Effect of Maternal Methadone Use on Neonatal Outcomes: Results of a Cohort Study

Background: Substance abuse treatment is challenging in pregnancy, and methadone maintenance therapy (MMT) is a therapeutic choice. Methadone can cross the placenta and is poorly secreted in breast milk. Given these inconsistent findings of methadone effect on neonatal outcomes, this study was done to investigate the results in neonates of mothers treated with methadone in Mashhad. Methods: In this retrospective cohort study, mothers referring to two academic hospitals of Mashhad University of Medical Sciences were studied. Three groups were considered: MMT, other drug abusers, and healthy control. Maternal information, including demographic characteristics, fertility characteristics, and methadone treatment-related characteristics, and neonatal information, including demographic characteristics and neonatal outcomes, were assessed. Results: Overall, 122 pregnant women with a mean age of 29.14 ± 4.44 years were studied in three groups: control (n = 59), MMT (n = 32), and other drug abusers (n = 31). Baseline characteristics (mothers’ age, residence, chronic hypertension, preeclampsia, diabetes, heart disease, thyroid disease, and other diseases) were not different between the three groups. The highest history of miscarriage was seen in other drug abusers (35.5%) (P = 0.023). The mean weight, height, and head circumference of neonates in the control group were significantly higher than the methadone group (P < 0.001), and in the methadone group was higher than in the other drugs abusers (P < 0.001). The highest prevalence of malformations (16.1%) and hospitalization in the NICU (51.6%) was observed in infants of other drug abusers. After adjusting for confounding variables, the odds ratio (OR) of low-birth-weight infants was 13.7 in the methadone group and 1946 in the other drugs group compared to the healthy control group. The OR of neonates less than 50cm in height was 11.4 in the methadone group and 22.5 in the other drugs. Besides, the OR of neonates less than 35cm was 4.7 in the methadone group and 7.3 in other drugs. Conclusions: Although the neonates of mothers who used methadone had a higher rate of inappropriate intrauterine growth indices than healthy women, methadone consumption compared to other drugs had significantly reduced unacceptable outcomes in neonates. Increased gestational age and reduced preterm delivery risk were observed in methadone-treated mothers.

Intraoperative Intravenous Methadone and Ketamine Combination versus Intravenous Morphine and Ketamine Combination for Post-Operative Analgesia in Patients Undergoing Lower Extremity Fracture Surgery

Background: Pain management for lower extremity fracture surgeries can be challenging. The purpose of this study is to determine whether the use of ketamine and methadone are more effective than ketamine and morphine to reduce postoperative pain and morphine requirements in patients undergoing lower extremity fracture surgery. Materials and Methods: Seventy-five patients 18-65 years of age, ASA class I-III, were enrolled in this study, which scheduled for elective lower extremity orthopedic surgery involving fracture of femur or tibia were recruited for the study. Thirty-eight randomized to the Methadone group and 37 randomized into the Morphine group. Participants were randomized to either one of the two groups: methadone (2ug/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg methadone IV) versus control (2 ug/kg fentanyl, 0.2mg/kg ketamine and 0.2 mg/kg morphine IV). The primary outcome was total morphine equivalent (MEQ) during the first 24 and 48 hours after surgery. Secondary outcomes included postoperative pain scores in PACU, at 24 and 48 hours, as well as postoperative nausea and vomiting (PONV). Results: There was no difference in intraoperative consumption of fentanyl between the Methadone group 360mcg and Morphine group 344mcg. In the first 24 hours postoperatively, the Methadone group consumed less MEQ compared with the Morphine group (36.1 mg vs 54.8 mg, p=0.0072), showed lower pain scores than the Morphine group (p=0.0146), and experienced more nausea and vomiting than the Morphine group. There were no differences in sedation in both groups. Conclusion: The intraoperative use of intravenous methadone significantly reduced post-operative opioid requirement in patients undergoing lower extremity fracture surgery. The results also demonstrated the methadone group had a higher rate of PONV.

Evaluation of functional status among patients undergoing maintenance treatments for opioid use disorders

