SA EMS DRUG PROTOCOL FIELD

ADRENALINE (EPINEPHRINE)

Direct Sympathomimetic Agonist • Endogenous Catecholamine • Vasopressor & InotropeHPCSA CDST v1.3 (Oct 2025)

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ADRENALINE (EPINEPHRINE)

Adrenaline Acid Tartrate / Epinephrine (Brand Names: Adrenalin, EpiPen, Anapen)

Clinical Summary: A non-selective endogenous catecholamine that exerts potent direct alpha-1, beta-1, and beta-2 adrenergic receptor stimulation to restore coronary perfusion in arrest, reverse bronchospasm, and stabilize catastrophic anaphylactic shock.

Authorized HPCSA Emergency Care Scope of Practice (Annexure A 2022)Statutory Board Mandate

LEGENDARY BAA (PLAIN TEXT - NO COLOR)ECA (*)AEA (*)ECT (*)LEGENDARY CCA (^) [ANT PARAMEDIC]NDIP EMC (^) [ANT PARAMEDIC]ECP ONLY (~)

⚖️ Cadre Governance:HPCSA Annexure A (2022): IM Anaphylaxis authorized across ALL cadres (Legendary BAA, AEA, ECA, ECT, CCA, NDip, ECP). IV Cardiac Arrest: AEA, ECA, ECT, ANT, ECP. IV Infusion/Push-dose: ANT and ECP (ECT requires supervising MO consult).

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1. Mechanism of Action

How this drug operates physiologically in the human body

Primary Molecular Mechanism of Action

Adrenaline is a potent, non-selective agonist at all major adrenoreceptors. Through G-protein-coupled transmembrane signaling, it drives three distinct organ pathways: Alpha-1 stimulation (Gq-coupled): Activates phospholipase C and raises intracellular calcium in vascular smooth muscle, producing intense arteriolar vasoconstriction that dramatically elevates Systemic Vascular Resistance (SVR) and increases aortic diastolic pressure. Beta-1 stimulation (Gs-coupled): Stimulates adenylyl cyclase to increase cyclic AMP (cAMP) in cardiac myocytes, inducing potent positive inotropy (contractility), chronotropy (heart rate), dromotropy (conduction speed), and lusitropy (relaxation). Beta-2 stimulation (Gs-coupled): Relaxes bronchial smooth muscle via protein kinase A phosphorylation and stabilizes mast cell membranes, halting the systemic release of histamine and inflammatory mediators.

Clinical Physiology Alert

Textbook Teaching vs. Research-Proven Physiological Paradoxes

Standard emergency texts often present Adrenaline as a universal miracle drug. However, high-level cellular research demonstrates that Adrenaline introduces severe physiological trade-offs that can paradoxically worsen patient outcomes if mismanaged:

1. The Coronary Perfusion vs. Myocardial Oxygen Debt Paradox Resuscitation

📖 Textbook Teaching: “Adrenaline is the primary drug that jump-starts the arrested heart into spontaneous contraction.”

🔬 Research Fact: Adrenaline does NOT directly restart the heart. Its sole benefit in CPR is alpha-1 mediated peripheral vasoconstriction that elevates Coronary Perfusion Pressure (CPP > 15 mmHg) during compressions.

⚡ The Physiological “Why” Across Other Sections: In an ischemic, fibrillating heart, beta-1 stimulation dramatically spikes myocardial oxygen demand (MVO2) and intracellular calcium overload. This precipitates recurrent refractory ventricular fibrillation and triggers severe post-resuscitation myocardial stunning!

2. The Anaphylaxis Route Paradox (IM Thigh vs. Rapid IV Push) Anaphylaxis Pharmacokinetics

📖 Textbook Teaching: “If anaphylaxis is severe, push Adrenaline straight into the IV line immediately.”

🔬 Research Fact: Uncontrolled IV boluses of Adrenaline (1:1,000 or 1:10,000) in patients with a pulse trigger lethal intracranial hemorrhage, Takotsubo cardiomyopathy, and fatal ventricular fibrillation.

