Study Notes: Vasopressors and Inotropes

1. Definition and Purpose:

• Vasopressors: Drugs that increase blood pressure by vasoconstriction (narrowing blood vessels).

• Inotropes: Drugs that increase myocardial contractility (pumping strength).

• Chronotropes: Drugs that affect heart rate.

• Main Indication: Management of shock (MAP < 60 mmHg or SBP drop >30 mmHg from baseline).

2. Types of Shock

• Hypovolemic shock: Loss of intravascular volume (trauma, bleeding, diarrhea, third spacing).
  → Treat with fluids/blood first; vasopressors are not primary therapy.

• Cardiogenic shock: Pump failure (MI, myocarditis, severe valve disease).
  → Inotropes required to improve contractility.

• Obstructive shock: Adequate volume and pump, but blocked flow (PE, tamponade, tension pneumothorax).
  → Remove obstruction; vasopressors only supportive.

• Distributive shock: Vasodilation with loss of vascular tone (sepsis, anaphylaxis, neurogenic shock, toxins, burns).
  → Vasopressors restore vascular tone.

3. Determinants of Mean Arterial Pressure (MAP)

• MAP = Cardiac Output × Systemic Vascular Resistance

• Cardiac Output depends on:

  • Preload

  • Contractility

  • Heart rate

• Clinical application:

  • Low preload → give fluids

  • Low contractility → inotrope

  • Low HR → chronotrope (e.g., atropine)

  • Low SVR → vasopressor

4. Receptor Targets

• α1 receptors: Vasoconstriction → ↑SVR, ↑BP

• β1 receptors: ↑Contractility + ↑HR → ↑CO

• β2 receptors: Vasodilation → ↓SVR

• Dopamine receptors (DA1, DA2): Renal, mesenteric, cerebral vasodilation (dose-dependent effect)

• V1 receptors: Potent vasoconstriction (via vasopressin)

• Angiotensin II receptors: Vasoconstriction

• Phosphodiesterase-3 inhibitors: ↑cAMP → ↑contractility + vasodilation

5. Common Agents

Norepinephrine (Noradrenaline)

• Receptors: Strong α1, some β1

• ↑SVR (primary effect), mild ↑contractility, reflex bradycardia

• First-line agent in septic shock

• Also useful in cardiogenic shock (often combined with dobutamine)

Epinephrine (Adrenaline)

• Receptors: α1, β1, β2 (all strong)

• Low dose → β1/β2 (↑CO, vasodilation)

• High dose → α1 (↑SVR, ↑BP)

• Uses: Anaphylaxis (first-line), refractory septic shock, cardiac arrest

• Risk: arrhythmias, ↑lactate

Dobutamine

• Receptors: β1 (↑contractility), β2 (vasodilation)

• ↑CO but may ↓BP (due to vasodilation)

• Use: Cardiogenic shock with preserved BP or septic shock with myocardial dysfunction

• Often combined with norepinephrine to counter hypotension

Dopamine

• Dose-dependent effects:

  • Low dose (<3 mcg/kg/min): "renal dose" (not evidence-based)

  • Medium dose (3–10 mcg/kg/min): β1 → ↑CO

  • High dose (>10 mcg/kg/min): α1 → vasoconstriction

• Rarely used now due to arrhythmia risk

• May be considered in cardiogenic shock with bradycardia

Vasopressin

• Receptors: V1 (vasoconstriction, non-adrenergic)

• Use: Add-on in refractory septic shock (esp. if norepinephrine failing)

• Fixed-dose infusion, not titrated

• Risks: digital ischemia, mesenteric ischemia

Phenylephrine

• Pure α1 agonist (vasoconstrictor only)

• Use: peri-intubation hypotension, sometimes in septic shock when tachyarrhythmias limit NE use

Other agents

• Milrinone (PDE-3 inhibitor): ↑contractility, vasodilation → used in decompensated heart failure

• Angiotensin II: Vasoconstriction via AT1 receptor (reserved for refractory vasodilatory shock)

6. Clinical Application

• If shock type unknown → start norepinephrine

• Hypovolemic shock: Fluids/blood first

• Cardiogenic shock: Dobutamine or dopamine (if low BP), often with norepinephrine

• Distributive shock: Norepinephrine first-line, add vasopressin or epinephrine if refractory

• Anaphylaxis: Epinephrine IM (first-line)

7. Key Principles

• Always identify type of shock before starting therapy.

• Use lowest effective dose, titrated to perfusion goals (MAP ≥ 65 mmHg).

• Norepinephrine is the go-to vasopressor in most ICU shock scenarios.

• Avoid relying on dopamine for "renal protection" (no proven benefit).

• Combination therapy is often required in mixed shock states.