Associations of markers of inflammation and coagulation with delirium during critical illness
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To assess the associations between a priori-selected markers of inflammation and coagulation and delirium during critical illness.
In this prospective cohort study, we collected blood from mechanically ventilated medical intensive care unit (ICU) patients and measured nine plasma markers of inflammation and coagulation. We assessed patients daily for delirium using the Confusion Assessment Method for the ICU and used multivariable regression to analyze the associations between plasma markers and subsequent delirium, after adjusting for age, severity of illness, and sepsis.
Among the 138 patients studied, with median age of 66 years and median Acute Physiology and Chronic Health Evaluation (APACHE) II of 27, 107 (78 %) were delirious at some point during the study. Two markers of inflammation and one of coagulation were significantly associated with delirium. After adjusting for covariates, lower plasma concentrations of matrix metalloproteinase-9 (MMP-9) and protein C were associated with increased probability of delirium (p = 0.04 and 0.01, respectively), and higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were associated with increased probability of delirium (p < 0.01). Concentrations of C-reactive protein (p = 0.82), myeloperoxidase (p = 0.11), neutrophil gelatinase-associated lipocalin (p = 0.70), D-dimer (p = 0.83), plasminogen activator inhibitor type 1 (p = 0.98), and Von Willebrand factor antigen (p = 0.65) were not associated with delirium.
In this study, MMP-9, protein C, and sTNFR1 were independently associated with subsequent ICU delirium. These results suggest that specific aspects of inflammation and coagulation may play a role in the evolution of delirium during critical illness and that these markers should be examined in larger studies of ICU patients.
KeywordsDelirium Inflammation Blood coagulation Critical illness Mechanical ventilation
Dr. Girard is supported by the National Institutes of Health (NIH) (AG034257) and the Veterans Affairs (VA) Tennessee Valley Geriatric Research, Education, and Clinical Center (GRECC), Dr. Ware is supported by the NIH (HL103836) and an American Heart Association Established Investigator Award, Dr. Pandharipande is supported by the VA Clinical Science Research and Development Service (VA Career Development Award), Dr. Jackson is supported by the NIH (AG031322), and Dr. Ely is supported by the NIH (AG027472 and AG035117) and the VA Tennessee Valley GRECC. Additional funding for this research project was provided by the Saint Thomas Foundation (Nashville, TN, USA), National Institutes of Health (AG001023 and HL007123), Hartford Geriatrics Health Outcomes Research Scholars Award Program, Vanderbilt Physician Scientist Development Program, and Alere Inc. These sponsors had no role in study design; data collection, analysis, and interpretation; or publication of results.
Conflicts of interest
Drs. Girard, Pandharipande, Shintani, and Ely have received honoraria from Hospira Inc. Dr. Pandharipande has received honoraria from Orion Corporation. Drs. Pandharipande and Ely have received grant support from Hospira Inc. Dr. Ely has also received grant support from Eli Lilly and Company and Masimo Corporation and is an advisor to Healthways Inc. All other authors have no disclosures.
- 24.Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW (2008) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 371:126–134PubMedCrossRefGoogle Scholar
- 28.Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R (2001) Delirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the intensive care unit (CAM-ICU). JAMA 286:2703–2710PubMedCrossRefGoogle Scholar
- 31.Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR (2003) Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation–Sedation Scale (RASS). JAMA 289:2983–2991PubMedCrossRefGoogle Scholar
- 32.Harrell FE Jr (2001) Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New YorkGoogle Scholar
- 33.Ihaka R, Gentlemen R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5:299–314Google Scholar
- 37.Tsuruta R, Girard TD, Ely EW, Fujimoto K, Ono T, Tanaka R, Oda Y, Kasaoka S, Maekawa T (2008) Associations between markers of inflammation and cholinergic blockade and delirium in intensive care unit patients: a pilot study. Bull Yamaguchi Med School 55:35–42Google Scholar
- 41.van den Boogaard M, Kox M, Quinn KL, van Achterberg T, van der Hoeven JG, Schoonhoven L, Pickkers P (2011) Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care 15:R297PubMedCrossRefGoogle Scholar
- 55.Morandi A, Pandharipande PP, Shintani AK, Hughes CG, Vasilevskis EE, Thompson JL, Han JH, Jackson JC, Bernard GR, Laskowitz DT, Ely EW, Girard TD (2012) Statin use and the daily risk of delirium in a prospective cohort of critically ill patients. Am J Respir Crit Care Med 185:A3646Google Scholar