Diagnosing, treating and preventing delirium

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1 081 Diagnosing, treating and preventing delirium Delirium is a common disorder in the elderly, particularly those with previous cognitive impairment, and is associated with adverse outcomes. Early recognition and adequate management is essential but prevention is a highly effective strategy. Dr Joaquim Cerejeira* Psychiatrist Serviço de Psiquiatria, Hospitais da Universidade de Coimbra, Coimbra, Portugal Dr John-Paul Taylor Wellcome Intermediate Clinical Fellow and Honorary Consultant in Old Age, Institute for Ageing and Health, Wolfson Research Centre, Newcastle University NE4 5PL * jcerejeira@netcabo.pt Delirium is a syndrome characterised by an acute impairment of consciousness, alertness and global cognition. It is commonly diagnosed in hospital settings, especially in acute medical and surgical wards, where incidences can be as high as 40% in medically ill patients 1 and up to 60% in patients following hipfracture. 2 Although it can occur across all ages, it is particularly frequent in older patients and in those with previous cognitive dysfunction. Once considered to be merely a benign and reversible manifestation of organic disorders, delirium has been revealed to be the result of complex pathophysiologic, neurotoxic processes that produce long-term sequelae. Follow-up studies suggest that not only is delirium associated with a shortterm increase in morbidity and mortality, but it is also a risk factor for long-term deterioration in cognitive function. 3 6 The economic impact of delirium to healthcare systems is equivalent in cost to major medical disorders such as diabetes. 7 Preventive measures and early intervention have been proven to be effective in improving delirium outcomes. 8 Therefore given the significant health and economic impact of delirium, it is important that all professionals are skilled in recognising the presence of delirium in the elderly and managing it appropriately. Clinical features Clinical manifestations of delirium arise after acute disruption in two main neurophysiological processes: consciousness (the awareness and reactivity to stimuli); and attention (the ability to focus on relevant stimuli). In the initial stages, patients with delirium present with reduced consciousness and attention that affects their ability to monitor, select and integrate inputs, such as a conversation. As the delirium progresses, the major domains of cognition orientation, memory, perception, judgement 9 become affected and the full syndrome is established. A striking characteristic of delirium is fluctuation with repeated cycles of sudden improvement followed by the dramatic reoccurrence of symptoms within minutes or hours. Implicitly, the condition is time limited and usually lasts no more than days or weeks; the International Classification of Diseases (ICD-10) stipulates that for a diagnosis of delirium, the mental changes should not last more than six months. 10 This contrasts with dementia in which cognitive impairments appear progressively over months or years. In patients with preexisting dementia, delirium can be recognised by a sudden decrease in mental status although often in clinical practice this can be difficult to discern. Associated clinical features of delirium include motor agitation or retardation, disturbance of the sleep-wake cycle and emotional/ behavioural symptoms. Three

2 082 clinical subtypes have been proposed to define delirium: Hyperactive delirium: this is the classical presentation of delirium and is characterised by psychomotor agitation, hallucinations, delusions, emotional lability and disorientation; these features commonly bring this form of delirium to the attention of medical and nursing staff. However this form represents less than 10% of cases in the elderly. Hypoactive delirium: this presents with psychomotor retardation, somnolence and lethargy. It is three times more frequent in the elderly, and is associated with higher burden of comorbidity as well as illness severity, being often overlooked or misdiagnosed. This can explain why this subtype is associated with a worse outcome than hyperactive delirium. 11,12 Mixed delirium: patients show a mixed profile of the two subtypes during the course of delirium. Mixed and hypoactive forms represent 80% of all delirium cases. 13 Pathophysiology Delirium pathophysiology involves the combined action of predisposing factors and precipitating causes (insults) that act together to disrupt brain function. Virtually any type of insult, if sufficiently strong, can produce delirium either directly (eg trauma) or indirectly by activating a cascade of mediators that ultimately give rise to neuronal dysfunction. Table 1: Predisposing and precipitating causes of delirium Predisposing Precipitating Age over 65 Infection especially UTI Sensory impairment Medications (see Table 3) Dementia or neurological disease Dehydration Previous history of stroke Shock Alcohol dependency Hypoxia Depression Severe acute physical illness Immobility Drug/alcohol withdrawal Malnutrition Traumatic brain injury Dehydration Metabolic imbalance Chronic renal/hepatic impairment Anaemia Surgery Urinary catheterisation Pain Common precipitating factors of delirium include medication, metabolic disorders, infection, surgical procedures and primary central nervous system disorders (Table 1). Predisposing factors to delirium are conditions (such as ageing and dementia) that, by affecting brain integrity and vulnerability, lower the threshold for delirium. The exact pathophysiological processes that give rise to delirium remain unclear. This is partially reflected by the heterogeneity of precipitating and predisposing causes and the fact that there are often multiple contributory factors. A l t e r a t i o n s i n neurotransmitter function have been suggested as an aetiological mechanism; in particular, cholinergic deficiency and dopamine excess have been observed, although imbalances in other transmitter systems have been noted as well. 14,15 More recently, cortisol and inflammatory markers have been implicated in pathophysiology of delirium Brain hypoperfusion may be a feature of delirium; functional neuroimaging studies consistently report significant, a l t h o u g h n o n - s p e c i f i c, reductions in brain blood perfusion during delirium. 19 Diagnosis Delirium, particularly the hypoactive subtype where the symptoms are subtle, can be easily missed, particularly in elderly patients. In this population, a regular screening of all patients with cognitive impairment or presenting with other risk factors, made by trained staff, is recommended in hospitals to improve early delirium recognition. 20 Considering that delirium often occurs in dementia, it is crucial to have knowledge of GM Midlife and Beyond February 2011

