epinephrine
Contents
Non-selective alpha + beta agonist. First-line for anaphylaxis and cardiac arrest; rescue agent in refractory septic shock and shock with myocardial dysfunction. Powerful but metabolically expensive — arrhythmias and a confusing lactate rise are the price.
mechanism
- Alpha-1 +++ → vasoconstriction, ↑SVR, ↓mucosal oedema
- Beta-1 +++ → ↑contractility, ↑HR, ↑conduction velocity
- Beta-2 ++ → bronchodilation, mast-cell/basophil stabilisation (↓further mediator release), skeletal-muscle vasodilation and aerobic glycolysis
Dose-dependence: at low doses beta effects dominate (↑CO, ↓SVR, may see MAP dip); at higher doses alpha dominates (↑SVR, ↑MAP)
Net haemodynamics: ↑↑CO, ↑↑HR, ↑MAP, ↑SVR (dose-dependent)
dosing
| indication | dose |
|---|---|
| anaphylaxis | 0.5 mg IM (1:1000) anterolateral thigh, repeat q5–15 min. Paeds 0.01 mg/kg (max 0.5 mg) |
| anaphylaxis refractory | infusion 0.05–0.2 mcg/kg/min |
| cardiac arrest | 1 mg IV/IO (1:10,000) q3–5 min |
| shock infusion | 0.01–0.5 mcg/kg/min (≈1–30 mcg/min) |
| push-dose | 5–20 mcg IV boluses for transient peri-intubation/peri-procedural hypotension |
| symptomatic bradycardia | 2–10 mcg/min infusion |
| croup / stridor | 5 mg nebulised (1:1000) |
- PK: onset immediate (IV) / 5–10 min (IM) · half-life 2–3 min · metabolised by MAO and COMT
key points
Beta-2 stimulation drives aerobic glycolysis (Na+/K+-ATPase → pyruvate → lactate). Lactate rises without tissue hypoperfusion. Before escalating resuscitation, check the rest of the perfusion picture (cap refill, urine output, mentation, ScvO2).
1:1000 = 1 mg/mL (IM) · 1:10,000 = 0.1 mg/mL (IV arrest). Getting these backwards is a sentinel event. IV push epinephrine in a perfusing anaphylaxis patient causes hypertensive crisis and arrhythmia — the answer is 0.5 mg IM.
- In anaphylaxis, antihistamines and steroids treat urticaria and (maybe) biphasic reactions — they do not treat shock or airway oedema
- Beta-blocked patients may not respond in anaphylaxis → glucagon 1–5 mg IV
- Adding epinephrine in refractory septic shock is often as much about inotropy as pressure — get an echo first
- Push-dose epi: dilute 1 mL of 1:10,000 (100 mcg) into 9 mL NS = 10 mcg/mL; give 0.5–2 mL boluses. Bridge in ED/OR/peri-intubation, not a maintenance strategy
adverse effects
- Arrhythmia — AF, SVT, VT; ↑myocardial oxygen demand and ischaemia risk
- Type B lactic acidosis (see above) — the classic bedside dilemma
- Hyperglycaemia (glycogenolysis/gluconeogenesis) and hypokalaemia (beta-2 intracellular K+ shift)
- Splanchnic vasoconstriction — reduces gut perfusion more than norepinephrine
- Extravasation necrosis — same management as norepinephrine (phentolamine)
evidence
- PARAMEDIC-2 (2018) — in OHCA, epinephrine ↑ROSC and ↑30-day survival but did not improve favourable neurological outcome — more survivors, more with severe neurological impairment
- Levy, JACC. 2018 — vs norepinephrine in cardiogenic shock: RCT stopped early for excess refractory shock with epi; meta-analyses suggest ~3x mortality risk → avoid as pressor of choice in cardiogenic shock
- Myburgh, Intensive Care Med. 2008 — vs norepinephrine in septic shock (CAT trial): comparable mortality but more tachycardia, lactate, and metabolic disturbance → reserved as add-on
- Anaphylaxis — no RCT exists; observational data consistently show delay in epinephrine administration is the strongest predictor of fatality