Download Neurological Prognostication Post Cardiac Arrest

Anoxic Auguring:
Neurological Prognostication After
Cardiopulmonary Resuscitation
Where do we stand in 2011?
Robert Altman
PGY 4, Neurology Resident
McGill University
Division of Neurology, McGill University Health Center
May 18th 2011
πρόγνωση
• Prognosis
• “Fore-knowing”
Φρόνησις
• Phronesis
• “Practical wisdom”
Case 1
•
•
•
•
55 M collapses while jogging
CPR immediately initiated by bystander
V-fib arrest; circulation restored after 6 minutes
Exam (day 1): comatose, absent pupillary and corneal
reflexes, extensor posturing to pain, myoclonic status
epilepticus
• CT head (day 2): Normal study
• SSEP (day 3): Absent N20 responses
• Exam (day 3): Unchanged
Case 2
•
•
•
•
•
35 M collapses while playing basketball
CPR immediately initiated by bystander
PEA arrest; circulation restored after 20 minutes
Induced hypothermia x 24 hours (32 degrees C)
Exam (day 1): Comatose, pupils fixed, triggers ventilator but
otherwise no evidence of intact brainstem function, no
spontaneous movements or motor response to noxious stimuli
• EEG (day 2): Severe diffuse slowing of cerebral activity
• Exam (day 3): Comatose, pupils reactive, oculocephalic,
corneal, and gag reflexes intact, triggers ventilator, flexor
posturing of upper limbs to pain, no spontaneous movements
Case 3
• 71M with HTN, CAD (previous CABG), collapsed at
home
• No CPR administered
• PEA arrest; circulation restored after 20 minutes
• Exam (day 1): Comatose, R pupil reactive/L pupil fixed,
corneal reflex present but sluggish, no ocular response to cold
calorics, no spontaneous movements, left arm and leg withdraw
to painful stimuli, bilateral Babinski signs
• MRI brain (day 2): Cerebral infarctions in superficial and
deep watershed territories bilaterally (L > R)
• SSEP (day 3): N20 response present on right, absent on left
• Exam (day 3): Unchanged
Outcome?
Poor or favourable?
Why? What do you base your
judgement on?
Outline
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Cases
Historical Perspective
Prognostication Guidelines
The Era of Hypothermia
Approaching the Family
Return to Cases
Take Home Points
Mission (im)possible?
The neurologists role: To predict with perfect accuracy the likelihood
of awakening and (if the patient survives) future morbidity.
Self-fulfilling prophecy?
•A physician’s negative expectation or overreliance on laboratory tests affects
management decisions and thus outcome.
•Therefore paramount that studies adhere strictly to independent assessment of
prognostic indicators and outcomes
‘Poor’ Prognosis
• Glasgow Outcome Scale (GOS) ≤ 3
– Cerebral Performance Scale (CPC) ≥ 3
• Emphasis on the ‘poor’ because may facilitate
decision for withdrawal of life-sustaining
therapies
• Tests ideally have a 0% FPR for determining
poor prognosis, narrow CI’s
N.B. No postarrest physical examination finding or diagnostic study has
as yet predicted poor outcome of comatose cardiac arrest survivors
during the first 24 hours after ROSC
N Engl J Med 2009;361:605-11
C. Booth JAMA, February 18, 2004—Vol 291, No. 7
Outcomes
Severe
Disability
Vegetative (GOS3)
State
(GOS2)
Moderate
Disability
(GOS4)
Good
(GOS5)
Dead
(GOS 1)
Bernat. Neurology® Clinical Practice 2010;75(Suppl 1):S33–S38
History of Prognostication
• Levy et al (1985) establishes algorithms for
neurological prognosis
– Determinations derived from a single cohort study, 211
patients
– Not without limitations
• Statistical uncertainty
• Since (late 70’s); revolution in critical care since this era
• How many patients suffered from a cardiac arrest in the Levy
cohort? How many were cooled?
– Only 71% suffered cardiac arrest
– TH only introduced in 2002
Levy DE, et al. JAMA 1985;253:1420-1426
Meta-analysis of relevant literature from 1966-2006;
391 papers reviewed and rated.
