Legacy of Critical Illness

8/14/2019 Legacy of Critical Illness

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,Nerves

Margaret Herridge MD MPH

Associate Professor of Medicine

n vers y ea e wor

University of Toronto

Canadian Critical Care Trials Grou


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Objectives

Definition and diagnosis of Brain, CIP/ CIM

Prevalence and risk factors

- -outcomes


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Nerve, Muscle and Brain represent

the 3 end organs responsible for

most long-term morbidity after a

severe episode of critical illness.

Dur ng t e ICU stay, t ese organ

systems are largely ignored.


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Major Morbidities

Hopkins et al. AJRCCM 1999;160:50-6.

Schelling et al. Int Care Med 2000; 26:1304-11.

Jones and Griffiths CCM 2001; 29: 573-80 Orme et al. AJRCCM 2003; 167: 690-4.

Ho kins et.al. AJRCCM 2005 171:340-7.

Kapfhammer et al. Am J Psychiatry 2004; 161: 45-52.

Hopkins and Jackson Clin Chest Med 2009; 30: 143-153

-.


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ARDSControls

Women, 36 Years

Volumetric CT Data

40

ARDS

Controls

10

20

30

cm3

0

Lateral

Ventricles

Total

Ventricles

Ventricle-

B rain-Ratio

Men, 54 Years

Hopkins 2006 Brain Injury 20;263-71.

Courtesy of Mona Hopkins


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1 & 2 Year Cognitive Outcomes

60

80

hDeficits

Hospital DC

1 Year

2 Years

20

40

Percentwit

0Process ing

Speed

Mem ory Exe cutive Attention IQ

Hopkins et al. AJRCCM 1999; 160:50

op ns e a . n europsyc ssoc ; :

Persecutory Delusions

Griffiths and Jones BMJ 1999; 319:427-9.


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Potential Mechanisms of CognitiveSequelae

. ypox a (Hopkins 1999, 2004; Fries 2004)

2. Hypotension (Hopkins 2005)

3. Delirium Jackson 2004 El 2001

4. Corticosteroids (Belanoff 2001; DeQuervain 2000)

5. Cortisol (Sapolsky 1996; Bremner 1997)6. Genetic Markers (ApoE)

7. Neurologic Markers (S100-B; NSE) (Herrmann 2000;

Rosen 1998)

8. Inflammatory mediators (Arvin 1995)

9. Sedatives & Analgesics (Kress 2000, 2001)

Courtesy of Mona Hopkins


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Psychiatric Morbidity

Depression 17% - 43%

Anxiety 23% - 48%

PTSD 21% - 35%

ar a ty n nstruments, t res o s or c n ca s gn cance,

baseline psychiatric history exclusions and timing of

assessment

Dav dow et al. Ps chosom Med 2008; 70: 512-9.


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Potential Mechanisms ofPs chiatric D sfunction

Duration of mechanical ventilation, sedation

and ICU sta - de ressive and PTSD

symptoms in ALI / ARDS survivors

Recall of ICU-related pain, breathing

cu t es, n g tmares, m te soc a

support , anxiety associated with PTSD

s m tomsSchelling et al. Crit Care Med 1998; 26:651-9

Stoll et al. Int Care Med 1999; 25:697-704.

Kapfhammer et al. Am J Psychiatry 2004; 161: 45-52.

Jones Griffiths et al. Crit Care Med 2001 29: 573-80.


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Evidence for Weakness as Major Morbidity

McHugh et al. AJRCCM 1994;150:90-4.

Weinert et al. AJRCCM 1997 156:1120-8.

Davidson et al. JAMA 1999; 281:354-60.

Angus et al. AJRCCM 2001;163:1389-94.

. -

Combes et al. CCM 2003; 31: 1373-1381

Herridge et al. NEJM 2003; 348:683-93.

Chelluri et al. CCM 2004; 32: 61-69.


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- cqu re ea ness

CIPN

CIPNM ICUAP

Incidence25% - 60%

CINMAsurveillance, definition,

diagnostic testing, bias,

confoundin , case-mix

De Letter et al. Crit Care Med 2001; 29: 2281-6

DeJonghe et al. JAMA 2002; 288: 2859-67.

Stevens et al. Int Care Med 2007; 33:1876-91

Hough et al. Int Care Med 2008 In Press


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Critical Illness Polyneuropathy (CIP)

Acute axonal sensory-motor polyneuropathy

In ur related to microcirculator dama e

Mediated by E-selectin and induced byproinflammatory cytokines

Pure functional impairment in the absence ofstructural change

Bolton et al. J Neurol Neurosurg Psychiatry 1986; 49: 563-573

Hotchkiss et al. CCM 1999;27:1230-1251.

Fenzi et al. Acta Neuropathol 2003; 106:75-82

Hermans et al. Critical Care 2008; 12: 238


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ncrease n -se ect n on ep neur um an en oneur um

-, -

n o e a ce eu ocy e a es on an ex ravasa on

of activated leukocytes within the endoneurium

T ssue In ury


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Latronico et al. Current Opinion in Critical Care 2005; 11:126-132


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Acute primary myopathy causing muscleweakness or paralysis in critically ill patients-

u can a so coex s w 3 Forms: 1) Diffuse non-necrotizing cachetic

2) thick- filament myopathy


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-

reduced excitability - so-called acquired NaChannelopathy

NO mediated mitochondrial dysfunction Cytokine-mediated activation of the

u qu n-pro easome, ca pa n, ysosomasystems- intracellular proteolytic systems-

effect catabolism ossibl to liberate moreamino acids etc.with stress

Brealey et al. Lancet 2002; 360:219-223

DiGiovanni et al. Ann Neurol 2004;55:195-206

Novak et al. J Clin Invest 2009; 119: 1150-1158


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Latronico et al. Current Opinion in Critical Care 2005; 11:126-132


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All bio sies were abnormal 6-2 months after ICU dischar eNo patients were exposed to steroids or paralytics

Most common abnormality was type II fiber atrophy

Manifested as narrow angulated fibers; myofibers were reduced to

clumps of myonuclei

Myofibrillary disarray on EM

Changes not exclusively attributable to disuse atrophy


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Ev ence o ap ragmat c atrop y an ncrease proteo ys sat 18 hours of mechanical ventilation

De Jonghe, B. et al. JAMA 2002;288:2859-2867

Ali N et al. AJRCCM 2008; 178:261-268


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Five-Year Outcomes in

ARDS

Herridge et al. 2009

and reduction in Physical

QOL at 5-years after ICU

discharge


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outpatient

rehabilitation

homecare

pharmacy

imaging and labs

physicians

Other

Subsequent hospitalization

Inpatient rehabilitation

os - sc arge os s

$28,350

Cheung et al AJRCCM 2006; 174: 538-544


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Prevalence and Risk Factors

True prevalence difficult to ascertain and-

examination and diagnostic criteria

Linked to sepsis, MODS, female sex, use ofcorticosteroids, asthma, ionic (Na)abnormalities, immobility and malnutrition

Hermans et al. Crit Care 2008; 12 : 238


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,

and Nerve Injury

Brain dysfunction may complicate ICU and post-ICUstay and may be irreversible in some patients

Similarly, nerve and muscle dysfunction maycomplicate short and long-term outcomes aftercritical illness

Pathophysiology of these lesions is complex andmultifactorial

uncertainty about how best to intervene Significant impact on quality of life and caregiver

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Legacy of Critical Illness