Neuroprognostication

San Francisco, September 28TH 2018

Disclosures:

➢No stocks, stock options etc.

➢ I have received restricted educational grants from, or given lectures at sponsored events for, the following companies: Zoll, Baxter, Otsuka, and Medivance (now Bard).

➢No relevance to the content of this presentation

➢The conclusions and recommendations in this talk are my own.

“Predicting is tricky, especially about the future”

– Niels Bohr / Yogi Berra

The problem:

“Predicting is tricky, especially about the future”

– Niels Bohr / Yogi Berra

The problem:

What are the causes of death in cardiac arrest

patients who achieve ROSC and reach the

hospital alive?

➢Early mortality is usually related to initial myocardial stunning and cardiogenic shock, leading to tissue hypoperfusion and development of multiple organ failure [5, 6].

➢ In patients who survive the first 24-48 hours of admission, prognosis is mostly related to the severity of brain injury

Lemiale V et al. Intensive Care Med 2013;39:1972–1980; Sandroni C et al. Minerva Anestesiol

2016;82:989–999

Hemodynamic monitoring…….

The simple measurements:

➢ Blood pressure

➢ Heart rate

➢ Urinary output, capillary refill, peripheral temperature, etc.

More sophisticated measurements: continuous or intermittent, pressure or volume

➢ Cardiac output (PA catheter, PiCCO, LidCO, FloTrac, Echocardiography)

➢ Stroke volume variation (arterial line, PiCCO, LidCO, FloTrac)

➢ Venous saturation (Central venous catheter)

➢ Mixed venous saturation (PA catheter)

➢ Extra-vascular lung water (PiCCO device)

➢ Blood volume (PiCCO, LidCO device)

➢ Intra-thoracic blood volume (PiCCO device)

➢ Systolic/diastolic function (TEE/TTE, PiCCO, LidCO)

➢ Biochemical parameters: base excess, (serial) lactate measurements, creatinin

Neuromonitoring:

➢ To guide treatment

➢ To predict prognosis

➢ Clinical assessment: sensorium, reflexes, “wake up test”, GCS, clinical assessment of epileptic activity

➢ “General” monitoring: lab values, circulation, oxygenation/ saturation

CNS monitoring - 1

➢ Clinical assessment: sensorium, reflexes, “wake up test”, GCS, clinical assessment of epileptic activity

➢ “General” monitoring: lab values, circulation, oxygenation/ saturation

➢ Radiological evaluation: CT scan, MRI

➢ Electroencephalography (raw EEG, compressed spectral arrays (CSA), 95% spectral edge, etc.)

CNS monitoring - 1

➢ Non-invasive monitoring: Near infrared spectroscopy (NIRS)

➢ Invasive monitoring: Intracranial pressure (ICP, Licox,), other

➢ Evoked potentials (esp. somatosensory evoked potentials)

➢ Transcranial doppler studies (MCA flow velocity)

➢ Jugular bulb saturation (central line)

➢ Lab: neuron-specific enolase, CRP, others?

➢ Automated Pupillometry

CNS monitoring - 2

➢ Clinical exam

➢ EEG

➢ Evoked potentials (esp. somatosensory evoked potentials)

➢ CT

➢ MRI

➢ Automated Pupillometry

CNS monitoring - 3

Monitoring patients with brain injuries…

If and when you decide to use a device

to obtain hemodynamic and CNS

measurements:

Always ask yourself beforehand:

➢Which data do I really need? Which

parameters am I actually going to use?

➢What am I going to do with these data?? (how will this improve the outcome in my patients??)

➢ Is this information worth the (procedural) risk in

this patient? (The more invasive a measurement, the more urgent this question becomes!)

Production of

free radicals (O2,

NO2, H2O2, OH-)

Reperfusion

injury

Immune response,

neuroinflammation

Ion pump

dysfunction, influx of

calcium into cell,

neuroexcitotoxicity

Cell membrane leakage, formation of

cytotoxic edema, intracellular acidosis

Mitochondrial

injury and

dysfunction

Increased

vascular permeability,

edema formation

“Cerebral thermo-

pooling” and local

hyperthermia

Coagulation

activation,

formation of

micro-thrombi

Harmful

changes in

cerebral

metabolism

Permeability of the

blood-brain barrier,

edema formation

Epileptic activity &

seizures

Apoptosis, calpain-

mediated proteolysis,

DNA injury

Local generation of

endothelin & TxA2;

generation of

prostaglandins

Decreased

tolerance for

ischemia

Spreading

depression-like

depolarizations

Activation of

protective

“Early genes”

Destructive processes following

ischemia/reperfusion. that can be

Blue lettering = early mechanisms

Red lettering = late mechanisms

Adapted from: Polderman KH. Mechanisms of action,

physiologic effects and complications of hypothermia.

