Prevalence and Associated Factors of Opioid Withdrawal Syndrome in Adults Admitted to an Intensive Care Unit: A Retrospective Observational Descriptive Study

Abstract

Background: Prolonged opioid administration for pain control and to facilitate tolerance of mechanical ventilation in the intensive care unit (ICU) may lead to tolerance and physical dependence. Following opioid discontinuation, opioid withdrawal syndrome (OWS) may occur. Although this condition has been well described in pediatric populations, its incidence and associated factors in critically ill adults remain uncertain because of diagnostic heterogeneity and the frequent clinical overlap with delirium. The aim of this study was to assess the prevalence of OWS and to identify factors associated with its development in adult patients.

Methods: We conducted a retrospective, descriptive, observational study including patients evaluated at the post ICU follow-up clinic of Lozano Blesa University Clinical Hospital (Zaragoza, Spain) over a 12-month period. This study investigated the association between multiple opioid medications and adjunctive medications and the occurrence of OWS. Eligible patients had an ICU stay of >7 days, received mechanical ventilation for >48 hours, and had been exposed to opioids. Demographic, clinical, and pharmaco logical variables were collected, including types of opioids, weight-adjusted cumulative dose, and use of adjuvant medications. OWS was diagnosed during the first 48 hours after opioid discontinuation using a combination of the Clinical Opiate Withdrawal Scale (COWS) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the impact of morphine exposure.

Results: A total of 66 patients were included (mean age 59.9 ± 13.6 years; predominantly male). The leading cause of ICU admission was respiratory disease (48.5%). Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score at admission was 17.0 ± 6.1, and median ICU length of stay was 19 days. Twenty-two patients (33.3%) developed OWS, which was mild in 90.9% and moderate in 9.1% according to the COWS. No significant differences were observed between groups in baseline characteristics or delirium occurrence. Patients who developed OWS were more likely to have received morphine (100% vs. 75%; p = 0.010) and had a higher weight-adjusted cumulative morphine dose (3.15 ± 2.33 vs. 2.21 ± 2.50 mg/kg; p = 0.047), whereas no differences were found for fentanyl exposure. In addition, they more frequently required benzodiazepines (68.2% vs. 18.2%), neuroleptics (68.2% vs. 6.8%), and dexmedetomidine (31.8% vs. 4.5%) (p <0.01 for all comparisons). Cumulative morphine dose showed modest discriminatory performance for OWS (area under the curve (AUC) 0.653; p = 0.048).

Conclusions: OWS is a common complication among adult ICU survivors, although it is predominantly mild in severity. A higher cumulative dose of morphine was associated with its onset, although no association was found with the total duration of exposure. Clinical overlap with delirium and the reactive use of psychoactive medications may contribute to under-recognition of this condition, under scoring the need for structured OWS screening during ICU stay and in post-intensive care syndrome (PICS) follow-up.