Adrenaline (Epinephrine) - Dosage and Route by Indication

1. Anaphylaxis

• IM is preferred over SC (faster absorption, higher and more reliable peak levels)
• Repeat IM dose every 5-15 min if no improvement
• The 1:1000 concentration is used IM; the 1:10,000 concentration is used IV

2. Cardiac Arrest (Adult - ACLS)

• Indications: VF/pulseless VT unresponsive to initial shock, asystole, PEA, profound symptomatic bradycardia
• High-dose epinephrine (2-5 mg IV every 3-5 min) has NOT improved long-term survival - not routinely recommended
• Endotracheal route is no longer recommended (unreliable absorption in pulmonary oedema)
• Do not mix with alkaline solutions (inactivates the drug)

3. Cardiac Arrest (Paediatric - PALS)

• Repeat every 3-5 minutes
• High-dose epinephrine (0.1 mg/kg) does not improve survival and is not recommended for routine use
• Subsequent doses at same standard dose even if first dose ineffective

4. Symptomatic Bradycardia / Cardiogenic Shock

• Used when atropine fails or is contraindicated
• Also used in paediatric bradycardia: 0.01 mg/kg IV every 3-5 min (max 1 mg)

5. Croup (Laryngotracheobronchitis) - Moderate to Severe

• For stridor at rest or moderate-severe disease
• Clinical effect seen within 10 minutes (α-receptor vasoconstriction reduces airway mucosal oedema)
• Observe for at least 3 hours post-dose (croup scores can worsen at 2-3 hours - "rebound effect")
• L-epinephrine and racemic epinephrine have comparable early effects; L-epinephrine shows lower croup scores at 2 hours

6. Local Anaesthesia Adjunct

• Typical concentration used: 1:100,000 to 1:200,000 epinephrine
• Contraindicated in ring blocks (fingers, toes, ears, nose, penis) due to risk of ischaemic necrosis - though this is increasingly questioned in literature

7. Septic Shock / Vasopressor Support

• Epinephrine is a second-line vasopressor in septic shock (norepinephrine is first-line)
• Useful in combined septic + cardiogenic shock (dual vasopressor + inotropic activity)
• Dose: 0.1-0.5 mcg/kg/min IV infusion, titrated to effect

Concentration Reference Table

Key Safety Points

• Never give 1:1000 concentration IV undiluted (cardiac toxicity)
• IM thigh (vastus lateralis) is preferred over deltoid for anaphylaxis - faster and more reliable absorption
• In cardiac arrest, administer early (within first 3-5 min of arrest for non-shockable rhythms; after 2nd shock for shockable rhythms)
• Adverse effects: tachycardia, hypertension, myocardial ischaemia, intracranial hypertension in overdose
• A 2018 NEJM trial (PARAMEDIC2) confirmed improved ROSC with epinephrine in cardiac arrest but found higher rates of severe neurological disability in survivors

Why Noradrenaline (Norepinephrine) is First-Line in Shock (Not Adrenaline)

The Short Answer

1. Receptor Profile Comparison

• α1 - peripheral vasoconstriction, raises SVR and MAP (this is what you WANT in septic shock - the vasodilated state)
• β1 - increases heart rate and cardiac contractility
• β2 - peripheral vasodilation, bronchodilation, skeletal muscle vasodilation, glycogenolysis/lipolysis

2. Why Adrenaline is NOT First-Line - Specific Problems

A. Tachyarrhythmias

• Adrenaline's potent β1 and β2 stimulation causes marked tachycardia
• Associated with atrial fibrillation and other dysrhythmias
• Tachycardia increases myocardial oxygen demand in an already stressed heart
• Noradrenaline causes far fewer arrhythmias - this was specifically confirmed in the landmark SOAP II trial (De Backer et al., NEJM 2010), which compared dopamine vs norepinephrine and highlighted arrhythmia as a key differentiator

B. Elevated Lactate (False Elevation - "Aerobic Lactic Acidosis")

• Adrenaline's β2 stimulation drives skeletal muscle glycogenolysis and Na+/K+-ATPase pump activity, generating lactate even without tissue hypoxia
• This produces a spurious rise in serum lactate that masks the true resuscitation endpoint
• Lactate clearance is a primary target in sepsis management - if adrenaline falsely elevates it, you lose your most important monitoring tool
• Per Rosen's Emergency Medicine: "Epinephrine infusion is associated with increased oxygen consumption, increased systemic lactate concentrations, and decreased splanchnic blood flow"

C. Decreased Splanchnic Blood Flow

• β2-mediated vasodilation in skeletal muscle redistributes blood away from the gut
• Decreased mesenteric perfusion risks gut mucosal ischaemia and bacterial translocation - worsening the septic process
• Noradrenaline maintains or improves splanchnic perfusion at therapeutic doses

D. Myocardial Ischaemia

• High β1 activity + tachycardia = increased myocardial oxygen demand
• In septic cardiomyopathy (common in septic shock), this worsens cardiac function
• Noradrenaline's more controlled inotropic effect is better tolerated

E. Pulmonary Hypertension

• Adrenaline can increase pulmonary vascular resistance
• This is problematic in patients with right ventricular dysfunction (common in sepsis)
• Vasopressin is preferred in those with pulmonary hypertension for the same reason

3. Evidence Base

• SOAP II Trial (De Backer et al., NEJM 2010): RCT of 1679 shock patients - norepinephrine vs dopamine. No mortality difference overall, but significantly more arrhythmias with dopamine and higher mortality in cardiogenic shock subgroup. Reinforced norepinephrine as first choice.
• Multiple meta-analyses: No survival benefit with adrenaline over noradrenaline, but consistently more adverse effects with adrenaline.
• Surviving Sepsis Campaign Guidelines: Norepinephrine recommended as first-line vasopressor; adrenaline added only as a second agent when noradrenaline is insufficient.

4. When IS Adrenaline Used in Shock?

5. Summary - The Core Reasoning

Noradrenaline raises SVR and MAP in septic shock without the metabolic penalty of adrenaline. It does not falsely elevate lactate, causes fewer arrhythmias, preserves splanchnic flow better, and does not increase pulmonary vascular resistance. The β2 activity of adrenaline - useful in anaphylaxis and cardiac arrest - becomes a liability in septic shock.