⚡ The Physiological “Why” Across Other Sections: The rich vascular bed of the vastus lateralis muscle (mid-anterolateral thigh) achieves rapid, steady systemic therapeutic absorption within 8 minutes with zero spike in lethal SVR. Rapid IV push spikes systolic BP past 260 mmHg, rupturing cerebral aneurysms and overwhelming ischemic ventricles!

3. The Aerobic Hyperlactatemia Paradox Cellular Metabolism

📖 Textbook Teaching: “Elevated serum lactate always means your patient is suffering from anaerobic tissue hypoxia and inadequate perfusion.”

🔬 Research Fact: Adrenaline infusions directly stimulate beta-2 receptors on skeletal muscle, driving aerobic glycolysis and hyperlactatemia despite excellent oxygenation!

⚡ The Physiological “Why” Across Other Sections: Beta-2 activation stimulates adenylate cyclase and glycogenolysis, accelerating pyruvate production faster than the mitochondria can oxidize it. The excess pyruvate converts into lactate in the presence of normal oxygen! Medics misinterpret this lactate spike as worsening shock and dangerously overdose fluids.

4. The Cerebral No-Reflow Paradox (ROSC vs. Brain Death) Cerebral Microcirculation

📖 Textbook Teaching: “High-dose adrenaline improves cardiac output and maximizes survival to hospital discharge.”

🔬 Research Fact: The PARAMEDIC-2 trial proved Adrenaline increases ROSC, but does not improve long-term neurologically intact survival.

⚡ The Physiological “Why” Across Other Sections: Massive alpha-1 arteriolar constriction combined with platelet aggregation completely collapses the cerebral microvasculature. Even after the heart restarts, the brain suffers from persistent microcirculatory ischemia (the "no-reflow" phenomenon), leading to severe anoxic brain damage.

2. Statutory Clinical Indications3 Authorized Uses

Strictly per HPCSA CDST v1.3, Annexure A & CPG

1. Severe Systemic Anaphylaxis & Life-Threatening Allergic Collapse

All Cadres (BAA, AEA, ECT, ECA, ANT, ECP - Annexure A p. 7)

Statutory Dosing & Administration Route:

Adult Dose: 0.5 mg (0.5 mL of 1:1,000) IM into anterolateral mid-thigh.
Paediatric Dose: 0.01 mg/kg (0.01 mL/kg of 1:1,000) IM (maximum single dose 0.3 mg).
Repeat Interval: Repeat every 5 minutes if respiratory distress or hemodynamic collapse persists.

Diagnostic Confirmation: Signs & Symptoms Required

✓Acute onset (minutes to hours) of generalized urticaria, flushing, pruritus, or angioedema
✓Upper airway compromise with inspiratory stridor, hoarseness, or globus sensation
✓Lower airway bronchospasm with refractory expiratory wheezing, tachypnea, and chest tightness
✓Distributive cardiovascular collapse with SBP < 90 mmHg, diaphoresis, and syncope

Rule of Engagement:

Must ALWAYS be administered via the intramuscular route into the mid-anterolateral thigh (vastus lateralis). NEVER administer undiluted 1:1,000 via the intravenous route in a perfusing patient! Subcutaneous administration is strictly discouraged due to severe localized vasoconstriction halting systemic absorption.

Source: HPCSA CDST v1.3 (October 2025) p. 25; Annexure A (April 2022) p. 7; CPG 2018 p. 95

2. Cardiopulmonary Arrest (Shockable & Non-Shockable Rhythms)

AEA, ECT, ECA, ANT, ECP (Annexure A p. 7)

Statutory Dosing & Administration Route:

Adult Cardiac Arrest: 1.0 mg IV/IO (10 mL of 1:10,000 dilution) every 3 to 5 minutes during active CPR.
Paediatric Cardiac Arrest: 0.01 mg/kg IV/IO (0.1 mL/kg of 1:10,000 dilution) every 3 to 5 minutes.
Timing Rule: In non-shockable rhythms (Asystole / PEA), administer immediately upon access. In shockable rhythms (VF / Pulseless VT), administer after the 2nd defibrillation cycle.

