Clinical trial NCT03435614: Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults
Official title: Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Substance Withdrawal Syndrome
Keywords: Opioid
Withdrawal
Critically ill adults
Cortisol
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2018-02-19
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Mechanically ventilated adult ICU patients receiving continuous or regular intermittent opioids for more than 72 hours.

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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:
measure: Change in Serum Cortisol Level
timeFrame: 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.
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Marie-Soleil Delisle, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Marc M Perreault, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Marc-Alexandre Duceppe, MSc
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
citation: 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.