Titration of Noradrenaline (Norepinephrine) and Vasopressin

Overview

Noradrenaline (Norepinephrine)

Mechanism

Initiation

• First-line vasopressor in septic shock, neurogenic shock, and most forms of distributive shock
• Start after a 30 mL/kg crystalloid bolus has failed to maintain MAP ≥ 65 mmHg
• Administration via central venous catheter is preferred; peripheral use is acceptable short-term in acute settings

Dosing and Titration

"Norepinephrine should be initiated at a rate of 0.05 mcg/kg/min, or 3 to 5 mcg/min for most adult patients, and titrated at 3- to 5-minute intervals until the mean arterial pressure is greater than 65 mm Hg." - Rosen's Emergency Medicine

MAP Target

• Default: ≥ 65 mmHg - no data show benefit from higher targets even in hypertensive patients
• Higher targets (up to 80-85 mmHg) are sometimes used in chronic hypertension or traumatic brain injury, though evidence is limited

Weaning

Vasopressin (Antidiuretic Hormone / ADH)

Mechanism

When to Add Vasopressin

• Surviving Sepsis Campaign (2021): Add vasopressin when norepinephrine dose is ≥ 0.25 mcg/kg/min to raise MAP or reduce norepinephrine dose
• Sabiston Surgery: Threshold cited at ≈ 5 mcg/min of norepinephrine
• Rosen's EM: May add vasopressin as a second agent to norepinephrine at any point of refractory shock
• Additional indications: Atrial fibrillation with rapid ventricular response (catecholamines worsen tachycardia; vasopressin is rate-neutral)

Dosing and Titration

"Vasopressin may be added as a second vasopressor agent, initiated at 0.03 to 0.04 units/min." - Rosen's Emergency Medicine

"Vasopressin (at 0.02 to 0.04 U/min) may raise blood pressure in patients who are refractory to catecholamines." - Goldman-Cecil Medicine

Key distinction: Unlike norepinephrine, vasopressin is a fixed low-dose adjunct, not a titratable vasopressor. The goal is vasopressin replacement/supplementation, not dose escalation. High-dose vasopressin is not recommended due to risks of mesenteric, digital, and coronary ischemia.

Combined Use: Practical Framework

Septic Shock with MAP < 65 mmHg despite adequate fluids
             |
         START Norepinephrine
         0.05 mcg/kg/min → titrate q3-5 min
             |
         MAP target met?
         YES → continue, reassess fluids
         NO → continue titrating NE upward
             |
         NE ≥ 0.25 mcg/kg/min (or ~5 mcg/min)
             |
         ADD Vasopressin 0.03 units/min (fixed)
         Goal: "vasopressin-sparing" of NE
             |
         Persistent refractory shock?
             |
         Consider: Epinephrine, Angiotensin II,
                   Hydrocortisone 200 mg/day

Monitoring During Titration

• Arterial line - mandatory for continuous MAP monitoring during vasopressor titration
• Lactate - guide resuscitation adequacy (target normalisation)
• Urine output - target ≥ 0.5 mL/kg/hr
• Skin/extremity perfusion - watch for digital/peripheral ischemia (especially with vasopressin)
• Cardiac rhythm - norepinephrine can worsen tachyarrhythmias; switch to vasopressin/phenylephrine if AF develops

Recent Evidence

• Adjunctive vasopressors may reduce short-term mortality (RR 0.92, 95% CI 0.85-1.00) - but evidence certainty is low
• Likely reduce kidney replacement therapy (RR 0.92, moderate certainty)
• May increase digital/peripheral ischemia risk (RR 2.44, 95% CI 1.17-5.10)
• Conclusion: Adjunctive vasopressor use in the US is "disconnected from the low evidence certainty for a favorable mortality-to-risk profile"

Summary Table