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
AAN Recommendations
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
The Tools
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•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
Clinical Exam
Brainstem
Physical exam, clinical findings
• Present vs. Absent (day 1 to 3)
– Pupils (CN II,III)
– Corneal reflex (CN V, VII)
– Cold calorics (CN VIII, VI, III, MLF)
• Motor responses (day 1 to 3)
– Flexion vs. extension / none
0 % FPR for poor
outcome, narrow
CI’s, 10 studies.
Clinical Exam
• Since Levy et al.
– Prospective, class I studies.
Zandbergen, et al. Neurology 2006;66:62–68.
Point in fact – Clinical Exam
• The brainstem is more resistant to anoxia than
the cortex, thus if abolished BS reflex, this
generally implies a severely damage cortex
• Preserved BS reflexes by no means imply
intact cortical function
• No direct way of evaluating cortical activity in
an unconscious patients
Related to Poor Outcome but
Insufficient Predictive Value
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•
•
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Age
Sex
Cause of arrest
Type of arrhythmia (vfib or asystole)
Total time of arrest
Duration of CPR
Based in 2 large prospective studies involving 774 patients
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
Blood work – Biochemical Signs
•
•
•
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NSE (neuron-specific enolase)
S100 (glial protein)
BB fraction of creatine kinase (serum or csf)
Neurofilament protein
• Combination panels
Blood work – Biochemical Signs
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•
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•
NSE (neuron-specific enolase)
S100 (glial protein)
BB fraction of creatine kinase (serum or csf)
Neurofilament protein
• Combination panels
Blood work – Biochemical Signs
• NSE (neuron-specific enolase)
– ≥33µg/L, b/w 1-3d post arrest
– Reflects diffuse CNS injury
• Only validated use in carcinoid & other
tumors
– Not commonly available in N.
America
• Not at MUHC, CHUM, Ontario
– Variability in assays and cut-off
values
– Class B
0 % FPR for poor
outcome, CI 0-3;
One class I study
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
Neuroimaging
• Findings correlate poorly with functional prognosis
• Performed to rule out primary neurological
catastrophe, as aetiology of cardiovascular event
• However,
– CT often normal on day 1
• Technical barriers may preclude neuroimaging
– i.e. Hemodynamic instability, inability to transfer
• Class U
Diagnostic value not prognostic
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
The Tools
•
•
•
•
Physical exam, clinical findings
Blood work – Biochemical Signs
Neuroimaging (CT, MRI)
Electrophysiology (EEG, SSEP)
Cortical and
subcortical GM
EEG , SSEP
EEG
• Early myoclonic status correlates with poor
outcome
– At 24hrs, 0% FP
– Bilaterally synchronous twitches of limb, trunk or
facial muscles
– Supported by autopsy and multiple trials
• Status epilepticus, GTC seizures, multifocal
asynchronous myoclonus
– Represent nonspecific indicator of metabolic
encephalopathy without real prognostic value
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
EEG
• FPR for poor outcome 3% (95% CI: 0.9% to
11%) with malignant EEG patterns
– Malignant categories include suppression, burstsuppression, alpha and theta pattern coma, and
generalized periodic complexes combined;
“(malignant EEG group)...therefore strongly but
not invariably associated with poor outcome”
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
Status Epilepticus
Burst Suppression
Myoclonic Status
86 F, post cardiac rest
Etiology unclear
Duration of downtime unknown
18 hours after
resuscitation, patient was
in coma with intact
brainstem reflexes
Clinical movements q3-5
Video of myoclonic status
epilepticus
What is SSEP?
• SSEP = Somatosensory Evoked Potential
• N20 response primary somatosensory cortex
– 200 consecutive rapid stimulations are given to
the median nerve
– Recorded at
• brachial plexus
• cervical spinal cord
• At 20 msec, contralateral somatosensory cortex
N Engl J Med 2009;361:605-11
SSEP and Prognosis
• Bilateral absence of the N20 component of
the SSEP with median nerve stimulation
recorded on days 1 to 3 after CPR accurately
predicts a poor outcome
Zandbergen, et al. Neurology 2006;66:62–68.
Pros/Cons of SSEP
+: not influenced by medications, able to be
performed when brainstem testing limited
– mechanical or metabolic reasons; including
hypothermia
- : confounded in many ways
– any interruption in somatosensory pathways
invalidates test
Tiainen M, et al. Crit Care Med 2005; 33: 1736–1740
SSEP’s: Clinical Practice
• Physicians’ use of SSEP fuel decisions about
withdrawal of life support.
