delirium in the icu

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)


Delirium

Vs.

Acute confusional state / Encephalopathy

THE DISEASE

DIAGNOSIS

MANAGEMENT

DEFINITIONS


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.


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


THE DISEASE

DIAGNOSIS

MANAGEMENT

PATHOGENESIS

Pathophysiology is poorly understood

Many different etiologies


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


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


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)


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


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


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


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


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)

Why should we care?


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


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


Expert consensus

Observational studies

(few RCT)

SCCM guidelines (2013)

NICE guidelines (2010)

THE DISEASE

DIAGNOSIS

MANAGEMENT

MANAGEMENT


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


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)


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


Metabolic derangements

Infections

Systemic organ failure

Drugs and toxins

Brain disorders

Physical disorders

Immobility & restraints

THE DISEASE

DIAGNOSIS

MANAGEMENT

2. DIRECTED TREATMENT


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


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


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

delirium in the icu

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