In assessing the overall risk for developing CD posed by medications with central anticholinergic activity in a given patient, individual differences in drug pharmacokinetics make the dose received a poor estimate of a patient's overall anticholinergic burden [21, 22] . However, we can objectively measure anticholinergic burden in individual patients using an assay referred to as serum anticholinergic activity (SAA) [16] . First described by Tune and Coyle [23] , SAA measures the ability of a individual's serum to block central muscarinic receptors using a rat forebrain preparation. Elevated SAA levels are associated with cognitive impairment in studies of medical ward inpatients and community dwelling seniors [16, [24] [25] [26] [27] . Only a single, small study has used this assay to investigate CD in ICU patients. Golinger and colleagues [28] examined SAA levels in surgical ICU patients and found the mean SAA level drawn 4 hours after mental status change was significantly greater in delirious patients (n = 9) than in those without delirium (n = 16; 4.67 ng/ml versus 0.81 ng/ml; P = 0.007). Whether these results apply to all critically ill patients is uncertain because no study has examined SAA across a broad range of ICU admitting diagnoses or in medical ICU settings. Furthermore, because SAA measurement requires fresh rat brain preparations, its use is likely to remain limited to research settings for the foreseeable future. Pathophysiologic mechanisms and predisposing factors thought to underlie critical illness-associated cognitive dysfunction [5, 14, 15] . Apo, apolipoprotein; HIV, human immunodeficiiency virus; 5-HT, serotonin (5-hydroxytryptamine); GABA, γ-aminobutyric acid; NE, norepinephrine (noradrenaline).