Chapter 1: The concept of delirium: Historical antecedents and present meanings.

This topic has been recently reviewed by Francis (2004) in a journal issue devoted to delirium.

Emerging themes

The need to embrace complexity

In a thoughtful commentary on a systematic review of delirium prevention and treatment interventions- one which comes to no firmer conclusions than its predecessor (Weber, Coverdale, & Kunik (2004), Rockwood and Bhat have called for an end to univariate thinking in relation to the complexities of delirium causation and management (2004). They argue that we need to think more about the phenomenology (e.g distinguishing visuospatial from other forms of attention), shift emphasis away from primary causes of delirium within the brain, acquire more scepticism about Occam’s razor, and what they call decerebrate evidence-based medicine. They conclude with a call for “scholarly enquiry in the face of complexity”. Rockwood provides an example of this in a review of the relationship between frailty and delirium (2004). The former concept attracts much suspicion from psychiatrists, and in this analysis which is heavily dependent on self-reported variables, the influence of dementia is not really considered.

The relevance of taxonomy: distinguishing delirium and dementia

Cole and colleagues in Montreal have examined the phenomenology of delirium in relation to dementia (Cole, McCusker, Dendukuri et al (2002). Subjects screen-positive (incident or prevalent) for any cognitive impairment were administered the Confusion Assessment Method (Inouye, van Dyck, Alessi et al (1990) and supplementary information gathered to make a DSM-IIIR diagnosis of delirium. Dementia was “diagnosed” by categorisation using the IQCODE (Jorm (1994). Over half their sample had both diagnoses. They found some differences in symptoms between delirious patients with and without dementia, but there was generally much overlap. They conclude that the criteria of DSM-IIIR delirium discriminate reasonably well between delirium and non-delirium, irrespective of “diagnosis” of pre-existing dementia. Lundstrom and colleagues followed up 78 patients who were not obviously demented but with a femoral neck fracture for 5 years (2003). They found that both pre- and post-operative delirium were highly correlated with the emergence of dementia. They reassert the increasingly accepted possibility that delirium after such an event is a marker for previously unrecognised dementia, as well as the possibility discussed in the textbook that delirium accelerates the onset of dementia.

The relevance of taxonomy: official classifications of delirium

Cole and colleagues have compared the application of DSM-IIIR and DSM-IV criteria for delirium to the same population (Cole, Dendukuri, McCusker et al (2003) and found the latter more inclusive. This has been confirmed by Laurila et al (2004) who compared the application of DSM-III, DSM-III-R, DSM-IV and ICD-10 criteria in 230 patients with and without dementia. DSM-IV identified the highest rates- almost double that by the earlier DSM versions in people without dementia The ICD-10 criteria appear very minimalist indeed. It must be remembered, however, that ICD-10 specifies a maximum duration for dementia which no DSM version does. These differences make comparisons between studies over time difficult. Laurila and colleagues have gone on to present data on the outcomes for patients with delirium diagnosed using the different criteria are available (Laurila, Pitkala, Strandberg et al (2003). At baseline there were differences in the presence of pre-existing dementia, and whether or not living in permanent institutional care in a total sample of 425 patients. However, there were no differences in outcome between patients identified as delirious by the different criteria but they concluded that the DSM-IV has identified new subjects who would not previously have been identified as delirious but who shared the same dismal prognosis.

The relevance of subsyndromal delirium

Cole et al have examined the impact of delirium symptoms in 181 patients that did not meet DSM-IV delirium criteria - “sub-syndromal delirium: SSD” (Levkoff, Liptzin, Cleary et al (1996) at medical admission, of whom 164 had at least one follow-up assessment (Cole, McCusker, Dendukuri et al (2003). In terms of demographics and outcomes patients with SSD were intermediate between patients meeting DSM-IV criteria for delirium and those with no symptoms of delirium at all, and the authors confirm Levkoff’s view that the category “delirium” represents the tip of a dimensional iceberg. Marcantonio and colleagues have also suggested that patients with some symptoms of delirium after hip fracture but who fall short of current diagnostic criteria may have similarly poor outcomes to those with definite but mild delirium (2002) . Bourdel-Marchasson et al. have found that subsyndromal delirium, especially incident, is as important as full delirium as a predictor of institutionalisation in 427 patients admitted to a Bordeaux geriatric department. Other factor include nutritional impairment, female sex, falls or stroke (but not known pre-admission cognitive impairment) (2004). It is perhaps a pity that this concept was not referred to in a study of the prodromes of delirium in hip fracture in which certain behaviours were found to be predictive of full delirium, rising in frequency before the frank state emerged (Duppils and Wikblad (2004). Such a study deserves replication in a new sample before any clinically useful guidelines can be derived.

