Influence of Aging on Perioperative Methadone Dosing
- Conditions
- Methadone Overdose of Undetermined IntentPain, PostoperativeOpioid Use
- Interventions
- Registration Number
- NCT04526236
- Lead Sponsor
- Pontificia Universidad Catolica de Chile
- Brief Summary
Increasingly, elderly patients undergo anesthesia and surgery. Methadone is a great opioid for perioperative pain management, however, to date there are no pharmacokinetic or pharmacodynamic studies that asses a methadone dose adjustment in the elderly patient. The present study is aimed to characterize the pharmacokinetic and pharmacodynamic age-related changes of methadone in the adult population and further to design reference dosing protocols for intraoperative methadone use according to patient age.
- Detailed Description
The subjects will be recruited from adult patients who undergo elective laparoscopic abdominal surgery at UC Christus Clinical Hospital (Santiago, de Chile). Patients will be randomly divided into four groups according to the dose of intravenous methadone to be administered during anaesthetic induction.
BIS-guided and standard general anaesthesia will be administered with routine monitoring. Methadone will be administered once the patient is intubated and has hemodynamic stability. The only opioids that patients will receive will be remifentanil and methadone.
Upon admission to the Post-anesthesia care unit, the patient is given a Patient-Control Analgesia pump for intravenous administration of morphine. Clinic evaluations will be carried out periodically and blood samples for measurement of plasma methadone will be taken at different times. Samples will be analyzed using high-performance liquid chromatography spectrofluorometric method. The data obtained will be collected in a form within the REDCAP application, to subsequently generate an encrypted database. Groups will be compared regarding pain score, drugs used, opioid consumption, side effects, time of recovery, and patient satisfaction.
One, two and three-compartment linear models will be used to fit the plasma methadone concentration data over time. Models are parameterized in terms of elimination clearance, compartment distribution clearance, central volume and peripheral volume of distribution, as appropriate. The use of rescue morphine in the Post-anesthesia care unit will be used as a measure to relate the methadone dose (mg/kg) with the analgesic efficacy using an EMAX model. The data will be modelled using NONMEM VII. A proportional term will be used for variability between subjects. Additive and proportional terms will be used to characterize the unknown residual variability.
Sample size calculations were estimated using a simulation-based approach and previous work with a similar methodology. To achieve an adequate representation of all age groups 60 patients will be required, distributed among 20 patients between 18 and 40 years, 20 patients between 41 and 65 years, and 20 patients\> 65 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Over 18 years.
- ASA I, II or III.
- Laparoscopic Abdominal Surgery.
- BMI> 35
- Use of opioids up to 5 days before surgery.
- Acute Liver Failure or Chronic Liver Damage Child C.
- Kidney damage with creatinine clearance estimated by Cockcroft-Gault formula <60 ml/min.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Methadone 0 Methadone Injectable Product Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered the placebo drug. Methadone 2 Methadone Injectable Product Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.1 mg/kg. Methadone 3 Methadone Injectable Product Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.2 mg/kg. Methadone 1 Methadone Injectable Product Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.05 mg/kg.
- Primary Outcome Measures
Name Time Method Methadone plasmatic levels Measured by high pressure liquid chromatography From the first dose up to 24 hours. Five venous blood samples will be taken from each patient for methadone plasmatic level analysis. Patients will be randomly divided into two groups with different sample collection times. Group 1 at 0.05, 0.75, 1.5, 6, 18 hours post drug administration and Group 2 at 0.25, 1, 3, 12 and 24 hours.
- Secondary Outcome Measures
Name Time Method Respiratory rate Every 30 minutes. Since entering the recovery room up to 180 mins. bpm
Heart Rate Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes. Heart rate (bpm)
Intestinal transit recovery Since the admission to the recovery room up to 2 hours. Time to first flatus, fist bowel movement and stool. Presence of abdominal bloating.
Other opioids and pain management drugs used during recovery stay Since the admission to the recovery room up to 2 hours. Name and total doses, including Morphine PCA.
Numeric Pain Rating Scale Every 30 minutes. Since entering the recovery room up to 180 mins. Numeric Pain rating scale in rest and movement, from 0 (no pain) to 10 (maximum pain).
Sedation (Ramsay Scale) Every 30 minutes. Since entering the recovery room up to 180 mins. Ramsay scale (1-6)
Hemodynamics Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes. Non invasive systolic and diastolic blood pressure monitoring (mmHg).
Pulse oximetry Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes. % oximetry saturation
BIS Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Depth of anesthesia will be recorded with BIS monitor. From 60 - 40
Nausea or vomiting Every 30 minutes. Since entering the recovery room up to 180 mins. Presence of nausea or vomiting in the recovery room.
Respiratory depression Every 30 minutes. Since entering the recovery room up to 180 mins. Presence of respiratory depression in the recovery room. (Respiratory rate less than 8 bpm requiring oxygen therapy).
Trial Locations
- Locations (1)
Pontificia Universidad Católica de Chile
🇨🇱Santiago, Metropolitana, Chile