Vasopressors and inotropes

Surgical approach

• Not an operation: pharmacological support used peri-operatively, in ICU, ED, cath lab, obstetrics, and during anaesthesia.
• Typical clinical scenarios prompting use
  • Septic shock (vasoplegia ± myocardial depression)
  • Spinal/epidural sympathectomy, GA-induced vasodilation
  • Cardiogenic shock, post-cardiac surgery low output state
  • Anaphylaxis
  • Right ventricular (RV) failure / pulmonary hypertension crises

Anaesthetic management

• Type of anaesthesia
  • Usually adjunct to GA, also common with neuraxial anaesthesia (e.g., obstetrics) and sedation (e.g., endoscopy, cath lab).
• Airway
  • ETT often required in shock/ICU, SGA possible for short cases if haemodynamics stable and aspiration risk low.
• Duration
  • Minutes (boluses for transient hypotension) to days (ICU infusions).
• How painful
  • Pain relates to underlying pathology/surgery, vasopressor/inotrope therapy itself is not painful but requires invasive lines and close monitoring.
• Core practical approach
  • Treat cause first: bleeding, anaesthetic depth, sepsis source control, tamponade, tension pneumothorax, anaphylaxis, arrhythmia.
  • Optimise preload/afterload/contractility/HR: fluid responsiveness assessment, echocardiography, lactate/ScvO2 trends, urine output.
  • Monitoring: arterial line early, central access for prolonged infusions, consider cardiac output monitoring/echo in shock.
  • Infusion safety: dedicated lumen, smart pumps, clear concentrations, frequent site checks if peripheral.

Definitions and haemodynamic concepts

• Vasopressor: increases vascular tone (↑SVR) and usually ↑MAP, may have inotropic/chronotropic effects depending on receptor profile.
• Inotrope: increases myocardial contractility (↑stroke volume/CO), may also affect HR and SVR.
• MAP ≈ CO × SVR (CVP usually small), CO = HR × SV. Choose agent based on which variable is failing.
• Oxygen delivery (DO2) = CO × CaO2, raising MAP alone does not guarantee improved DO2 or microcirculatory flow.
• Shock phenotypes
  • Distributive (sepsis, anaphylaxis, neuraxial): low SVR ± high CO early, treat with vasopressor ± inotrope if myocardial depression.
  • Cardiogenic: low CO, high filling pressures, inotrope ± vasopressor to maintain coronary perfusion, avoid excessive tachycardia.
  • Obstructive (PE, tamponade, tension PTX): fix obstruction, temporise with vasopressor/inotrope as appropriate.
  • Hypovolaemic: volume first, vasopressor only as bridge if profound hypotension while controlling bleeding.

Receptor pharmacology (high-yield)

• α1: vasoconstriction (arterial + venous) → ↑SVR, ↑venous return, adverse: ischaemia, ↑afterload, reflex bradycardia.
• β1: ↑inotropy + ↑chronotropy + ↑dromotropy, adverse: tachyarrhythmias, ↑MVO2, myocardial ischaemia.
• β2: vasodilation (skeletal muscle), bronchodilation, can ↓SVR and cause hypokalaemia, hyperglycaemia, tremor.
• Dopamine receptors: D1 renal/mesenteric vasodilation (not reliably renal-protective), D2 presynaptic ↓NE release.
• V1 (vasopressin): vascular smooth muscle constriction via IP3/Ca2+, works in acidosis/hypoxia, may reduce pulmonary vasoconstriction relative to catecholamines in some settings.
• PDE3 inhibition (milrinone/enoximone): ↑cAMP in myocardium (inotropy) + vascular smooth muscle (vasodilation) → &#039,inodilator&#039,.
• Calcium sensitiser (levosimendan): increases troponin C sensitivity + KATP opening → inotropy + vasodilation, long-acting metabolite.
• Angiotensin II: potent vasoconstrictor, stimulates aldosterone, used in refractory vasodilatory shock in some ICUs.

