Neurologic Complications in Adult ECMO

Joseph B. Zwischenberger MD Johnston-Wright Professor

Chairman: Department of SurgerySurgeon-in-Chief UK Healthcare

859-229-6635 (mobile)jzwis2@uky.edu

The University of KentuckyLexington, Kentucky

Presenter Disclosure InformationResearch supported in part through Competitive funding:

National Institutes of Health (SBIR,STTR,T-32)Contracts:

MC3, Ann Arbor MiExotherm, Lexington Ky W-Z Biotek, Lexington KyMaquet

Patent: Avalon Elite™ (4 more, 3 pending)Novalung

Free App: “Zwisch Me”

Joseph B. Zwischenberger, M.D.

Z-Bergerism #12

Innovation is never evidence-based

Stroke In ECMO

Multi-institutional study of ECMO 1992-2005 in pediatric patients

CNS Injury = Brain death, stroke, hemorrhage

Ischemic stroke in 7%

Hemorrhagic stroke in 7%

Barrett et al. Pediatr Crit Care. 2009 10(4):445-51.

Neurologic Complications in Adult ECMO?• Neurologic sequelae:

SeizuresHemorrhage: Intraventricular, intracerebral, subduralStrokeBrain death

• Multifactorial: thromboembolic events, hemorrhage, anticoagulation

• Neurologic sequelae patient selection and managementECMO Red Book

Incidence of ECMO Neurologic Complications

• Downward trend (last 10 yrs) attributed to experience, technology, and patient selection/management

• Neurologic complications underestimated due to:lack of diagnostic imaging in critically ill patientslimited participation in registries (voluntary)lack of standardized reporting

ECMO Red Book

Neurologic Complications (VV/VA) 2006 2015

ECMO runs (VV/VA) runs 121 / 141 1568 / 1769Brain Death % 5.8 / 2.1 1.9* / 2.9Seizures (EEG) % 2.5 / 1.1 0.2* / 0.9Seizures (Clinical) % 1.7 / 1.4 1.1 / 1.1CNS Infarction % 5.0 / 2.8 2.1* / 3.8CNS Hemorrhage 2.0 / 1.4 3.2 / 1.4*

Table 52-1. ECMO Red Book

Neurologic Risk FactorsECMO circumstances:

Pre-existing decreased cerebral oxygenationECMO assisted CPR: up to 50% neurologic events

Resuscitation. 2017;121:166-171Pre-existing neurologic pathologies

ECMO circuit configuration TABLE 52-2Veno-arterial (VA) ECMO versus veno-venous (VV) ECMO

ELSO Registry shows no major differences

Peripheral cannulation thought to decrease riskCarotid artery cannulation highest stroke risk in adults (~3-5%)

J Pediatr Surg. 2012;47:68-75

Neurologic Complications and Survival 1991-2015Neurologic

Complications VV

(9102) VA

(7850) n % Survival

% n % Survival %

Brain Death (Clinical) 227 2.4 0 354 4.2 0Seizures (EEG) 36 0.4 47* 50 0.6 20Seizures (Clinical) 100 1.1 42* 135 1.6 24CNS Infarction (US / CT) 191 2.0 30* 322 3.8 23CNS Hemorrhage (US / CT) 352 3.8 21* 184 2.2* 9

Table 52-2. ECMO Red Book

Time IS BrainAs many as 14 billion synapses may be lost during every one minute that a stroke goes untreatedThe average stroke patient loses approximately 32,000 brain cells every one second

Saver, J., 2005

General Considerations• Supplemental Oxygen to keep O2 saturation at 94% +• Cardiac monitoring for arrhythmias (atrial fibrillation) • Addressing cause, while lowering (elevated) temperature• Glucose goal 140-180• Pneumatic compression devices (and/or pharmacologic

means) to prevent deep venous thromboses • Early mobilization • No oral intake to avoid aspiration pneumonia• Mechanical intravascular or neurosurgical intervention for

thrombectomy in select cases• Early intervention Jauch, et. al., 2013

Stroke Mimics• Metabolic Disorders

o Hypoglycemia• Migraine• Seizures, Todd’s Paralysis• Bell’s Palsy• Syncope• Transient Global Amnesia• Peripheral Nerve Disorders• Intracranial Masses• Hypertensive Crisis• Psychogenic Presentations