• 58 comatose CPR survivors referred for
neurologic consultation
• SSEP testing correlated best with waiting time to
withdrawal of life-sustaining therapies.
– 40 patients whose life support was eventually
withdrawn, the median waiting time was 7 days for
patients with preserved SSEPs and only 1 day in
patients with bilaterally absent N20 SSEP components.
Geocadin RG et al. Neurologic prognosis and withdrawal of life support after
resuscitation from cardiac arrest. Neurology 2006 Jul 11; 67:105-8.
AAN 2006
Practice
Parameter
Confounders
•Hypothermia
•NM blocking agents
•Large dose sedatives
•Organ failure
•Shock
Absent pupils/corneal
and extensor/no motor
response.
Outline
•
•
•
•
•
•
•
Cases
Historical Perspective
Prognostication Guidelines
The Era of Hypothermia
Approaching the Family
Return to Cases
Take Home Points
History of Prognostication
• Levy et al (1985) establishes algorithms for
neurological prognosis
– determinations derived from a single cohort study
– Not without limitations
Levy DE, et al. JAMA 1985;253:1420-1426
• Therapeutic hypothermia early 2000’s, 2 major
publications in the NEJM 2002
– TH Increased the rate of a favourable neurologic outcome and
reduced mortality.
N Engl J Med 2002;346:549-56
N Engl J Med 2002;346:557-63
The Conundrum
• TH now used for neurological protection for a
multitude of other life-threatening catastrophes
– Worldwide 25% - 75% of all admitted resuscitated
patients
• Prognostication tools thus need revalidation
• Life-sustaining therapies outpacing our capacity for
accurately predicting outcomes
Era of Therapeutic Hypothermia (TH)
• Studies ongoing and constantly emerging
• Single studies show cooling:
1. Delayed motor response up to 6 days; 3 of 37 regained
awareness
– E. Thenayan, M. Savard et al. Neurology 2008;71:1535–1537
2. Hypothermia to 32°C or above increases latency of SSEP’s
by approximately 15%, reductions of temperature below
30°C can decrease the N20 amplitude by up to 20%
3. Decreases NSE levels
• May reflect neuroprotection?
– M.Tiainen, Risto O. Roine. et al. Stroke 2003;34;2881-2886
Dr. Bryan Young
“It is highly likely that the factors that have been
shown to be reliable predictors in the past —
such as loss of pupillary and corneal reflexes
and of somatosensory-evoked responses —
will be validated.”
“However, the timing of the testing of some
variables may require adjustment”
• 192 patients (103 TH vs 89 NT)
• Primary outcome = in hospital death (GOS 1)
• The absence of pupillary light responses, corneal reflexes, and
extensor or absent motor response at 72h remained accurate
predictors (p < 0.0001 for all)
• Myoclonic status epilepticus (p < 0.0002)
• NSE > 33 ng/ml has a high false-positive rate in patients treated
with hypothermia and should be interpreted with caution
J Fugate, E F.M. Wijdicks et al ANN NEUROL 2010;68:907–914
Nov 2010
Outline
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•
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•
•
Cases
Historical Perspective
Prognostication Guidelines
The Era of Hypothermia
Approaching the Family
Return to Cases
Take Home Points
Discussion with family
• Uncertainty furthers emotional distress of a grieving and
anxious family
• Respect decision made by the patient’s lawful surrogate
decision-maker who attempts to faithfully represent the
treatment preferences of the patient
• Compassionate communication
• Encouragement of emotions
• Appreciation of personal values and religious
preferences
• Define “poor outcome”
– PVS
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
“Poor outcome”
• Terms
– “Severely disabled state, requiring long-lasting or
indefinite comprehensive nursing care”
– “Hope for significant recovery is unrealistic”
– “Chances of meaningful recovery extremely negligible”
– “Fully dependent state of living”
• Some possible reasonable options
–
–
–
–
Extubation
Discontinuation of ionotropes, vasopressors
Discontinuation of ivf, nutrition
Turn off monitor
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
Persistent Vegetative State (PVS)
Wakefulness without awareness
Observation
Exam
Sleeps with eyes closed, open during the
day
Nonpurposeful limb movements, posturing
Blinking, roving, pursuit (brief and
unsustained)
Flexion withdrawal from noxious
stimulation
Nystagmus
Brief movements of head or eyes towards
stimulus without localization or fixation
Vocalizations
Startle (auditory, or myoclonus)
Swallowing saliva
ANS function intact (neuro-vegetative)
Bernat JLAnnu Rev Med 2009;60:381–392.
