Delirium Paul Borghesani MD-PhD Assistant Professor Psychiatry and Behavioral Sciences paulrb@uw.edu Delirium: Defining delirium “an acute mental disturbance characterized by confused thinking and disrupted attention usually accompanied by disordered speech and hallucinations” aka acute confusional state acute brain failure encephalopathy global cognitive impairment Hippocrates “phrenitis” “the great imitator” Delirium: A gestalt Etiology Pathophysiology ? Neuronal level Systems level Cognitive dysfunction Goals for today Review the epidemiology and importance of detecting delirium Learn the key features and subtypes of delirium Explore the pathophysiology of delirium Learn how to evaluate and treat delirium Learn to recognize co-morbid delirium in mental illness Who could be delirious? An agitated, combative patient who does not follow instructions An obtunded, minimally interactive patient An emotionally erratic patient who makes contradictory remarks and who staff cannot logically engage A calm, confused patient who is suspicious and oppositional Clinical case: 31 y/o with confusion A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits. Questions: 1)What factors suggest this is delirium? 2)What is a possible etiology? Clinical case: 31 y/o with confusion A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits. Questions: 1)What factors suggest this is delirium? 2)What is a possible etiology? Clinical keys of delirium Abrupt onset Fluctuating symptoms Difficulty sustaining attention Appear to have cognitive dysfunction Clinical case: 31 y/o with confusion A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits. Questions: 1)What factors suggest this is delirium? 2)What is a possible etiology? Clinical case: Serotonin syndrome (SS) Can be caused by any antidepressant Most cases are associated with polypharmacy Typical symptoms include - mental status changes, tremor, myoclonus, hyperreflexia, GI symptoms, diaphoresis, fever, inducible clonus Most often confused with neuroleptic malignant syndrome - SS is associated with GI symptoms, myoclonus, mild or no laboratory changes - NMS is associated with more severe rigidity and laboratory changes (low Fe, dramatically elevated creatine kinase, elevated WBCs) Perry and Wilborn. Annals of Clinical Psychiatry. 24(2) 155 (2012) Epidemiology and diagnosis of delirium Epidemiology of delirium: It’s common! Common in the general population - 0.4% of all people - 1.0% in individuals over 55 (over 10% in those > 85) - 60% of nursing home residents Common in the medical setting - 10-30% of elderly in the ER - 20% of all medical admissions - 4-53% among hip fracture patients - 4-28% of elective surgery patients - 13-72% of cardiac surgery patients Hall R et at. Best Pract & Research Clin Anaesth, 2012 Inouye, S.K. N Engl J Med, 2006. Consequences of delirium Increased length of stay Increased mortality and morbidity - Perhaps between 25-75%, as high as MI and sepsis Prolonged cognitive difficulties Institutionalization Delirium: DSM-5 diagnostic criteria A. A disturbance in attention and awareness B. The disturbance develops over a short period of time, represents a change in function, and fluctuates C. There is a disturbance in cognition memory, disorientation, language, visuospatial ability, or perception D. A and C are not better explained by an established neurocognitive disorder E. Evidence from the history, PE or laboratory findings that this represents another medical condition, substance intoxication or withdrawal, toxin exposure or due to multiple etiologies. DSM-5 Delirium: DSM-5 specifiers Specify etiology - Substance intoxication delirium - Substance withdrawal delirium - Medication-induced delirium - Delirium due to another medical condition - Delirium due to multiple etiologies Specify characteristics - acute (hours to days) or persistent (weeks to months) - hyperactive, hypoactive or mixed DSM-5 Classification of delirium: Hyperactive subtype Agitated, uncooperative and often combative Psychotic and responding to internal stimuli Loud and fast speech Wandering, restless Appear intoxicated Classification of delirium: Hypoactive subtype Somnolent, inattentive, and uninterested Poor memory and cognitive