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Delirium An overview Pre test • A) B) C) D) E) If you have 100 patients aged 65 and older in a hospital, how many- at any given time-will be delirious? 5 10 20 50 80 • A) B) C) D) Delirium is reversible: sometimes. Always. Never. Sometimes, and to a variable degree. • Delirium in older people is: A) Inevitable. B) Preventable, but through very costly and complicated measures. C) Very simple measures can prevent many cases. • • • • • • Definition Burden Classification Pathophysiology Clinical features Diagnosis • Complications • Prognosis • Prevention … Delirium • An acute, fluctuating disturbance of consciousness, associated with a change in cognition or the development of perceptual disturbances. • It is the pathophysiologic consequence of an underlying general medical condition such as infection, coronary ischemia, hypoxemia, or metabolic derangement. Burden • • Mortality rates among hospitalized patients with delirium range from 22-76 %. (just like acute MIs or sepsis!!) One-year mortality rate 35-40 %. Inouye SK. Delirium in older persons, review article. N Eng J Med 2006; 354:1157-65. Burden • 20 % of in patients 65 years of age or older. • Increases hospital costs by $2,500(US) per patient. • Substantial additional costs accrue after discharge (institutionalization, rehabilitation, formal home health care, and informal caregiving). • Prevalence at hospital admission:14-24 %. • Incidence during hospitalization: 6-56%. Pathophysiology • Poorly understood. • EEG: diffuse slowing of cortical background activity, which does not correlate with underlying causes. • Neuropsychological and neuroimaging studies reveal generalized disruption in higher cortical function, with dysfunction in the prefrontal cortex, subcortical structures, thalamus, basal ganglia, frontal and temporoparietal cortex, fusiform cortex, and lingual gyri, particularly on the nondominant side. Cholinergic deficiency • The leading hypotheses for the pathogenesis of delirium focus on the roles of neurotransmission, inflammation, and chronic stress. • Extensive evidence supports the role of cholinergic deficiency. • Anticholinergic drugs induce delirium in humans and animals. • Serum anticholinergic activity is increased. • Physostigmine reverses delirium associated with anticholinergic drugs, and cholinesterase inhibitors appear to have some benefit even in cases of delirium that are not induced by drugs. Dopamine • Dopaminergic excess also appears to contribute. • Possibly owing to its regulatory influence on the release of acetylcholine. • Dopaminergic drugs (e.g., levodopa and bupropion) are recognized precipitants of delirium, and dopamine antagonists (e.g., antipsychotic agents) effectively treat delirium symptoms. Other neurotransmitters • • • • • Norepinephrine. Serotonin. Aminobutyric acid Glutamate. Melatonin. 1.Lewis M, Barnett S. post operative delirium: the tryptophan dyregulation model 2.Medical hypotheses (2004) 63, 402-406 Others • Cytokines(IL-1,2,&6), TNF, and interferon, may contribute increasing the permeability of the blood–brain barrier and altering neurotransmission. • Chronic stress brought on by illness or trauma activates the sympathetic nervous system and hypothalamic–pituitary–adrenocortical axis, resulting in increased cytokine levels and chronic hypercortisolism. • Chronic hypercortisolism has deleterious effects on hippocampal serotonin 5-HT1A receptors. Risk factors • Cognitive impairment: • 25% of delirious patients are demented • 40% of demented hospitalized are delirious. • Five independent risk factors for delirium at discharge were identified: • Dementia (OR: 2.3; 95% CI, 1.4-3.7). • Vision impairment (OR, 2.1; 95% CI, 1.3-3.2). • Functional impairment (OR, 1.7; 95% CI, 1.23.0). • High comorbidity (OR, 1.7; 95% CI, 1.1-2.6). • Use of physical restraints during delirium (OR, 3.2; 95% CI, 1.9-5.2). Risk Factors for Delirium at Discharge . Development and Validation of a Predictive Model Inouye et al.,Arch Intern Med. 2007;167:1406-1413 • A risk stratification system was created by adding 1 point for