Diagnostic Confirmation: Signs & Symptoms Required

✓Patient unresponsive to voice and painful stimuli
✓Absence of a palpable central carotid pulse within 10 seconds
✓Apnea or agonal gasping respirations
✓ECG confirming Ventricular Fibrillation, Pulseless Ventricular Tachycardia, PEA, or Asystole

Rule of Engagement:

Every IV/IO dose must be immediately followed by a 20 mL Normal Saline flush and limb elevation for 20 seconds. Drug delivery must NEVER interrupt continuous, high-quality chest compressions and timely defibrillation cycles.

Source: HPCSA CDST v1.3 (October 2025) p. 36–38; Annexure A p. 7; CPG 2018 p. 112

3. Push-Dose Vasopressor & Post-ROSC Cardiogenic Shock Infusion

ANT / ECP (Schedule 6; ECT with Mandatory Medical Officer Consult)

Statutory Dosing & Administration Route:

Push-Dose Pressor: 5 – 20 mcg IV slow bolus every 2–5 minutes (Prepared by mixing 1 mL of 1:10,000 [100 mcg] with 9 mL Normal Saline = 10 mcg/mL).
Continuous Infusion: 0.1 – 0.5 mcg/kg/min (titrated to maintain MAP ≥ 65 mmHg).

Diagnostic Confirmation: Signs & Symptoms Required

✓Post-Cardiac Arrest syndrome with persistent hypotension (MAP < 65 mmHg) despite 20 mL/kg fluid bolus
✓Peri-induction RSI hemodynamic collapse in trauma patients with exhausted sympathetic tone
✓Refractory neurogenic shock with loss of sympathetic vascular tone and refractory vasodilation

Rule of Engagement:

Requires continuous quantitative ECG rhythm monitoring and automated NIBP cycling every 2–3 minutes. Correct hypovolemia prior to or concurrent with pressor therapy to prevent severe end-organ ischemic necrosis.

Source: HPCSA CDST v1.3 p. 13, 29 & 39; Annexure A p. 7

3. Adverse Effects & Pathophysiological Impact

Why the body reacts and why it occurs in specific indications

ADVERSE RISK 01

Severe Tachyarrhythmias & Ventricular Fibrillation

Physiological Effect on Body (The "Why"):

Intense stimulation of cardiac beta-1 adrenoreceptors increases intracellular cyclic AMP and overloads the sarcoplasmic reticulum with calcium. This drastically shortens the refractory period of ventricular conductive tissue, precipitating triggered activity, non-sustained ventricular tachycardia, and degeneration into fatal Ventricular Fibrillation.

Why in This Specific Indication It Occurs:

Most dangerous when high doses or rapid IV boluses are given to elderly patients or individuals with occult coronary artery disease during severe bronchospasm or anaphylaxis.

ADVERSE RISK 02

Acute Malignant Hypertensive Crisis & Intracranial Hemorrhage

Physiological Effect on Body (The "Why"):

Profound alpha-1 mediated constriction of peripheral resistance arterioles produces an instantaneous surge in Systemic Vascular Resistance (SVR) and left ventricular afterload, skyrocketing mean arterial pressure well past physiological autoregulatory limits.

Why in This Specific Indication It Occurs:

Occurs primarily when undiluted Adrenaline (1:1,000) is mistakenly administered as an intravenous push instead of intramuscular injection, causing catastrophic intracranial hemorrhage or acute aortic dissection.

ADVERSE RISK 03

Peripheral Extravasation Necrosis & Digital Gangrene

Physiological Effect on Body (The "Why"):

Extreme alpha-1 vasoconstriction in local microcirculatory beds produces complete cessation of microvascular capillary blood flow, resulting in localized tissue ischemia, infarction, and full-thickness gangrene.

