Vasopressin Addition at Norepinephrine 0.25-0.5 µg/kg/min
Add vasopressin at 0.03 units/minute when norepinephrine reaches 0.25-0.5 µg/kg/min in septic shock. 1
Rationale for Early Vasopressin Addition
The Surviving Sepsis Campaign guidelines explicitly recommend adding vasopressin when norepinephrine requirements remain elevated or when you need to decrease norepinephrine dosage to achieve target MAP ≥65 mmHg. 1 At 0.25-0.5 µg/kg/min (approximately 17.5-35 µg/min in a 70 kg patient), you are already in the moderate-to-high dose range where adjunctive therapy becomes appropriate. 1
The FDA-approved starting dose for vasopressin in septic shock is 0.01 units/minute, titrated up by 0.005 units/minute at 10-15 minute intervals to a maximum of 0.03 units/minute. 2 However, the Society of Critical Care Medicine recommends starting directly at 0.03 units/minute when adding vasopressin to norepinephrine. 1
Why Vasopressin Over Other Options
Vasopressin is the preferred second-line agent because it works through a different mechanism (V1 receptor activation) than catecholamines, restoring vascular tone without increasing heart rate or myocardial oxygen demand. 1
Vasopressin allows norepinephrine dose reduction, which decreases the risk of tachyarrhythmias and excessive adrenergic stimulation. 3 This is particularly important because norepinephrine doses above 1 µg/kg/min are associated with mortality rates exceeding 80%. 4
Do not use epinephrine as your second agent at this dose range—epinephrine should be reserved as a third-line agent when norepinephrine plus vasopressin fail to achieve target MAP. 1 Epinephrine increases the risk of tachyarrhythmias (RR 0.35 for ventricular arrhythmias when avoided), causes transient lactic acidosis, and increases myocardial oxygen consumption more than norepinephrine. 1
Dosing Protocol
Start vasopressin at 0.03 units/minute as a continuous infusion through central venous access. 1, 2
Never exceed 0.03-0.04 units/minute for routine use—higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit. 1, 3
Titrate norepinephrine down gradually once vasopressin is added, maintaining MAP ≥65 mmHg while monitoring tissue perfusion markers (lactate clearance, urine output ≥0.5 mL/kg/h, mental status, capillary refill). 1, 5
Critical Monitoring Requirements
Maintain continuous arterial blood pressure monitoring via arterial catheter—this is a class I recommendation for all patients on vasopressors. 1, 5
Assess tissue perfusion continuously, not just MAP numbers: 5
- Lactate clearance every 2-4 hours
- Urine output ≥0.5 mL/kg/h
- Mental status and skin perfusion
- Capillary refill time
If Target MAP Still Not Achieved
Add epinephrine 0.05-2 µg/kg/min as your third vasopressor if norepinephrine plus vasopressin at maximum doses fail to achieve MAP ≥65 mmHg. 1, 5
Consider dobutamine 2.5-20 µg/kg/min instead of escalating vasopressors further if persistent hypoperfusion exists despite adequate MAP, particularly when myocardial dysfunction is evident. 1, 5
Add hydrocortisone 200 mg/day IV for refractory shock after 4 hours of high-dose vasopressor therapy. 1, 5
Common Pitfalls to Avoid
Do not delay vasopressin addition—waiting until norepinephrine exceeds 1 µg/kg/min is associated with dramatically worse outcomes. 4 Practice pattern data show wide variation (6.4-92.6 µg/min) in when clinicians add adjunctive agents, but earlier is better. 6
Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used alone. 1, 2
Avoid dopamine entirely—it increases mortality by 11% absolute risk and causes significantly more tachyarrhythmias (RR 0.47 for supraventricular arrhythmias when avoided). 1, 3
Do not use phenylephrine except in rare circumstances (norepinephrine-induced arrhythmias, documented high cardiac output with persistent hypotension)—it can raise blood pressure numbers while actually worsening tissue perfusion. 1