Delirium in acute stroke: a preliminary study of the role of anticholinergic medications L. Caeiro a , J. M. Ferro a , M. I. Claro a , J. Coelho a , R. Albuquerque b and M. L. Figueira b a Servic ¸ o de Neurologia; b Servic ¸ o de Psiquiatria, Stroke Unit, Hospital de Santa Maria, Faculdade de Medicina de Lisboa, Portugal Keywords: acute intracerebral haemorrhage, anticholinergics, complications, delirium Received 7 January 2004 Accepted 28 March 2004 The pathogenesis of delirium in acute stroke is incompletely understood. The use of medications with anticholinergic (ACH) activity is associated with an increased fre- quency of delirium. We hypothesized that the intake of medications with ACH activity is associated with delirium in acute stroke patients. Delirium was assessed using the DSM- IV-TR criteria and the Delirium Rating Scale, in a sample of consecutive patients with an acute (£4 days) cerebral infarct or intracerebral haemorrhage (ICH). We performed a gender and age matched case–control study. Twenty-two delirious stroke patients (cases) and 52 non-delirious patients (controls) were compared concerning the intake of ACH medications (i) before stroke, (ii) during hospitalization but before the assessment. The variables associated with delirium on bivariate analysis were entered in a stepwise logistic regression analysis. The final regression model (Nagelkerke R 2 ¼ 0.65) retained non- neuroleptics ACH medication during hospitalization (OR ¼ 24.4; 95% CI ¼ 2.18– 250), medical complications (OR ¼ 20.8; 95% CI ¼ 3.46–125), ACH medication taken before stroke (OR ¼ 17.5; 95% CI ¼ 1.00–333.3) and ICH (OR ¼ 16.9; 95% CI ¼ 2.73–100) as independent predictors of delirium. This preliminary result indicates that drugs with subtle ACH activity play a role in the pathogeneses of delirium in acute stroke. Medication with ACH activity should be avoided in acute stroke patients. Introduction Delirium is a disturbance of consciousness with reduced ability to focus, sustain, or shift attention accompanied by a change in cognition or develop- ment of perceptual disturbance. This disturbance is not explained by pre-existing dementia. Delirium develops over hours to days and fluctuates in severity (American Psychiatric Association (APA), 2002). Predisposing and precipitating factors of delirium include age, co-morbid physical illness, previous dementia/cognitive impairment or psychiatric disease (Inouye, 1999). Iatrogenic factors such as polyphar- macy, high number of procedures during early hospi- talization and intensive care treatment can also precipitate delirium (Martin et al., 2000). Many prescribed drugs can cause delirium, in par- ticularly those with anticholinergic (ACH) activity (Francis, 1996; Karlsson, 1999). In series of surgical patients and of elderly medical patients, delirious patients were found to have higher levels of serum acetylcholinesterase activity and to have received more medications with ACH activity prior to the develop- ment of delirium than their non-delirious counterparts (Mach et al., 1995; Tune and Egeli, 1999; Han et al., 2001). Delirium is a frequent complication of stroke (24–48%) (Gustafson et al., 1991; Gustafson et al., 1993; He´non et al., 1999) and it increases the risk of an unfavourable outcome (Gustafson et al., 1991; Karlsson, 1999). The pathogenesis of delirium in acute stroke is incompletely understood. Delirium is most frequent in elderly patients and can be because of the underlying medical conditions, intoxication or drug withdrawal, metabolic causes, infections and previous cognitive decline. In this investigation we tested the hypothesis that the intake of medications with ACH activity is associated with an increased frequency of delirium in acute stroke patients. Patients and methods Patients From April 2000 to June 2001 we investigated pro- spectively the presence, severity and correlates of delirium in consecutive acute stroke patients admitted to a 12-bed Stroke Unit located at the Neurology department of a University Hospital. The inclusion criteria in this study were: (i) an admission diagnosis of cerebral infarct (CI) or intracerebral haemorrhage/in- traventricular haemorrhage (ICH), (ii) assessment of Correspondence: Lara Caeiro, Centro de Estudos de Egas Moniz, Hospital de Santa Maria, 1649-035 Lisboa, Portugal (tel.:/fax: +351 21 795 7474; e-mail: jmferro@fm.ul.pt). Ó 2004 EFNS 699 European Journal of Neurology 2004, 11: 699–704