Altered mental status risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]


Risk Factors

The etiology of delirium (and other forms of acute brain dysfunction) involves a complex interplay between patient vulnerability (or predisposing) factors and precipitating factors. Patients who are highly vulnerable (e.g. 92 year old with severe dementia, poor functional status, and multiple comorbidities) will require a relatively benign insult to develop delirium. For these patients, a relatively benign insult such as a simple urinary tract infection or small dose of narcotic medication can precipitate delirium. Because elderly patients are more likely to have multiple vulnerability factors, they are more susceptible to becoming delirious compared with their younger counterparts. Nursing home patients are particularly vulnerable. For patients who are less vulnerable (e.g. 67 year old with no dementia, little comorbidity burden, and who is still functionally independent), higher doses of noxious stimuli such as severe sepsis are required to develop delirium. Consequently, when a patient with little or no vulnerability factors presents to the ED with delirium, stupor, or coma, the clinician should have more concern for an underlying life threatening illness. To develop stupor of coma, even higher doses of noxious stimuli are required.

Patient Vulnerability Factors for Acute Brain Dysfunction

A multitude of patient vulnerability factors for delirium have been identified in the hospital literature and can likely be extrapolated to stupor and coma. Dementia is the most consistently observed vulnerability factor for delirium regardless of clinical setting. A dose-response relationship seems to exist; as the severity of dementia worsens, the risk of developing delirium increases. Similarly, low education attainment also increases the patient’s susceptibility to developing delirium. Both dementia and education attainment may be indicative of poor cognitive reserve and reflect the inability of the brain to adequately compensate for any noxious or stressful physiological insult. Other commonly observed vulnerability factors for delirium include poor functional status, advanced age, home psychoactive medication use such as narcotics, benzodiazepines, and medications with anticholinergic properties, history of alcohol abuse, visual impairment, high comorbidity burden, and malnutrition. There are limited data from the ED setting, but one study identified dementia, premorbid functional impairment, and hearing impairment as risk factors for delirium in the ED.14 Another ED study also identified dementia as a risk factor for delirium. They also observed that patients with advanced age, or a past history of cerebrovascular disease and seizure disorder were more likely to be delirious in the ED.

Medication Risk Factors for Delirium

Medications are important vulnerability and precipitating risk factors factor for delirium, because polypharmacy is highly prevalent in the older patient population. Clegg et al. performed a systematic review and observed that benzodiazepines, opioids, dihydropyridines (e.g. nifedpine), and antihistamines may increase the risk for delirium. Of the opioids, meperidine is probably the most deliriogenic. These medications, especially benzodiazepines and opioids, can also induce stupor and coma at higher doses.

Medications with anticholinergic properties are thought to be frequent causes of delirium. There are over 600 medications with anticholinergic properties, and of these, 11% are frequently prescribed to the older patients.80 Some examples of commonly prescribed medications with anticholinergic properties are diphenhydramine, promethazine, hydroxyzine, meclizine, lomotil, and heterocyclic antidepressants (e.g. amitriptyline, nortriptyline, doxepin). In acute stroke patients, Caerio et al. found that that patients on home medications with anticholinergic properties were more susceptible to developing delirium during hospitalization. In 278 older medical patients, Han et al. observed that anticholinergic medications were associated with increased delirium severity. However, the evidence linking medications with anticholinergic properties and delirium is not consistently observed. Agostini et al. observed a trend towards increase risk (relative risk = 2.1, 95%CI: 0.9 – 4.7) of developing delirium in older hospitalized patients when diphenhydramine was used.83 Luukkanen et al. found that older patients who used more than one medication with anticholinergic properties were more likely to have delirium in the unadjusted analysis (27.0% versus 16.7%, p-value = 0.05). However, this relationship became non-significant after adjusting for age, gender, and comorbidity. In 147 hospitalized older patients, Campbell et al. observed that anticholinergic medications were not associated with delirium that developed in the hospital. These discrepant observations may be a result of patient characteristics (stroke versus non-stroke, race, etc.,) or the method in which anticholinergic burden was measured. Despite these discrepant findings, the general consensus among geriatric and psychiatric experts is that medications with anticholinergic properties in older patients should be avoided, especially if safer alternatives exist.