Crit Care Med 2009; 37[Suppl.]:S186 –S202

Decrease in cerebral

repair mechanisms;

acidosis, production of

toxic metabolites

Direct neuronal disruption Blood-brain barrier injury

Cytotoxic oedemaVasogenic oedema

IschemiaHyperemia

Intracranial hypertension

Hematoma

CSF volume(due to blocking of ventricular drainage)

Increased cerebral blood volume

100

0

40

60

80

20

Volume

ICP mm Hg

ICP controlled due

to compensation

Small volume

marked ICP

ICP-Volume Curve

So:

ICP may be a marker for ongoing cerebral injury

ICP may be a cause of additional cerebral injury

➢Brain tissue oxygen monitoring

Partial Pressure of Brain oxygen tension

• Licox® : brain oxygen tension monitor : PbtO2

– pO2 sensitive area is 14 mm3

– Normal white matter PbtO2 = 25 mmHg

Normal tissue

• PbtO2 normal

• Autoregulation intact

Penumbral tissue

• PbtO2 low

• Autoregulation may be disturbed,

Dead tissue

• PtiO2

DIRECT Cerebral blood flow

• Measuring method

– CTP/MRP : Temporal resolution

– Xenon CT: Availability?

– TCD: surrogate for CBF (mFV )

– Laser Doppler

– Hemedex Perfusion monitor

ρсδΤ/δt = Δ(K ΔT) + CBF*ρblood*сblood*ρ(ΔT) + Qm

Thermal energy

movementPassive

Conduction

Active

convection by

CBF

Metabolic heat

generation

stable

Calculation after

calibration

May help guide appropriate CPP

target in individual patients• Range of autoregulation • Clinical utility: trend monitor

– Vasospasm after SAH Vajkoczy P J Neurosurg 2003

– Aneurysm surgery and

vessel occlusion

Thome C J Neurosurg 2001

– Traumatic brain injury

deterioration

Jaeger M Acta Neurochir (Wien) 2005

– Ischemic stroke progression

– ECA/ICA bypass

– Early detection of hyperperfusion

syndrome after stenting

Trans-cranial Doppler (TCD)

➢ Ultrasound at frequencies of 2 MHz

➢ Trans-temporal route above the zygomatic arch➢ ACA, MCA, PCA

➢ Trans-orbital approach➢ Carotid artery

➢ Sub-occipital route through the foramen magnum➢ BA, VA

➢ Limitation: ➢ Small or absent trans-temporal

windows or thick calvaria

➢ Keeping the probe in the same position

-Nousheh Saidi et al. Sem Cardiothor Vasc Anesth 2005; 9:17 - 23.

Near-infrared Reflectance

Spectroscopy (NIRS)

➢ Cerebral Oximetry

➢ Wavelength of 650~1100nm

➢ Bi-hemispheric measure of cerebral

regional oxygen saturation (rSO2)

through the intact calvarium

➢ A positive predictive value between low

rSO2 and adverse CNS outcomes

Murkin JM. Semin Cardiothor Vasc Anesth 2004; 8:167 - 171.

Brain metabolism: Microdialysis

Cerebral microdialysis

(Continuous) EEG

➢ Requirement of a dedicated technician

for placement of the electrodes

➢ Subjective nature of interpretation

➢ Electrical signal interference

(Continuous) EEG

➢ 12-45% of cardiac arrest patients may

develop seizure activity, which is often sub-

clinical

Jugular Bulb oximetry

➢ Normal SjO2 55-70 %

➢ Higher extraction in case of ischemia; lower SjO2

➢ Global indicator for brain oxygenaton

➢Monitor hyperventilation

MRI, CT, ultrasound, TEE etc. in the ICU…

• Portable, 64 Slice

• High-resolution

• CT, CTA, CTP

CT scan

MRI scan

MRI scan

Automated Pupillometry

➢ Tamura T, Namiki J, Sugawara Y, Sekine K, Yo K, KanayaT, Yokobori S, Roberts R, Abe T, Yokota H, Sasaki J. Quantitative assessment of pupillary light reflex for early prediction of outcomes after out-of-hospital cardiac arrest: A multicentre prospective observational study. Resuscitation. 2018 Oct;131:108-113. doi: 10.1016/j.resuscitation.2018.06.027. Epub 2018 Jun 26.