PVS Pathophysiology
•
Extreme reductions in cerebral blood flow and
metabolism, measured with positron emission
tomography (PET)
CT and MRI scans show progressive and
profound cerebral atrophy in cases of
vegetative state
•
–
Terry Schiavo
• Brain at autopsy weighed 615g
• Normal adult brain 1300-1500g
Terri Schiavo; cardiorespiratory arrest 1990
1996
2002
Food for Thought
• Recent fMRI has thrown into question our
understanding of disordered consciousness
• Case reports
• 2006, Owen and colleagues; Science
• 23 yo TBI victim in PVS for 5 months able to “wilfully
modulate” brain regions required for volleying a
tennis ball and looking at objects in her home while
navigating room to room
• 2010, Monti and colleagues; NEJM
• 4/23 subjects in PVS able to activate appropriate brain
regions
Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting
awareness in the vegetative state. Science 2006;313:1402
“Prognosis” in PVS
• Major grey area
– depends mostly on the cause and extent of the
brain damage producing the syndrome
• Certain patients that modulate brain activity
(fMRI; Owen, Monti et al.) may have better prognoses
/ predictors of recovery.
– Need validation studies, larger cohorts
– Not available outside select centers
– Still very far from clinical practice guidelines
Bernat JL. Chronic consciousness disorders. Annu Rev
Med 2009;60:381–392.
Costs of maintaining PVS
• Psychological
– Was the test a false positive?
– Will recovery occur?
• Emotional
– Family / loved-ones
• Financial
– Hospital
– Caregiver
Outline
•
•
•
•
•
•
•
Cases
Historical Perspective
Prognostication Guidelines
The Era of Hypothermia
Approaching the Family
Return to Cases
Take Home Points
Case 1
•
•
•
•
55 M collapsed while jogging
CPR immediately initiated by bystander
V-fib
arrest;
circulation restored after 6 minutes
*Final
outcome:
Exam
(day 1):secondary
comatose, absentto
pupillary
and from
corneal
1) Death
sepsis
reflexes, extensor posturing to pain, myoclonic status
pneumonia <30d.
epilepticus
Glasgow
Outcome
• CT2)head
(day 2): Normal
study Scale 1.
• SSEP (day 3): Absent N20 responses
• Exam (day 3): Unchanged
Case 2
•
•
•
•
•
35 M collapses while playing basketball
CPR immediately initiated by bystander
PEA arrest; circulation restored after 20 minutes
*Final outcome:
Induced hypothermia x 24 hours (32 degrees C)
1) Probable HOCM.
Exam (day 1): Comatose, pupils fixed, triggers ventilator but
2)
Post anoxic encephalopathy.
otherwise no evidence of intact brainstem function, no
Persistent
Vegetative
State.
spontaneous
movements
or motor response
to noxious stimuli
EEGGlasgow
(day 2): Severe
diffuse slowing
of cerebral
3)
Outcome
Scale
2 at activity
6 months.
• Exam (day 3): Comatose, pupils reactive, oculocephalic,
corneal, and gag reflexes intact, triggers ventilator, flexor
posturing of upper limbs to pain, no spontaneous movements
Case 3
• 71M with HTN, CAD (previous CABG), collapsed at
home
• No CPR administered
•*Final
PEA arrest;
circulation restored after 20 minutes
outcome:
•1)Exam
1): Comatose,
R pupil
pupil fixed,
Mild(day
ischemic
cortical
& reactive/L
subcortical
damage.
corneal reflex present but sluggish, no ocular response to cold
2)calorics,
Residual
R hemiparesis.
no spontaneous
movements, left arm and leg withdraw
painful stimuli, bilateral
Babinski(Lance-Adams).
