Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults

NCT03435614 | Completed Results

• 1 other identifier: 2018-4305
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Mechanically ventilated critically ill adults may require prolonged administration of opioids to facilitate ventilator support and maintain comfort. The prolonged use has been associated with withdrawal symptoms upon rapid weaning in critically ill patients, known as the opioid-associated withdrawal syndrome (OIWS). Such withdrawal symptoms are well described in the paediatric population, however there is a lack of information in the adult population. Currently there is no bedside tool to rapidly identify such patients. Recognition of withdrawal symptoms is the basis for the development of an assessment tool to identify patients with OIWS.

Conditions

Substance Withdrawal Syndrome

Keywords

Opioid; Withdrawal; Critically ill adults; Cortisol

Outcome Measures

Primary Outcomes (1)

• Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria

  Percentage of daily assessments associated with each of the following signs and symptoms experienced by patients with and without OIWS (Restlessness (Richmond Agitation-Sedation scale = 1), Agitation (RASS \> 1), Anxiety, Hallucinations, Insomnia/sleep disturbance (\< 4 hours of continuous sleep), Mydriasis (Pupil diameter \> 2 mm) and systolic blood pressure (SBP) \> 140 mmHg. These assessments were performed once daily. Note that for the group of patients experiencing IWS, the data on signs and symptoms are limited to the assessment on the day that patients experienced OIWS. The signs and symptoms presented (Restlessness; Agitation; Anxiety, Hallucinations, Insomnia/sleep disturbance; mydriasis; SBP \> 140) were selected based on a \> 15 % absolute difference between both groups which was judged to be clinically significant.

  From first day of opioid dose reduction until transfer out of Intensive care unit (ICU) or a maximum of 14 days, including one further assessment post-ICU transfer

Secondary Outcomes (1)

• Change in Serum Cortisol Level

  Baseline cortisol on first day of opioid dose reduction and on day 3 post-dose reduction, or on day of transfer out of ICU if patient is transferred before day 3.

Study Arms (1)

Critically ill patients

Mechanically ventilated critically ill adults receiving regular opioids for more than 72 hours will be prospectively followed for the emergence of withdrawal symptoms upon weaning of opioids.

Drug: Opioids

Interventions

Opioids DRUG

Once an opioid dose reduction of 10% or greater is achieved, a daily assessment will be conducted by a physician using the DSM-5 criteria for opioid withdrawal. In addition, signs and symptoms of withdrawal will be collected daily by a blinded investigator.

Also known as: Analgesics, Narcotics

Critically ill patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Mechanically ventilated adult ICU patients receiving continuous or regular intermittent opioids for more than 72 hours.

You may qualify if:

• Patients requiring mechanical ventilation and receiving continuous or regular intermittent opioids for at least 72 hours.
• Weaning of at least 10% from previous stable opioid dose. A weaning episode is defined as a ≥ 10% decrease in the total stable opioid dose received over 4 hours for opioid infusions and over 12 hours for intermittent opioid administration.

You may not qualify if:

• Patient for whom consent cannot be obtained
• Patient and/or family unable to communicate in French or English
• Patient who is deaf without appropriate hearing aid
• Imminent and predictable death (\< 72 hours) according to medical team
• Severe brain injury, defined as Glasgow Coma Scale (GCS) score of 8 or less at ICU admission
• Moderate brain injury, defined as GCS between 9 and 12, with elevated intracranial pressure (ICP \> 20 mmHg) which requires ICP monitoring and osmotherapy
• Acute neurological condition (e.g. status epilepticus, encephalopathy, stroke). If the acute neurological condition resolves within 72 hours, the patient may be included in the study.
• Substance abuse prior to ICU admission.
• Chronic alcohol use defined as alcohol consumption of more than 2 drinks/day and/or more than 14 drinks/week for men and 9 drinks/week for women.
• Chronic use of illicit drugs and amphetamines (except amphetamines taken for therapeutic purposes) defined as a consumption of at least 3 times per week.
• Chronic use of opioids (e.g. transdermal fentanyl, methadone, hydromorphone, etc.) defined as a consumption of at least 3 times per week.
• Readmission to the MGH or RVH ICU during the recruitment period (limit of one study entry per patient)
• Spinal cord injury above the lumbar region

Sponsors & Collaborators

• Marc M. Perreault: lead

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

Location

Related Publications (3)

• Chiu AW, Contreras S, Mehta S, Korman J, Perreault MM, Williamson DR, Burry LD. Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management. Ann Pharmacother. 2017 Dec;51(12):1099-1111. doi: 10.1177/1060028017724538. Epub 2017 Aug 9.

  PMID: 28793780 BACKGROUND

• Wang PP, Huang E, Feng X, Bray CA, Perreault MM, Rico P, Bellemare P, Murgoi P, Gelinas C, Lecavalier A, Jayaraman D, Frenette AJ, Williamson D. Opioid-associated iatrogenic withdrawal in critically ill adult patients: a multicenter prospective observational study. Ann Intensive Care. 2017 Sep 2;7(1):88. doi: 10.1186/s13613-017-0310-5.

  PMID: 28866754 BACKGROUND

• Cammarano WB, Pittet JF, Weitz S, Schlobohm RM, Marks JD. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med. 1998 Apr;26(4):676-84. doi: 10.1097/00003246-199804000-00015.

  PMID: 9559604 BACKGROUND

MeSH Terms

Conditions

Substance Withdrawal Syndrome

Interventions

Analgesics, Opioid; Analgesics; Narcotics

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses

Results Point of Contact

• Title: Marc Perreault
• Organization: MUHC-RIMUHC

marc.perreault@umontreal.ca

514-343-6111

Study Officials

• Marie-Soleil Delisle, MSc

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Marc M Perreault, PharmD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Marc-Alexandre Duceppe, MSc

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pharmacist

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 19, 2018
• Study Start: February 26, 2018
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: January 1, 2025
• Results First Posted: January 28, 2021

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)