Inotropes and vasopressors

Norepinephrine:

Receptors; α1 + α2 + mild β1

Effect: 

• SVR ↑↑ (powerful vasoconstrictor) 

• BP ↑ 

• CO slightly ↑

Indication: 

• First-line in septic shock (survival benefit)

• Restore MAP without tachycardia (good in tachyarrhythmia patients)

• Distributive shock (anaphylaxis after epi, neurogenic)

• Vasoplegia post-CPB

Contraindications:

• Cardiogenic shock with low EF (may ↑ afterload too much)

• Mesenteric ischemia risk

Dilution/rate

• 4 mg in 50 mL (0.08 mg/mL) or 16 mg in 50 mL (0.32 mg/mL, ICU conc)

• Start 0.02–0.1 μg/kg/min → titrate

Lactate after NE infusion:

• High lactate = shock is getting worse. However, after starting norepinephrine, a rise in lactate in the first 1–3 hours is often a GOOD sign.

• Before norepinephrine: Global hypoperfusion

  • • • Cardiac output is shunted to the heart and brain only, & Skin, muscle, and gut = ischemic --> the lactate in shock initially is from anaerobic metabolism + impaired clearance. However, the rate of production is still very low because tissues are dying and NOT metabolically active.

• After NE infusion

  • • • Norepi restores MAP and re-perfuses muscle and splanchnic beds --> Tissues start using glucose again --> Glycolysis kicks back to life → pyruvate production increases --> Mitochondria are still not fully recovered → more pyruvate converts to lactate

      • So lactate increases because metabolism is restarting, not because shock is worse.

      • More perfusion = more metabolism = more pyruvate = more lactate (temporarily). And lactate clears once mitochondria recover

• Timeline after starting NE

  • • • • 0-3 hours: Lactate ↑ (Perfusion returning, mitochondria still weak)

        • 3–12 hours: Lactate plateau (meaning improving)

        • 12 - 24 hours: Lactate ↓ (good prognosis)

• Clinical point: Patients whose lactate does NOT rise after norepinephrine actually do worse. Because:

  • • • • They may remain hypoperfused (no metabolic restart)

        • Lactate production machinery (glycolysis) is failing

        • The prognosis is worse

• Adrenaline also raises lactate, but for a metabolic reason, not perfusion alone: β₂ stimulation → ↑ glycolysis → ↑ pyruvate → ↑ lactate

• Lactate Trends After Norepinephrine: Early rise means perfusion is improving, cells are waking up and producing pyruvate again. But rising lactate despite good MAP after 6–12 hours is bad lactate.

Epinephrine:

Receptors; 

• Low dose → β (inotropy + chronotropy)

• High dose → α (vasoconstriction)

Effect: 

• It behaves like an inotrope at low doses: β1 + β2  (↑ HR, ↑ contractility, bronchodilation, vasodilation)

• It acts as vasopressor at high doses: α1 (Vasoconstriction → ↑ SVR → ↑ BP)

Indication: 

• Anaphylaxis (first line)

• Cardiac arrest (ACLS)

• Refractory septic shock (second line)

• Cardiogenic shock with bradycardia

Contraindications:

• Severe tachyarrhythmias: Because β1 stimulaiton → risk of VF / VT

• Digoxin toxicity: Its a pro-arrhythmic condition

• LVOT obstruction (HOCM): ↑ contractility worsens LVOT obstruction

• Uncontrolled hyperthyroidism: Exaggerated response

Dilution/rate

• 4 mg in 50 mL (0.08 mg/mL) standard ICU

• Start 0.02–0.1 μg/kg/min, titrate

Clinical points:

• • Increases lactate because of β2 glycolysis — not always shock worsening

  • Lactate rises on epinephrine even if perfusion is good because β2 stimulation→ glycolysis --> generates lactate

  • Use in anaphylaxis BEFORE fluids if airway collapse suspicion: to prevent refractory shock

  • If BP drops on low-dose epi → increase dose (switch to α effect): β → α transition

  • Best drug for asthma peri-arrest: because it provides Bronchodilation + stabilises airway oedema

  • Epinephrine = β at low dose, α at high dose.

  • First-line for anaphylaxis — IM, not IV.

  • Raises lactate, not always due to shock — β2 metabolic effect.

  • Great for bradycardic shock, bad for tachyarrhythmias.

Dobutamine:

Receptors: β1 (++), β2 (+)

Effect: 

• CO ↑↑ 

• SVR ↓ 

• HR ↑

Indications

• Cardiogenic shock with high SVR

• Acute heart failure with low output

• Bradycardic heart failure when pacing is unavailable

Contraindications

• Hypotension without vasopressors (needs NE support)

• Septic shock without cardiac dysfunction

Dilution/rate

• 250 mg in 50 mL (5 mg/mL)

• Start 2.5–10 μg/kg/min, titrate slowly; arrhythmias are dose-dependent.

