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Reducing Pain With Methadone and Ketamine in Liver Transplant

Phase 4
Not yet recruiting
Conditions
Liver Transplantation
Interventions
Registration Number
NCT06868589
Lead Sponsor
Lahey Clinic
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
50
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
M+K groupMethadoneParticipants in this arm will receive the intervention with methadone and ketamine
M+K groupketamineParticipants in this arm will receive the intervention with methadone and ketamine
SOC groupHydromorphoneParticipants in this arm will receive the standard of care with combination of hydromorphone and fentanyl
SOC groupfentanylParticipants in this arm will receive the standard of care with combination of hydromorphone and fentanyl
Primary Outcome Measures
NameTimeMethod
Postoperative Pain8, 16, 24, 32, 40 and 48hours post-surgery finish

Subjective postoperative pain scores measured as 0-10 (10 being the worst pain)

Secondary Outcome Measures
NameTimeMethod
Length of stay in intensive care unitPost surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days

Duration of length of stay in intensive care unit in hours

Length of stay in hospitalPost surgery finish until discharge from hospital, or date of death from any cause, whichever came first, assessed up to 30 days

Duration of length of stay in the hospital in days

DeliriumPost surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days

Incidence of postoperative delirium measured by standard CAM-ICU scores, ICD-10 diagnosis of delirium, any use of anti-agitation medication such as haloperidol, dexmedetomidine or seroquel

Respiratory complicationsPost surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days

Any significant respiratory complications such as re-intubation, need for invasive ventilation such as BIPAP or CPAP

Postoperative adjunct pain modalitiesPost surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days

Incidence of usage of any additional pain modalities such as nerve blocks, neuraxial anesthesia, non-narcotic pain medications such as additional ketamine dose, ketorolac, methocarbamol, ketorolac, etc

Narcotics reversal agentPost surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days

Any need for narcotics reversal agents such as Naloxone after administration of study drugs

Trial Locations

Locations (1)

Lahey Hospital and Medical Center

🇺🇸

Burlington, Massachusetts, United States

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