The aetiology of delirium is usually multifactorial.[41]Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65.
http://www.ncbi.nlm.nih.gov/pubmed/16540616?tool=bestpractice.com
[43]Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research - a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640527/pdf/452459.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22684893?tool=bestpractice.com
In general, delirium occurs due to a complex interplay of reduced functional reserve (secondary to predisposing factors) and precipitating insults such as infection, metabolic derangements, environmental factors, sleep deprivation, surgery, and/or primary illness.[41]Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65.
http://www.ncbi.nlm.nih.gov/pubmed/16540616?tool=bestpractice.com
[43]Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research - a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640527/pdf/452459.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22684893?tool=bestpractice.com
This interplay explains why some patients, particularly those with cognitive and functional impairments, become delirious with relatively minor insults such as a UTI while more robust individuals are unaffected.
Predisposing factors
Key predisposing factors for delirium include:[42]Ormseth CH, LaHue SC, Oldham MA, et al. Predisposing and precipitating factors associated with delirium: a systematic review. JAMA Netw Open. 2023 Jan 3;6(1):e2249950.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9856673
http://www.ncbi.nlm.nih.gov/pubmed/36607634?tool=bestpractice.com
[43]Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research - a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640527/pdf/452459.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22684893?tool=bestpractice.com
[44]Tow A, Holtzer R, Wang C, et al. Cognitive reserve and postoperative delirium in older adults. J Am Geriatr Soc. 2016 Jun;64(6):1341-6.
http://www.ncbi.nlm.nih.gov/pubmed/27321616?tool=bestpractice.com
Older age
Dementia or cognitive impairment
Visual or hearing impairment
Functional impairment or immobility
History of delirium
Decreased oral intake (e.g., dehydration)
Polypharmacy
Co-existing medical illness
Physical frailty
Surgery.
Precipitating insults
Important precipitating insults that can result in delirium include the following:[42]Ormseth CH, LaHue SC, Oldham MA, et al. Predisposing and precipitating factors associated with delirium: a systematic review. JAMA Netw Open. 2023 Jan 3;6(1):e2249950.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9856673
http://www.ncbi.nlm.nih.gov/pubmed/36607634?tool=bestpractice.com
[43]Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research - a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640527/pdf/452459.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22684893?tool=bestpractice.com
[45]Leong AY, Edginton S, Lee LA, et al. The association between pain, analgesia, and delirium among critically ill adults: a systematic review and meta-analysis. Intensive Care Med. 2025 Feb;51(2):342-52.
http://www.ncbi.nlm.nih.gov/pubmed/39841212?tool=bestpractice.com
[46]White N, Bazo-Alvarez JC, Koopmans M, et al. Understanding the association between pain and delirium in older hospital inpatients: systematic review and meta-analysis. Age Ageing. 2024 Apr 1;53(4):afae073.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11014791
http://www.ncbi.nlm.nih.gov/pubmed/38610062?tool=bestpractice.com
[47]Rothberg MB, Herzig SJ, Pekow PS, et al. Association between sedating medications and delirium in older inpatients. J Am Geriatr Soc. 2013 Jun;61(6):923-30.
http://www.ncbi.nlm.nih.gov/pubmed/23631415?tool=bestpractice.com
[48]McPherson JA, Wagner CE, Boehm LM, et al. Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit Care Med. 2013 Feb;41(2):405-13.
http://www.ncbi.nlm.nih.gov/pubmed/23263581?tool=bestpractice.com
[49]Fox C, Smith T, Maidment I, et al. Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review. Age Ageing. 2014 Sep;43(5):604-15.
http://ageing.oxfordjournals.org/content/43/5/604.long
http://www.ncbi.nlm.nih.gov/pubmed/25038833?tool=bestpractice.com
[50]Guenther U, Theuerkauf N, Frommann I, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013 Jun;257(6):1160-7.
http://www.ncbi.nlm.nih.gov/pubmed/23426334?tool=bestpractice.com
[51]Slatore CG, Goy ER, OʼHearn DJ, et al. Sleep quality and its association with delirium among veterans enrolled in hospice. Am J Geriatr Psychiatry. 2012 Apr;20(4):317-26.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440244
http://www.ncbi.nlm.nih.gov/pubmed/22367162?tool=bestpractice.com
Drugs: sedatives, anticholinergics, multiple drug use, alcohol, tricyclic antidepressants, stimulants, opiods, corticosteroids, analgesics, cardiac glycosides, anti-Parkinson's drugs. The general use of these drugs can contribute to delirium, particularly in the elderly and critically unwell; in the setting of overdose, they may cause delirium at any age.
Primary neurological injury: stroke, intracranial bleeding, meningitis
Acute illness: infection (e.g., pneumonia, urinary tract infection, sepsis), cardiac illness (e.g., myocardial infarction), hypoxia, shock, dehydration, fever, constipation, iatrogenic complications
Metabolic abnormalities
Surgery (e.g., orthopaedic, cardiac): duration of cardiopulmonary bypass
Environmental factors: use of physical restraint, use of catheters/invasive monitoring, intensive care unit stay
Pain
Prolonged sleep deprivation
Drug withdrawal: benzodiazepines, alcohol.