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

Substance Withdrawal Syndrome Clinical Trial

— SOWA-ICU  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03435614
• Other study ID #: 2018-4305
• Status: Completed
• Start date: February 26, 2018
• Est. completion date: September 30, 2018

Study information

• Verified date: January 2021
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Objectives:

1. To identify specific signs and symptoms of OIWS in mechanically ventilated adult intensive care unit (ICU) patients receiving at least 72 hours of regular opioids at the Montreal General Hospital (MGH) and the Royal Victoria Hospital (RVH) from February to October 2018.

2. To determine if a change in serum cortisol is associated with the presence of OIWS.

Hypotheses:

1. Considering our first objective is purely descriptive, no hypothesis can be stated.

2. OIWS is associated with an increase in serum cortisol.

Methods:

A prospective multicentre observational study will be carried out in two university-affiliated hospital ICUs (Montreal General Hospital and Royal Victoria Hospital). All mechanically ventilated adult ICU patients receiving regular (continuous or intermittent) opioids for more than 72 hours will be prospectively screened daily for withdrawal symptoms once the opioid dose is reduced by 10% or more. From that moment, daily evaluation by a physician using the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for opioid withdrawal will be conducted. Concomitantly, signs and symptoms of withdrawal will be collected by an investigator blinded to the DSM-5 assessment. These assessments will continue daily until the patient is transferred out of ICU or a maximum of 14 days and will be repeated once more between day 1 and day 4 post-transfer out of ICU.

A serum cortisol will be drawn on the first day of dose reduction by 10% or more (baseline) and will be repeated either after 72 hours or upon patient discharge from the ICU, whichever one occurs first.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: September 30, 2018
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Critical Illness
• Substance Withdrawal Syndrome

Intervention

Drug:
• Opioids
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.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Marc M. Perreault

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View Citation

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. Review. — View Citation

Wang PP, Huang E, Feng X, Bray CA, Perreault MM, Rico P, Bellemare P, Murgoi P, Gélinas 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Serum Cortisol Level	Cortisol level were drawn on the first day of opioid weaning and repeated 72 hours after onset of weaning	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.