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Delirium in the ICU

Muhammad K. Ali, MD Emory University School of Medicine 09/08/2011. Delirium in the ICU. Definition.

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Delirium in the ICU

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  1. Muhammad K. Ali, MD Emory University School of Medicine 09/08/2011 Delirium in the ICU

  2. Definition • Acute cognitive impairment in critically ill patients with disturbance of consciousness accompanied by a change in cognition or perceptual disturbance that develops over a short period (hours to days) and fluctuates over time.

  3. Core Features* • The American Psychiatric Association's Diagnostic and Statistical Manual, 4th edition* (DSM-IV) lists four key features that characterize delirium: • Disturbance of consciousness with reduced ability to focus, sustain, or shift attention. • A change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia.

  4. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. • There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a medical condition, substance intoxication, or medication side effect.

  5. Additional features that may accompany delirium include the following: • Psychomotor behavioral disturbances such as hypoactivity, hyperactivity with increased sympathetic activity, and impairment in sleep duration and architecture. • Variable emotional disturbances, including fear, depression, euphoria, or perplexity.

  6. Terminology • Various terms are used in the literature* • ICU psychosis • ICU syndrome • Acute confusional state • Septic encephalopathy • Metabolic encephalopathy • Acute brain failure • Acute organic psychosis *Ely et al, SeminRespCrit Care Med 2001; 22: 115-126

  7. Epidemiology • Underdiagnosed condition* • Delirium goes undiagnosed in >66% of patients • Increased incidence in ventilated patients • Incidence in critically ill patients range from 35-60%. • Up to 81.7% of mechanically ventilated pts developed delirium at some point during a Vanderbilt study. *Inouye SK et al. Arch Intern Med. 2001; 161: 2467-2473.

  8. 10 to > 50% older surgical patients at risk for delirium • Upto 25% of general inpatient geriatric patient and 80% of ICU patients experience delirium* • 26% of geriatric patients meet diagnostic criteria for delirium in the emergency department * Hustey, FM et al. Ann of Emerg Med,2002 Mar;39(3):248-53.

  9. Morbidity/ Mortality • Increased ICU complications* • Nosocomial pneumonia • Self extubation • Three fold higher reintubation rates • More than 10 additional inpatient days • 20% increased risk of prolonged hospitalization • 10% increased risk of death • Three fold increase in 6 month mortality * Ely et al, JAMA, 2004; 291: 1753-1762

  10. * Ely et al. JAMA 2004; 291: 1773-1762

  11. May lead to or acceleration of acquisition of Dementia post delirium • 10 & 24 % have persistent delirium • May lead to long term cognitive impairment • 1 year MMSE 5 points lower in patients with delirium

  12. Poorer functional status at 3 months and 6 months* • Significant association b/w days spent in delirium/ coma and increased likelihood of discharge to postacute care facility * Nelson et al. Arch Intern Med 2006: 166, 1993-1999

  13. Economic burden • Healthcare cost for delirium in the US estimated from $38 billion to $152 billion per year*. • Compare with estimated costs for nonfatal falls ($19 billion) or diabetes ($91.8 billion). * Leslie, D et al. Arch Intern Med. 2008; 168:27-32

  14. Mean total healthcare costs (2005 dollars) per survival day in the year after hospital discharge was $461 (± $570) in the patients with delirium vs $166 (± $195) in the patients without delirium (P < .001). • Total healthcare costs attributable to delirium ranged from $16,303 per year per patient to $64,421 per year per patient.

  15. * Milbradnt et al. Crit Care med 2004; 32:955-962

  16. MIND-ICU STUDY • MIND (Measuring the incidence and Development of Delirium and Dementia in Veterans Surviving ICU Care)* • First large cohort study to define the epidemiology of and identify modifiable risk factors for long-term CI and functional deficits of ICU survivors • To develop preventive and/or treatment strategies to reduce the incidence, severity and/or duration of long-term Cognitive impairment and improve functional recovery of patients with acute critical illness. * http:// clinicaltrials.gov/ct2/show/NCT00400062

  17. BRAIN-ICU Study • BRAIN (Bringing to Light the Risk Factors & incidence of Neuropsychological Dysfunction in ICU survivors)* • Primary purpose is to identify potentially modifiable risk factors of long term cognitive impairment i.e. development of Delirium & exposure to sedative and analgesic medications in ICU patients. * http://clinicaltrials.gov/ct2/show/NCT00392795