➢ Solari D, Rossetti AO, Carteron L, Miroz JP, Novy J, Eckert P, Oddo M. Early prediction of coma recovery after cardiac arrest with blinded pupillometry. Ann Neurol. 2017 Jun;81(6):804-810. doi: 10.1002/ana.24943. Epub 2017 Jun 2.

➢ Suys T, Bouzat P, Marques-Vidal P, Sala N, Payen JF, Rossetti AO, Oddo M. Automated quantitative pupillometry for the prognostication of coma after cardiac arrest.NeurocritCare. 2014 Oct;21(2):300-8. doi: 10.1007/s12028-014-9981-z.n

Automated Pupillometry➢ The 0-hour PLR best predicted both 90-day survival

(AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA.

➢ At 48 hours, a quantitative PLR 0.20).

Automated Pupillometry➢ The 0-hour PLR best predicted both 90-day survival

(AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA.

➢ At 48 hours, a quantitative PLR 0.20).

➢ However, presence of pupillary reflexes at 72 h does not reliably predict good neurological recovery (PPV 60%). Absence in the first 24 hrs still has FPR of 10%

Outcome prediction…..

https://www.resus.org.uk/resuscitation-guidelines/post-resuscitation-

care/#prognostication

https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjw0YOJ_5DbAhVDVLwKHejGCbcQjRx6BAgBEAU&url=https://www.pinterest.com/pin/529947081137319786/&psig=AOvVaw207uaA2vJ5j5sdtYv7q7N5&ust=1526792388595745

➢ Poor neuro exam

➢ (Absence of) sensory-evoked potentials

➢ MRI (edema, low DWI)

➢ CT (cerebral edema, decreased gray–white

differentiation)

➢ Neuron-specific enolase

➢ “Flat” EEG…

Outcome prediction…..

➢ Poor neuro exam: Bilateral absence of pupillary light

reflex at 72hrs from ROSC predicts poor outcome (0-4%

FPR) but the sensitivity is only 19%➢ I.E., only 1 in 5 of those who eventually have a bad outcome will have fixed

pupils at 72 h.

➢ Similar numbers for bilaterally absent corneal reflex

➢ Absent or extensor motor response at 72hrs from ROSC

has a 75% sensitivity for prediction of poor outcome, with

an FPR of 27%.

➢ Presence of myoclonic jerks is not consistently associated

with poor outcome (FPR 9%). Status myoclonus >48hrs

from ROSC is associated with poor outcome (FPR 0-2%.

95% CI 0–5%; sensitivity 8–16%.

Outcome prediction…..

➢ The most sensitive indicator is (absence of)

sensory-evoked potentials, though even this should

not be used by itself to make decisions to withdraw

care (false-negative 0-4%)

➢ FPR 0–2% with upper 95% CI of about 4%

➢ SSEP recording requires appropriate skills and

experience, and utmost care should be taken to

avoid electrical interference from muscle artefacts

Outcome prediction…..

➢ “Flat” EEG… FPR of 0–2% (upper 95% CI of about

7%).

Outcome prediction…..

Outcome prediction…..

➢ Poor neuro exam with no improvement in several

days; no sedation effect; absent pupillary, corneal

reflex➢ (Remember, TTM can slow hepatic clearance of sedatives, especially

benzo’s!!)

➢ Absent sensory-evoked potentials: high sensitivity and specificity.

➢ MRI (edema, low DWI) high sensitivity, decent specificity.

➢ CT (cerebral edema, decreased gray–white

differentiation) high sensitivity, decent specificity

➢ Neuron-specific enolase moderate sensitivity and specificity

➢ “Flat” EEG… high sensitivity and specificity

➢ Automated pupillometry: very promising initial data.

Outcome prediction…..

Jackson MJ et al.

Prognostication of patients after

cardiopulmonary resuscitation

BJA Education,2018;1e7

https://www.resus.org.uk/resuscit

ation-guidelines/post-

resuscitation-

care/#prognostication

Thank you for your attention!

k.polderman@tip.nl

Thank you!

Monitoring patients with brain injuries…

☺ My aim today is to get you to look at

a few things that you may take for

granted in a slightly different way.