Methadone vs. Transdermal Fentanyl for Opioid Withdrawal Syndrome

Methadone vs. Transdermal Fentanyl for Opioid Withdrawal Syndrome : Comparison of Two Groups of Intubated and Ventilated Patients in the Intensive Care Unit: Before-after Intervention Study

Many patients in the general intensive care unit experience pain, as a result of an injury or underlying disease, surgery or an invasive procedure.

Pain management is an integral part of the treatment of critical patients, and this is first and foremost to alleviate their suffering. Along with this, there is another therapeutic benefit in the form of relief from symptoms accompanying pain such as an increase in oxygen consumption, immune changes, hyper metabolism etc.

Currently, the pain treatment is based on a multi-modal analgesia approach in which drugs from several drug groups and different mechanisms are given, in order to relieve the pain by suppressing several nerve and inflammatory pathways. However, the treatment is still based on opioids, despite multiple adverse effects, including tolerance and withdrawal syndrome.

Opioids affect several receptors, mainly the µ receptor, in an agonistic, antagonistic or agonistic-antagonistic manner. The main opioids used for pain relief in the intensive care unit are morphine, fentanyl and remifentanil.

After prolonged treatment with opioids, a sudden cessation of their use will result in a withdrawal syndrome which will manifest itself in delirium, restlessness, hypertension, anxiety, sweating, vomiting etc. (2-3). In order to avoid the withdrawal syndrome, the dose must be tapered down gradually, often using alternative long-term opioids, such as methadone and buprenorphine (-4).

In the general intensive care unit at our institution, patients were treated with fentanyl patches in decreasing doses in order to lead the patient safely through the withdrawal syndrome, while trying to reduce the negative physiological effects as much as possible. In November 2021, we started using oral methadone instead of fentanyl patches, as a long acting opioid, as used in many ICU's worldwide, in order to avoid withdrawal syndrome in patients who received continuous infusion of short-acting opioids, such as remifentanil, for long periods of time while being intubated and ventilated. In the past year since the methadone treatment was started, 50 patients were treated in the unit with methadone with the indication of relieving the withdrawal symptoms from opioids.

We intent to investigate whether there is a difference in the incidence of delirium in patients who were treated with methadone vs patients who were treated with fentanyl patches in order to alleviate withdrawal symptoms.

Study Overview

• Status: Completed
• Conditions: Delirium in the Intensive Care Unit
• Intervention / Treatment: Drug: Administration of methadone instead of fentanyl patch

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Israel
  • Kfar Saba, Israel
    • Meir medical center Kfar Saba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients aged 18-99 who were treated with methadone in the intensive care unit from November 2021 to November 2022, as well as all patients aged 18-99 who were admitted to the intensive care unit from November 2020 to November 2021 and were treated with a fentanyl patch as a control group.

Description

Inclusion Criteria:All patients aged 18-99 who were treated with methadone in the intensive care unit from November 2021 to November 2022, as well as all patients aged 18-99 who were admitted to the intensive care unit from November 2020 to November 2021 and were treated with a fentanyl patch as a control group.

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Exclusion Criteria:None

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Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Methadone-treated group	Drug: Administration of methadone instead of fentanyl patch; comparison of delirium rates in methadone vs fentanyl patch treated patients; Other Names: comparison of delirium rates in methadone vs fentanyl patch treated patients
Fentanyl-patch treated group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium	Delirium as estimated by RASS score	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Meir Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 15, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Respiratory System Agents; Antitussive Agents; Fentanyl; Methadone
• Other Study ID Numbers: 0008-23-MMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No