Vasopressors

Vasopressors raise blood pressure by vasoconstriction (and sometimes by increased cardiac output) and are used in shock when fluids alone do not restore perfusion. The choice depends on the type of shock and receptor effect.

Members. Noradrenaline, adrenaline, vasopressin, phenylephrine, dopamine, angiotensin II, metaraminol, ephedrine, and methylene blue as a rescue agent.

Mechanism. Alpha-1 agonists contract vascular smooth muscle. Vasopressin acts on V1 receptors, independent of catecholamines. Angiotensin II acts on AT1 receptors. Methylene blue inhibits guanylate cyclase and nitric oxide activity.

Targets. A mean arterial pressure of about 65 mmHg is a usual first target, adjusted for chronic hypertension and for lactate, capillary refill, mental state and urine output. Pressors are started early rather than waiting for large fluid volumes, after an initial crystalloid bolus of about 30 mL/kg in sepsis-induced hypoperfusion.

Pharmacokinetics. Catecholamines act within seconds and stop within minutes of stopping the infusion. Vasopressin lasts 10 to 20 minutes. Angiotensin II acts within minutes.

• Noradrenaline: first line in septic shock, cardiogenic shock and most vasodilatory states.
• Adrenaline: second line; adds inotropy and is first line in anaphylaxis; raises lactate.
• Vasopressin: fixed-dose add-on to noradrenaline; no inotropy.
• Phenylephrine: pure alpha agonist; for tachyarrhythmia or spinal hypotension.
• Dopamine: alternative in low-risk patients; more arrhythmia.
• Angiotensin II: refractory vasodilatory shock, where available.
• Methylene blue: refractory vasoplegia.

• Septic shock: noradrenaline infusion starting 0.05 to 0.1 micrograms/kg/minute, titrated every 5 to 15 minutes to a mean arterial pressure of about 65 mmHg (usual range 0.01 to 1 microgram/kg/minute). Add vasopressin 0.03 units/minute (range 0.01 to 0.04) when noradrenaline reaches 0.25 to 0.5 micrograms/kg/minute. Add adrenaline 0.01 to 0.5 micrograms/kg/minute if still short of target. Hydrocortisone 200 mg daily (50 mg every 6 hours) if noradrenaline needs persist at 0.25 micrograms/kg/minute or over for 4 hours.
• Cardiogenic shock: noradrenaline, with dobutamine for low output.
• Anaphylaxis: adrenaline 500 micrograms intramuscularly, repeated after 5 minutes, then infusion if refractory.
• Spinal or neurogenic hypotension: phenylephrine 50 to 200 micrograms/minute infusion or noradrenaline.
• Post-cardiac surgery vasoplegia: vasopressin 0.03 units/minute, with methylene blue 1 to 2 mg/kg over 20 to 60 minutes as rescue.
• Angiotensin II: 20 nanograms/kg/minute, titrated to a maximum of 80 nanograms/kg/minute in the first 3 hours, then 40 or under for maintenance.
• Access: peripheral infusion through a good proximal vein is acceptable for short periods at low concentration while central access is arranged. Do not delay.
• Selection: match to the cause. Correct volume first, treat the cause, and avoid dopamine where noradrenaline is available.

Contraindications. Uncorrected hypovolaemia, and mesenteric or limb ischaemia (vasopressin, angiotensin II relative). Methylene blue is contraindicated in G6PD deficiency (which is common in many African populations) and with serotonergic drugs because of serotonin syndrome.

Adverse effects. Peripheral, digital and mesenteric ischaemia, kidney injury, tachyarrhythmia (dopamine, adrenaline), hyperglycaemia, lactic acidosis (adrenaline), hyponatraemia (vasopressin), thrombosis (angiotensin II), and tissue necrosis on extravasation.

Extravasation. Stop the infusion, aspirate through the cannula, and infiltrate phentolamine 5 to 10 mg in 10 mL of 0.9% sodium chloride around the site.

Interactions. Monoamine oxidase inhibitors and linezolid with dopamine, ephedrine and metaraminol. Beta blockers with adrenaline (unopposed alpha). Halothane with catecholamines.

Monitoring. Invasive arterial pressure, heart rhythm, lactate, urine output, limb and skin perfusion, sodium (vasopressin), and cannula site.

Referral and escalation. Rising vasopressor requirement, lactate over 4 mmol/L or failure to reach target needs critical care review and source control.

Special groups. Pregnancy: phenylephrine and noradrenaline are used at caesarean section. Children: weight-based infusions, with adrenaline and noradrenaline preferred. Older adults: avoid dopamine. Renal impairment: no adjustment of dose.