Opioid Use Increases the Risk of Delirium in Critically Ill Adults Independently of Pain

It is unclear whether opioid use increases the risk of ICU delirium. Prior studies have not accounted for confounding including daily severity of illness, pain and competing events that may preclude delirium detection. To evaluate the association between ICU opioid exposure, opioid dose, and delirium occurrence. In consecutive adults admitted >24 hours to the ICU, daily mental status was classified as awake without delirium, delirium, or unarousable. A first-order Markov model with multinomial logistic regression analysis considered four possible next-day outcomes (i.e., awake without delirium, delirium, unarousable, and ICU discharge or death) and 11 delirium-related covariables (baseline: admission type, age, gender, APACHE IV, Charlson; daily: ICU day, modified SOFA, ventilation use, benzodiazepine use, severe pain). This model was used to quantify the association between opioid use, opioid dose, and delirium occurrence the following day. The 4075 adults had 26,250 ICU days; an opioid was administered on 57.0% (n=14,975), severe pain occurred on 7.0% (n=1,829), and delirium occurred on 23.5% (n=6,176). Severe pain was inversely associated with a transition to delirium (OR 0.72; 95% CI 0.53-0.97). Any opioid administration in awake patients without delirium was associated with an increased risk for delirium the next day [OR 1.45, 95% CI 1.24-1.69]. Each daily 10 mg IV morphine equivalent dose was associated with a 2.4% increased risk for delirium the next day. Receipt of an opioid in the ICU increases the odds of transitioning to delirium in a dose-dependent fashion.