When should vasopressin be added to noradrenaline (norepinephrine) therapy in cases of high dosage requirements, specifically above 10ml per hour?

Adding Vasopressin to Noradrenaline in Septic Shock

Vasopressin should be added to noradrenaline when the noradrenaline dose reaches 0.25 mcg/kg/min (approximately 10ml/hour for an average adult) and hypotension persists, to either raise mean arterial pressure to target or decrease noradrenaline dosage. 1

Rationale for Adding Vasopressin

• Noradrenaline is the first-choice vasopressor for treating hypotension in septic shock, with an initial target mean arterial pressure (MAP) of 65 mmHg 2, 3
• High doses of noradrenaline may have cardiac and immunological adverse effects and be associated with poorer outcomes 4
• Up to one-third of patients with septic shock may have vasopressin deficiency, which contributes to refractory shock 4
• Adding vasopressin provides a noradrenaline-sparing effect, which may reduce complications induced by high doses of noradrenaline (concept of decatecholaminization) 4

Dosing and Administration Protocol

• The recommended dose of vasopressin is 0.03 units/minute when added to noradrenaline 2, 3
• Vasopressin should not be used as the single initial vasopressor for septic shock 2
• Doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (when other vasopressors have failed to achieve target MAP) 3
• Continuous arterial blood pressure monitoring via arterial catheter is essential for all patients receiving vasopressors 3

Benefits of Adding Vasopressin

• Allows achievement of target MAP with lower doses of noradrenaline 3
• May reduce the incidence of supraventricular arrhythmias compared to high doses of noradrenaline alone 1
• In the VASST trial, patients with less severe septic shock (defined as noradrenaline <15 μg/min) had lower mortality rates when treated with vasopressin compared to noradrenaline alone (26.5% vs. 35.7%) 5

Alternative Second-Line Vasopressors

• Epinephrine may be considered as an alternative when an additional agent is needed to maintain adequate blood pressure 2, 1
• Epinephrine has more metabolic and cardiac adverse effects compared to noradrenaline but may be useful in patients with refractory shock and myocardial dysfunction 6
• Phenylephrine should only be used in specific circumstances such as when noradrenaline causes serious arrhythmias or when cardiac output is known to be high but blood pressure remains low 2, 1

Important Considerations and Precautions

• Ensure adequate fluid resuscitation has been provided before or alongside vasopressor therapy 3
• Dopamine is no longer recommended in patients with septic shock due to higher rates of cardiac arrhythmias 6
• Low-dose dopamine should not be used for renal protection 2
• Monitor for potential adverse effects of vasopressin, including digital ischemia 6
• Consider higher MAP targets (>65 mmHg) in patients with chronic hypertension 7