  18. Types of Delirium • Subcategorized into three types based on psychomotor symptoms • Hyperactive: • Previously termed as ICU Psychosis • Less common, 1.6% in its pure form • Restlessness, agitation, emotional lability, attempts to remove lines and catheters • Overall better long term prognosis* *Meagher, DJ et al. Semin Clinic Neuropsyhciatry, 2000; 5:75-85

  19. Hypoactive: • Sometimes referred to as encephalopathy • Very common (43.5 % pure form) • Remains unrecognized in 66-84% of hospitalized hospitalized* • Withdrawal, flat affect, apathy, lethargy and decreased affect • Worse long term prognosis compared to hyperactive *Inoye et al. Am J Med 1994; 97:278-288

  20. Mixed type • Patients can present with a mixed clinical picture or sequentially experience both subtypes. • Hpoactive part rarely gets recognized • Commonest, upto 54% of the patients

  21. * Peterson et al. J Am Geriatr Soc 2006; 54: 479-484

  22. Pathophysiology/ Neurobiology • Poorly understood biologic basis with several over simplified theories • Global cortical dysfunction manifested by slow alpha rhythm and abnormal slow wave activity (EEG)* • Brain lesions involving the Ascending Reticular activating system, specifically the dorsal tegmental pathway projecting from the mesenencephalic reticular formation to the tectum and the thalamus • Main hypothesis is a reversible impairment of cerebral oxidative metabolism and mutliple neurotransmitter abnormalities * Romano et al. AcrhNeurolPsychiatr 1944; 51:356

  23. Cerebral hypoperfusion • Several studies support the fact that CNS blood flow may be disrupted in delirium • Using xenon-enhanced CT during and after acute delirious states, a 42% reduction in overall cerebral blood flow has been found • Similar findings using PET-CT scans have been reported in Geriatric patients with delirium

  24. Neuroanatomic changes • In one study CT scans revealed that 61% of critically ill patients with delirium had gross white and gray matter atrophy, white matter lesions with hyperintensities, cortical and subcortical lesions, or ventricular enlargement • Periventricular cerebral atrophy on CT scanning found in in elderly psychiatric patients experiencing delirium when compared with matched controls

  25. Neurotransmitter imbalance • Acetylcholine and its precursor Choline • Serum anticholinergic activity “SAA” is a surrogate biomarker of anticholinergic processes • High levels of Phenylalanine and low levels of Tryptophan seen in delirium • Melatonin and Cortisol have also been linked • Imbalance in release, synthesis & degradation of GABA, glutamate,Monoamines (Serotonin, norepinephrine & Dopamine).

  26. Genetic variants* • Gene encoding for APOE4 (Apolipoprotein) variant • MAO metabolism regulatory genes: • COMT variants • X-linked MAOA variant (Xp11.23 locus) • DrD3 polymorphism/ SLC6A3 (GABA and Dopamine transmission) • Brain derived Neurotrophic factor (BDNF) variant * Gunther et al. Critical Care Clinics 24; 2008: 45-65

  27. * Flacker et al. J Geronto Bio Sci Med Sci 1999; 54A; B 243

  28. Risk factors • Dementia, strongest and most consistent • Apolipoprotein E4 phenotype • Chronic illness (including hypertension) • Advanced age • Depression • Smoking • Alcoholism • Severity of illness on hospital admission

  29. * McNicoll et al. J Am Geriatric Soc 2003; 51: 591-598

  30. Conceptual framework for exploring the interrelationship between delirium and dementia.

  31. Five important independent risk factors • Use of physical restraints • Malnutrition • Use of a bladder catheter • Any iatrogenic event • Use of three or more medications

  32. Causes • Systemic Illnesses • Hepatic failure • Uremia • Respiratory failure • Sepsis • Infections • Meningitis, Encephalitis, Brain abscess • HIV related CNS infections • Pneumonia, UTI

  33. Heart failure, dysrhythmias • Anemias • Heat stroke, hypothermia • Seizures • Primary or secondary brain tumors • Vascular catastrophies • CHI, ICH • CVA, SAH or Hypertensive encephalopathy

  34. Metabolic Causes • Fluid & Electrolyte Abnormalities • Hyper and hypoglycemia • Acidosis/alkalosis • Hyper and hypo Osmolar states • Endocrinopathies associated with Thyroid and Parathyroid • V itamin deficiency states, especially B1 and B12

  35. Toxic Causes • Substance intoxication, ETOH, Heroin, Cannabis, PCP, LSD • Medications: • Anitcholinerigcs (Diphenhydramine, TCAs) • Opioids (Meperidine), Sedative/ Hypnotics (Benzos) • H2RAs (Cimetidine), Corticosteroids • Anti-Parkinson drugs (Levodopa) • Drug withdrawal (ETOH, Opioids, Benzos) • Environmental- Poisoning- CO, CN, Insect Bites, Toxic Plants

