Elsevier

Critical Care Clinics

Volume 24, Issue 1, January 2008, Pages 45-65
Critical Care Clinics

Pathophysiology of Delirium in the Intensive Care Unit

https://doi.org/10.1016/j.ccc.2007.10.002Get rights and content

Delirium, or acute brain dysfunction, is a life-threatening global disturbance in cognitive functioning that frequently manifests in critically ill patients. This review examines the current status of knowledge regarding the pathophysiology of delirium in the ICU, in particular, evaluating the role of iatrogenic factors such as sedatives and analgesic administration in brain dysfunction. This hypothesis is considered along with several other plausible mechanisms of ICU delirium, including sepsis, postoperative cognitive dysfunction, and changes in biomarkers and neurotransmitters. The review concludes by highlighting potential future directions in molecular genetics for the elucidation of delirium and its long-term consequences.

Section snippets

Neuroimaging and neuroanatomic correlates of delirium

To understand delirium and its long-term consequences, it is necessary to explain acute brain dysfunction at the neurologic level. Delirium research has only recently begun to employ neuroimaging. The studies described herein are beginning to provide evidence that delirium may be caused by widespread brain dysfunction rather than localized disruption [17], [18]. Further evidence suggests that this may lead to cell death in the central nervous system (CNS). The few functional neuroimaging

Sedatives and analgesics

Sedatives and analgesics currently represent the leading modifiable iatrogenic risk factors for transitioning to delirium in the ICU [42], [43], [44], [45], [46], [47], [48]. Marcantonio and colleagues [44] found an association between benzodiazepines and meperidine and delirium. Pandharipande and colleagues [49], [50], [51] recently reported that the administration of benzodiazepines was an independent risk factor for the development of delirium in surgical and trauma ICU patients. Dubois and

Sepsis

Sepsis, a known or suspected infection leading to the systemic inflammatory response syndrome, frequently presents with delirium and represents perhaps the most common causal factor for ICU delirium [68], [69], [70]. Several plausible explanations suggest that sepsis may be a gateway to acute CNS dysfunction and brain damage via degradation of the blood-brain barrier and neuroinflammation [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82]. The prevalence of

Biomarkers and neurotransmitters

To adequately define a syndrome, biomarkers provide invaluable information to aid clinicians and researchers; however, in delirium, biomarkers to date have proven less than definitive. Several lines of research suggest that prolonged delirium causes brain damage [13], [16], [25], [38], [86]. If this is indeed true, to the extent that brain damage is occurring in these patients, biomarkers that are sensitive to neuronal or glial cell death should also be highly correlated with delirium. Serum

Surgical factors and postoperative cognitive dysfunction

Several reports suggest that delirium may be a side effect of anesthesia or surgery [15], [133], [134], [135], [136], [137], [138], [139], [140], [141], [142], [143], [144], [145], [146], [147], [148]. To date, studies examining associations between surgery and delirium have investigated microemboli migration [149], [150], [151], hypoperfusion [64], [137], [152], [153], [154], inflammatory responses [155], [156], [157], changes in hormone levels [158], [159], [160], [161], and local and general

Future directions: molecular genetics

Recent advances in molecular genetics have begun to bridge gaps between bench science and bedside care. The concept of “personalized medicine” suggests that it may eventually be possible to tailor health care to an individual's needs based on the patient's specific genotype and phenotype. Genetic approaches may offer several opportunities to realize this goal and may also shed light on underlying metabolic and molecular mechanisms of acute brain dysfunction. One of the first genes that drew

Summary

The current review summarizes recent research into the pathophysiology of ICU-related delirium. Although this research has generated several important hypotheses, most require further evaluation. Advances in our understanding of how sedatives and analgesics impact brain functioning appear to be particularly promising for the prevention of ICU delirium and its long-term neurologic sequelae (see Table 1). These approaches hold great potential for increasing our understanding of delirium and

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