delirium affects a substantial proportion of hospitalized patients and increases their likelihood of unfavorable outcomes . this burden is especially high in critically ill populations in whom delirium is arguably the most prevalent form of organ dysfunction . in the previous issue of critical care , salluh and colleagues   present the results of delirium epidemiology in critical care ( decca ) , an international cross - sectional study evaluating the prevalence and short - term outcome of delirium in a sample of 232 patients admitted to 104 intensive care units ( icus ) across latin america with two centers in spain and the us . when patients were screened with the confusion assessment method for the icu ( cam - icu ) , delirium was identified in 32% of subjects and was associated with an adjusted threefold increase in icu mortality and a greater than twofold increase in median icu length of stay . this study has the merit of evaluating delirium in a range of countries with diverse cultures and levels of economic development and across a large number of medical institutions with heterogeneous practice patterns . the decca results reinforce the generalizability of findings from single - center observations   and closely match pooled prevalence and mortality estimates from a recently completed meta - analysis ( rd stevens , unpublished data ) . inferences from decca are limited by the inability to account for pre - icu neurological and cognitive status , the exclusion of a high proportion of potentially eligible patients because of concurrent sedation , and the absence of information on the underlying etiologies of delirium , on the treatments administered , or on the causes of death . another limitation is that the saps3 ( simplified acute physiology score ) and sofa ( sequential organ failure assessment ) scores , used here to adjust mortality risk in a multivariable model , can underestimate neurological failure indicating potential bias that would inflate adjusted odds ratios of death in delirious patients . finally , as is the case with much delirium research , fundamental questions of nosology , mechanism , and causation are overlooked . a central question is whether delirium , as it is currently defined , is a satisfactory construct . the spectrum of brain dysfunction encountered in hospitalized , acutely ill patients includes significant neurobehavioral abnormalities that fall outside the scope of this definition , either because sedation or coma prevented access to the patient 's mental life , a problem that was encountered in decca , or because delirium criteria are not met . further work is warranted to rationalize the nosology of neurobehavioral syndromes associated with critical illness . many have argued that delirium is etiologically heterogeneous and pathobiologically complex , reflecting not a unified mechanism but an array of processes such as exposure to pharmacological agents with neuromodulatory effects , the actions of pro - inflammatory signaling molecules on the brain , or changes in neurotransmitter release and reuptake   - suggesting considerable obstacles to mechanistic research . however , recent advances in neuroimaging , neurophysiology , and biomarker analysis suggest powerful methods that will enhance our ability to probe brain - behavior relationships in delirium and potentially identify novel therapeutic targets . a third question concerns the relationship between delirium and outcomes . why are critically ill patients with delirium at increased risk of dying , even after adjustment in multivariable models ? this independent relationship with mortality , found in several recent studies [ 1 - 3,6,9,10 ] , challenges widely held concepts of delirium as a reversible ' derivative ' of disorders that are more serious . recent research indicates a link between delirium in the icu and cognitive dysfunction in the long term , and these data are consistent with observations of decreased cognitive performance among long - term survivors of critical illnesses such as acute respiratory distress syndrome   and severe sepsis . the data are also consonant with results of a large prospective cohort that found a link between hospitalization , particularly involving icu admission , and subsequent cognitive decline and even dementia . it is certain that many patients survive the icu without developing long - lasting neurological or behavioral sequelae . collectively , however , available studies suggest that a subset of critically ill patients are at increased risk for chronic cognitive impairments that can have a dramatic impact on functional independence and quality of life . known as an indicator of acute - and often temporary - brain dysfunction , delirium is also emerging , in selected cases , as a predictor of cognitive decline . but who are these ' selected cases ' ? clearly , a research priority will be to develop tools to help answer this question . in summary , abundant evidence indicates that delirium is a common and deadly complication of critical illness . research must now aim to broaden knowledge on the biological mechanisms of delirium , unraveling its complex relationship to cognitive decline and mortality , with the goal of identifying effective protective and therapeutic interventions .
prevalent in critically ill patients , delirium remains poorly understood and difficult to treat . in a cross - sectional study conducted in 12 countries , 
 delirium was identified in close to one third of patients and was independently associated with increased mortality . while such epidemiological accounts represent an important cornerstone for research , scientific efforts are needed to elucidate the causes of delirium and the mechanisms underlying its association with poor outcomes .