Pathoetiological Model of Delirium: a Comprehensive Understanding of the Neurobiology of Delirium and an Evidence-Based Approach to Prevention and Treatment
Section snippets
Aging: acetylcholine, vascular supply, and delirium
Human studies have revealed that the cholinergic system is widely involved in arousal, attention, memory, and rapid-eye-movement (REM) sleep. A deficiency of cholinergic function relative to that of other neurotransmitters can be expected to alter the efficiency of these mental mechanisms [17]. In fact, one leading hypothesis is that delirium results from an impairment of central cholinergic transmission [18], [19], [20]. Low levels of acetylcholine (ACh) in plasma and cerebrospinal fluid (CSF)
Common pathways
At the end, it may very well be that all the known etiologic “factors” for the development of delirium may all act by similar mechanisms, namely causing changes to neuronal membrane function, which in turn leads to a number of neurotransmitter aberrations. Affected neurons begin to experience abnormalities of membrane function and polarization. This may lead to a domino-like effect known as “spreading depression” by which, as one neuron looses membrane integrity and stability, neighboring
Theoretic implications for prevention and treatment options
This is meant to be a theoretic treatise on the prevention and management of delirium. For a more clinical approach, please see Maldonado JR, Delirium in the Acute Care Setting: Characteristics, Diagnosis and Treatment, 2008 [384].
Future directions
Given the complexities already described and the multiple pathways and mechanisms that likely “go wrong together” or “cause a domino-like” effect, it would make sense to consider a treatment strategy that addresses all these factors simultaneously. Unfortunately, there are very limited data to support any of these approaches, let alone in combination. But only well-designed treatment trials will be able to determine whether the theory bears out in clinical success. The basic approach of
Summary
Delirium is an acute or subacute organic mental syndrome characterized by disturbance of consciousness, cognition, orientation, attention, psychomotor activity, sleep-wake cycle, and behavior. Delirium is likely to be the most common and the most serious complication in the medically ill, particularly the elderly and the critically ill. Not only does it cause distress to patients, families, and medical caregivers, but its presence is associated with increased morbidity and mortality, prolonged
Acknowledgment
The author thanks Emma Bakes, MS for her assistance in locating, reviewing and helping select many of the papers referenced throughout the manuscript. The author also acknowledges the thoughtful suggestions of Gregory Kapinos, MD particularly in the area of hypoxia & hypoperfusion, as well as his critique of the original manuscript.
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Parts of the article were presented at the annual meetings of the Academy of Psychosomatic Medicine, Fort Myers, FL, November 9, 2004; the Canadian Academy of Psychosomatic Medicine (CAPM), Toronto, Canada. November 10, 2006; and. U.S. Psychiatric Congress & Mental Health Congress, Orlando, Florida, October 12, 2007.