Background Methadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional status of patients with pharmacological opioid maintenance treatments according to different socio-demographic characteristic, health and disabilities domains and sexual difficulties. Methods A total of 593 patients from the Andalusia community, 329 were undergoing methadone treatment and 264 were undergoing buprenorphine treatment. The patients were interviewed by socio-demographic and opioid-related variables, assessed by functioning, disability and health domains (WHODAS 2.0.) and for sexual problems (PRSexDQ-SALSEX). Results We found significant differences in the socio-demographic and the opioid-related variables as the onset of opioid use, being on previous maintenance programs, opioid intravenous use, the length of previous maintenance programs, polydrug use and elevated seroprevalence rates (HCV and HIV) between the methadone group and the buprenorphine group. Regarding health and disability domains there were differences in the Understanding and communication domain, Getting around domain, Participation in society domain and in the WHODAS 2.0. simple and complex score, favoring buprenorphine-treated patients. The methadone group referred elevated sexual impairments compared with the buprenorphine group. Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups. Participation in society variables and sexual problems were the most important clinical variables in distinguishing the methadone group from the buprenorphine group regarding their functional status. Conclusions The methadone group showed higher prevalence in opioid dependence-related variables, elevated disabilities in participation in society activities and sexual problems compared with the buprenorphine group. This study shows the importance of carry out a functional evaluation in the healthcare follow-up, especially in those areas related with social activity and with sexual problems.

589 Methadone in Procedural Care for Burn Injuries of 20–30% Total Burn Surface Area: A Retrospective Chart Review

Introduction Prolonged opioid usage remains a concern in pain management in procedural care. Recent evidence also suggests that a considerable number of patients who were prescribed opioids struggle with transitioning to non-opioid pain medications. As a continuous effort to reduce opioid consumption following burn surgical procedures, our institution recently evaluated methadone administration for burn procedural care in patients with 20–30% total burn surface area (TBSA) requiring excision and grafting. Methods After IRB approval, we performed a retrospective chart review of patients who underwent excision and grafting procedure for 20–30% TBSA burn injuries between January 1, 2019 and June 30, 2020. The following data was evaluated: postoperative opioid consumption, postoperative pain intensity (rated as “No Pain” [NRS=0], “Minor Pain” [NRS 1 to 3], “Moderate Pain” [NRS 4 to 6], “Severe Pain” [NRS 7 to 10]), time to physical therapy and time to hospital discharge. Data was analyzed using chi square/Fisher exact test for categorical variables and t-test/Wilcoxon rank sum test for continuous variables. Results Our preliminary data included 12 patients who met inclusion criteria, of which two patients received methadone administration. Our patient sample consisted of average age of 43 years, 75% male, and 24% TBSA (92% were flame burns). Patients in both methadone and non-methadone groups had no significant differences in medical histories and TBSA (23% TBSA in methadone, 25% TBSA in non-methadone). There was no significant difference in reported preoperative pain intensity between the two groups, rating moderate to severe. Postoperative pain intensity remained the same, rating moderate to severe and controlled with fentanyl, oxycodone, morphine and non-opioid analgesics. While there was no difference in postoperative fentanyl, opioid and non-opioid analgesic consumptions between the two groups, morphine consumption was significantly lower in the methadone group compared to non-methadone group (2±2 mg vs 51±54 mg, respectively, p=0.02). There was no significant difference between average time from surgery to first physical therapy session and time to hospital discharge (about 21 days after surgery) between the two groups. Conclusions This evaluation shows a potential trend in reduction of inpatient postoperative opioid consumption with the conjunctive administration of methadone, although a bigger sample size is needed for further assessment.

587 Methadone and Morphine for Outpatient CO2 Laser Pain Management

Introduction Burn reconstruction with CO2 laser is now very popular. Providing adequate analgesia is imperative for large total body surface area (TBSA) resurfacing. CO2 lasers’ cause significant pain during the procedure and pain similar to that of a severe sunburn post-operatively. Thus, adequate analgesia that provides peri-operative and post discharge management without delaying discharge is beneficial. At our institution, we use a multimodal analgesic preoperative and intra-operative approach to deal with this issue. The preoperative intervention utilizes a novel approach of oral methadone for older children and avoids the use of intra-operative morphine as a preemptive measure for pain management. The purpose of this outcomes review was to determine if our peri-operative analgesic practices were effective in controlling peri-operative pain. Methods After corporate IRB review, this project was undertaken as a quality improvement initiative and was not formally supervised by an institutional review board. A chart review of all patients who received CO2 laser treatment (CLT) was conducted. Using a Donabedian model for outcomes measure, postoperative and pre-discharge observational pain scores (scale 1–10), peri-operative analgesics, demographics, percent burn treated, incidents of rescue medication before discharge home, time to discharge and adverse reactions were collected. Results 74 patients were reviewed (47 male, 27 female), ages 4 to 30, average age 17. Average percent body surface area treated was 17.5%. Out of 74 cases, 18 received intra-operative morphine and 56 received oral methadone pre-operatively. All patients received routine intra-operative ketorolac and lidocaine/prilocaine cream, based on weight. In the PACU there were 2 recorded rescue doses of morphine in the morphine group and 0 in the methadone group. There was one post- operative recorded observational pain score of 5 in the methadone group and one each of 3 and 8 in the morphine group, both of which received rescue morphine. There were no differences in mean times to discharge between groups. Observational pain scores were 0 for both groups at discharge. Chi square analysis showed no statistical difference between groups. No adverse outcomes (respiratory arrest or readmission for pain) were recorded in either group. Conclusions Both pre-operative oral methadone and intra-operative morphine are effective in controlling peri-operative pain in our children undergoing laser surgery. Categorical age differences and low group sizes may have contributed to outcomes and should be considered in the next review.

