IDENTIFYING AND MANAGING PSYCHIATRIC EMERGENCIES Delirium: Presentation, Epidemiology, and Diagnostic Evaluation (Part 1) COLIN J. HARRINGTON, MD; KALYA VARDI, MD 18 23 EN ABSTRACT state, acute brain dysfunction, acute brain failure, acute Delirium is a highly prevalent and complex neuro- organic brain syndrome, ICU psychosis, and metabolic en- psychiatric disorder marked by attentional dysfunction, cephalopathy, amongst others. The term delirium is derived disturbances in multiple cognitive domains, and changes from the Latin roots de (translated “away from”) and lira in motor behavior, perception, sleep, and thought pro- (translated “furrow of a field”) thus suggesting that one is cess. Delirium results from diverse toxic, metabolic, in- derailed from the plowed or straight path.11 fectious, and structural etiologies and is associated with The term encephalopathy is often employed in place of or a number of adverse outcomes. Delirium pathophysiol- alongside delirium and allows for the proper grouping togeth- ogy involves perturbation of multiple neurotransmitter er of delirium and dementia as cognitive disorders – while systems. Behavioral presentations of delirium are com- also providing for the longitudinal course-based distinction mon and are often misattributed to primary psychiatric between delirium and dementia, as acute and reversible, and processes. Diagnostic assessment of delirium includes chronic and progressive forms of encephalopathy, respec- thorough physical examination, careful cognitive test- tively. Use of this terminology also allows for description ing, appropriate metabolic and infectious studies, re- of the intermediate syndrome of sub-acute encephalopathy view of medications, and structural brain imaging and where cognitive dysfunction is often less obvious and electroencephalography as indicated. Pharmacologic and neuropsychiatric symptoms predominate. non-pharmacologic interventions have been documented to reduce the incidence and severity of delirium. Anti- EPIDEMIOLOGY, RISK FACTORS, AND OUTCOMES psychotics are the treatment of choice for delirium-related Delirium is a highly prevalent disorder estimated to occur agitation and psychosis. in 10%-15% of general medical-surgical inpatients, in 25%- KEYWORDS: Delirium, encephalopathy, cognitive disorder, 45% of hospitalized cancer patients, and in 80%-90% of agitation terminally ill palliative care patients.1,4,5,11,12 Rates of delir- ium are particularly high in the intensive care unit (ICU) where studies suggest that 30% of patients are delirious on admission and 60% develop delirium during the course of INTRODUCTION their critical illness.1,3,5,13-15 Upwards of 80% of mechanically Delirium is a complex neuropsychiatric disorder marked ventilated ICU patients are estimated to be delirious.14-16 by an alteration in level of consciousness, attentional dys- Models of delirium etiology suggest predisposing, pre- function, disturbances in other cognitive domains including cipitating, and perpetuating factors.1,2,4,11,17 Illness, pharma- memory, orientation, and language, and associated chang- cologic, and environmental factors likely play roles in the es in non-cognitive domains of motor behavior, perception, development and persistence of delirium. Identification of affect, sleep-wake cycle, and thought process.1,2 Delirium modifiable factors is crucial to prevention and optimal man- results from diverse etiologies and is associated with a agement of delirium. Older age, premorbid cognitive dys- number of adverse clinical and systems outcomes including function, medical illness burden, baseline poor functional secondary infections, falls, violence, and increased hospital status, and medication exposure are most highly predictive length-of-stay, healthcare costs, and mortality.1-8 While the of delirium development.1,2,4,5,11 Baseline cognitive dys- pathophysiology of delirium is poorly understood, the neuro- function is the most robust predictor of incident delirium behavioral syndrome likely represents a final common path- in the hospitalized patient with upwards of 60% of acute way of perturbation of multiple neurotransmitter systems encephalopathy episodes thought to occur atop a baseline operative across widely distributed neural networks.1,9-11 of cognitive impairment.1,13,17,18 Delirium superimposed on At its core delirium is a cognitive disorder and, as such, dementia or other types of cognitive dysfunction appears associated neurobehavioral changes and psychiatric signs more resistant to treatment.1,19 Surgical patients, especially and symptoms are considered secondary. Delirium has been those undergoing total joint replacement and cardiac proce- described in the medical literature since antiquity and has dures requiring bypass, are