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Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD Professor and Chair, Department of Emergency Medicine University of Michigan Ann Arbor, Michigan, USA [email protected] @neumar_robert

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Page 1: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Year in Review: Cardiac Arrest 2019

Robert W. Neumar, MD, PhDProfessor and Chair,

Department of Emergency MedicineUniversity of Michigan

Ann Arbor, Michigan, [email protected] @neumar_robert

Page 2: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Disclosures

• Co-Chair: International Liaison Committee on Resuscitation (ILCOR)

• Member: ILCOR ALS Task Force• President and Board Chair, SaveMiHeart• NIH and AHA Research Funding• PhysioControl/Stryker: Equipment support for research

Page 3: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

IncludedOriginal research published since

ReSS 2018

Excluded• Systematic reviews

• Meta-analyses

• Practice guidelines

Year in Review: Cardiac Arrest 2019

Page 4: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Year in Review: Cardiac Arrest 2019

Post-Cardiac Arrest• Ventilation/oxygenation targets• Blood pressure targets• Targeted temperature management (TTM)• Coronary angiography• Antibiotics• Neuroprognostication

CPR• Ventilation

Page 5: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Sutton Ped Crit Care 2019

Page 6: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Ventilation Rates and Pediatric IHCA Outcomes Sutton Ped Crit Care 2019

Design: Prospective, multicenter observational studySetting: Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network.Population: 47 Intubated children (> 37 week <19 yrs) who received at least 1 minute of CPRVariables Studied: Ventilation rate and arterial diastolic pressureOutcome: Survival to hospital discharge

Page 7: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Ventilation Rates and Pediatric IHCA Outcomes

Children < 1 Year Old Children > 1 Year Old

Prob

abili

ty o

f Sur

viva

l

Sutton Ped Crit Care 2019

Odds ratio for survival with good neurologic function 4.7 (1.2-19) if > 30 bpm for infants <1 yr or >25 bpm for children > 1 yr

Median ventilation rate was 30 breaths/min (IQR 24–36)

Page 8: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Jakkula ICM 2018

Jakkula ICM 2018

COMACARE Study

Page 9: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

COMACARE StudyJakkula ICM 2018

Design: Prospective, randomized 23 factorial design multicenter clinical trialSetting: Adult ICUs of the COMACARE Research NetworkSubjects: 123 unconscious intubated post-arrest patients with witnessed VF/VT as initial rhythmIntervention: Targeted PaCO2, PaO2, and MAP x 36 hours Primary Outcome: Neuron specific enolase at 48 hoursSecondary Outcome: Survival with good neurologic function (CPC 1-2 at 6 months)

Page 10: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

PaCO

2(m

mHg

)

MAP

(mm

Hg)

75

150

PaCO

2(m

mHg

)

225

30

37

45

52

COMACARE StudyJakkula ICM 2018

PaCO2 PaO2 MAP

65-75 mmHg80-100 mmHg150-187 mmHg 75-112 mmHg34-35 mmHg43-45mmHg

Page 11: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Brain Near-Infrared Spectroscopy (NIRS)

COMACARE StudyJakkula ICM 2018

65-75 mmHg80-100 mmHg150-187 mmHg 75-112 mmHg34-35 mmHg43-45mmHg

Page 12: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

0%

10%

20%

30%

40%

50%

60%

70%

80%

Low-NormalPaCO2

High-NormalPaCO2

Normoxia ModerateHyperoxia

Low-NormalMAP

High-NormalMAP

p = 0.20 p > 0.37 p > 0.44

Survival with Good Neurologic Function (CPC 1-2)

COMACARE StudyJakkula ICM 2018

PaCO2 PaO2 MAP

Page 13: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,
Page 14: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial

Ameloot Eur Heart J 2019

Design: Prospective, single center, randomized clinical trialSetting: Adult ICUSubjects: 112 unconscious OHCA patients with all presenting rhythmsIntervention: Early goal-directed hemodynamic optimization (EGDHO) MAP 80-100 mmHg + SVO2 65-75% vs. MAP 65 mmHg for first 36 hours in ICUPrimary Outcome: MRI evidence of anoxic brain injurySecondary Outcome: Survival with good neurologic function (CPC 1-2) at 180 days

