Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution. A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neurotransmitter abnormalities and occult diffuse brain injury. Markers that could be used to evaluate the influence of specific mechanisms in individual patients include serum anticholinergic activity, certain brain proteins, and tissue sodium concentration determination via high-resolution three-dimensional magnetic resonance imaging. Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care. Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illnessassociated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention.
IntroductionSince its advent more than 40 years ago, the specialty of critical care has made remarkable advances in the care of severely ill patients. Mortality rates for many commonly encountered critical illnesses such as severe sepsis [1] and acute respiratory distress syndrome (ARDS) [2] have declined sharply over the past 2 decades. As greater numbers of patients survive intensive care, it is becoming increasingly evident that quality of life after critical illness is not always optimal. For instance, nearly half of ARDS survivors manifest neurocognitive sequelae 2 years after their illness, falling to below the 6th percentile of the normal distribution of cognitive function [3]. Considering that 89% of Americans would not wish to be kept alive if they had severe, irreversible neurologic damage [4], these findings are quite concerning.Cognitive dysfunction (CD) is quite common in critically ill patients, not only during the acute illness but also long after the acute illness resolves [5]. Delirium, a form of acute CD that manifests as a fluctuating change in mental status, with inattention and altered level of consciousness, occurs in as many as 80% of mechanically ventilated intensive care unit (ICU) patients [6]. Most clinicians consider ICU delirium to be expected, iatrogenic, and without consequence. However, recent data associate delirium with increased duration of mechanical ventilation and ICU stay [7], worse 6-month mortality [8], and higher costs [9]. Chronically, critical illnessassociated CD manifests as difficulties with memory, attention, executive function, mental processing speed, spatial abilities, and general intelligence. Interestingly, patients who develop acute CD often go on to develop chronic CD after hospital discharge [10][11][12][13], suggesting that the two entities may share a common etiology.Although there are clearly defined risk factors for critical illness-associated CD, there is little understanding of the underlying pathophysiology. The precise mechanisms are unknown and there are likely to be mul...