Opioid Withdrawal Symptoms in Critically Ill Patients

Most critically ill patients encounter pain and distress from acute illness, medical procedures and devices as well as routine care in the intensive care units (ICU). Opioids are principal analgesics that alleviate moderate to severe pain and facilitate patients to co-operate the course of treatment. However, prolong administration of opioids especially in mechanically ventilated patients can cause withdrawal symptoms if analgesics are rapidly weaning or acutely disruption. The opioid withdrawal symptoms (OWS) are well reported in critically ill children that cause discomfort and prolong weaning from mechanical ventilation. Weaning opioids and treatment of withdrawal symptoms are needed in order to decrease ventilator days, ICU and hospital length of stay. Conversely, there is lack of knowledge about incidence, clinical presentation, time course and appropriated assessment tool for withdrawal detection. Therefore, we conduct the study to explore an incidence of OWS, to identify factors associated OWS, to establish the assessment tool for OWS, and to report efficacy of the pharmacological treatment for OWS, in adult critically ill patients.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Substance Withdrawal Syndrome
• Intervention / Treatment: Drug: Opioids

Detailed Description

The primary objective of the study is to explore incidence of OWS in adult critically ill patients. The secondary objectives are 1) to identify factor associated OWS, 2) establish the assessment tool for OWS for adults and 3) to report efficacy of the pharmacological treatment in OWS in adults patients.

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Faculty of Pharmacy, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Intensive care units

Description

Inclusion Criteria:

• Age ≥18 years
• On mechanical ventilator at least 24 hours
• Received continuous infusion of opioid at least 24 hours
• Patient or legal surrogate who is willing and able to provide written informed consent and comply with all protocol requirements

Exclusion Criteria:

• Severely disturbed behavior pattern on account of underlying neurological disease (status epilepticus, encephalopathy, head trauma, brain injury, spinal cord injury)
• Preexisting psychiatric diagnosis
• Substance abuse prior to ICU admission
• Chronic alcohol drinking
• Pregnancy
• End-of-life care
• Death during ICU admission or during opioid IV infusion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mechanically ventilated critically ill patients; Mechanically ventilated critically ill patients who receive opioid as continuous infusion for more than 24 hours	Drug: Opioids; Mechanically ventilated critically ill patients who receive continuous opioid infusion for more than 24 hours will be observed for withdrawal symptoms when rate of opioid infusion is disrupted or decreased

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of opioid withdrawal symptoms	Incidence of opioid withdrawal symptoms detected by self-developed assessment tool or the Diagnostic and Statistical Manual 5th edition (DSM-V)	0, 1, 3, 6, 24 and 72 hour after reduction or discontinuation of intravenous opioid

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weaning days	Time from initial weaning from mechanical ventilator until extubation	28 days
Ventilator days	Time from intubation until extubation	28 days
ICU length of stay	Time from admission to ICU until discharge from ICU	28 days

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Suthinee Taesotikul, Pharm.D., Faculty of Pharmacy, Mahidol University

Publications and helpful links

General Publications

• Brown C, Albrecht R, Pettit H, McFadden T, Schermer C. Opioid and benzodiazepine withdrawal syndrome in adult burn patients. Am Surg. 2000 Apr;66(4):367-70; discussion 370-1.
• 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.
• 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.
• Korak-Leiter M, Likar R, Oher M, Trampitsch E, Ziervogel G, Levy JV, Freye EC. Withdrawal following sufentanil/propofol and sufentanil/midazolam. Sedation in surgical ICU patients: correlation with central nervous parameters and endogenous opioids. Intensive Care Med. 2005 Mar;31(3):380-7. doi: 10.1007/s00134-005-2579-3. Epub 2005 Feb 16.
• Taesotikul S, Dilokpattanamongkol P, Tangsujaritvijit V, Suthisisang C. Incidence and clinical manifestation of iatrogenic opioid withdrawal syndrome in mechanically ventilated patients. Curr Med Res Opin. 2021 Jul;37(7):1213-1219. doi: 10.1080/03007995.2021.1928616. Epub 2021 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): October 7, 2018

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 15, 2017

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 8, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease Attributes; Critical Illness; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: 10-60-68

Drug and device information, study documents

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