Delirium in the ICU: Prevention and Treatment S. Andrew Josephson, MD Director, Neurohospitalist Service Medical Director, Inpatient Neurology June 2, 2011 Delirium Defined Officially (DSM-IV-TR) criteria for delirium (a) Disturbance of consciousness (that is, reduced clarity of awareness of the environment, with reduced ability to focus, sustain, or shift attention) (b) A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a pre-existing established or evolving dementia (c) The disturbance developed over a short period of time (usually hours to days) and tends to fluctuate during the course of the day Delirium: Really Defined Relatively acute onset of encephalopathy Cognitive change Attentional deficit the hallmark Test at bedside with digits forwards All domains may be impaired Fluctuations key Associated symptoms that may be present Hallucinations, delusions, altered sleep-wake cycle, changes in affect, autonomic instability Worse in the late evening
Delirium vs. Dementia This distinction is easy : Not so easy Dementia has been shown to be a major risk factor for development of delirium in many settings Some degenerative illness can present just like delirium: ex.) Dementia with Lewy Bodies Clinical Spectrum of Delirium Hyperactive Subtype Classically: EtOH withdrawal DTs Hypoactive Subtype (40-45%) Classically: narcotic or benzo administration This type more likely to be missed by clinicians Studies show associated with a worse outcome In reality, delirium is likely a spectrum between these two subtypes Many clinicians do not recognize this spectrum Epidemiology Wide ranging estimates Depends on group studied 30-50% of ICU non-intubated patients 80% of those on mechanical ventilation Caveats No good definition Likely 1/3 cases missed Especially more hypoactive presentations in the ICU
Who cares? Viewed in the past as a transient benign condition Significant morbidity and mortality demonstrated Prolonged hospitalization and therefore costs Estimated $38-152 billion/year in U.S. in delirium costs Delirious pts have increased hospital and ICU mortality Delirious patients have longer ICU stays and more likely to be d/c d to a nursing home Long-term cognitive effects? PTSD, dementia Pathophysiology of Delirium Anatomical final common pathway Some focal strokes: anteromedial thalamus and right MCA territory suggest these areas involved Cholinergic deficit is key in these patients Baseline decreased cerebral reserve present in most Hospitalization and illness leading to delirium a sort of stress test for the brain Patients with underlying (often unrecognized) cognitive illness are at highest risk Delirium: A Stress Test for the Brain Threshold for cognitive dysfunction Patient A Patient B 25mg PO Nortriptyline UTI 200mg IV Benadryl
Risk Factors for Delirium Patient characteristics Increasing age Baseline cognitive impairment Baseline vision, hearing or functional impairment Previous episode of delirium Dehydration Fever or hypothermia In-hospital characteristics Sensory overload Isolation Bladder Catheterization Physical Restraints Adding three or more new medications Why care about delirium in the ICU? Important example of organ dysfunction ( brain failure ) caused by multiple etiologies Similar to pulmonary or cardiac failure, there is a general treatment approach as well as a specific approach based on etiology Should be relatively easy to standardize assessment and care Thought to be underrecognized and often quite treatable Evaluating Patients for Delirium Multiple screening tools have been examined for delirium, each with its own caveats Compared with DSM-IV criteria: likely insensitive Would like to design a tool that is short and easy to use by nurses as well as physicians ABCDE bundle
Confusion Assessment Method (CAM-ICU) Sensitivity and specificity > 90% Four elements (need 1 and 2 and 3 or 4) used to define delirium at the bedside 1. Acute Onset and Fluctuating Course 2. Inattention 3. Disorganized Thinking 4. Altered Level of Consciousness (RASS) icudelirium.org Evaluating the Delirious Patient Delirium should be approached as a sign of serious underlying illness Check medication list thoroughly first Any medicines with anticholinergic properties Identify any sedatives and analgesics administered during the hospital stay Many other medicines associated with delirium Look for temporal correlation between medication changes and the onset symptoms Evaluating the Delirious Patient Initial Laboratory Tests: CBC, BUN/Cr, Lytes, Ca/Mg/Phos, LFTs Seemingly small abnormalities (i.e. Na=130) can contribute ABG Utox CXR, blood cultures, urine cultures for systemic infection Initial Imaging with CT or MRI
Further Evaluation If no cause identified 1. Consider LP To exclude meningitis (bacterial, viral) To exclude other inflammatory conditions For diagnosis of other specific conditions 2. Consider EEG Estimates of 10-20% seizure frequency in this population Often without outward clinical signs Oddo M et al: Crit Care Med 2009 Goal-Directed Sedation Therapy? Challenging to select a good agent for ICU patients at risk for developing delirium Likely should be individualized Benzodiazepines should be avoided except in treating withdrawal syndromes Pain control is important for delirium prevention, but agents commonly used often make delirium worse Preferred Agents Often choose to select agents with short duration of action that are rapidly reversible Can frequently fully wake up the patient In order to monitor exam and screen for delirium Benefit of frequent reorientation to prevent delirium? Propofol, dexmedetomidine common choices
Dexmedetomidine: SEDCOM/MENDS Compared with lorazepam and midazolam in two key trials Decreased incidence of delirium, coma, days on the ventilator Better comparator studies are pending Ricker RR et al: JAMA 2009 Pandharipande PP et al: JAMA 2007 How about Aricept? Given the striking cholinergic deficit in delirium, mechanistically makes sense Previous use of IV pyridostigmine decades ago anecdotally was successful Recent prevention trials of cholinesterase inhibitors in various perioperative settings were unsuccessful Gamberini M et al: Crit Care Med 2009 Management of Delirium Swift identification and treatment important Delays increase mortality, length of intubation, and nosocomial infections Treat underlying precipitant first! Correct lytes, treat infection, remove offending medications, etc
Management of Delirium Then use environmental methods proven to help in delirium management Turn off lights to establish sleep-wake cycles at night Remove all physical restraints (key contributor in multiple studies of delirium) D/C unnecessary monitors and catheters Provide reorientation frequently Maintain adequate hydration Daytime mobilization and exercise Make sure hearing aids, glasses used at home are present Familiar pictures, objects, visitors can help Evidence for These Simple Measures Randomized trial showed that these simple measures decrease incidence of delirium in hospitalized elderly Shouldn t We Just Treat the Symptoms? Two theories 1. We have to treat uncomfortable, disruptive symptoms for the sake of the patient and staff 2. As a last resort, consider medical management only when the patient poses a harm to themselves or others Again: always avoid benzos unless patient has EtOH or benzo withdrawal
Antipsychotics Commonly used for this purpose but evidence is quite limited that outcomes are improved Caution in elderly given risk of sudden death QT needs to be monitored but is likely only part of the story Antipsychotics: Do they work? Recent study of haldol vs ziprasidone vs placebo showed no difference in resolution of delirium, length of delirium, length of stay in the ICU, or 21-day mortality A separate study showed haldol superior to placebo (especially when paired with quetiapine) in resolution of delirium and agitation Multiple key studies ongoing Girard TD et al: Crit Care Med 2010 Devlin JW et al: Crit Care Med 2010 Similar Choices to Prevention Literature Dexmedetomidine Pilot study suggests shorter time to extubation and shorter length of stay compared with haldol Cholinesterase inhibitors do not decrease the duration of delirium based on recent data May increase mortality Reade MC et al: Crit Care 2009 van Eijk MM et al: Lancet 2010
Take-Home Points Delirium is an under-recognized significant cause of morbidity and mortality in the ICU All patients should be screened frequently for delirium: you may be surprised what you find Treatment involves specific measures and simple measures with only occasional use of agents directed against hallucinations/agitation Research has a long way to go but were getting there slowly