Page 15: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

MAP65 EGDHO

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial

Ameloot Eur Heart J 2019 Survival with Good Neurologic

Function (CPC 1-2)

p > 0.96

MAP 80-100 mmHgSVO2 65-75%

MAP 65 mmHg

Page 16: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Lemkes NEJM 2019

Page 17: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Coronary Angiography after Cardiac Arrest Without ST-Segment Elevation (COACT Trial)

Lemkes NEJM 2019

Design: Prospective randomize open-label multicenter clinical trialSetting: Adult ICUSubjects: 522 unconscious adult patients s/p OHCA who had initial shockable rhythm and without signs of STEMI, shock or obvious non-cardiac cause of the arrestIntervention: Immediate coronary angiography vs. coronary angiography that was delayed until after neurologic recoveryPrimary Outcome: Survival at 90 days

Page 18: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Coronary Angiography after Cardiac Arrest Without ST-Segment Elevation (COACT Trial)

Lemkes NEJM 2019

Incidence of acute thrombotic occlusion:• 3.4% immediate angiography • 7.6% delayed angiography

Time to target temperature (hrs):• 6.5 (5.9 to 7.1) immediate angiography• 5.5 (5.0 to 6.0) delayed angiography

Page 19: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Francois NEJM 2019

Page 20: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Prevention of Early Ventilator Associated Pneumonia After Cardiac Arrest

Francois NEJM 2019

Design: Prospective multicenter, double-blind, randomized, placebo-controlled trialSetting: Adult ICUSubjects: 198 adult mechanically ventilated adult patients s/p witnessed OHCA who had initial shockable rhythmIntervention: Intravenous amoxicillin–clavulanate or placebo x 2 days starting less than 6 hours after the cardiac arrest.Primary Outcome: Early ventilator-associated pneumonia (first 7 days of hospitalization).

Page 21: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Prevention of Early Ventilator Associated Pneumonia After Cardiac Arrest

Francois NEJM 2019

0%

10%

20%

30%

40%

50%

Control Anibiotics

4 % (95% CI: −10% to 18%)

Survival 90 days

Page 22: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,
Page 23: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

PRINCESS TrialNordberg JAMA 2019

Design: Prospective multicenter open-label randomized controlled clinical trialSetting: Out-of-hospitalSubjects: 677 adult patients with bystander witnessed OHCAIntervention: Intra-arrest transnasal evaporative cooling vs. standard carePrimary Outcome: Survival with good neurologic function (CPC 1-2 at 90 days)

Page 24: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

PRINCESS TrialNordberg JAMA 2019

0%

10%

20%

30%

40%

All Patients Shockable Nonshockable

ControlIntervention

RR 1.2 (0.9-1.7)

RR 1.3 (0.9-1.7)

RR 0.8 (0.3-2.0)

Page 25: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

PRINCESS TrialNordberg JAMA 2019

Page 26: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Lascarrou NEJM 2019

Page 27: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

HYPERION TrialLascarrou NEJM 2019

Design: Prospective open-label multicenter randomized controlled clinical trialSetting: Adult ICUSubjects: 584 adult comatose patients following IHCA (27%) or OHCA (73%) with nonshockable initial rhythmIntervention: 33°C vs. 37°C during the first 24 hoursPrimary Outcome: Survival with good neurologic function (CPC 1-2 at 90 days)

Page 28: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Lascarrou NEJM 2019HYPERION Trial

Hours Since Randomization

Tem

pera

ture

(o C)

Mea

n +

2 SD

Enrollment up to 5 hours post-ROSC

Median time from randomization to 33oC was 317 min [214 ; 477]

Page 29: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Lascarrou NEJM 2019

0%

2%

4%

6%

8%

10%

12%

37C 33C

Survival with Good Neurologic Function (CPC 1-2)

Difference 4.5% (0.1% to 8.9%)

HYPERION Trial

Page 30: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Lascarrou NEJM 2019

Subgroup AnalysisSurvival with Good Neurologic Function (CPC 1-2)

HYPERION Trial

Page 31: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,
Page 32: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

ProNeCA StudyScarpino Resuscitation 2019

Design: Prospective multicenter prognostication studySetting: 13 mixed medical-surgical intensive care units(ICUs)Population: Adult comatose cardiac arrest survivors admitted to ICUVariables Studied: Somatosensory evoked potentials (SSEP), Brain CT, and EEGOutcome: Poor neurologic outcome (CPC 4-5) at 6 months

“Withdrawal of life sustaining therapy (WLST) was not performed in any of the participating centres and treatment was continued in all patients, except when brain death occurred.”