at particularly high risk for the acquired many diagnostic labels including acute confusional development of delirium.4,20-22 WWW.RIMED.ORG | RIMJ ARCHIVES | JUNE WEBPAGE JUNE 2014 RHODE ISLAND MEDICAL JOURNAL 18 IDENTIFYING AND MANAGING PSYCHIATRIC EMERGENCIES Delirium is associated with numerous adverse outcomes can sometimes “borrow the frontal lobe” of the organized including prolonged hospital length of stay,1 increased rates examiner and respond more appropriately than expected – of discharge to institutional care settings,3 increased health- a particularly relevant issue in the assessment of the less care costs,8 reduced quality of life,1,11 increased short- and obviously encephalopathic patient where proper diagnosis long-term mortality,5-7 and long-term cognitive impair- of abnormal behavior hinges on a comprehensive neuropsy- ment.9,13,14,18 Delirium in the ICU, after controlling for numer- chiatric assessment. In this regard, the act of examining the ous confounders, is associated with an increase in ventilator patient may change the examined – and thus should come dependent days and ICU length of stay, and is an independent after a period of simple observation and casual engagement. predictor of increased mortality in mechanically ventilated Delirium typically develops over hours to days. Subacute patients.16 Delays in diagnosis and treatment of delirium encephalopathies due to smoldering infection, slowly devel- are associated with increased mortality in ICU patients.23 oping metabolic derangements, chronic lithium intoxica- tion, and other drug toxicities can evolve over days to weeks. Cognitive and behavioral changes frequently fluctuate and CLINICAL PRESENTATION, EXAMINATION, follow a diurnal pattern. Assessment during periods of more AND COURSE lucid behavior can lead to the conclusion that patients are There are many definitions of delirium in the literature. cognitively intact, making subsequent behavioral changes Factor analysis studies suggest that the broad and hetero- and agitation diagnostically difficult to understand. geneous phenotype of delirium loads onto three core symp- Changes in motor behavior are common in delirium. Hy- tom domains including a “cognitive” domain (orientation, poactive and hyperactive subtypes of delirium have been attention, short-term memory, long-term memory, and visu- identified. Different pathophysiologies have been proposed ospatial ability), a “higher level thinking” domain (language for the two motor subtypes but have not been supported and thought process), and a “circadian” domain (sleep-wake to date. Patients often fluctuate between these two forms cycle and motor behavior).24 Common to all definitions of of delirium making single cross-sectional assessment di- delirium is a disruption in attention, often signaled by a agnostically insufficient. Hyperactive delirium, often the frank alteration in level of consciousness or sensorium. On result of drug intoxication and withdrawal states, can be as- a spectrum between stupor and normal consciousness, de- sociated with agitation and related patient and staff injury. lirium presentations can range from frank somnolence to Some studies suggest prognostic relevance to the motor sub- more awake and alert states marked by subtle concentra- types, with hyperactive delirium more responsive to phar- tional difficulty.1 Intact attentional function includes the macologic treatment and hypoactive delirium predictive of ability to focus, maintain, and shift attention according to worse outcome.1,2,11 environmental demands. Attentional dysfunction may man- Psychiatric symptoms and neurobehavioral changes ifest in clinical findings of obvious confusion with incongru- are common in delirium and range from frank agitation, ent responses to the examiner’s queries and in more subtle to restlessness, anxiety, dysphoria, tearfulness, apathy, ways where patients can focus initially but are distractible, withdrawal, disinhibition, disordered thinking, and per- impersistent, or perseverative on bedside and formal neu- ceptual disturbances of hallucinations and delusions. In rocognitive testing. If basic attention and concentration are contrast to behavioral symptoms of primary psychiat- impaired, then more complex cognitive functions of lan- ric syndromes that occur in a clear sensorium, behavioral guage, orientation, memory, and thought process are sec- changes in delirium occur atop a substrate of clinically de- ondarily disturbed. In cases of severe delirium, attentional monstrable abnormal brain function and are properly con- impairment can frankly preclude adequate assessment of sidered secondary phenomena. New onset psychiatric other higher order cognitive domains. symptoms should trigger examination of cognitive func-