Risk Factors Associated With Opioid/Benzodiazepine Iatrogenic Withdrawal Syndrome in COVID-19 Acute Respiratory Distress Syndrome

Abstract

Background Mechanically ventilated COVID-19 acute respiratory distress syndrome (ARDS) patients often receive deeper sedation and analgesia to maintain respiratory compliance and minimize staff exposure, which incurs greater risk of iatrogenic withdrawal syndrome (IWS) and has been associated with worse patient outcomes. Objective: To identify potential risk factors and differences in patient outcomes associated with the development of IWS in COVID-19 ARDS patients. Methods: Retrospective analysis of ventilated COVID-19 ARDS intensive care unit (ICU) patients who received continuous intravenous (IV) analgesia and sedation for ≥5 days from March 2020–May 2021. Patients were classified as IWS and non-IWS based on receipt of scheduled oral sedative/analgesic regimens after cessation of IV therapy. Risk factors were assessed in univariate analyses and multivariable modeling. Results: A total of 115 patients were included. The final multivariable model showed: (1) each additional day of IV opioid therapy was associated with an 8% increase in odds of IWS (95% CI, 1.02-1.14), (2) among sedatives, receipt of lorazepam was associated with 3 times higher odds of IWS (95% CI 1.12-8.15), and (3) each 1-point increase in Simplified Acute Physiology Score (SAPS) II was associated with a 4% reduction in odds of IWS (95% CI 0.93-0.999). Conclusion: Prolonged and high dose exposures to IV opioids and benzodiazepines should be limited when possible. Additional prospective studies are needed to identify modifiable risk factors to prevent IWS.