  36. Surgery related Delirium • Preoperative • Polypharmacy, fluid and electrolyte imbalance • Intraoperative • Primarily drugs, anticholinergics, long acting Benzos • Postoperative • Hypoxia, hypotension, drug withdrawal

  37. Differential Diagnosis • Dementia • Psychiatric illnesses • Depression • Psychosis • Mania • Schizophrenia • Sundowning • Nonconvulsive Status Epilepticus • Focal Syndromes • Temporoparietal: Wenincke’s aphasia • Bitemporal dysfunction: KluverBucy syndrome • Occipital: Anton’s syndrome • Frontal/ Bifrontal: Tumor/ Trauma

  38. Monitoring • Society for Critical Medicine (SCCM) recommends routine monitoring of patients receiving mechanical ventilation • Two validated tools currently available • The Intensive Care Screening Checklist (ISSC) • Confusion Assessment Method for the ICU (CAM-ICU)

  39. ISSC • Eight item checklist • Score of > 4 indicates delirium • 99% sensitivity and 64% specificity • Inter-rater reliability 0.94

  40. Altered level of consciousness (if A or B, do not complete patient evaluation for the period) • A: No response, score: none • B: Response to intense and repeated simulation (loud voice and pain), score: none • C: Response to mild or moderate stimulation, score: 1 • D: Normal wakefulness, score: 0 • E: Exaggerated response to normal stimulation, score: 1

  41. Inattention (0 to 1) • Disorientation (0 to 1) • Hallucination-delusion-psychosis (0 to 1) • Psychomotor agitation or retardation (0 to 1) • Inappropriate speech or mood (0 to 1) • Sleep/wake cycle disturbance (0 to 1) • Symptom fluctuation (0 to 1) • Total score 0 – 8 (4 is the cutoff)

  42. CAM-ICU • Adapted from the original CAM to be used for nonverbal ICU patients • > 90% sensitivity and specificity • Relatively quick and easy to administer* • High compliance and accuracy *http://www.mc.vanderbilt.edu/icudelirium/

  43. * Ely et al. JAMA 2001; 286;2703-2710

  44. Management • Definitive treatment is to correct the underlying medical condition causing the disorder • Initial steps in management: • Conduct a careful review of the medical history • Physical examination findings, laboratory evaluations • Drugs including over-the-counter agents, illicit drugs, and ETOH • Selective neuroimaging studies may be inidcated • Often the etiology will be fairly obvious from the history and basic laboratory tests

  45. Nonpharmacological • Primarily for the non ICU setting • Repeated reorientation of patients • Repetitive provision of cognitively stimulating activities • Nonpharmacologic sleep protocol • Early mobilization, range-of-motion exercises

  46. Timely removal of catheters and physical restraints, • Use of eye glasses and magnifying lenses, hearing aids and earwax disimpaction • Adequate hydration • Use of scheduled pain protocol • Minimization of unnecessary noise/stimuli

  47. Dexmedetomidine (Precedex) • α-2 receptor agonist • Inhibits norepinehrine release • Downstream affects on neurotransmitters • Histamine, Orexin, GABA, Serotonin • Sedation and NREM sleep like effects • Lower incidence of delirium in post cardiac surgery patients*

  48. Pharmacological • Currently no drugs with regulatory approval for the treatment of delirium. • Haloperidol: SCCM guidelines recommend haloperidol as the preferred agent for the treatment of delirium • Adverse effects include • Extrapyramidal symptoms • Prolongation of the QTc, torsades depointes • Neuroleptic malignant syndrome, and akathisia

  49. Atypical Antipsychotics • Aripriparazole, Olanzapine, Quetiapine, Ziprasodone • Mechanism similar to Haldol, however besides Dopamine also affect Norepinephrine, Serotonin, Acetylcholine etc • Side effect spectrum similar to Haloperidol • 2005 FDA warning, mortality risk in elederly patients

  50. Summary points for Delirium management in ICU* • Monitor delirium regularly in ICU patients using a valid, reliable tool (ISSC or CAM-ICU). • Remember that the most is hypoactive and will be missed if not actively “looked for” • Discuss results of delirium assessments on all patients daily on interdisciplinary rounds • Identify patients with high number of risk factors for the development or persistence of delirium (eg, electrolyte imbalance, fever, addition of new medications; especially those with anticholinergic properties, uncontrolled pain, new onset of congestive heart failure or nosocomial infection, prolonged immobility and restrain use, sleep/wake cycle disturbance).

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