Common agents: key properties, dosing, and adverse effects

• Noradrenaline (norepinephrine)
  • Receptors: strong α1, moderate β1.
  • Effects: ↑SVR and ↑MAP, modest ↑CO if preload responsive, may cause reflex bradycardia.
  • Indications: first-line vasopressor in septic shock, vasoplegia (incl. post-CPB), hypotension under GA when SVR low.
  • Dose (adult infusion): commonly 0.02–1 microgram/kg/min titrated to MAP/perfusion, local practice varies.
  • Adverse: peripheral/mesenteric ischaemia, extravasation necrosis, arrhythmias (less than adrenaline/dopamine).
• Adrenaline (epinephrine)
  • Receptors: β1/β2 at lower doses, α1 increasingly at higher doses.
  • Effects: ↑CO (inotropy/chronotropy), ↓SVR at low dose (β2) then ↑SVR at higher dose (α1).
  • Indications: anaphylaxis (first-line), cardiac arrest, severe bronchospasm with shock, refractory septic shock (second-line), peri-arrest hypotension.
  • Dose: infusion often 0.02–1 microgram/kg/min, anaphylaxis IM 500 micrograms (adult) repeated, IV titrated boluses in anaesthesia (e.g., 10–100 micrograms) with extreme caution.
  • Adverse: tachyarrhythmias, myocardial ischaemia, hyperlactataemia (β2-driven), hyperglycaemia, splanchnic hypoperfusion at high dose.
• Phenylephrine
  • Receptors: pure α1 agonist.
  • Effects: ↑SVR and venous return, often ↓HR and may ↓CO (especially if preload limited or RV failure).
  • Indications: anaesthesia-related vasodilation with tachycardia, obstetric spinal hypotension (common), short-term bolus therapy.
  • Dose: bolus 50–100 micrograms IV (titrate), infusion commonly 0.25–2 micrograms/kg/min or 10–100 micrograms/min depending on protocol.
  • Adverse: reflex bradycardia, reduced stroke volume/CO, tissue ischaemia at high doses.
• Metaraminol
  • Mechanism: predominantly α1 agonist with some indirect sympathomimetic action (NE release).
  • Use: common UK theatre vasopressor for bolus/infusion to treat GA/neuraxial hypotension.
  • Dose: bolus often 0.25–1 mg IV, infusion concentration varies locally (e.g., 0.5–5 mg/h titrated).
  • Cautions: tachyphylaxis possible (indirect component), extravasation risk, may reduce CO if excessive afterload.
• Ephedrine
  • Mechanism: mixed acting (indirect NE release + direct α/β).
  • Effects: ↑HR and ↑CO with some ↑SVR, useful when hypotension with bradycardia.
  • Dose: 3–6 mg IV boluses (up to 9–12 mg depending on context) titrated.
  • Limitations: tachyphylaxis with repeated dosing, less effective in catecholamine-depleted states (sepsis, chronic sympathetic activation).
• Vasopressin
  • Mechanism: V1-mediated vasoconstriction, restores vascular tone in relative vasopressin deficiency (septic shock).
  • Indications: adjunct to noradrenaline in septic shock/vasoplegia, useful in acidosis where catecholamines less effective.
  • Dose: fixed-dose infusion commonly 0.03 units/min (range often 0.01–0.06 units/min per local policy).
  • Adverse: digital/mesenteric ischaemia (esp. with high catecholamine doses), hyponatraemia (V2), reduced CO in some patients, avoid bolus dosing in shock.
• Dobutamine
  • Receptors: β1 predominant with β2 and some α effects, net often inotropy + vasodilation.
  • Effects: ↑CO, ↓SVR (may drop BP if vasodilated), can increase HR.
  • Indications: low cardiac output with adequate/raised SVR (cardiogenic shock with high afterload, septic myocardial depression with adequate MAP), stress echo.
  • Dose: 2.5–20 micrograms/kg/min titrated.
  • Adverse: tachyarrhythmias, hypotension (from β2), myocardial ischaemia, may worsen dynamic LVOT obstruction.
• Dopamine
  • Dose-dependent receptor profile (conceptual): low dose D1, moderate β1, high α1—clinically variable and unpredictable.
  • Use: now uncommon due to arrhythmias and worse outcomes vs noradrenaline in shock, may have niche in selected bradycardic hypotension with low arrhythmia risk (rare).
  • Adverse: tachyarrhythmias, endocrine effects (↓pituitary hormones), immunosuppression, no renal-protective benefit.
• Milrinone (PDE3 inhibitor)
  • Effects: inodilator, reduces PVR and SVR, useful in RV failure/pulmonary hypertension and post-cardiac surgery low output.
  • Dose: loading dose sometimes avoided due to hypotension, infusion commonly 0.25–0.75 micrograms/kg/min (adjust in renal impairment).
  • Adverse: hypotension, arrhythmias, prolonged effect in renal failure.
• Levosimendan
  • Effects: inotropy with less increase in intracellular Ca2+, vasodilation, may improve RV function.
  • Use: selected cases of acute decompensated heart failure/post-cardiac surgery, practice varies in UK.
  • Adverse: hypotension, headache, arrhythmias, long duration due to active metabolite.
• Isoprenaline (isoproterenol)
  • Receptors: β1 and β2 agonist (no α).
  • Effects: marked tachycardia + inotropy with vasodilation → can reduce MAP.
  • Use: bradyarrhythmias/overdrive pacing temporisation, post-transplant bradycardia, less common for shock.
  • Adverse: tachyarrhythmias, myocardial ischaemia, hypotension.