However, a note of caution has been sounded by Royall (2004) in a careful and thought-provoking editorial. He has questioned the nature of subsyndromal states, and has produced evidence for his scepticism in relation to subsyndromal cognitive impairment as a concept (but not about subsyndromal depression). He asks if the presence, in a subsyndromal state, of an outcome intermediate between that of normals and the full-blown state necessarily validates the former. He asks "is shortness of breath equivalent to subsyndromal pneumonia if it presents in the absence of fever?". A provoking questioned for most clinicians, but most of us are then lost in the remainder of his argument, in which he suggests that if the introduction of nonlinear variables into a regression analysis alongside the linear one under question subverts its importance then the case is not made for a subsyndromal state.

The possibility of ungeneralisable results from ethical research

Many delirium and dementia researchers are increasingly anxious about the impact of tightening ethical strictures on the validity of their research. We have shown how applying the most ethically sensitive methods of assessing capacity to consent to a delirium study led to both a catastrophic shortage of recruits to the study, but more importantly introduced bias: patients who could tolerate a tedious test of their understanding of the project were less impaired than those admitted to the project in the usual fashion (Adamis, Martin, Treloar et al (2005). Refusal rates were also highest in the group subjected to the formal capacity assessment. The American Alzheimer's association has published generally helpful consensus guidelines on the ethical framework of research with cognitively impaired adults (Alzheimer's Association (2004);Alzheimer's Association. (2004) . Although they require that the capacity of all patients possibly lacking it is formally tested, the rigour of the capacity assessment should be related to the risks presented by the research. Sensibly, for low-risk projects, an informal assessment of capacity is all that is required. This is in keeping with our study showing the baleful effects of an over-zealous capacity assessment. Less helpful, however, is that there is no provision whatsoever for any research on patients with cognitive impairment for whom no proxy can be identified. Also, the guidelines are predictably vague in relation to fluctuating capacity -- the state particularly affecting delirium research. These two issues (need for a proxy and fluctuating capacity) pose definite difficulties for delirium research in acute medical settings, especially in countries who have not yet formally adopted any sort of legal proxy system for non-financial matters. Until pseudoethical strictures are removed from research with impaired adults there is a real danger that our knowledge about delirium will be confined to a peculiar subset of these states in a peculiar subset of individuals.

Footnotes

ICD-10 has been found wanting in a brief account of an exhaustive search of the literature on delirium in people with learning disabilities by Simpson (2003). Specifically, he suggests that the criteria should include a statement “compared to the person’s usual ability” and that symptoms suggestive of delirium include abnormal rate of transition (slow or rapid) between levels of wakefulness, increased time to respond to prompts, emotional lability and irritability.

Philpott (2002) has claimed precedence over Lipowski in the genesis of the idea of hypoactive delirium.

Charlton & Kavanau (2002) have suggested that the standard definitions of delirium exclude phenomenologically identical states in acute psychiatric disorders, and thus proscribe useful investigation in these disorders. (For example, two cases of delirious mania in older people have recently been reported (Weintraub and Lippmann (2001)). Charlton & Kavanau also agree with Fleminger (2002) on the importance of sleep disturbance in the phenomenology, and perhaps genesis of, delirium- this has been observed in an intensive care unit (Shiihara, Nogami, Chigira et al (2001).

Eikelenboom and colleagues have constructed a cogent neuroinflammatory hypothesis to explain both the genesis of delirium and depression in dementia (2002). En passant, they question the distinction between delirium and dementia, reviving spectrum concepts from 19th century German psychiatry. If they are discrete conditions, as is assumed by Cole et al (2002) and Fick et al (2002) in their review of studies with “validated operational definition/measure of dementia and delirium” then all well and good; if they are not, then such work loses value.

An interesting question about the relationship between delirium and depression is raised by Ueki and Ogawa who report 3 cases of patients whose recovery from severe delusional depression was associated with the onset and disappearance of a delirium (2004). In two there was an apparent independent cause (cerebral infarction and asphyxia) but in the other there was not. Does delirium have an effect on depression similar to ECT (Borchardt and Popkin (1987)? Or does the extra care given when delirium supervenes have psychological benefits? The possibility that the delirium marks a milestone in the evolution of late onset depression to dementia is not applicable in these cases, who were followed up, in one instance for 5 years.

Hobson (2004) has drawn a parallel between delirium and dreaming, and suggests that some of the neurobiology of sleep might be studied with benefits in delirium research

In a thoughtful review of the nature of delirium subtypes Stagno, Gibson, & Breitbart (2005) have pointed out that the classic distinction between hypoactive and hypoactive delirium relies on motor activity, and a more telling distinction might be between higher and lower arousal states independent of physical activity. Although the classic distinction has already yielded fruit in discovering differences in outcome, they argue for further elaboration of the subtypes, and clarification of the best way to "cleave nature at its joints".

Chapter 1 Reference List 

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