Treatment Windows from Recognition

• Intravenous (IV) Activase® (Alteplase) (rt-PA) is FDA approved within 3 hours and recommended by AHA and AAN within 4.5 hrs

• Mechanical thrombectomy is recommended with large vessel occlusion within 6 hours

• Neuro-interventionalists are increasingly using imaging rather than time to determine candidacy for intervention

Demaerschalk, et. al., 2016Powers, et. al., 2015

Ischemic Stroke

Is the patient acandidate for IV-tPA?

No Yes

No

No Yes IV-tPA Protocol

Is the patient acandidate for endovascular Rx?

Yes EndovascularProtocolInitiate Secondary Prevention

Prevent ComplicationsRecovery

General Measures

Hemorrhagic Stroke

No Yes

Acute Focal Neurologic Deficit

Dx & manageDx & manage

Modified from Goldstein Methodist DeBakey Cardiovascular Journal. 2014;10:39-44

Modified from 2018 AHA Guidelines for Early Management of Patients with AIS

Ischemic Stroke: Large Vessel Occlusion

Large Ischemic Stroke

Efficacy of tPA by Stroke Subtype

0

10

20

30

40

50

60

70

80

% w

ith g

ood

outc

ome

tPAPlacebo

Small vessel Large vessel Cardioembolic

Thrombectomy

Turk AS. J Neurointerv Surg. 2013.

Thrombectomy

Thrombectomy

Thrombectomy

ELVO Trials

MR-CLEAN

EXTEND-IA

SWIFT PRIME

ESCAPE

Halted early for efficacy

ELVO - Time is BrainSTUDY Time to

IVt-PATime to Groin

Time to Recan

TICI 2b-3 MRS 0-2 Medical

MRS 0-2 IA

MR CLEAN 85-87 min

260 min N/A 58.7% 19.1% 32.6%*

ESCAPE (1)

110-125 min

185 min 241 min 72.4% 29.3% 53%*

EXTEND IA (2)

127-145 min

210 min 248 min 86% 40% 71%*

SWIFT PR. (3)

167.5 min

184 min 213 min 88% 35.5% 60.2%*

(2) Campbell, B. C. V., et al NEJM 2015. doi:10.1056/NEJMoa1414792(1) Goyal, M., et al. NEJM 2015, 150211090353006–12. doi:10.1056/NEJMoa1414905

(3) Saver, J., et al Presented at ISC 2015. Nashville, TN

Stroke Intake Process

ED Prenotification to Stroke Pager From Bay/Pad to CT NIHSS and quick history

outside/inside CT CT/CTA performed NIR attending called from CT

– Thrombectomy pager?– tPA?

Hemorrhagic Stroke

Hemorrhagic Stroke

Post Evacuation

BOTTOM LINE Interventions and outcomes are

time-dependent TIME IS BRAIN ECMO patients should be monitored

for neurological changes Any neurological change should

prompt a Stroke Alert (including rapid CT and CTA imaging)

Thiagarajan RR, et al. ASAIO 2017, 63(1):60-67

40%

30%

(26 patients)

54% neurologically intact survival

ECPR 13% increased 30-day survivalBetter neurological outcome

ECMO for cariogenic shock33% higher 30-day survival than IABPSimilar to Tandem Heart/Impella