abilities Will be described as having lapses or variable behavior Reduced amount and rate of speech Often missed because they can be left alone Classification of delirium: Mixed subtype Combination of both Hypoactive and mixed account for about 80% of all cases Delirium: Other DSM-5 delirium syndromes Other specified delirium - the full criteria for delirium are not met - you choose to specify WHY the criteria are not met - e.g., “attenuated delirium syndrome” Unspecified delirium - the full criteria for delirium are not met - you choose NOT to specify why the criteria are not med - often appropriate in the ED when etiologies are unknown DSM-5 Clinical case: 44 y/o non-compliant patient A 44 y/o male is sustained multiple injures after being hit by a car. Two days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality. Questions: 1)What suggests he is having visual hallucinations? 2)What is a possible etiology of his delirium? Clinical case: 44 y/o non-compliant patient A 44 y/o male is sustained multiple injures after being hit by a car. Three days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality. Questions: 1)What suggests he is having visual hallucinations? 2)What is a possible etiology of his delirium? (Hint: he vitals are unstable) Clinical case: Delirium tremens Onset 2-3 days after last drink Peaks 4-5 days Severe autonomic hyperactivity - fever, tachycardia, tachypnea, hypertension, tremor diaphoresis Delirium - confusion, disorientation, agitation, perceptual disturbances including visual hallucinations - may/may not be accompanied by seizures Treat with benzodiazepines The confusion assessment method (CAM): An alternative to the DSM-5 Feature 1: Acute onset or fluctuating course - usually obtained from an informant Feature 2: Inattention - from your evaluation, are they distractible or unable to follow the conversation Feature 3: Disorganized thinking - rambling, confused, derailment, illogical, loose associations Feature 4: Altered level of consciousness - normal to comatose Must have Features 1 & 2 and either 3 or 4 Levels of consciousness Agitated (out of control) Hyperalert (vigilant) Alert (normal) Drowsy (lethargic) Obtunded (difficult to wake) Stuporous (v. difficult to wake) Comatose (unable to wake) http://www.icudelirium.org/docs/CAM_ICU_training.pdf Using the PRE-DELIRIC: PREdiction of DELIRium in ICu patients van den Boogaard et al. BMJ 2012 Diagnosis of delirium: Differentiating it from mental illness Age of onset and history of mental illness Assess risk factors for delirium Disorientation Reduced level of alertness and fluctuations Speech not typically dysarthric in mental illness (except in intoxication or withdrawal) Visual hallucinations are atypical Diagnosis of delirium: Differentiating it from dementia Delirum Dementia Attention impaired intact early, impaired late Course acute, fluctuating chronic, progressive Speech rambling, mumbling impoverished Perception illusions and hallucinations often normal Thinking disorganized impoverished Alertness agitated/obtunded normal Algahtani and Abdu. Neurosciences 17(3) 205 (2012) Clinical case: 79 y/o with confusion A 79 y/o male who is being treated for a pneumonia is referred to psychiatry consults for after waking up at night screaming and disoriented. The consult resident establishes that the patient’s attention is poor, their memory is impaired, and their speech and behavior is disorganized. They believe he is delirious and are considering treatment with haloperidol. Questions: 1)What is the KEY historical point missing? 2)What should be done before recommending haloperidol? Etiology, pathophysiology and clinical assessment of delirium Etiology: General principles Trying to establish and etiology of delirium is essential Often multifactorial Take heed of the vulnerable patient! - always think about the vulnerability X exposure interaction The most important graph in medicine Exposure High Sick Low Not sick Low High Risk Etiology of delirium: Risks Age, age, age and age Cognitive dysfunction - intellectual disabilities, visual impairment, depression, dementia Prior neuropathology - stroke, tumor, vasculitis, trauma, history of trauma Major medical/surgical illness - hip fracture, ICU stays, Etiology of delirium: Exposures Metabolic and systemic illness - sepsis, organ failure, electrolyte abnormalities, hypoxia, hypoglycemia, UTI Endocrinopathies CNS infections and lesions Nutritional deficiencies - thiamine, niacin, B12, folate Intoxication and withdrawal Others… - heat stoke, electrocution, sleep deprivation, MEDICATIONS Algahtani and Abdu. Neurosciences 17(3) 205 (2012) Etiology of delirium: Medications Anticholinergics/antihistamines Analgesics Steroids/sympathomimetics Sedatives Anticonvulsants Antiarrythmics/antihypertensives Antibiotics (PCN, cephalosporins, quiolones) “I watch death” Etiology of delirium: Life threatening causes Wernicke’s encephalopathy Hypoxia Hypoglycemia Hypertensive encephalopathy Intracerebral hemorrhage Meningitis/encephalitis Poisoning Note the mnemonic “WHHHIMP” Pathophysiology of delirium: Several hypotheses Neurotransmitter hypothesis - hypocholinergic state i. supported by deliriogenic effects of anticholinergic medications and dementia - dopamine (and norepinephrine) excess ii. supported by intoxicating effects of numerous dopaminergic agonists and the beneficial effects of antipsychotics Neuroinflammatory hypothesis - elevated cortisol, elevated CRP, elevated procalcitonin - alteration of the BBB and microglia activation disrupts brain function Hypoxia hypothesis - disrupted oxygen supply or neurovascular coupling causing neuronal dysfunction Neurovascular coupling Examples of neuropathology associated with delirium Atrophy CT White matter hyperintensities MRI Hughes, Patel and Pandharipande. Curr Opinion in Critical Care 2012 Neuroimaging in delirium: Not generally recommended Structural changes - atrophy - vascular lesions and white matter hyperintesities - white matter changes (evaluated with diffusion tensor MRI) Perfusion/metabolic changes - Reduced blood flow (SPECT imaging) - Reduced metabolism (PET imaging) EEG - diffuse slowing with moderate amplitude common but nonspecific - useful in ruling out non-convulsive status epilepticus, hepatic encephalopathy (triphasic waves) and some viral encephalopathies Functional MRI: Defining large networks potentially disrupted in delirium Fox et al. PNAS 2005 Clinical assessment of delirium: General principles Review chart for fluctuating course, recent illness, baseline function Review medications including PRNs Review history of substance use, CNS pathology and mental illness Gather collateral with emphasis on recent change in function Physical exam findings in delirium Hypotension - dehydration, sepsis, cardiac disease Tachycardia - dehydration, sepsis, cardiac disease, hyperthyroidism, intoxication Fever - infection, withdrawal states, NMS Hypothermia - sepsis, myxedema, Wernicke’s encephalopathy Using the MMSE in delirium Scores < 24 have been suggested to be a threshold 4 key questions of the MMSE - Year - Date - Backward spelling (“DLROW”) - Figure copying Fayes et al. J Pain Symptom Manage 30: 41 (2005) Clinical assessment of delirium: Laboratory tests Recommended tests - Electrolytes, glucose, calcium, CBC, LFTs, UA, Utox and drug levels when appropriate Not necessarily recommended, but should be considered - CXR, blood cultures, blood gasses, EEG Use only in appropriate cases - Neuroimaging (structural with CT or MRI, functional with PET or SPECT) Clinical case: 24 y/o with acute confusion A 24 y/o male with history of bipolar disorder presents to the ED on a hot Seattle summer day with acute confusion, agitation, and aggressive behavior. He is hyperthermic and has various routine laboratory abnormalities including elevated WBCs and hypernatremia. Although poorly cooperative with the exam you note some rigidity, tremor, tachycardia, diaphoresis, and tachypnea. Questions: 1)What other labs would you like to know? 2)What is a possible diagnosis? Treatment, prevention and prognosis of delirium Management: Basic principles Search for the underlying cause! - Medications only treat symptoms, not etiology. Minimize psychoactive medications Provide supportive care - oxygen, hydration and nutrition - positioning and mobilization - avoid restraints - maximize non-pharmacologic care The goal is an alert and manageable patent, not a sedated and lethargic patient Treating delirium: Non-pharmacologic approaches Promote sleep hygiene - visible clock, provide light cycle, avoid night time awakenings Low stimuli environment - reduce IV “beeps”, move away from the nursing station Encourage family visits, consistent staffing Minimize interrupting patient and unnecessary moves/tests Inouye et al., A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med, 1999. 