Chapter 6: The causes of delirium

NB This chapter includes updates on precipitating causes for delirium but predisposing risk factors are discussed in the update for Chapter 3: the epidemiology of delirium

Emerging themes

Anaesthetics

Of 921 hip fracture patients reported by Edelstein et al (2004) almost exactly half had spinal and half general anaesthetic and the latter, together with dementia and higher operative risk were independent risk factors for delirium. This was an observational finding, but surprising, since spinal anaesthetic may be reserved for patients with higher morbidity. Wu et al (2004) have systematically reviewed the evidence that general anaesthetics are more likely to be associated with cognitive dysfunction postoperatively than regional anaesthetics. 20 of the 23 studies tabled were RCTs. They could find no evidence for this. Many studies showed no difference, and in those that did the effect size were very weak. As usual, methodological differences played a huge role in the variance between the studies. Helpfully they list all the psychometric tests carried out in the various studies that they report.

 

Sleep-wake cycles and melatonin

Charlton & Kavanau (2002) agree with Fleminger (2002) on the importance of sleep disturbance in the phenomenology of delirium and it may be a causal factor as well as a result. In what appears to be only the second study of the role of melatonin in the genesis of delirium Balan and colleagues tested the hypothesis that high levels would be associated with hypoactive delirium and vice versa (2003). They measured urinary 6-sulphatoxymelatonin in 31 medical inpatients with delirium as assessed by DRS cut point. 7 were classified as hyperactive, 10 hypoactive and the remainder mixed. Using level after recovery as a comparator, they confirmed their hypothesis and raise some interesting questions about the mechanism. Following observations on the emergence of delirium after sleep deprivation by Shiihara, Nogami, Chigira et al (2001), a study of eight patients requiring ventilator therapy in intensive care, four of whom were over 65, is reported of melatonin levels in relation to sleep-wake pattern disturbances such as are found in delirium (Olofsson, Alling, Lundberg et al (2004). They found a disturbed melatonin secretion rhythm in these patients, and suggested that bright light and medication may be responsible. Their findings supported a trial of melatonin in this situation in order to prevent delirium. It is interesting that 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.

Footnotes

A promising mathematical model based on preoperative and operative factors predicting delirium in vascular surgery patients has been developed by Bohner and colleagues (2003) in 153 patients including an unknown number of older ones. 39% developed postoperative delirium. The model contains some surprises- for instance, no history of supraaortic occlusive disease appears to increase risk. However it has not yet been tested on a new cohort of patients.

In a review of 240 admissions of patients aged 75 and over admitted to hospital, 30% were considered to have been admitted because of adverse drug events. Of the 83 adverse reactions found, 12 (14%) were manifest as delirium (Chan, Nicklason, & Vial (2001).

Kibry & Ames have reviewed the connection between selective serotonin re-uptake inhibitor antidepressants and delirium mediated by hyponatraemia (2001).

Roffe (2001) has pointed out that non-convulsive status epilepticus (NCSE) should be considered as a rare cause of delirium in older people- especially when neuroleptic malignant syndrome is possible. Cocito et al (2001) found NCSE in 5 (6%) of a series of 84 cancer patients with altered cognition.

The association of stroke with delirium may be mediated in some cases by sleep apnoea (Sandberg, Franklin, Bucht et al (2001). They found a prevalence of 59% in first-stroke patients, with an association between a high apnoea-hypopnoea index and delirium.

One of several problems in interpreting the results of an observational study on the need for haloperidol in those administered intravenous dopamine for cardiogenic shock (Sommer, Wise, & Kraemer (2002) is that the shock may have provoked the need for both medications independently. Further, equating haloperidol administration with delirium seems unwise.

Adunsky and colleagues (2002)have shown in an observational study an excess incidence of delirium and the use of meperidine (pethidine) as opposed to morphine analgesia for 92 older people with hip fracture surgery in an orthogeriatric ward. However, meperidene was forbidden in the ward itself, so the differences could have been due to other factors; it was only administered in the emergency room or recovery room. Nevertheless, a similar association has been reported by Morrison & colleagues (2003). Further work is needed on this important topic to find the least deliriogenic analgesic for this very high-risk group of patients.

A case study of belladonna ingestion in an older person from an ethnic minority reminds us of the importance of history in the assessment of recurrent delirium (Joshi, Wicks, & Munshi (2003)

The importance of sensory deprivation in the genesis of delirium in acute settings has been confirmed in long-term care by Cacchione, Culp, Dyck et al (2003)

The anecdotal connections between many herbal medicines and delirium is comprehensively covered in a general review of adverse herbal events by Ernst (2003)

Recent case reports apparently link delirium to celiac disease (Desplat-Jego, Bernard, Bagneres et al (2003), the macrolide antibiotic azithromycin (Cone, Padilla, & Potts (2003), the abrupt discontinuation of paroxetine (Hayakawa, Sekine, & Shimizu (2004), olanzapine treatment (Samuels and Fang (2004), hyperammonia caused by ornithine carbamoyltransferase (OTC) deficiency, myeloma, valproic acid toxicity and chemotherapy for gastric cancer (Weng, Shih, & Chen (2004) bismuth toxicity (Youngman and Harris (2004), levofloxacin (Hakko, Mete, Ozaras et al (2005) and anticholinergic

 

Reference List Chapter 6 

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