Sunday, October 19, 2025

Adrenaline (Epinephrine)

Adrenaline is a potent **β₁/β₂/α₁ agonist** with **dose-dependent** inotropy, chronotropy, bronchodilation, and vasoconstriction. 

It’s the **drug of choice for anaphylaxis**, a powerful **inopressor** for LCOS/post-CPB or refractory septic vasoplegia, and the standard **ALS** vasopressor. 

Typical ICU/OR infusion **0.02–0.2 (up to 0.5) mcg/kg/min**; use central access and be vigilant for **arrhythmias, ischaemia, lactate rise, hypokalaemia**, and **extravasation injury.



# 1) Receptor-level action → clinical effects


**Primary receptors (dose-dependent):**


* **β₁ agonist** → ↑ inotropy, ↑ chronotropy, ↑ dromotropy → ↑ **CO**.

* **β₂ agonist** → **bronchodilation**, skeletal-muscle vasodilation, **↓ mast-cell mediator release**; metabolic effects (↑ glucose, **↓ K⁺** via cellular shift).

* **α₁ agonist** (more prominent at higher doses) → **arterial/venous vasoconstriction** → ↑ **SVR/MAP**.


**Clinical phenotype by dose (rule of thumb):**


* **Very low–low** (≤0.02–0.05 mcg/kg/min): β₁/β₂ dominant → ↑ CO, mild ↓ SVR.

* **Moderate** (0.05–0.2): balanced β + α → ↑ CO **and** ↑ SVR.

* **High** (>0.2): α₁ predominant → marked vasoconstriction; risk of ↑ afterload, ischaemia, lactate rise.


**Key bedside effects**


* **Heart:** powerful inotrope/chronotrope; may precipitate **AF/VT/VF**, ↑ myocardial O₂ demand → **ischaemia**.

* **Vessels:** dose-dependent vasoconstriction (skin/splanchnic) or vasodilation (muscle) → net MAP usually rises with moderate–high doses.

* **Lungs:** **bronchodilation**; cornerstone for **anaphylaxis**.

* **Metabolic:** **hyperglycaemia**, **lactataemia** (β-driven glycolysis; not always tissue hypoperfusion), **hypokalaemia** (β₂ shift).


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# 2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)


**Common presentations**


* **1 mg/mL** (1:1000) amp (IM use; can be diluted for infusions).

* **0.1 mg/mL** (1 mg in 10 mL; 1:10,000) prefilled syringe (IV bolus for ALS).

* Infusion mixes (ICU/OR): **4 mg in 50 mL** (80 mcg/mL) or **1 mg in 50 mL** (20 mcg/mL). Central line preferred.


**PK**


* **Onset IV:** < 1 min; **peak:** minutes; **offset:** 1–3 min after stop.

* **t½:** ~2–3 min; **metabolism:** MAO & COMT → inactive; **excretion:** renal metabolites.


**Disadvantages from PK/PD**


* Requires **continuous infusion**; narrow titration window.

* **Tachyarrhythmias**, **lactate rise**, **hyperglycaemia**.

* **Peripheral extravasation** can cause **ischaemic necrosis**.


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# 3) Practical dosing


## A. Anaesthesia / Cardiac theatre


**Indications:** post-CPB myocardial stunning/LCOS, anaphylaxis under anaesthesia, refractory hypotension with low CO.


* **Post-CPB/LCOS infusion:** start **0.02–0.05 mcg/kg/min**, titrate q2–5 min by 0.01–0.02; typical **0.02–0.2 mcg/kg/min** (higher if refractory).

* **Rescue bolus (careful):** 10–20 **mcg** IV aliquots (0.1–0.2 mL of 1:10,000) for transient hypotension while starting infusion.

* **Math example (70 kg @ 0.1 mcg/kg/min = 7 mcg/min):** with **80 mcg/mL** → **5.25 mL/h**.


## B. ICU


**Indications:** vasodilatory shock with low CO (septic/post-CPB vasoplegia), cardiogenic shock as an inopressor when dobutamine/milrinone insufficient.