3 083 the pre-morbid mental status to help differentiate between the two conditions; this can be achieved by taking an informant history from carers and reviewing previous clinical notes. C l i n i c a l a s s e s s m e n t for delirium can be easily integrated in daily practice; brief conversations with the patient can be informative about the level of consciousness, as well as the degree of attention and cognitive function, while observation of the patient can reveal motor agitation or retardation. In the assessment of patients with dementia, it is best to focus on the level of consciousness and any fluctuations in attention rather than assessing cognitive domains that are likely to be chronically impaired. Furthermore it is important to be alert to the fact that, in the late stages of dementia, clinical differentiation between the two syndromes becomes difficult as severe brain degeneration lowers the threshold for development of delirium such that even relatively minor undetected insults can precipitate delirium. Table 2 shows features that can help differentiate delirium from dementia. S e v e r a l s t a n d a r d i s e d instruments are also useful to help clinicians in screening for delirium. The Mini-Mental State Examination 21 and the Clock Drawing Test 22 are commonly used to assess cognition at the bedside. While these tests cannot distinguish delirium from dementia with only a single assessment, they are suggestive of delirium if there is a significant and sudden (within hours or days) drop from previous test scores. Therefore, these instruments are Table 2: Differentiating delirium from dementia Features Delirium Dementia Onset Clear cut, acute (hours to days) Insidious (months to years) Precipitant Identifiable Not identifiable Course Fluctuating Symptoms stable Reversibility Reversible Not reversible Duration Resolves in days or weeks useful in establishing a baseline and for monitoring cognitive status/response to treatment. Once delirium is suspected, a clinical assessment should be done to confirm the diagnosis. Alongside the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, making a diagnosis of delirium can be aided by use of the Confusion Assessment Method (CAM). 23 CAM is an easy to use instrument that has been shown to have high sensitivity and specificity when used by trained healthcare professionals. Other instruments, such as Delirium Rating Scale, 24 are available to address the severity of symptoms and measure treatment response. As noted above, given that there may be fluctuations in the Continual, progressive Consciousness Impaired Usually not impaired* Attention Impaired Usually not impaired** Hallucination + (mostly visual) +/- Delusions + (fluctuating and fragmented) +/- Motor activity Hyperactive/ hypoactive/ mixed presentation, it is best to repeat these assessments on several different occasions at different times of the day. Management Often unaffected until later stages * Exceptions include dementia with Lewis bodies (DLB) and vascular dementia (VD) ** Exceptions include DLB, VD and frontotemporal dementia A prompt and thorough clinical evaluation including appropriate laboratory test work-up should be made to identify and treat the precipitating causes of delirium. Often given the risks associated with psychomotor agitation (eg, falls), environmental and/or pharmacological measures may be required for symptom control A detailed medical history, preferably from different sources, should be obtained to assess comorbidities. Medication should be reviewed with particular