signs
3)toPost-anoxic
myoclonus
•4)MRI
brain (day
2): Cerebral
infarction
Glasgow
Outcome
Scale
4 atin6superficial
months.and deep
watershed territories bilaterally (L > R)
• SSEP (day 3): N20 response present on right, absent on left
• Exam (day 3): Unchanged
Take-Home Points
Neurologic Prognostication
1. Our tools allow for an accurate prediction of poor
neurologic outcome
–
“Indeterminate” largely equals =
2. Timing of exam
3. Clinical exam remains the most reliable method for
determining poor outcomes
4. Current prognostication evidence predates TH era;
and thus need to interpret with caution
5. Structured, compassionate approach to family;
define what ‘poor’ outcome means in appropriate
terms
3 Key References
N Engl J Med 2009;361:605-11
Neurology 2006;67;203
JAMA. 2004;291:870-879
References Cited
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Young B. N Engl J Med 2009;361:605-11
E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203
Mayo Clin Proc. 2005;80(8):1037-1046
Bernat. Neurology® Clinical Practice 2010;75(Suppl 1):S33–S38
Bernard SA, Gray TW, Buist MD, et al: Treatment of comatose survivors of out-ofhospital
cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557–563
Circulation 2010;122;S768-S786
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl
J Med 2002; 346:549–556
Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the
vegetative state. Science 2006;313:1402
Thenayan EA, et al. Electroencephalogram for prognosis after cardiac arrest. J Crit Care. 2010
Jun;25(2):300-4.
Monti et al. Willful Modulation of Brain Activity in Disorders of Consciousness. N Engl J Med
2010;362:579-89
Neuroopthalmology review manual: Kline
MedLink: myoclonic status epilepticus
NDD (neurological determination of
death)
• Aetiology established that can cause irreversible death
• Deep coma
– Absence of motor responses to stimuli, no spontaneous or abnormal
mvmts (dyskinesia, posturing) or seizures
•
•
•
•
•
•
Absence of BS reflexes
No spontaneous breathing during apnea test
No confounders
2 exams, 2 independent MD’s
Infants (≥30d and <1yr); rpt exam recommended
In case of cardiac arrest, clinical evaluation of NDD delayed
24hrs subsequent to CPR
– N.b. spinal reflexes may exist
• Date and time of death = first NDD
Brain Death Exam
• Brainstem
– Pupils
• ≥4mm, unresponsive to light
– Corneals
• Movement of jaw or lids excludes NDD
– OCR
• Ignore if trauma
– Calorics
• 30 degrees
• ≥50cc ICE water quickly. If no eye movement, wait 5 min and try
contralateral side
– Pharyngeal
• Stimulate posterior pharynx
• Suction the ETT
• Depress larynx, swallow reflex
– Apnea test
VOR: vestibulo-ocular reflex
Cold Caloric Testing
Vestibulo-Ocular Reflex (VOR)
Pearl:
COWS mneumonic
implies intact
cortex (frontal eye
fields). If on coma
/ sedated, will not
get corrective
nystagmus.
Attenuates
resting state
vestibular
tone
Warm Caloric Testing
Vestibulo-Ocular Reflex (VOR)
Increases
resting state
vestibular
tone
Rarely done
in neurology
Apnea Test
• Pre-oxygenate with 100% FiO2 for 10-15 min
• Baseline ABG
– PH 7.35-7.40
– PC02 40+/- 5 mmHg
• Disconnect ventilator
– T piece with CPAP at 10 CM H20, deliver FiO2 at 10L/min or insert
catheter into ETT and deliver FiO2 at 6L/min (at carina)
• Observe for resp. effort x 10 min
• Repeat ABG and reconnect ventilator
– Test + if
•
•
•
•
PaCO2 >60mmHg and rise in 2mmHg/min
PH <7.28
No respiratory efforts demonstrated
Stop if HD instability or desaturation occurs
Ancillary test
• Cerebral angiography or radio-isotope scan
– Absence of intracranial blood
+ LR (CI)
- LR (CI)
Pooled Clinical Signs in
the Prognosis of Post–
Cardiac Arrest Coma
LR for poor
neurological outcome
demonstrated.
JAMA. 2004;291:870-879
Rational Clinical Exam – JAMA 2004
Pooled Clinical Signs in the Prognosis of Post–Cardiac Arrest Coma
+ LR (CI)
- LR (CI)
JAMA. 2004;291:870-879