The use of adrenaline in cardiac arrest resuscitation has been advocated since the 1960s. Laboratory studies and anecdotal experience showed improved rates of return of spontaneous circulation (ROSC) with the use of adrenaline at a dosage of approximately 0.01 mg/kg. This led to the widespread adoption of adrenaline administration during cardiac arrest into every resuscitation guideline for decades to come. Extensive laboratory studies characterized the beneficial physiological effects of adrenaline during cardiac arrest and closed-chest cardiopulmonary resuscitation (CC-CPR). Adrenaline administered during CC-CPR results in peripheral arterial vasoconstriction that raises the aortic pressure, particularly during the relaxation phase of CC-CPR. This increase in aortic pressure results in an increased aortic to right atrial pressure gradient that drives blood flow to the myocardium during CC-CPR. This pressure gradient is known as the coronary perfusion pressure (CPP) and has been shown to correlate with ROSC in both laboratory investigations and clinical studies. During the 1990s, the use of “high-dose” adrenaline showed increased rates of ROSC compared to “standard-dose” adrenaline. However, it was subsequently recognized that larger doses of adrenaline did not result in improved survival. Furthermore, questions have been raised as to whether or not “standard-dose” adrenaline improves survival from cardiac arrest. Recent meta-analyses have raised serious questions about the value of adrenaline, showing a benefit for achieving ROSC but no clear evidence of improved long-term survival. Controlled clinical trials to address this question are now underway. However, there is another important issue that needs to be addressed: the “route” of administration. With the growing interest in endovascular resuscitation, the use of intra-aortic adrenaline titration offers a means of rapidly and effectively delivering adrenaline to peripheral arterial effector sites while providing arterial pressure and CPP monitoring to guide titration of adrenaline doses to achieve an optimal hemodynamic effects while avoiding excessive adrenaline doses. To enable screen reader support, press shortcut Ctrl+Alt+Z. To learn about keyboard shortcuts, press shortcut Ctrl+slash.

1. Rethinking Adrenaline in Cardiac Arrest
James E. Manning, MD @JManning_UNC
Department of Emergency Medicine
University of North Carolina at Chapel Hill School of Medicine
SMACC-DUB #smaccDUB
Dublin, 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.

2. Adrenaline in Cardiac Arrest:
How did we get here?

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

5. Why Adrenaline in Cardiac Arrest?
!! Kickstart the Heart !!

6. A range of doses
“anecdotally”
recommended

8. Resuscitation Medicine
Key Concept: The “Chain of Survival”
Early Recognition
& Activation (911)
Early CPR
Rapid
Defibrillation
ACLS &
Transport
Post-Resuscitation
ICU/Neuro Care

9. 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

10. 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

11. Adrenaline Effect in Cardiac Arrest:
Mechanism of Action is
Peripheral Arterial Vasoconstriction
↑ AoP ↑ CPP

12. CPR-diastolic Aortic Pressure

13. CPR-diastolic Coronary Perfusion Pressure (CPP)

14. 60+ Years of Adrenaline in Cardiac Arrest:
Is there any evidence of benefit?

15. Standard Dose Adrenaline in Cardiac Arrest:
…Survival rates disappointing…

16. High-Dose Adrenaline in Cardiac Arrest:
…Come & Gone…
No benefit over Standard Dose Adrenaline
….so what about SD Adrenaline

17. 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

18. A Series of Recent Meta-Analyses & Reviews
Lin, et al: Resuscitation 2014; 85:732-740.

19. Meta-Analysis & Review
Standard Dose versus High Dose Adrenaline
Rate of ROSC greater with HDA
Lin, et al: Resuscitation 2014; 85:732-740

20. Meta-Analysis & Review
Standard Dose versus High Dose Adrenaline
Admission Rate greater with HDA
Lin, et al: Resuscitation 2014; 85:732-740

21. Meta-Analysis & Review
Standard Dose versus High Dose Adrenaline
Hospital Discharge Rate: Not Different
Lin, et al: Resuscitation 2014; 85:732-740

22. Meta-Analysis & Review
Standard Dose versus High Dose Adrenaline
Neurological Outcome: Not Different
Lin, et al: Resuscitation 2014; 85:732-740

23. Meta-Analysis & Review
SDE: no increase in survival with good neurological outcome
HDE: no better than SDE
SDE + Vasopressin: no better than SDE alone
Lin, et al: Resuscitation 2014; 85:732-740.

24. The “Adrenaline Dilemma” in Cardiac Arrest:
Why is it not working?

25. Route of Adrenaline delivery
Intravenous…….what we do & have always done.
……IV route is just not effective in Cardiac Arrest

26. “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 may
not circulate, be beneficial, but not be needed!
Minimal-No Effect risk of excessive “may” even be
dosing detrimental

27. So…....
Should we abandon the use of
Adrenaline in cardiac arrest?
......maybe not just yet.

28. What about route of delivery?
Intravenous…….what we do & have always done.
Intra-Aortic / Intra-Arterial……….???

29. Ann Emerg Med 1992; 21:1068-1065

30. Ann Emerg Med 1993; 22:703-708

37. CPR-diastolic Coronary Perfusion Pressure (CPP)

38. 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