and alpha-1 acid glycoprotein (AAG), the primary methadone-binding protein. Peak and trough concentrations of enantiomers, total methadone, and AAG levels were correlated with clinical outcomes including pain scores, postoperative nausea and vomiting (PONV), respiratory depression, and QT interval prolongation. RESULTS: The study population included 38 children (10.8–17.9 years): 25 PSF and 13 PE patients. Median total methadone peak plasma concentration was 24.7 (interquartile range [IQR], 19.2–40.8) ng/mL and the median trough was 4.09 (IQR, 2.74–6.4) ng/mL. AAG concentration almost doubled at 48 hours after surgery (median = 193.9, IQR = 86.3–279.5 µg/mL) from intraoperative levels (median = 87.4, IQR = 70.6–115.8 µg/mL; P < .001), and change of AAG from intraoperative period to 48 hours postoperatively correlated with R-EDDP (P < .001) levels, S-EDDP (P < .001) levels, and pain scores (P = .008). Median opioid usage was minimal, 0.66 (IQR, 0.59–0.75) mg/kg morphine equivalents/d. No respiratory depression (95% Wilson binomial confidence, 0–0.09) or clinically significant QT prolongation (median = 9, IQR = −10 to 28 milliseconds) occurred. PONV occurred in 12 patients and was correlated with morphine equivalent dose (P = .005). CONCLUSIONS: Novel multiple small perioperative methadone doses resulted in safe and lower blood methadone levels, <100 ng/mL, a threshold previously associated with respiratory depression. This methadone dosing in a multimodal regimen resulted in lower blood methadone analgesia concentrations than the historically described minimum analgesic concentrations of methadone from an era before multimodal postoperative analgesia without postoperative respiratory depression and prolonged corrected QT (QTc). Larger studies are needed to further study the safety and efficacy of this methadone dosing strategy.

Introduction: Posterior spinal fusion for idiopathic scoliosis is extremely painful, with no superior single analgesic modality. We introduced a methadone-based multimodal analgesia protocol, aiming to decrease the length of hospital stay (LOS), improve pain control, and decrease the need for additional opioids. Methods: We analyzed 122 idiopathic scoliosis patients with posterior instrumented spinal fusion. They were matched by age, sex, surgeon, and the number of levels fused before and after the implementation of the new protocol. This analysis included 61 controls (intrathecal morphine, gabapentin, intravenous opioids, and adjuncts) and 61 patients on the new protocol (scheduled methadone, methocarbamol, ketorolac/ibuprofen, acetaminophen, and oxycodone with intravenous opioids as needed). The primary outcome was LOS. Secondary outcomes included pain scores, total opioid use (morphine milligram equivalents), time to a first bowel movement, and postdischarge phone calls. Results: New protocol patients were discharged earlier (median LOS, 2 days) compared with control patients (3 days; P < 0.001). Total inpatient morphine consumption was lower in the protocol group ( P < 0.001). Pain scores were higher in the protocol group on the day of surgery, similar on postoperative day (POD) 1, and lower by POD 2 ( P = 0.01). The new protocol also reduced the median time to first bowel movement ( P < 0.001), and the number of postdischarge pain-related phone calls ( P < 0.006). Conclusion: Methadone-based multimodal analgesia resulted in significantly lower LOS compared with the conventional regimen. It also provided improved pain control, reduced total opioid consumption, and early bowel movement compared with the control group.

Genetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and neuropathic pain models, females have been reported to have more pain than males. This review focuses on literature evidence of differences in pain relief due to multiple genetic variations and gender of the patient.