Why in This Specific Indication It Occurs:

Occurs when Adrenaline infusions or push doses extravasate from fragile peripheral IV lines in the hand or wrist. Antidote: Infiltrate area immediately with Phentolamine mesylate (5–10 mg in 10 mL saline).

4. Contraindications & Lethal Risks

Biological consequences & why it threatens life

ABSOLUTE CONTRAINDICATION

Absolute in Cardiac Arrest: None (Life-Saving Emergency)

Physiological Consequence on Hemodynamics / Organs:

In confirmed cardiopulmonary arrest, there are zero absolute pharmacological contraindications. The biological priority is restoring coronary perfusion pressure above 15 mmHg to achieve return of spontaneous circulation (ROSC).

Why It Is Lethal or Dangerous:

Clinical Mandate: Withholding Adrenaline in cardiac arrest due to pre-existing hypertension or cardiac disease guarantees 100% mortality. Never delay or withhold during active CPR.

RELATIVE / CAUTION

Uncorrected Severe Hypovolemic Shock

Physiological Consequence on Hemodynamics / Organs:

Intense alpha-1 vasoconstriction in an empty, exsanguinated vascular tree produces extreme afterload mismatch without improving preload or stroke volume.

Why It Is Lethal or Dangerous:

Lethal Danger: Induces profound splanchnic, renal, and peripheral microvascular ischemia without restoring cerebral or coronary perfusion. Always co-resuscitate with warmed balanced crystalloids or blood products.

RELATIVE / CAUTION

Pheochromocytoma / Hypertensive Crisis

Physiological Consequence on Hemodynamics / Organs:

Exogenous catecholamines administered on top of massive endogenous adrenaline/noradrenaline secretion from adrenal medullary tumors provoke uncontrollable adrenergic storms.

Why It Is Lethal or Dangerous:

Lethal Danger: Drives systolic pressures exceeding 280 mmHg, precipitating acute hemorrhagic stroke, ruptured cerebral berry aneurysms, acute pulmonary edema, and immediate circulatory collapse.

5. Statutory Resources & Verbatim Quotes

Verbatim regulatory excerpts with deep external links

HPCSA Clinical Decision Support Tools (CDST v1.3)

Professional Board for Emergency Care (October 2025), Cardiac Arrest & Anaphylaxis Protocols, Pages 25 & 36–39

Source

"Anaphylaxis: Give Adrenaline 0.5mg IM into mid-anterolateral thigh. Repeat every 5min. Cardiac Arrest: 1mg IV/IO (10mL 1:10 000) every 3-5min. Flush with 20mL normal saline. In shockable rhythms give after 2nd shock; in non-shockable give immediately upon access."

HPCSA Annexure A - List of Capabilities and Medications

PBEC Statutory Register (April 2022), Page 7

Source

"Adrenaline – use in anaphylaxis and cardiac arrest (Intramuscular and Intravenous): Authorised for BAA (IM only), AEA, ECT, ECA, ANT, ECP. Adrenaline other than anaphylaxis and cardiac arrest (Inhaled, Subcutaneous, Intravenous): Authorised for ANT and ECP (ECT with MO consultation)."

HPCSA Clinical Practice Guidelines (CPG 2018)

Pharmacology Monograph: Adrenaline (Epinephrine), Pages 95 & 112

Source

"The IM route is preferred over SC for anaphylaxis. IV adrenaline is associated with a high risk of fatal arrhythmias and acute myocardial ischemia; should only be given by experienced ALS providers in profound shock. Flush thoroughly following every cardiac arrest dose."

SA EMS FIELD PROTOCOLS • STATUTORY GOVERNANCE

All clinical indications, dosages, and contraindications reflect the HPCSA PBEC Clinical Decision Support Tools (CDST Version 1.3, October 2025), read in direct conjunction with Annexure A (April 2022) and Clinical Practice Guidelines (2018).

Author: Jacoline (Jax) Geldenhuys, BEMC • HPCSA Registered Emergency Care Practitioner (ECP)