Adrenaline or Epinephrine in ACLS

 History & Background

• Adrenaline (epinephrine) has been used in cardiac arrest for >60 years.

• Became standard after the development of CPR in the 1960s (closed chest cardiac massage + mouth-to-mouth/ventilation).

• Added as a way to "kick-start" the heart when chest compressions alone seemed insufficient.

• Initial use based on animal studies; not rigorously tested in humans for dosing.

• Standard ACLS dose (1 mg IV every 3–5 minutes) originated from early anecdotal use, not a formal dose-response study.

Mechanism in Cardiac Arrest

• Goal: improve artificial perfusion during CPR.

• Key concept: Coronary perfusion pressure (CPP) = Aortic diastolic pressure – Right atrial pressure.

• Effective ROSC usually requires CPP >15 mmHg; higher CPP correlates with better outcomes.

• Adrenaline works primarily via α-adrenergic vasoconstriction → raises aortic diastolic pressure → increases CPP → improves chances of ROSC.

• Not primarily beneficial as inotrope/chronotrope during arrest (heart not circulating effectively).

Evidence & Outcomes

• Adrenaline improves ROSC and hospital admission rates.

• Does not improve survival to discharge or neurological outcomes (per RCTs and meta-analyses).

• High-dose adrenaline (5–10 mg) increased ROSC/admission but worsened long-term survival due to toxic/overdose effects.

• Only one RCT comparing adrenaline vs placebo (2011): ROSC higher with adrenaline, but no difference in hospital discharge or neuro outcomes.

Problems with IV Adrenaline

• Given during low-flow/no-flow states → drug often not delivered effectively to arterial side.

• In severe low-flow arrest (CPP <8–10 mmHg), IV adrenaline may not reach target tissues.

• In patients with already high CPP (>30 mmHg), adrenaline may not be necessary and could be harmful (overstimulation, myocardial injury, post-ROSC arrhythmias).

• Overdose risk: standard 1 mg is a very large dose compared to physiologic levels.

Alternative Approaches

• Intra-aortic (IA) adrenaline delivery:

  • More rapid, predictable effect compared to IV.

  • Allows smaller titrated doses (e.g., 0.25 mg effective vs 1 mg IV).

  • Prevents large “backlog” of drug that circulates later as overdose.

  • IA line also provides real-time CPP monitoring → titration possible.

• Endovascular resuscitation (ECMO, REBOA, intra-aortic balloon occlusion) now increasingly feasible; adrenaline may need to be rethought in this context.

• Possible role of vasopressin or continuous low-dose infusion instead of repeated boluses; not well studied yet.

Summary

• Adrenaline is the cornerstone of ACLS because it reliably improves ROSC.

• However, it has not been shown to improve long-term survival or neurological outcomes.

• High doses are harmful; standard dose remains common but controversial.

• The real issue may not be whether adrenaline works, but how it is delivered.

• Future: intra-aortic delivery, titration guided by CPP monitoring, or alternatives (ECMO/vasopressin).

• Current dilemma: still part of ACLS, but must be re-evaluated as resuscitation moves toward endovascular strategies.