Hemorrhage on ECMOCommon Cause

• Inflammation, altered coagulation, transfusionsManagement

• Monitor lab values ACT, aPTT, AT, Antifactor-Xa Assay, thromboelastography

ECMO Red Book• Ideal transfusion protocol not yet established

JCVA. 2017;31:1836–46.• Anticoagulation reversed, increase pump flow

ECMO Red BookOutcomes

• Intracranial hemorrhage mortality of 80-90% ELSO Registry

Seizures on ECMOCommon Cause

• Thromboembolic and bleeding eventsManagement

• Conventional to date• Clinically diagnosed, verified by EEG

Outcomes• Survival to discharge rate decreased to 30%

versus all ECMO patients 40-60% ECMO Red Book

Stroke on ECMOCommon Cause

• Thromboembolic events, rapid ↓PaCO2, sedation, hemodynamic instability, shock

Management• Monitor: Transcranial Doppler Sonography (TCD)

Cerebral Near-Infrared Spectroscopy (NIRS)Hemodynamics

• Optimal transfusion management not yet determinedECMO Red Book

Outcomes• Carotid artery cannulation highest stroke risk ~3-5%

J Pediatr Surg. 2012;47:68-75

Brain Death on ECMO

Most frequent in ECMO assisted CPRCommon Cause: Pre-ECMO insult, unrecognized decline during cannulationAfter resuscitation induce hypothermia with ECMO circuit heater-coolerMonitor clinical neurologic signs, cerebral oximetryNo standard criteria for diagnosis

CCM. 2016;44:e964-72

Risk/Benefit: Survival v. Quality of LifeELSO Registry: No functional neurologic outcomes, only

voluntary short-term data from single centers

Survival to discharge (Adults)• Highest: Viral ARDS (H1N1) Rx with VV ECMO: 70-80%• Lowest: ECMO assisted CPR: 25-35%

ECMO Red Book

Return to work: Single center study of 465 VA ECMO patients found a 25% return to work rate

Camboni and Schmid, not yet published

Future Directions

Adult ECMO use is rapidly expandingECMO use increased 650% 2001-2011

JCN. 2015;11:383-89Identify predictive markers

Optimize anticoagulation, transfusion, sedation strategies

Will play for drinks and tips

You should ALWAYS listen to a harmonica player

Neurologic Complications in Adult ECMO

Joseph B. Zwischenberger MD Johnston-Wright Professor

Chairman: Department of SurgerySurgeon-in-Chief UK Healthcare

859-229-6635 (mobile)jzwis2@uky.edu

The University of KentuckyLexington, Kentucky

References1. Camboni D, Schmid C. Neurologic and pulmonary complications in adult ECLS.

The ELSO Red Book. 5th edition. Ann Arbor, MI: Extracorporeal Life Support Organization (ELSO); 2012: 575-82

2. Table 52-1. Adapted from Extracorporeal Life Support: The ELSO Red Book. 5th

edition. Ann Arbor, MI: Extracorporeal Life Support Organization (ELSO); 2012: 576.3. Floerchinger, Philipp A, Camboni D, Foltan M, Lunz D, Lubnow M, Zausig Y, Schmid C.

NSE serum levels in extracorporeal life support patients-Relevance for neurological outcome? Resuscitation. 2017;121:166-171.

4. Rollins D, Hubbard A, Zabrocki L, Douglas BC, Bratton, SL. Extracorporeal membrane oxygenation cannulation trends for pediatric respiratory failure and central nervous system injury. J Pediatr Surg. 2012;47(1):68-75.

5. Table 52-2. Neurologic Complications and Survival 1991-2015. The ELSO Red Book.5th edition. Ann Arbor, MI: Extracorporeal Life Support Organization (ELSO); 2012: 577.

6. Xie A, Lo P, Yan TD, Forrest P. Neurologic complications of extracorporeal membrane oxygenation: a review. JCVA. 2017;31:1836–46.

7. Lorusso et al. In-Hospital Neurologic Complications in Adult Patients UndergoingVenoarterial Extracorporeal Membrane Oxygenation: Results From the ExtracorporealLife Support Organization Registry. Crit Care Med. 2016 Oct;44(10):e964-72

ECMO FUTURECatheter based Technology (Ambulatory)

– Recipient Support– Donor Support: DCD– Organ Block Support : Lung in a Box

Transplantation

Neonates, Children, Adults Acute Severe Respiratory failure Acute Cardiac support

ER Transport Resuscitation/Shock