4 084 Table 3: Medications associated with delirium 25 Opioid analgesics pethidine, fentanyl, morphine, hydromorphone Sedative hypnotics benzodiazepines, antihistamines, diphenhydramine, hydroxyzine, chlorphenamine NSAIDs naproxen, ibuprofen, indometacin Anticholinergics atropine, hyoscine Antiparkinsonian benzatropine, trihexyphenidyl, levodopa agents Neuroleptics clozapine, chlorpromazine, Tricyclic antidepressants amitriptyline, imipramine Cardiac drugs digoxin, β-blockers, methyldopa H2 blockers cimetidine, ranitidine attention given to new or discontinued drugs and those with anticholinergic potential (Table 3). Physical examination should evaluate major systems to determine any obvious medical or surgical causes of delirium. In addition, assess for any pain and sensorial impairment Investigations should include blood count, electrolytes, renal and hepatic function, urine analysis, chest X-ray and ECG. If specific causes of delirium are being entertained in light of the history and physical examination, other investigations, for example toxicological analysis, neuroimaging and lumbar puncture, may be required for a complete evaluation. Frequently, patients with dementia simultaneously have multiple sub-threshold clinical conditions such as pressure ulcers, urinary retention, faecal impaction, and dehydration which additively may precipitate delirium. In these cases, although no sole predominant cause can be identified, the aim is to correct as many as possible. As precipitating factors are being corrected, management of delirium should include environmental measures and supportive care to provide a quiet and familiar surrounding to the patient. Consider low-dose haloperidol 26 or olanzapine for a brief period (usually less than a week) in distressed patients if pharmacological intervention is required for behavioural control. 27 Alternatives include risperidone (0.5 1 mg) and quetiapine (25 50 mg). 28 Antipsychotics should be used with a high degree of caution given their propensity for extrapyramidal side effects, their negative effects on cognition Table 4: Prevention of delirium Risk factor Cognitive impairment Sleep deprivation Visual impairment Hearing impairment Dehydration Immobility and their potential association (particularly when used for a prolonged period in patients with dementia) with an increased risk of cerebrovascular events and overall mortality Prevention Primary prevention of delirium is one of the most effective strategies in managing delirium. 8 Inouye et al (1999) identified six different risk factors for delirium in older people that could be reduced by using a number of effective intervention strategies (Table 4). Conclusion Delirium is a common disorder in the elderly population, particularly those with previous cognitive impairment, and is associated with adverse outcomes. Early recognition and adequate management of delirium is mandatory and only possible with systematic screening by skilled healthcare professionals. An integrated management a n d c a r e p a c k a g e f o r patients with delirium with a multidisciplinary team is Intervention Cognitive stimulation Improved sleeping conditions Visual aids Wax disimpaction, hearing aids Early recognition, oral fluids Early mobilisation, minimising drips and catheters, etc. GM Midlife and Beyond February 2011

5 085 warranted both in the acute phase and in follow-up. Prevention of delirium in the first place may be a highly effective strategy. Conflict of interest: none declared References 1. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing 2006; 35: Holmes JD, House AO. Psychiatric illness in hip fracture. Age Ageing 2000; 29: Ely EW, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291: McCusker J, Cole M, Dendukuri N, et al. Delirium in older elder inpatients and subsequent cognitive and functional status: a prospective study. CMAJ 2001; 165; McCuster J, Cole M, Dendukuri N, Belzile E. Does delirium increase hospital stay? JAGS 2003; 51: Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with delirium. J Am Geriatr Soc 1992; 40: Leslie DL, Marcantonio ER, Zhang Y et al. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168: Inouye SK, Bogardus ST, Charpentier BA, et al. A clinical trial of a multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999; 340: MacLeod AD, Delirium: the clinical concept. Palliative and supportive care 2006; 4: World Health Organization: The ICD-10 classification of mental and behavioural disorders. Geneva, WHO, Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J 1992; 161: O Keeffe ST, Lavan JN. Clinical significance of delirium subtypes in older people. Age Ageing : Stagno D, Gibson C, Breitbart W. The delirium subtypes: A review of prevalence, phenomenology, pathophysiology, and treatment response. Palliat Support Care 2004; 2: Trzepacz P. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry 2000 ; 5: van der Mast RC, Fekkes D. Serotonin and amino acids: partners in delirium pathophysiology? Semin Clin Neuropsychiatry 2000; 5: Beloosesky Y, Hendel D, Weiss A, et al. Cytokines and C-reactive protein production in hipfracture-operated elderly patients. J Gerontol A Biol Sci Med Sci 2007; 62: Ramlawi B, Rudolph JL, Mieno S, et al. Serologic markers of brain injury and cognitive function after cardiopulmonary bypass. Ann Surg 2006; 244: Marcantonio ER, Rudolph JL, Culley et al. Serum biomarkers for delirium. J Gerontol A Biol Sci Med Sci 2006; 61: Fong TG, Bogardus Jr ST, Daftary A, et al. Cerebral perfusion changes in older delirious patients using 99mTc HMPAO SPECT. J Gerontol A Biol Sci Med Sci 2006 ; 61: British Geriatric Society. Guidelines for the prevention, diagnosis and management of delirium in older people in hospital. January Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: Shulman KI. Clock-drawing: Is it the ideal cognitive screening test? Int J Geriatr 2000; 15: Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113: Rolfson D, McElhaney JE, Jhangri GS, Rockwood K. Validity of the confusion assessment method in detecting post-operative delirium in the elderly. International Psychogeriatrics 1999; 11: Fong HK, Sands LP, Leung JM. The role of postoperative analgesia in delirium and cognitive decline in elderly patients: a systematic review. Anesth Analg 2006; 102: American Psychiatric Association. Practice guidelines for the treatment of patients with delirium. Am J 1999; 156 (suppl 5); National Institute for Health and Clinical Excellence (2010) Clinical Guideline Delirium. London: NICE. uk/cg103 (accessed 14 February 2010) 28. Ozbolt LB, Paniagua MA, Kaiser RM. Atypical antipsychotics for the treatment of delirious elders. J Am Med Dir Assoc 2008; 9(1): Committee on Safety of Medicines. Atypical antipsychotic drugs and stroke: message from Professor Gordon Duff, chairman, (CEM/CMO/2004/1). London: Committee on Safety of Medicines, Douglas IJ, Smeeth L Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ 2008; 337: a Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294: