Investigating for an association between delirium and autonomic impairment

Delirium is a common syndrome amongst acutely unwell older adults. It is associated with significant morbidity and mortality, yet it remains poorly researched in the literature. Several theories have been proposed to explain the development of delirium but despite this the pathophysiology remains poorly understood. My thesis aims to addresses one such theory that has been little researched in the past; could delirium be associated with autonomic impairment? My thesis outlines the rationale for looking for such an association, including changes in cerebral perfusion and the role of acetylcholine. My study had a prospective case-control design. Participants were recruited while they were an inpatient with an acute illness in University Hospital Limerick. Diagnostic and Statistical Manual of Mental Disorders 4 th Edition (DSM-IV) and Delirium Rated Scale Revised 1998 (DRS-R98) were used to evaluate for delirium. When the participant was free of acute illness a number of tests of autonomic function were carried out and consisted of a Head-Up Tilt test (HUT), baroreflex sensitivity testing measured using Baroreflex Effectiveness Index (BEI), 24-hour blood pressure variability (BPV), nocturnal blood pressure dipping status and 24-hour heart rate variability (HRV) measurements. A subgroup analysis of those without pre-existing cognitive impairment was carried out. During HUT the delirium group had a median decrease of 1mmHg (IQR 38.5) in systolic blood pressure compared to a median decrease of 17.5mmHg (IQR 20.75) in the control group (p=0.04). Increased delirium severity correlated with a reduction in the drop in systolic blood pressure during HUT (rs= -0.42, p=0.03). In those without pre-existing cognitive impairment, baroreflex sensitivity testing during HUT showed that increases in blood pressure were not followed by an appropriate corrective reduction in heart rate with a mean BEI of 36.87% (SD 22.26) in those with delirium and 56.03% (SD 23.04) in those without delirium (p=0.05). Nocturnal dipping status differed between the two groups during the subgroup analysis. 58.3% (7) of delirious participants were reverse dippers, 33.3% (4) were non dippers and 8.3% (1) had a normal dipping pattern. No participant was an extreme dipper. In the control group no participant was a reverse dipper, 57.1% (4) were non dippers, 14.3% (1) had a normal dipping pattern and 28.6% (2) were extreme dippers (p=0.01). BPV was measured by average real variability (ARV). In those without pre-existing cognitive impairment mean ARV was 13.81 (SD 5.98) in the control group and 9.69 (SD 2.75) in the delirium group (p=0.05). HRV was measured using a 24-hour holter monitor. No difference was detected between the two groups. This study identifies differences in autonomic function between delirious participants and non-delirious controls, particularly when the impact of pre-existing cognitive impairment is excluded. This is the first study to look at several components of autonomic function in delirium and thus can provide insights into physiological abnormalities present during, or contributing to delirium and can help to inform future research.