With the country’s opioid crisis in mind, anesthesiologists are on the lookout for ways to address pain after outpatient surgery while minimizing the possibility of diversion. A team of Missouri researchers may have found a possible solution in the unlikeliest of candidates: IV methadone. Their study found that a single intraoperative dose of the agent decreased opioid requirements and provided better analgesia than short-duration opioids in people undergoing ambulatory procedures.
“Outpatient surgery accounts for more than 60% of all surgeries in the U.S. every year,” said Helga Komen, MD, an instructor in anesthesiology at Washington University in St. Louis. “It’s very important to remember that our patients are expecting adequate postoperative pain relief, whether they’re inpatients or outpatients.
“Although clinical research has shown that long-acting opioids like methadone are effective in inpatient surgeries, our objective was to determine whether the agent would prove equally effective in outpatient surgery,” she added.
Dr. Komen and her colleagues enrolled 60 patients undergoing outpatient surgical procedures into this pilot study. Participants were randomly assigned 2:1 to receive either single-dose IV methadone or short-acting opioids (hydromorphone or fentanyl, at the practitioner’s discretion) upon induction of anesthesia.
“Since we couldn’t find anything like this in the literature, we had to determine the adequate methadone dose,” Dr. Komen said. Methadone patients received either 0.1 or 0.15 mg/kg (ideal body weight) of the agent in a dose-escalation protocol. “After interim analysis, we saw that the 0.1-mg/kg dose (n=18) did not decrease postoperative opioid consumption, so we decided to increase the dose to 0.15 mg/kg (n=21).” Twenty-one patients served as controls.
“They were mostly patients undergoing laparoscopic cholecystectomy, tubal ligation and inguinal hernia repair,” she said. The three groups all proved similar with respect to age, sex, body weight, ASA physical status, anesthesia duration and operative time.
The researchers measured a variety of data, including:
- intraoperative and postoperative opioid consumption (in morphine equivalents);
- patient pain intensity (at rest, with coughing and with activity); and
- sedation at a variety of times, including after admission to the PACU and at discharge.
Opioid side effects and ventilatory depression also were assessed. At discharge, patients were given diaries in which they recorded daily pain, opioid use and side effects, ending on postoperative day 30.
As Dr. Komen reported at the 2017 annual meeting of the American Society of Anesthesiologists (abstract JS03), patients receiving 0.1 and 0.15 mg/kg of methadone consumed significantly less intraoperative opioids (non-methadone morphine equivalents) than did controls (25.5, 1.3 and 0.16 mg, respectively). Patients who received 0.15 mg/kg of methadone also consumed fewer opioids in the PACU than did controls (2±3 vs. 8±7 mg), as well as throughout their entire postoperative hospital stay (4±4 vs. 9±7 mg).
Patients receiving 0.15 mg/kg of intraoperative methadone also used less total take-home opioids (22±2 mg for 30-day IV morphine equivalents) than did their control counterparts (30±1 mg), and stopped taking opioids earlier. “The higher dose methadone group used a mean of only five pills after discharge, compared to 10 for the control group,” she reported.
Pain at rest did not differ significantly between the groups in the immediate postoperative period.
“We measured pain every 15 minutes after surgery for the first hour and then every hour thereafter,” Dr. Komen explained. “And there was no difference between groups.”
Over the 30-day postoperative period, pain scores at rest were lower in patients receiving 0.15 mg/kg of intraoperative methadone than in those receiving short-acting opioids (summed numerical rating scores 10±2 vs. 23±3). Sedation and adverse events were similar in patients receiving methadone and short-acting opioids.
Nalini Vadivelu, MBBS, DNB, MD, a professor of anesthesiology at Yale School of Medicine, in New Haven, Conn., also saw a place for methadone in outpatient surgery, although she called for more safety studies. “The effectiveness of methadone for perioperative pain relief in inpatients is well known,” she said. “However, there is a dearth of information on the effectiveness and safety of methadone as an analgesic in outpatient surgery. This study is definitely a positive start in the right direction, although more outcome studies in the area of outpatient pain control with methadone are necessary.”
Yet, as Dr. Vadivelu added, there are potential drawbacks with use of the agent, including its extremely long, unpredictable half-life and high interindividual variability, which pose the potential for accumulation and overdose. “The long elimination half-life could also lead to interaction with other medications,” she added, noting that physicians using methadone in these patients need to closely monitor for sedation and prolongation of the QT interval.
“The use of regional anesthesia in outpatient surgery could also play a role in producing enhanced analgesia in conjunction with methadone in low doses,” she said.