An observational study in Substance Withdrawal Syndrome, sponsored by Marc M. Perreault. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-01.
Sponsored by Marc M. Perreault · Observational
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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.
Objectives:
Hypotheses:
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.
74 studies on the registry are indexed under Substance Withdrawal Syndrome; 7 are open to participants now.
This study's enrollment of 29 is below the median of 115 across 15 observational studies indexed under Substance Withdrawal Syndrome.
Browse Substance Withdrawal Syndrome studies →This is the only study on the registry with Marc M. Perreault as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Mechanically ventilated adult ICU patients receiving continuous or regular intermittent opioids for more than 72 hours.
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Exclusion Criteria:
Substance abuse prior to ICU admission.
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
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
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.
Time frame: 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
Change in Serum Cortisol Level
Cortisol level were drawn on the first day of opioid weaning and repeated 72 hours after onset of weaning
Time frame: 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.
| Milestone | Iatrogenic Withdrawal Syndrome (IWS) Positive | Iatrogenic Withdrawal Syndrome (IWS) Negative |
|---|---|---|
| Started | 6 | 23 |
| Completed | 6 | 23 |
| Not completed | 0 | 0 |
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.
| percentage of assessments | IWS Positive | IWS Negative |
|---|---|---|
| Restlessness (RASS = 1) | 28.6 | 13.6 |
| Agitation (RASS > 1) | 28.6 | 4.9 |
| Anxiety | 57.1 | 30.6 |
| Hallucinations | 28.6 | 11.2 |
| Insomnia/Sleep disturbance (< 4 hours of continuous sleep) | 66.7 | 21.4 |
| Mydriasis (pupil size > 2mm) | 100 | 77.8 |
| Systolic Blood Pressure (SBP) > 140 mmHg | 85.7 | 53 |
Cortisol level were drawn on the first day of opioid weaning and repeated 72 hours after onset of weaning
| nmol/L | IWS Positive | IWS Negative |
|---|---|---|
| Change in Serum Cortisol Level | -146 | -37 (-62 to 93) |
Collected over Symptom assessments were collected daily until transfer out of ICU, death or 14 days after start of patient remained in ICU; If patient was transferred, one additional data was collected up to 96 hours post-transfer out of ICU. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Critically Ill Patients | 0/29 (0%) | 0/29 (0%) | 0/29 (0%) |
1128 patients screened; 59 eligible as per entry criteria; 29 enrolled and included in the analysis
| Age, Continuous(years) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Median | 70 (62.0 to 77.3) | 64 (44.0 to 74.0) | 65 (47.5 to 75.0) |
| Sex: Female, Male(Participants) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Female | 2 | 6 | 8 |
| Male | 4 | 17 | 21 |
| Race/Ethnicity, Customized(Participants) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Caucasian | 6 | 17 | 23 |
| Hispanic | 0 | 2 | 2 |
| Black | 0 | 2 | 2 |
| MIddle Eastern | 0 | 2 | 2 |
| Serum Creatinine at ICU admission (umol/L)(umol/L) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Median | 124 (78 to 307) | 136 (71 to 223) | 132 (74 to 222) |
| Reason for ICU admission (ICD-10)(Participants) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Diseases of the circulatory system | 1 | 6 | 7 |
| External causes of morbidity and mortality (trauma) | 1 | 5 | 6 |
| Infectious and parasitic diseases | 0 | 5 | 5 |
| Diseases of the digestive system | 3 | 2 | 5 |
| Diseases of the respiratory system | 0 | 4 | 4 |
| Other | 1 | 1 | 2 |
| Length of ICU stay(Days) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Median | 16.5 (9.5 to 38.0) | 16 (9.0 to 34.0) | 16.0 (9.0 to 35.0) |
| Duration of mechanical ventilation(Days) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Median | 9.0 (7.3 to 37.3) | 9.0 (5.0 to 26.0) | 9.0 (5.5 to 27.0) |
| Co-morbidities(participants) | Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients | Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients | Total |
|---|---|---|---|
| Hypertension | 3 | 12 | 15 |
| Coronary artery disease | 2 | 11 | 13 |
| Diabetes | 1 | 8 | 9 |
| Chronic kidney disease | 1 | 5 | 6 |
| Chronic obstructive pulmonary disease | 2 | 4 | 6 |
| Other | 3 | 9 | 12 |
2 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Feb 2018 to primary completion in Sep 2018, 7 months.
Results were first posted in Jan 2021, 2 years 3 months after primary completion.
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This study is completed, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.
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Substance Withdrawal Syndrome →