340(9): p. 669-76. Pharmacologic treatment of delirium: Use only if patient is dangerous or physically/mentally uncomfortable Haloperidol is first line - not if concern for Parkinson’s, Lewy body or Parkinson’s Plus syndrome - start with 0.5 mg BID PO/IV with 0.5 mg q4 hours PRN - IV may cause less EPS but it has a short duration of actions Atypical antipsychotics (no IV forms) - Risperidone: start at 0.25-0.5 mg PO BID - Olanzapine: start 2.5-5 mg PO BID (IM form available) - Quetiapine: start at 12.5-25 mg BID (often preferred given low risk of EPS, can cause orthostasis) - All can cause metabolic syndrome if used long term and acutely disrupt glucose management complicating diabetes treatment Pharmacologic treatment of delirium: Guidelines regarding QTc prolongation Potentially causing V-fib/Torsades des pointes - men: < 430 normal, 431 - 450 increased, > 451 high - women: < 450 normal, 451 - 470 increased, > 471 high - watch for an increase of > 30 msec from baseline Contributing factors include - age, female gender, hx of heart disease, CHF, hepatic disease - low K/Mg, bradycardia, alcohol use, drug use (stimulants), rapid infusion of drugs Antipsychotics to be leery of: - Typical : pimozide, thioridazine, IV haloperidol - Atypical : ziprasidone > quetiapine > risperidone (newer agents also) Clinical case: 24 y/o with odd behavior A 24 y/o male with a history of schizophrenia presents with fluctuating behavior and cognitive disorganization that is different from his baseline. He is intermittently mute, postures while standing, resists movements (negativism), and engages in echolalia and echopraxia. At times he is conversant, at others fully unresponsive. Questions: 1) Is this delirium or catatonia? 2) What medications might be helpful? Clinical case: Catatonic symptoms in delirium Catatonia has 3 or more of the following - stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypy, agitation, grimacing, echolalia, echopraxia Catatonia can occur in any mental or medical disorder but should NOT be attributed exclusively to delirium Catatonia is frequently treated with benzodiazepines which can worsen delirium Recommendation: resolve delirium first, then deal with catatonia if it remains Prognosis: General considerations Will continue until the underlying cause resolves Typically resolves in days, but can take substantially longer in those with known CNS disease Subsyndromal symptoms can return, even after days, and caretakers should be informed Clinical case: 24 y/o with agitation and psychosis A 24 y/o women with a history of depression is brought to the ED because of increasing disorganization and hostility. She is intermittently communicative, and when speaking is pressured and preoccupied with being chosen by god to save the world. At other times he stares off into space, mute while performing odd gestures with her hands. At other times she is tearful, angry and accuses her family of trying to poison her. Questions: 1) What is odd about this presentation? 2) Why is the history of depression important here? 3) What is a possible diagnosis? Clinical case: Delirious mania (Bell’s Mania) Delirium may be present in 10-20% of manic patients Acute onset of both manic and delirium symptoms - psychosis and catatonic symptoms are also common Difficult to treat with antipsychotics and mood stabilizers ECT and benzodiazepines seem most effective As always….rule out all medical causes of delirium Jacobowski et al. Journal of Psychiatric Practice. 19(1):15 (2013) Essential take home points Delirium is common and represents the brain under stress Establish the patients baseline function Always review medication and substance use Search for an etiology and rectify Use antipsychotics only when necessary, behavioral measures should be used first