Rethinking Adrenaline in Cardiac Arrest

Rethinking Adrenaline in Cardiac Arrest

James E. Manning, MD@JManning_UNC

Department of Emergency MedicineUniversity of North Carolina at Chapel Hill School of Medicine

SMACC-DUB #smaccDUBDublin, Ireland June 14, 2016

Disclosure: Inventor on patents for the Selective Aortic Arch Perfusion assigned to the University of North Carolina at Chapel Hill. Co-Founder of Resusitech, Inc., a medical device company developing invasive resuscitation technologies.

Adrenaline in Cardiac Arrest:

How did we get here?

The “Achilles’ Heel” of Cardiac Arrest Resuscitation is “Artificial Perfusion”

Why Adrenaline in Cardiac Arrest?

!! Kickstart the Heart !!

A range of doses “anecdotally” recommended

Resuscitation Medicine Key Concept: The “Chain of Survival”

Early Recognition& Activation (911) Early CPR Rapid

Defibrillation ACLS &

Transport Post-Resuscitation

ICU/Neuro Care

Resuscitation Science

Coronary Perfusion Pressure: CPP

CPP = Aortic Pressure – Right Atrial Pressure

This is greatest during the relaxation phase of chest compression:

CPR diastolic CPP = CPR diastolic AoP – CPR diastolic RAP

CPP correlates with myocardial blood flow during CPR

Resuscitation Science

Coronary Perfusion Pressure & ROSC:

CPP ≥ 15 mmHg associated with ROSC

The higher the CPP, the better

CPR-diastolic Aortic Pressure:

CPR dAoP ≥ 30 mmHg associated with ROSC

Adrenaline Effect in Cardiac Arrest:

Mechanism of Action is

Peripheral Arterial Vasoconstriction

↑ AoP ↑ CPP

CPR-diastolic Aortic Pressure

CPR-diastolic Coronary Perfusion Pressure (CPP)

60+ Years of Adrenaline in Cardiac Arrest:

Is there any evidence of benefit?

Standard Dose Adrenaline in Cardiac Arrest:

…Survival rates disappointing…

High-Dose Adrenaline in Cardiac Arrest:

…Come & Gone…

No benefit over Standard Dose Adrenaline

….so what about SD Adrenaline

Standard Dose Adrenaline versus Placebo

Increased ROSC & Hospital Admission with SD Adrenaline

No difference in Hospital Discharge or Neurological Outcome

Jacobs, et al: Resuscitation 2011; 82:1138-1143

A Series of Recent Meta-Analyses & Reviews

Lin, et al: Resuscitation 2014; 85:732-740.

Meta-Analysis & Review

Standard Dose versus High Dose Adrenaline

Rate of ROSC greater with HDA

Lin, et al: Resuscitation 2014; 85:732-740



Admission Rate greater with HDA




Hospital Discharge Rate: Not Different




Neurological Outcome: Not Different



SDE: no increase in survival with good neurological outcomeHDE: no better than SDESDE + Vasopressin: no better than SDE alone

Lin, et al: Resuscitation 2014; 85:732-740.

The “Adrenaline Dilemma” in Cardiac Arrest:

Why is it not working?

Route of Adrenaline delivery

Intravenous…….what we do & have always done.

……IV route is just not effective in Cardiac Arrest

“Adrenaline Dilemma” in Cardiac Arrest

Poor CPP Borderline CPP Good CPP

≤ 8 – 10 mmHg 10 – 20/25 mmHg ≥ 25/30 mmHg

Adrenaline will Adrenaline “may” Adrenaline maynot circulate, be beneficial, but not be needed!Minimal-No Effect risk of excessive “may” even be

dosing detrimental

So…....

Should we abandon the use of Adrenaline in cardiac arrest?

......maybe not just yet.

What about route of delivery?

Intravenous…….what we do & have always done.

Intra-Aortic / Intra-Arterial……….???

Ann Emerg Med 1992; 21:1068-1065

Ann Emerg Med 1993; 22:703-708

CPR-diastolic Coronary Perfusion Pressure (CPP)

Rethinking Adrenaline in Cardiac Arrest

Intravenous Adrenaline improves ROSC & Admission Rate, but NOT Survival to Discharge or Neurological Outcome

ROSC & Admission MUST precede Discharge & Recovery

If not IV Adrenaline, then what are we going to do to improve perfusion during cardiac arrest?

Endovascular: Aortic Pressure catheters & Intra-aortic Adrenaline?

Extracorporeal Perfusion: ECMO, SAAP +/- Adrenaline

Health & Medicine

Rethinking Adrenaline in Cardiac Arrest