Clinical points

• If BP drops on dobutamine → add norepinephrine, don’t stop dobutamine

• Improves pulmonary oedema by increasing LV forward flow

• In recent years, the practice for Cardiogenic Shock (CS) has shifted such that Norepinephrine is increasingly recommended as the first-line vasoactive agent rather than Dopamine or even Dobutamine in many scenarios; The SOAP‑II trial. The recommended strategy is 

  • • • First: start norepinephrine to achieve an adequate MAP (>65)

      • Then: add dobutamine if hypoperfusion persists due to low contractility

Typical bedside markers prompting dobutamine addition

• • • • • • • • 1. Cold extremities, low urine output despite MAP >65

                2. Echo: low EF / low LV contractility

                3. High lactate despite restored BP

Dopamine:

Receptors: dose-dependent

• Low 1–3 μg/kg/min → dopaminergic (renal)

• Medium 3–10 → β1 (inotropy)

• High >10 → α1 (vasoconstriction)

Indications

• Almost obsolete

• Only niche: bradycardic shock if pacing/epi unavailable

Contraindications

• AF / tachyarrhythmias

• Cardiogenic shock with high filling pressures

• Never for “renal dose dopamine” — harmful

Clinical points

• Higher arrhythmia risk than any other catecholamine

• Higher mortality vs norepinephrine in septic shock (SOAP II trial)

Vasopressin:

Receptor: 

• V1 (vascular smooth muscle), 

• V2 (renal water retention)

Effect: 

• Intense vasoconstriction independent of pH + adrenergic receptors

Indications

• Septic shock after NE 0.2–0.3 μg/kg/min

• Vasoplegia post-cardiac surgery

• ACE-i induced refractory shock

• Anaphylaxis resistant to epinephrine

Contraindications

• Coronary or mesenteric ischemia (pure vasoconstrictor)

Dose

• Not weight-based

• 0.01–0.04 units/min (fixed rate)

Clinical points:

• Never give bolus → cardiac arrest

• Works even in severe acidosis & beta-blocker therapy

Pressor choice: (Shock type and best choice)

1. 1. Septic: Norepi → add Vasopressin → Epi

   2. Cardiogenic (cold, high SVR): Dobutamine ± Norepi

   3. Cardiogenic (warm, vasodilated): Norepi + Dobutamine

   4. Anaphylaxis: Epinephrine

   5. Neurogenic: Norepinephrine

   6. Bradycardic shock: Epi / Dopamine

   7. Acidosis, β-blocker on board: Vasopressin

Clinical pearls:

• • Norepinephrine is the MAP-restoring agent, dobutamine is the CO-restoring agent

  • If dobutamine drops BP → add norepi, don’t stop dobutamine

  • Rising lactate on adrenaline can mean good perfusion

  • Never use dopamine for kidneys — it kills kidneys

  • Vasopressin NEVER bolus

  • Vasopressin is an add-on, not a starter

  • Never use dopamine for kidneys.

  • Never treat all shock with fluids.

  • In shock + severe acidosis (pH < 7.1) → vasopressin works when catecholamines fail

  • Don’t run pressors through peripheral lines if >4 hours → necrosis risk

  • In cardiogenic shock with hypotension, dobutamine is not first-line. Norepinephrine → stabilise MAP → then add dobutamine only to fix poor pump function.

  • Central line preferred after 4 hours 

  • Dobutamine often needs NE support to maintain BP

Shock approach:

• 1. Identify shock type

     • • Cold? Warm? Bradycardic? Hypoxic? Anaphylaxis?

  2. Give fluids only if volume loss is suspected

     • • Sepsis? 20–30 mL/kg once

       • Cardiogenic shock? Fluids worsen → avoid

  3.  Choose pressor:

     • • Septic shock → Norepinephrine

       • If NE > 0.3 μg/kg/min → ADD Vasopressin

       • If CO low → ADD Dobutamine

       • Cardiogenic shock

         • • • Low output & high SVR → Dobutamine ± NE

             • Low output & vasodilated → NE + Dobutamine

• Anaphylaxis → IM Epinephrine → IV infusion if shock

• Neurogenic shock → Norepinephrine

• Bradycardic shock → Epinephrine or Dopamine

4.Reassess every 15 minutes

• 1. MAP > 65?

  2. Urine > 0.5 mL/kg/hr?

  3. Lactate falling after 6–12 h?

Crystelloids & Colloids

• Septic shock: Balanced fluids (RL, Plasma-Lyte) > NS

• Trauma with hypotension: 1:1:1 blood products, not crystalloids

• Burns: RL preferred

• DKA: NS first, then balanced fluids

• Cirrhosis: Albumin in SBP / post-paracentesis / hepatorenal syndrome