Who understands delirium?

This New York Times article on Pulitzer Prize-winning historian Justin Kaplan’s experience of delirium [1] provided welcome publicity of this enormously impactful but historically neglected syndrome. Nevertheless, the remarkable scarcity of such exposure in the mass media speaks to what is perhaps the most significant obstacle to progress in delirium research and practice: its invisibility. Why has delirium remained so obscure? There would appear to be several reasons. Patients rarely speak of their experiences of delirium, perhaps because of embarrassment or bewilderment; currently, there are no specific charities or patient advocacy groups. Healthcare staff use a wide variety of informal words and phrases to describe delirium. This diagnostic ambivalence and imprecision greatly hinders the implementation of formal methods of improving care. Another likely factor is that delirium is very challenging: it is heterogeneous in its precipitants, symptomatology, severity and course. The mixture of mental status abnormalities and complex medicine means that healthcare professionals require multiple skills to manage delirium. Indeed, these skills may be lacking: a recent survey of UK junior doctors suggested that there are serious deficiencies in knowledge of the diagnostic criteria [2]. However, there have been major advances over the last three or four decades that ought to be more widely disseminated [3]. We know that delirium is common and that it has several adverse consequences, including loss of independence, acceleration of dementia and death [3–5]. The clinical predisposing and precipitating factors are now well documented [3]. Recent work has shown that delirium persists for months in around 20% of cases [6]. The significance of delirium in critically ill patients and in palliative care settings is now far clearer [7–9]. Crucially, it is now established that multi-component prevention strategies are effective, and should be introduced into standard health-care practice [3]. What might be the current priorities for research? Direct brain insults such as oxygen deprivation, hyponatraemia and adverse drug effects are common causes of delirium, and in many such cases, the routes to disruption of cognitive processes are clear. In contrast, the mechanisms by which peripheral illness such as urinary tract infection can cause acute, severe mental deterioration over periods of as little as a few hours are poorly understood. Recent experiments in animal models and humans have found that in older individuals peripheral stimuli can induce adverse inflammatory and stress system responses in the central nervous system, with resultant maladaptive behavioural change including delirium [10–12]. Delirium could thus represent an exaggeration of the sickness behaviour syndrome (a set of normally adaptive behavioural responses to illness including sleepiness, fatigue, anhedonia and impaired concentration), but may also simply be due to the effects of pathologically sustained high cortisol levels [10]. These leads in dissecting the ‘indirect’ causes of delirium may suggest potential new treatments. The role of stress mediators is also relevant to the patient experience of delirium: studies in animal models suggest that chronic unpredictable psychological stress over periods of days can cause marked brain damage [13]. Patients with delirium are often in a comparable position, suffering pain, fear, an unpredictable environment and strangers undertaking invasive activities. All of this is exacerbated by the inability of the patient’s mind to fully comprehend what is happening to them. The implications here are that effective psychological care of patients with delirium may be particularly important, not simply to relieve distress, but to protect the brain. Detection is a pre-requisite for good care, but the problem of achieving acceptable levels of recognition of delirium has not yet been solved. This partly reflects the lack of validated brief screening tools that do not require special training and that discriminate delirium from dementia [14, 15]. Another need is for methods of recording the status of conscious but untestable patients, that is, those too drowsy to undergo cognitive testing or even a brief interview. Such patients are overwhelmingly likely to have a diagnosis of hypoactive delirium, but are often left without any label and resultant management plan. More broadly, further research on the neuropsychology of delirium is essential to the development of better testing instruments for screening and diagnosis in clinical practice and in research. There are many challenges here, not least because of the range of mental status change, from stupor to relatively mild deficits in attention. Subsyndromal delirium, where there are one or more features of delirium but in which full DSM-IV criteria are not met, has recently been shown to have prognostic significance [16]. Despite this, its neuropsychology is all but unexplored. The clinical role of other methods of assessment, such as neuroimaging, plasma biomarkers and lumbar puncture, also remain greatly under-researched. A recent systematic review of the literature on neuroimaging findings in delirium found that though there may be some relationships between white