Page 33: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

ProNeCA StudyScarpino Resuscitation 2019

57%

10%

7%

Multimodal

• Grade 2 SSEP or CT G/W ratio <1.21 or highly malignant EEG

• <24 hours• FPR 0% (0-3%)• Sensitivity 74.4% (68-80%)

Page 34: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Moseby-Knappe JAMA Neurology 2018

Page 35: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Design: Prospective clinical biobank study of data from TTM trialSetting: International multicenter study with 29 participating sitesPopulation: 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac originVariables Studied: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrestOutcome: Poor neurologic outcome at 6-months (CPC 3-5)

Serum Neurofilament Light Chain (NFL) for Prognosis of Outcome after Cardiac Arrest

Moseby-Knappe JAMA Neurology 2018

Page 36: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Serum NFL

• > 641 pg/mL

• 24 hours post-ROSC

• FPR <1% (0-5%)

• Sensitivity 31%

• 50% TTM33 and 50% TTM36

Serum Neurofilament Light Chain (NFL) for Prognosis of Outcome after Cardiac Arrest

Moseby-Knappe JAMA Neurology 2018

Page 37: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,
Page 38: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Design: Prospective international multicenter observational studySetting: 10 adult ICUsPopulation: Comatose cardiac arrest survivorsVariables Studied: Quantitative neurological pupil index (Npi) and standard manual pupillary light reflex (sPLR) day 1 to 3 after cardiac arrestOutcome: Poor outcome defined as CPC 3-5 (severe disability, vegetative state, or death) at 3-months

Quantitative Pupillometry: Neural Pupillary Index (Npi®)Oddo ICM 2019

Page 39: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Quantitative Pupillometry: Neurological Pupil Index (Npi®)

Neurological Pupil Index• NPi* <2.0• First 24 hours post-ROSC• FPR 0% (0-2%)• Sensitivity 22%• 42% TTM33 40% TTM36

* NPi®-200 pupillometer, Neuroptics®, Irvine, CA, USAN

Piva

lue

5

4

3

2

1

0

Oddo ICM 2019

Page 40: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Brain-Ex

Page 41: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

N A T U RE 2 0 1 9

Page 42: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

N A T U RE 2 0 1 9

• Preservation of cytoarchitecture• Attenuation of cell death• Vascular dilatory responses• Glial inflammatory responses• Spontaneous synaptic activity• Active cerebral metabolism

OBSERVED

NOT OBSERVED• Global electrocortical activity

Page 43: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

What Did We Learn In 2019?

• Ventilation rates in pediatric CPR need to be re-evaluated

• Post-cardiac arrest normoxia, normocarbia, and normotension are reasonable. Studies needed to evaluate individualized goal-directed strategies

• Empiric antibiotics prevented pneumonia in post-cardiac arrest patients treated with hypothermic TTM but did not improves survival

• Immediate post-cardiac arrest PCI for patients without STEMI criteria does not improve survival in a population with low incidence of acute coronary occlusion

Page 44: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

What Did We Learn In 2019?• Intra-arrest intranasal evaporative cooling does not improve

overall survival with good neurologic function in bystander witnessed OHCA, but may benefit subpopulations such as those with an initial shockable rhythm

• TTM at 33oC improves survival with good neurologic function compared to TTM at 37oC in post-cardiac arrest patients with non-shockable initial rhythm

• Reliable neuroprognostication of futility within 24 hours of ROSC may be feasible using a multimodal approach

• BrainEx has challenged the limits of total brain ischemia after which restoration of brain function can be achieved.

Page 45: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

AHA 2019 Focused Updates for First Aid, CPR, and Emergency Cardiovascular Care

Page 46: Year in Review: Cardiac Arrest 2019 - Perelman School of ... › resuscitation › assets › ... · Year in Review: Cardiac Arrest 2019 Robert W. Neumar, MD, PhD. Professor and Chair,

Year in Review: Cardiac Arrest 2019

Robert W. Neumar, MD, PhDProfessor and Chair,

Department of Emergency MedicineUniversity of Michigan

Ann Arbor, Michigan, [email protected] @neumar_robert