Choosing the right agent (pattern recognition)

• Low SVR (warm peripheries, wide pulse pressure, low diastolic): choose noradrenaline first, add vasopressin if escalating, consider adrenaline if poor cardiac output too.
• Low CO with high SVR (cold peripheries, narrow pulse pressure, high filling pressures): dobutamine or milrinone, add noradrenaline if MAP inadequate.
• Hypotension with bradycardia (e.g., high spinal, vagal episodes): ephedrine or atropine, consider adrenaline infusion if severe, treat cause.
• Anaphylaxis: adrenaline is first-line, large-volume crystalloid, add vasopressin/noradrenaline if refractory, consider glucagon if on beta-blocker.
• RV failure / pulmonary hypertension: avoid excessive α-mediated rise in PVR/afterload, consider noradrenaline (to support coronary perfusion) + milrinone (reduce PVR) ± vasopressin, optimise oxygenation/ventilation and avoid acidosis.
• Dynamic LVOT obstruction (HOCM, severe hypovolaemia, sepsis with hyperdynamic LV): avoid inotropes, give fluid, increase afterload (phenylephrine), reduce HR (beta-blocker) if appropriate.

Practicalities: access, preparation, and monitoring

• Access
  • Central line preferred for prolonged/high-dose vasopressors, however, short-term peripheral noradrenaline via large-bore cannula in a proximal vein can be acceptable with strict protocols and frequent checks.
  • Avoid distal sites (hand/wrist) for vasopressors if possible, use dedicated line/lumen.
• Extravasation management
  • Stop infusion, leave cannula in situ, aspirate, elevate limb, warm compress, infiltrate phentolamine if available (or topical nitroglycerin per local policy) and seek plastics advice if severe.
• Monitoring endpoints
  • MAP target commonly ≥65 mmHg in septic shock, individualise (chronic hypertension, head injury, aortic stenosis).
  • Perfusion: mentation, capillary refill, skin temperature, urine output, lactate clearance, ScvO2/ SvO2, echo-derived stroke volume changes.
• Acid–base and electrolytes
  • Acidosis reduces catecholamine responsiveness, correct hypoxia, hypercapnia, and severe metabolic derangements, consider vasopressin as adjunct in refractory vasoplegia.
  • β2 agonism may cause hypokalaemia and hyperglycaemia (adrenaline, dobutamine, salbutamol).

Special situations

• Obstetric spinal hypotension
  • Phenylephrine infusion/bolus commonly first-line, ephedrine if associated bradycardia, maintain left uterine displacement and give fluid judiciously.
  • Fetal considerations: ephedrine associated with more fetal acidosis than phenylephrine (likely via increased maternal catecholamines and fetal metabolism).
• Sepsis bundles (haemodynamic component)
  • Fluid resuscitation guided by responsiveness, noradrenaline first-line, add vasopressin to reduce noradrenaline dose, consider dobutamine if myocardial dysfunction with persistent hypoperfusion despite adequate MAP and volume.
• Cardiogenic shock / acute MI
  • Aim to maintain coronary perfusion (diastolic pressure) while improving CO, noradrenaline often preferred vasopressor, add dobutamine for inotropy if needed.
  • Avoid excessive tachycardia, consider mechanical support (IABP/Impella/VA-ECMO) early in refractory cases (specialist decision).
• Aortic stenosis
  • Maintain sinus rhythm, preload, and SVR, phenylephrine or noradrenaline commonly used, avoid vasodilatory inotropes that drop SVR.

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