Clinical trial NCT06868589: Reducing Pain With Methadone and Ketamine in Liver Transplant
Official title: Randomized Clinical Trial of Methadone and Ketamine for Pain Management During Deceased Donor Liver Transplant
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Liver Transplantation
Keywords: Liver Transplantation
Deceased Donor Liver Transplant
Postoperative Pain
Methadone
Ketamine
Perioperative Analgesia
Anesthesiology
Acute Pain
Transplant Surgery
Opioids
Lead sponsor: Lahey Clinic
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to either intervention or standard of care group at the ratio of 1:1
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if using methadone and ketamine during an adult deceased donor liver transplant can help decrease pain after surgery.

The main questions it aims to answer are:

* What impact does using methadone and ketamine during a deceased donor liver transplant have on pain after surgery?
* Does the use of methadone and ketamine also have an impact on mental confusion (delirium) after surgery?

Researchers will compare the use of methadone and ketamine to standard of care to see if the two drugs work to decrease pain and impact delirium after liver transplant.

Participants will:

* Receive either methadone and ketamine or standard of care during their deceased donor liver transplant.
* Allow researchers to follow medical care throughout inpatient stay.

Detailed description: Pain control following liver transplantation (LT) has been the subject of interest of many research projects due to invasive nature of the procedure, significant comorbidities of recipients, effect of hepatic metabolism on many common pain medications and difficulties in performing some neuraxial and regional techniques given patient coagulopathy. Some newer regional nerve blocks such as External Oblique Intercostal (EOI) block has also been successfully utilized in pain management of patients undergoing liver resections but their utilization in perioperative setting for high-MELD patients and after-hour operations are limited. Methadone and ketamine are well-known drugs that have been recently emerged as components of new pain management pathways in many open surgeries due to their availability, cost, well-known metabolism, good safety profile and prolonged effects. Evidence has emerged that their use is associated with decreased likelihood of development of chronic pain and need for long term opioids. The combination of methadone and ketamine has been shown to be superior to opioids alone due to synergistic effect on N-methyl-d-aspartate and μ-opioid receptors. But these medications have not been extensively studied in LT recipients except for a few case reports and small studies. Current standards of care for intraoperative pain management during LT are systemic short and medium long-acting opioids such as fentanyl and hydromorphone which both have numerous concerns such as respiratory depression and opioid dependency. The aim of this study is to prospectively evaluate the effect of intraoperative methadone and ketamine administration on postoperative pain in liver transplant recipients. These drugs have been safely used during liver transplantation at LHMC and other centers and showed to be effective and safe, but the exact dosing and timing of administration requires further studies.

Eligibility criteria: Inclusion Criteria:

* Adult patients ≥ 18 years of age at the time of LT.
* Undergoing LT from a deceased donor.
* Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

Living donor liver transplantation (LDLT).

* Split liver transplantation (isolated right or left lobe).
* Acute liver failure (ALF) as the indication for LT.
* Simultaneous liver and kidney Transplant (SLK)
* Repeat liver transplant
* Sedation or high vasopressor use
* Subject is intubated and/or mechanically ventilated prior to entering the operating room for LT.
* Severe hepatic encephalopathy
* History of psychiatric disorders such as schizophrenia or bipolar mood disorders
* History of substance abuse or opioid maintenance therapies
* Any history of allergic reaction to methadone or ketamine
* History of prolonged QT syndrome or QTc in preoperative setting
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Primary outcomes:
measure: Postoperative Pain
timeFrame: 8, 16, 24, 32, 40 and 48hours post-surgery finish
measure: Postoperative Pain
timeFrame: 8, 16, 24, 32, 40 and 48hours post-surgery finish
Secondary outcomes:
measure: Length of stay in intensive care unit
timeFrame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
measure: Length of stay in hospital
timeFrame: Post surgery finish until discharge from hospital, or date of death from any cause, whichever came first, assessed up to 30 days
measure: Delirium
timeFrame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
measure: Respiratory complications
timeFrame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
measure: Narcotics reversal agent
timeFrame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
measure: Postoperative adjunct pain modalities
timeFrame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
Study officials:
affiliation: Lahey Hospital and Medical Center, Department of Anesthesiology, Perioperative and Pain Medicine
name: Ryan Nazemian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: