delirium in the icu
TRANSCRIPT
DELIRIUM IN THE ICU
JOÃO MELO ALVES, MDLISBOA, PORTUGAL
--GENERAL ICU
DIRECTOR: PROF. CHARLES SPRUNG, MD
DEPARTMENT OF ANESTHESIOLOGY AND INTENSIVE CAREHADASSAH EIN KEREM UNIVERSITARY HOSPITAL
JERUSALEMHEAD OF DEP.: PROF. CHARLES WEISSMAN, MD
Der Schrei der Natur,by Edvard Munch, circa 1893-1910
2João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
INDEX
THE DISEASE
DIAGNOSIS
MANAGEMENT
THE DISEASE
El sueño de la razón produce monstruos(by Francisco Goya, circa 1797-1799
(Metropolitan Museum of Art, New York)
4João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Delirium
Vs.
Acute confusional state / Encephalopathy
THE DISEASE
DIAGNOSIS
MANAGEMENT
DEFINITIONS
5João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
DSM-IV: four key features
Disturbance of consciousness with reduced ability to focus, sustain or shift attention
Change in cognition or new perceptual disturbance not explained by preexisting
dementia
Acute onset (hours to days), fluctuating course
Evidence that it is secondary to a medical condition, intoxication or side effect (history,
physical examination, laboratory results, …)
Psychomotor behavioral disturbances
Emotional disturbances
THE DISEASE
DIAGNOSIS
MANAGEMENT
DEFINITIONS
Diagnostic and Statistical Manual 4th ed. American Psychiatric Association. APA Press, 2013.
6João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Wherever there are (old) sick people…
30% of older medical patients experience delirium during hospitalization Francis J, J Am Geriatr Soc 1992; 40(8)
Up to 50% of older surgical patientsDyer CB et al., Arch Intern Med 1995; 155(5)
70% ICU patientsMcNicoll L et al. J Am Geriatr Soc 2003; 51 (5)
THE DISEASE
DIAGNOSIS
MANAGEMENT
EPIDEMIOLOGY
7João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
THE DISEASE
DIAGNOSIS
MANAGEMENT
PATHOGENESIS
Pathophysiology is poorly understood
Many different etiologies
8João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Global disturbance of cortical
function
EEG
Romano J, Engel GL. Arch Neurol Psych 1944; 51
Brainstem auditory evoked
potentials
Somatosensory evoked potentials
Neuroimaging
Trzepacz PT. Psychosomatics. 1994; 35(4)
THE DISEASE
DIAGNOSIS
MANAGEMENT
NEUROBIOLOGY OF ATTENTION
Ascending reticular activating
system (ARAS) – arousal and
attention
“Nondominant” parietal and
frontal lobes – attention
Higher order cortical function
– insight and judgement
9João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Acetylcholine disturbance – a final common pathway?
Anticholinergic drugs (vs. cholinesterase inhibitors)
Medical conditions that decrease acetycholine synthesis
Alzheimer’s diseaseMach JR et al. J Am Geriatr Soc 1995; 43 (5)
Campbell N et al. Clin Interv Aging 2009; 4
Golinger RC et al. Am J Psychiatry 1987; 144 (9)
Other neurotransmitters
Pro-inflammatory cytokines
(…)
THE DISEASE
DIAGNOSIS
MANAGEMENT
NEUROBIOLOGY OF ATTENTION
10João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Baseline vulnerability
Dementia
Stroke
Parkinson’s
Elie M et al. J Gen Intern Med 1998; 13 (3)
Fick DM et al. J Am Geriatr Soc 2002; 50(10)
THE DISEASE
DIAGNOSIS
MANAGEMENT
ETIOLOGY
Precipitants
Drugs and toxins
Infections
Metabolic derangements
Brain disorders
Systemic organ failure
Physical disorders
Immobility & restraints
DIAGNOSIS
Ward roundsby Robert Riggs, circa 1940
(Harvey Cushing/John Hay Whitney Medical Library, Yale University)
13João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Critically ill patients with…
Disturbance of consciousness
Change in cognition
Acute onset, fluctuating course
(Agitation, sleep disturbances, emotional disturbances…)
THE DISEASE
DIAGNOSIS
MANAGEMENT
CLINICAL PRESENTATION
14João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Classical medical approach is
limited on ICU patients
When in doubt…
Formal mental status testing
Specific validated tools
THE DISEASE
DIAGNOSIS
MANAGEMENT
RECOGNIZING THE DISORDER
16João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Confusion assessment method (CAM)
94-100% sensitivity, 90-95% specificityInouye SK et al. Ann Intern Med 1990; 113
Standard screening device in clinical studies
5’ to perform
Best of 11 bedside delirium dx toolsWong CL et al. JAMA 2010; 304
CAM-ICU
Validated for mechanically ventilated patientsEly EW et al. JAMA 2001; 286
Intensive Care Delirium Checklist for Screening
THE DISEASE
DIAGNOSIS
MANAGEMENT
ICU SCREENING TOOLS
MedCalc ©Pascal Pfiffner, Mathias Tschopp
17João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Targeted investigation
Fluid & electrolytes
Infections
Toxicity & withdrawal of drugs (abuse, BZD, SSRI, barbiturates, alcohol)
Metabolic derangements (glycemia, calcemia, uremia, liver, thyroid)
Low perfusion states
Inflammatory states
Hypercarbia and/or hypoxia
Seizures
Wernicke’s
Addison’s
CNS infection
Trauma
THE DISEASE
DIAGNOSIS
MANAGEMENT
INVESTIGATING THE CAUSE
