Delirium developed in approximately half of the patients in our cohort, and was associated with a one day longer stay in the ICU and a two day longer stay in the hospital. This is the first investigation to document the high prevalence of delirium among a strictly non-ventilated adult ICU cohort, and to reveal its associated negative clinical outcomes. Considering the rising overall resource use and economic burden of caring for critically ill patients [25
], our finding that ICU delirium is an independent predictor of longer stay in the hospital is of particular relevance. These data lend support to the SCCM clinical practice guideline recommendation [15
] for routine monitoring of delirium for all adult ICU patients using validated tools such as the CAM-ICU, which has been validated in ventilated and non-ventilated critically ill patients [2
We did not find a significant independent relationship between delirium and mortality after adjusting for multiple covariates. This may simply be a type II error due to the limited number of events, and our study was not prospectively powered to determine a definitive relationship between delirium and mortality. Furthermore, because we only followed patients until hospital death or discharge, our mortality analysis was not as comprehensive as previous reports that followed patients for 6 to 12 months [10
]. While these ICU patients had a lower severity of illness than those in prior ICU studies isolated to ventilated patients, the myriad of data in other non-ICU populations showing delirium to be associated with prolonged stay, greater dependency of care, subsequent institutionalization, and increased mortality [3
] would cause one to pause before assuming that our study disproves such a consistently strong association.
The dangerous and costly considerations of prolonged ICU and hospital stays shown in this cohort warrant strong consideration by multidisciplinary ICU teams. Standardized clinical monitoring of brain function (both arousal level and delirium) is in keeping with the 'systems approach' to patient assessment. Because the development of delirium is associated with untoward outcomes, one author has questioned whether or not missing the diagnosis is a medical error [36
]. Considering that symptoms of ICU delirium are largely hypo- rather than hyper-active [37
], anything short of objectively looking for delirium will result in undetected brain dysfunction. Thus, the alternative to daily monitoring for delirium is to persist with the status quo in which an estimated 60% to 80% of delirium is missed in the absence of standardized monitoring [37
The strengths of this report include the unique patient population (non-ventilated ICU patients), the large number of patients enrolled (n = 261), and the consecutive enrollment process that spanned nearly a year. All data were derived from sedation scoring and delirium assessments by the bedside nurses as part of a multidisciplinary approach to care within the ICU using well-validated tools (RASS and CAM-ICU) on a frequent basis (i.e., at least once every 12 hours). Previous studies regarding the incidence of delirium have used either q-24 hour or q-weekly assessments. Study personnel performed spot checks prospectively, accuracy was confirmed [16
], and data were analyzed using robust statistical methods. In fact, rather than simple logistic regression, we chose the more sophisticated approach using time-to-event analysis with Cox regression and treated both delirium and death as time-dependent covariates.
Several limitations of this study warrant comment. First of all, we did not have a tool to stratify by the severity of delirium. If such a tool had been available and employed, we may have been better able to recognize patients who were at the highest risk for negative outcomes. Currently, no validated measure to stratify the severity of delirium exists, though work in this area is ongoing. Second, a recurrent limitation in all cohort studies is that there may be unknown covariates that influence outcomes. Third, this observational investigation was not designed to prove a cause-and-effect relationship between delirium and clinical outcomes. It is certainly true that the delirium group was older and had a higher severity of illness, though our multivariable analysis was specifically designed to take these covariates into account. Ultimately, further research incorporating a randomized, prospective clinical trial focused either upon the prevention or treatment of delirium will be necessary to confirm such a relationship. Data from other investigations, however, suggest that such a cause-and-effect between delirium and negative clinical outcomes exists. For example, in response to systemic infections and injury, brain dysfunction may ensue, which will then lead to the generation of a central nervous system inflammatory response of its own. This process involves the production of specific cytokines, cell infiltration, and tissue damage [42
]. Additionally, activation of the central nervous system's immune response is accompanied by the peripheral production of tumor necrosis factor α, interleukin 1, and interferon δ [42
] that can contribute to multiple organ dysfunction syndrome. It is plausible, therefore, that the delirium experienced among our patients is not only a marker of end-organ damage, but also acts directly as a promoter of other organ system dysfunction.