Efficacy of methadone for the management of postoperative pain in laparoscopic cholecystectomy: A randomized clinical trial

Background Postoperative pain management contributes to reducing postoperative morbidity and unscheduled readmission. Compared to other opioids that manage postoperative pain like morphine, few randomized trials have tested the efficacy of intraoperatively administered methadone to provide evidence for its regular use or be included in clinical guidelines. Methods We conducted a randomized clinical trial comparing the use of intraoperative methadone to assess its impact on postoperative pain. Eighty-six patients undergoing elective laparoscopic cholecystectomy were allocated to receive either methadone (0.08 mg/kg) or morphine (0.08 mg/kg). Results Individuals who received methadone required less rescue morphine in the Post Anesthesia Care Unit for postoperative pain than those who received morphine (p = 0.0078). The patients from the methadone group reported less pain at 5 and 15 minutes and 12 and 24 hours following Post Anesthesia Care Unit discharge, exhibiting fewer episodes of nausea. Time to eye-opening was equivalent between the two groups. Conclusion Intraoperative use of methadone resulted in better management of postoperative pain, supporting its use as part of a multimodal pain management strategy for laparoscopic cholecystectomy under remifentanil-based anesthesia.

Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial

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 &lt; 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

Impact of Intravenous Methadone Administered Intraoperatively on Postoperative Opioid Utilization

Background: Studies have shown that intravenous methadone intraoperatively can reduce opioid usage postoperatively. Objective: This study’s purpose was to evaluate the effect of intravenous methadone on postoperative opioid use. Methods: A prospective, single-center observational study was conducted to evaluate patients who received intravenous methadone intraoperatively. A control group was identified by matching procedure, gender, and age in a 1:3 ratio of methadone to control. Exclusion criteria included patients less than 18 years old or on methadone maintenance therapy. The primary outcome was morphine milligram equivalents (MME) administered 24h postoperatively. Secondary outcomes included MME administered 48h and 72h postoperatively, discharge prescription MME, daily mean postoperative pain scores, and length of hospital stay. A subgroup analysis was performed comparing opioid-naïve patients. Results: A total of 240 patients were included in the analysis. At 24h, postoperative MME was increased in the methadone group (142.6 vs 84.5; P = 0.0026). Postoperative MME was also increased in the methadone group at 48h and 72h. Daily pain scores were similar between both groups at all time intervals. Discharge prescription MME was reduced in the methadone group compared with controls, but not statistically significant. A subgroup analysis of opioid-naïve patients showed a significant reduction in MME at 48h ( P = 0.0240) and daily pain scores at 24h ( P = 0.0366) in the methadone group. Conclusion and Relevance: Intravenous methadone intraoperatively did not show a significant reduction in postoperative opioid use and discharge prescription MMEs when comparing all patients; however, benefit was seen when examining opioid-naïve patients.

Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies

ObjectivesTo compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder.MethodsA cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10‐year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant.ResultsThere were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32–9.86; p=0.01).ConclusionsMedication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

Evaluation of Functional Status Among Patients Undergoing Maintenance Treatments for Opioid use Disorders

Objective Methadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional and health status of patients with pharmacological opioid maintenance treatments according to different socio-demographic characteristic, disabilities and sexual functioning difficulties. Methods A total of 593 patients from the Andalusia community, 329 were undergoing methadone treatment and 264 were undergoing buprenorphine treatment. The patients were interviewed by socio-demographic and opioid-related variables, assessed by functional disability and health variables ( WHODAS 2.0. ) and for sexual dysfunction ( PRSexDQ-SALSEX ). Results We found significant differences in the socio-demographic and the opioid-related variables as the onset of opioid use, being on previous maintenance programs, opioid intravenous use, the length of previous maintenance programs, polydrug use and elevated seroprevalence rates (HCV and HIV) between the methadone group and the buprenorphine group. There were differences in the Understanding and communication domain, Getting around domain, Participation in society domain and in the WHODAS 2.0. simple and complex score, favoring buprenorphine-treated patients. The methadone group had elevated sexual dysfunction than the buprenorphine group. Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups. Participation in society variables and sexual problems were the most important clinical variables in distinguishing the methadone group from the buprenorphine group. Conclusions The methadone group showed higher prevalence in opioid dependence-related variables, elevated disabilities in participation in society activities and sexual problems compared with the buprenorphine group.