Relationship Between Pain and Delirium in Critically Ill Adults

Ting Ting Wu, Lisette M. Vernooij, Matthew S. Duprey, Irene J. Zaal, Céline Gélinas, John W. Devlin, Arjen J.C. Slooter

Research output: Contribution to journalArticlepeer-review


OBJECTIVES: Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. DESIGN: Prospective cohort study. SETTING: A 32-bed academic medical-surgical ICU. PATIENTS: Critically ill adults (n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0–10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1–3/CPOT = 1–2), moderate (NRS = 4–6/CPOT = 3–4), or severe (NRS = 7–10/CPOT = 5–8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. RESULTS: Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days (p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76–1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. CONCLUSIONS: After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

Original languageEnglish
Pages (from-to)E1012
JournalCritical Care Explorations
Issue number12
StatePublished - Dec 1 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.


  • Multiple Imputation by Chained Equations
  • critical care
  • delirium
  • intensive care
  • opioid
  • pain

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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