* **Start:** **0.02–0.05 mcg/kg/min**; **range:** **0.02–0.5 mcg/kg/min**.

* Combine with **norepinephrine** when SVR is very low; or with **inodilator** (dobutamine/milrinone) if afterload high and contractility poor.


## C. Life-threatening emergencies (for completeness)


* **Adult cardiac arrest (ALS):** **1 mg IV** (1:10,000) every 3–5 min cycles.

* **Anaphylaxis (adult):** **0.5 mg IM** (1:1000) mid-outer thigh; repeat q5 min PRN. Refractory → **IV infusion** (e.g., 1–4 mcg/min then titrate) under monitoring.


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# 4) Special populations — dosing cautions


### Pregnancy


* First-line for **anaphylaxis** in pregnancy (maternal life priority); can reduce uterine blood flow at high IV doses—use **IM first** when appropriate and titrate IV carefully intra-op.


### Lactation


* Minimal oral bioavailability for infant; short t½; single/emergency doses acceptable.


### Hepatic impairment


* Widely metabolised extrahepatically; **no formal adjustment**—**titrate to effect**.


### Renal impairment


* Metabolites renally excreted but inactive; **no adjustment**. Watch perfusion and urine output.


### Obesity


* Start with **IBW/AdjBW-based** rates to avoid overshoot; titrate to haemodynamics.


### Paediatrics


* **Anaphylaxis IM:** **0.01 mg/kg** (1:1000), max **0.5 mg**.

* **Infusion:** **0.02–1 mcg/kg/min** titrated in specialist setting.

* **Cardiac arrest:** **0.01 mg/kg IV** (1:10,000 = 0.1 mL/kg).


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# 5) Drug interactions (clinically key)


* **MAO inhibitors / TCAs / SNRIs:** **exaggerated pressor** and arrhythmic responses → start at **very low doses** or avoid.

* **Non-selective β-blockers** (e.g., propranolol): **unopposed α₁ vasoconstriction** → severe hypertension/bradycardia; bronchospasm risk persists (β₂ blocked).

* **Halogenated volatiles (esp. halothane):** myocardial sensitisation → **ventricular arrhythmias**.

* **Digoxin:** arrhythmia risk ↑.

* **Insulin/oral hypoglycaemics:** hyperglycaemia from epi may necessitate higher insulin.

* **Inhaled β₂-agonists:** additive hypokalaemia—monitor K⁺.


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# 6) Significant complications & management


| Complication                                           | Mechanism / Features                                 | Management                                                                                                                                       |

| ------------------------------------------------------ | ---------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------ |

| **Tachyarrhythmias (AF/VT/VF)**                        | β₁ excess, esp. hypoxia/acidosis                     | Reduce/stop; correct K⁺/Mg²⁺; antiarrhythmics/defibrillate per ACLS.                                                                             |

| **Myocardial ischaemia**                               | ↑ MVO₂ + ↑ afterload                                 | Lower dose; add inodilator; ensure adequate MAP/CPP and treat pain/anaemia.                                                                      |

| **Severe hypertension / limb or mesenteric ischaemia** | α₁ vasoconstriction at high dose                     | Titrate down; reconsider target MAP; balance with inodilator.                                                                                    |

| **Lactataemia** (β-driven)                             | Accelerated glycolysis—not necessarily hypoperfusion | Interpret with context; check ScvO₂/echo; don’t chase lactate alone.                                                                             |

| **Hypokalaemia**                                       | β₂-mediated intracellular shift                      | Monitor K⁺; replace if needed.                                                                                                                   |

| **Hyperglycaemia**                                     | Glycogenolysis/gluconeogenesis                       | Adjust insulin.                                                                                                                                  |

| **Extravasation necrosis**                             | Intense local α₁ vasoconstriction                    | **Stop infusion, leave cannula**, **phentolamine 5–10 mg** in 10–15 mL saline infiltrated around site; warm compress; surgical review if severe. |

| **Pulmonary oedema**                                   | Afterload ↑ + tachycardia                            | Reduce dose; diuretics/vasodilator if appropriate; optimise ventilation.                                                                         |


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