each factor present. • Risk of delirium on discharge: • Low-risk (0-1 factors): 4% • Intermediate-risk (2-3 factors): 18% • High-risk (4-5 factors): 63%. (P < .001). Peri operative delirium • The incidence of delirium : 5.1%-52.2%. • Greater rates after hip fracture and aortic surgeries. • Risk factors: cognitive impairment, older age, functional impairment, sensory impairment, depression, preoperative psychotropic drug use, psychopathological symptoms, institutional residence, and greater comorbidity. • Evidence was most robust for an association between delirium and cognitive impairment or psychotropic drug use. Preoperative Risk Assessment for Delirium After Noncardiac Surgery: A Systematic Review M Dasgupta, C. Dumbrell, JAGS, Volume 54, Issue 10: 1578-1589 Clinical Features • Hyperactive: an increased state of arousal, psychomotor abnormalities, and hypervigilance. • Hypoactive: withdrawn, less active, and sleepy. • Maybe misdiagnosed as dementia or depression. • Poorer overall prognosis. • Mixed.. • Delirium often is the presenting symptom of an underlying illness DSM-IV Criteria – Disturbance of consciousness (ie, reduced clarity of awareness of the environment), with reduced ability to focus, sustain, or shift attention. – Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) that is not better accounted for by a preexisting, established, or evolving dementia. – The disturbance develops over a short period ( hours to days) and tends to fluctuate during the course of the day. – Evidence from the history, physical , or laboratory findings is present that indicates the disturbance is caused by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause CAM (Confusion assessment method) Sn 94-100% Sp 90-95%. • 1: Acute Onset and Fluctuating Course Usually obtained from a family member or nurse. Is there evidence of an acute change in mental status from the patient's baseline? Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity? • 2: Inattention Did the patient have difficulty focusing attention, ie. easily distractible, or having difficulty keeping track of what was being said? • 3: Disorganized thinking Was the patient's thinking disorganized or incoherent? ( rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject) • 4: Altered Level of consciousness Any answer other than "alert" to the following question:: Overall, how would you rate this patient's level of consciousness? (alert, vigilant, lethargic, stupor, or coma) • The diagnosis requires 1 and 2 and either 3 or 4. Other instruments • DRS (Delirium rating scale). • MDAS (Memorial delirium assessment scale). • DSI (Delirium symptom interview). • CTD (cognitive test for delirium). • Features • • • • • • • Delirium Onset Acute Course Fluctuating Duration Days to weeks Consciousness Altered Attention Impaired Psychomotor ↑ or ↓ Reversibility Usually Dementia Insidious Progressive Months to yrs Clear Normal Often normal Rarely Prognosis Prognosis • Persists in up to 25% of patients. • When is it not delirium anymore?? • Higher in-hospital and post discharge mortality. • Longer lengths of stay. • Functional decline – placement. Complications • Immobility and it’s complications: ( aspiration, thromboembolism, UTI, pressure ulcers) • Underlying cause. Prevention • Non pharmacological: Multicomponent Intervention to Prevent Delirium in Hospitalized OlderPatients Inouye SK, et al. N Engl J Med 340:669, March 4, 1999 Pharmacological Haloperidol: • RCT of 430 patients, 70 y and older. • Hip replacement surgery. • Haloperidol 1.5 mg preop and 3 days post. • Positive effect on the LOS, severity and duration of delirium, but not the incidence. • Well tolerated. Kalisvaar KJ, et al .Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005 Oct;53(10):1658-66 • • • Melatonin: Treated severe postoperative delirium unresponsive to antipsychotics or benzos in a 53y patient. prevented another episode of postop. delirium in a 78y patient with a prior history of postoperative delirium, after undergoing repeated LL surgery. Hanania m, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anasth Analg 2002;94:338-9