18João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Primary CNS problems Focal syndromes
• Language – Wernicke’s afasia
• Memory – TGA (bitemporal dysfunction)
• Vision – Anton’s syndrome of cortical blindness
• Bifrontal lesions – akinetic mutism, lack of spontaneity/judgement, loss of working memory, blunted emotions
Review of brain CTs for “altered mental status” in ICU pts (n=123): 21% positive, 9% new diagnosis, 5% management change
Salemo D et al. J Intensive Care 2009; 24
Lumbar puncture: delirium >> classic triad of meningites on old critically ill
• Mandatory when cause is not obvious
• Low treshold for delirious febrile pts (even with more obvious concurrent causes)
Nonconvulsive status epilepticus EEG in altered consciousness in critically ill (n=570) – 19% prevalence
Claassen J et al. Neurology 2004; 62
Dementia
Psychiatric disorders
THE DISEASE
DIAGNOSIS
MANAGEMENT
DIFFERENTIAL DIAGNOSIS AND WORKUP
MANAGEMENT
Extraction of the Stone of Folly, by Hieronymus Bosch circa 1488 - 1516
(Rijks Museum, Amsterdam)
21João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
70% incidence on ICU patientsMcNicoll L et al. J Am Geriatr Soc 2003; 51 (5)
Prolonged hospitalization
Higher mortality
Functional and cognitive decline
Higher risk for institucionalizationRobinson TN et al. Ann Surg 2009, 249(1)
Inouye SK et al. J Gen Intern Med 1998, 13(4)
McAvay GJ et al. J Am Geriatr Soc 2006, 54(8)
Witlox J et al. JAMA 2010, 304(4)
Fong TG et al. Ann Intern Med 2012, 156(12)
(…)
THE DISEASE
DIAGNOSIS
MANAGEMENT
THE PROBLEM
22João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Duration of delirium (a modifiable factor) on mechanically ventilated ICU pts is
independently associated with long term cognitive impairment (unlike duration of
ventilation)Girard TD et al. Crit Care Med 2010, 38(7)
Long-term cognitive impairment after critical illness (n=821)
Medical and surgical ICU pts
6% pts w baseline impairment, 74% new onset delirium in hospital,
• 3 months: 40% had cognitive scores 1.5 SD below population controls (= moderate TBI) and 26% 2 SD (= mild Alzheimer’s),
• 12 months: at 12m 34% and 24%
Longer duration was independently associated with worse global cognition and executive function
Sedatives and analgesics were not associated with cognitivr impairment
Pandharipande PP et al. NEJM 2013, 369 (14)
SR/MA, 17 trials (n=2849)
effective interventions (drugs, multimodal, nonpharmacological) don’t improve short term mortality (RR 0.90; 95% CI, 0.76-1.06; p = 0.19)
Al-Qadheeb NS et al. Crit Care Med 2014, 42(6)
THE DISEASE
DIAGNOSIS
MANAGEMENT
THE PROBLEM
23João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Expert consensus
Observational studies
(few RCT)
SCCM guidelines (2013)
NICE guidelines (2010)
THE DISEASE
DIAGNOSIS
MANAGEMENT
MANAGEMENT
24João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Principles
1. PREVENTION – avoiding risk factors
2. TREAT THE CAUSE – identifying and treating underlying acute illness
3. SYMPTOM MANAGEMENT – supportive care // low dose, short
acting pharmacological therapy PRN
THE DISEASE
DIAGNOSIS
MANAGEMENT
MANAGEMENT
25João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Modifying risk factors
Orientation protocols
Cognitive stimulation
Physiologic sleep
• Earplugs, RCT n=138
Van Rompaey B et al. Crit Care 2012, 16 (3)
Early mobilization, avoiding restraints
• Early physical and occupational
therapy, RCT n=104
Schweickert WD et al. Lancet 2009, 373 (9678)
Visual/hearing aids
Monitor orders (e.g. bzd)
Pain
• RCT n=58, 3 vs 31%
Hudetz JA et al. J Cardiothorac Vasc Anesth 2009, 23(5)
THE DISEASE
DIAGNOSIS
MANAGEMENT
1. PREVENTION
Intervention bundles
cognitive impairment, sleep
deprivation, immobility, visual
impairment, hearing impairment,
dehydration
Prospective, n=872 (ward), 62 vs 90
episodes, 105 vs 161d
Inouye SK et al. NEJM 1999, 340(9)
26João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Medications? Cholinesterase inhibitors
Antipsychotics
• SR+MA, prophylatic neuroleptics post-operative (6 studies,
n=1689)Hirota T, Kishi T. J Clin Psychiatry 2013, 74(12)
Melatonin / ramelteon
Analgesics
THE DISEASE
DIAGNOSIS
MANAGEMENT
1. PREVENTION
28João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Metabolic derangements
Infections
Systemic organ failure
Drugs and toxins
Brain disorders
Physical disorders
Immobility & restraints
THE DISEASE
DIAGNOSIS
MANAGEMENT
2. DIRECTED TREATMENT
29João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Hyperactive delirium
Less common in older patients
Alternates with hypoactive delirium
n=614 MICU pts
• 71.8% incidence 65+ yo
• Hyperactive 1.6% vs mixed 54.9% vs hypoactive 43.5%
Peterson JF et al. J Am Geriatr Soc 2006, 54(3)
Falls, removal of catheters, acidental extubation (…)
Hypoactive delirium – no role for symptomatic treatment
Nonpharmacollogical interventions – the mainstay of therapy
Physical restrains as a last resort!
Cautious PRN trial of low dose, short acting drugs might be warranted
THE DISEASE
DIAGNOSIS
MANAGEMENT
3. SYMPTOMATIC TREATMENT
30João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Severe agitation only!
Very limited data…
SR 1980-2010, elderly patients with delirium – studies with severe methodological
limitations
Flaherty JH et al. J Am Geriatr Soc 2011, 59 suppl 2
Multicenter RCT, n=101 ICU pts – no benefit nor risk (but feasible)
MIND placebo RCT. Girard TD et al. Crit Care Med 2010, 38(2)
THE DISEASE
DIAGNOSIS
MANAGEMENT
3. SYMPTOMATIC TREATMENT - DRUGS
31João Melo Alves, MD (Lisboa, Portugal) March 2015, GICU Hadassah Ein Kerem Universitary Hospital, Jerusalem
Haloperidol
Standard therapy
Adverse effects: extrapyramidal; QT prolongation & TdP (++IV)
0.5-1mg PRN PO/IV/IM (max 5mg qd); onset 30 min
Atypical antipsychotics – quetiapine, risperidone, ziprasidone, olanzapine
Fewer side effects, similar efficacy
Benzodiazepines
Role limited to sedative/alcohol withdrawal or 2nd line therapy
Carnes M et al. J Am Geriatr Soc 2003, 51(2)
Lorazepam ∆20% RR in ICU pts
Pandharipande P et al. Anesthesiology 2006, 104(1)
Midazolam 77% vs dexmedetomidine 54% in ICU mechanically ventilated pts
Riker RR et al. JAMA 2009, 301 (5)
Cholinesterase inhibitors
Placebo RCT (n=104) stopped due to higher mortality (22 vs 8%)
Van Ejik MM et al. Lancet 2010, 376 (9755)
THE DISEASE
DIAGNOSIS
MANAGEMENT
3. SYMPTOMATIC TREATMENT - DRUGS
KEY MESSAGES
Delirium is a disturbance of consciousness and cognition of acute onset and fluctuating course, secondary to a medical condition, intoxication or side effect
It is highly incident in the elderly sick, reaching 70% in the ICU
Underlying brain disease increases the risk, but common causes can precitate delirium even in its absence
The recognition of its clinical presentation should prompt formal screening with validated bedside tools (e.g. CAM-ICU) and targeted investigation for the underlying culprit
The relevance of the entity lies on the association with bad outcomes, namely higher mortality and long-term cognitive impairment, which can be prevented to an extent with the appropriate timely measures
There are available clinical guidelines, based on the limited evidence and expert consensus
Management is based on prevention (risk factors), cause-directed treatment, and symptom management
Nonpharmacological interventions are the mainstay of symptom management, but antipsychotics might be warranted on severe hyperactive delirium
The pharmacological treatment relies on antipsychotics, mainly typical (e.g. haloperidol) but atypical show promise with similar efficacy and better side effect profile
CORE REFERENCES
1. Barr J et al. Clinical practice guidelines for the management of pain, agitation and delirium in adult
patients in the intensive care unit. Crit Care Med 2013; 41(1):263
2. National Institute of Health and Care Excelence (NICE). Delirium: diagnosis, prevention and
management. NICE clinical guideline 103, July 2010. @ guidance.nice.org.uk/cg103
3. McNicoll et al. Delirium in the intensive care unit: ocurrence and clinical course in older patients. J Am
Geriatr Soc. 2003; 51(5):591
4. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability
of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001; 286:2703
5. Pandharipande PP et al. Long-term cognitive impairment after critical illness. NEJM 2013;
369(14):1306
6. Francis J, Young GB. Diagnosis of delirium and confusional states. UpToDate, Jan 2015, version 14.0
7. Francis J. Delirium and acute confusional states: prevention, treatment and prognosis. UpToDate, Jan
2015, version 10.0