Postoperative Pain Management
Conditions
Keywords
methadone pharmacokinetics, cardiac surgery, pain management, cardiac surgery recovery, methadone
Brief summary
Cardiac surgery frequently leads to significant postoperative pain, with multiple different drug regimens being utilized (both opioid and non-opioid) in an attempt to alleviate this surgical pain. Methadone is currently one of the drugs that is being utilized to help control the pain. It can be given during and/or after surgery. This study hopes to identify the optimal dose of methadone to use to treat this surgical pain.
Detailed description
The uncertainty regarding optimal methadone dosing and the necessity of post-cardiopulmonary bypass (CPB) supplementation provides a compelling rationale for this study. Specifically, it remains unknown whether a single higher initial dose of methadone can adequately maintain analgesic plasma concentrations throughout cardiac surgery and recovery, or if a split-dosing strategy administering a lower initial dose followed by an additional dose post-CPB might offer similar or improved analgesic outcomes with fewer side effects. This study will evaluate pharmacokinetics of methadone using three different dosing strategies in patients undergoing cardiac surgery with CPB.
Interventions
DRUGSingle dose of methadone
Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia
DRUGSplit dose of methadone
Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass
DRUGBalanced split dose of methadone
Balanced split dose of methadone 0.15 mg/kg actual body weight at induction and 0.15 mg/kg actual body weight post cardiopulmonary bypass
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Elective cardiac surgery requiring median sternotomy and cardiopulmonary bypass (CABG, valve, combined CABG/valve surgeries) * Anticipated extubation within 12 hours postoperatively * No prior opioid use within 30 days of surgery * Ability to provide informed consent
Exclusion criteria
* Severe liver or kidney dysfunction (Child-Pugh class B/C, eGFR \<30 mL/min/1.73m², creatinine \>2 mg/dL, dialysis) * Allergy to methadone or fentanyl * Use of CYP3A4 inducers (rifampin, phenytoin, carbamazepine), CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin, itraconazole), SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine) * Body mass index \>40 kg/m² * Corrected QT interval interval \>500 milliseconds * Intubation anticipated \>12 hours * History of illicit drug use or alcohol or opioid abuse use disorder within last 12 months * Mechanical circulatory support, heart transplant, deep hypothermic circulatory arrest procedures * Left Ventricular Ejection Fraction \<30% * Pulmonary disease requiring oxygen therapy * Preoperative inotropic support or intra-aortic balloon pump * Emergency surgery * Postoperative regional anesthesia * Hemofiltration during cardiopulmonary bypass
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma methadone concentration (ng/mL) 10 min post initial dose | 10 minutes | Plasma methadone concentration will be measured 10 minutes post initial methadone dose |
| Plasma methadone concentration (ng/mL) 30 min post initial dose | 30 minutes | Plasma methadone concentration will be measured 30 minutes post initial methadone dose pre cardiopulmonary bypass |
| Plasma methadone concentration (ng/mL) 60 min post initial dose | 60 minutes | Plasma methadone concentration will be measured 60 minutes post initial methadone dose pre cardiopulmonary bypass |
| Plasma methadone concentration (ng/mL) 10 min post start of cardiopulmonary bypass | 10 minutes | Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass started |
| Plasma methadone concentration (ng/mL) 30 min post start of cardiopulmonary bypass | 30 minutes | Plasma methadone concentration will be measured 30 minutes after cardiopulmonary bypass started |
| Plasma methadone concentration (ng/mL) 60 min post start of cardiopulmonary bypass | 60 minutes | Plasma methadone concentration will be measured 60 minutes after cardiopulmonary bypass started |
| Plasma methadone concentration (ng/mL) 10 min post cardiopulmonary bypass completion | 10 minutes | Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass ended |
| Plasma methadone concentration (ng/mL) 120 min post start of cardiopulmonary bypass | 120 minutes | Plasma methadone concentration will be measured 120 minutes after cardiopulmonary bypass started |
| Plasma methadone concentration (ng/mL) before first analgesic request | up to 72 hours | Plasma methadone concentration will be measured at the time of first analgesic request by participant |
| Plasma methadone concentration (ng/mL) 3 hours post Intensive Care Unit arrival | 3 hours | Plasma methadone concentration will be measured 3 hours post Intensive Care Unit arrival |
| Plasma methadone concentration (ng/mL) 12 hours post Intensive Care Unit arrival | 12 hours | Plasma methadone concentration will be measured 12 hours post Intensive Care Unit arrival |
| Plasma methadone concentration (ng/mL) 24 hours post Intensive Care Unit arrival | 24 hours | Plasma methadone concentration will be measured 24 hours post Intensive Care Unit arrival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pain intensity score | 2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3 | Pain intensity score will be measured using the visual analog scale. Scores will be measured on a scale of 0-10, with 0=no pain and 10=most severe pain |
| patient global impression of change | 24, 48, and 72 hours after removal of the breathing tube | Patient Global Impression of Change will be used to assess patient-perceived analgesic effectiveness and overall postoperative recovery. Total score range is 1-7 with a higher score indicating considerable improvement with treatment. |
| postoperative opioid consumption | up 72 hours postop | total postoperative opioid consumption in morphine milligram equivalents |
| duration of postoperative mechanical ventilation | up to 72 hours postop | number of minutes with postoperative mechanical ventilation |
| time of ambulation | up to 48 hours postop | number of minutes until patient first ambulates after surgery |
| length of Intensive Care Unit stay | up to 3 days postop | number of hours spent in Intensive Care Unit |
| length of hospital length stay | up to 7 days postop | number of days spent in hospital |
Contacts
PRINCIPAL_INVESTIGATOREttore Crimi, MD
Wake Forest University Health Sciences
Outcome results
None listed