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Can Opioids in the Critically Ill Induce Delirium?

October 6, 2021

Written by Jonathan Brewer

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The quick answer is yes. This has been a debate in the critical care and pain literature for quite some time, but according to this trial, we finally have our answer – receiving opioids in the ICU increases the odds of delirium in a dose-dependent fashion.

Why does this matter?
Pain is one of the most common presentations to the emergency department, for both critically ill and non-critically ill patients. We commonly associate the treatment of pain with our patient satisfaction scores. But could we be causing harm with some of the medications that we use to alleviate pain? Multiple cohort trials have investigated an association between ICU opioid use and the occurrence of delirium, but the evidence was determined to be insufficient for causality. This trial answers the question and provides us with evidence that exposure to any opioid during the ICU stay increases risk of delirium by 45% independent of other variables.

It’s making me crazy…
This was a prospective observational study of 4,075 adults that were admitted to the ICU for greater than 24 hours. Daily mental status was assessed in each patient by using commonly used tools, such as the Confusion Assessment Method for the ICU (CAM-ICU). This was then classified into three categories: awake without delirium, delirium, or unarousable. Medication data were retrieved, such as dose, route, and time of administration, and all administrations of opioids were converted into intravenous morphine-equivalent (MEQ) doses. Further tools, such as the Critical Care Pain Observation (CPOT) and Visual Analog Scale (VAS), were utilized to assess pain scores during this time as well. A first-order Markov model was utilized with multinomial logistic regression analysis to analyze 11 delirium-related covariables and possible next-day outcomes in order to create an analysis of the association between opioid use, opioid dose, and delirium occurrence the next day.

Within the 26,250 days that these patients spent in the ICU, an opioid was administered 57% (n = 14,975) of these days, with delirium occurring on 23.5% (n = 6,176). Any opioid administration in awake patients without delirium was associated with increased risk for delirium [OR, 1.45; 95% CI, 1.24-1.69]. When MEQ doses were analyzed, each daily 10-mg intravenous equivalent dose was associated with a 2.4% increased risk of delirium during the following day.

We know that predisposing and precipitating factors (i.e. age or severity of illness) can lead to an increased risk of delirium in the ICU, but we also know that medications are risk factors. What I take from this is that opioids can be amazing analgesics in the acute pain setting, but in our sickest patients, it is prudent to be aware of the downstream risks as well.

Opioid Use Increases the Risk of Delirium in Critically Ill Adults Independently of Pain. Am J Respir Crit Care Med. 2021 Sep 1;204(5):566-572. doi: 10.1164/rccm.202010-3794OC.

What are your thoughts?