Titration Priority in Septic Shock with Dual Vasopressors
When both norepinephrine and vasopressin are running, titrate norepinephrine first—vasopressin should remain fixed at 0.03 units/minute and never be titrated up or down during active shock management. 1, 2
Vasopressin Dosing Protocol
- Vasopressin is administered at a fixed, non-titrated dose of 0.03 units/minute when added to norepinephrine as a second-line agent 1, 3, 2
- Never exceed 0.03–0.04 units/minute except as salvage therapy when all other vasopressor combinations have failed to achieve target MAP, because higher doses cause cardiac, digital, and splanchnic ischemia without additional hemodynamic benefit 1, 4
- Vasopressin should never be used as monotherapy—it must always be combined with norepinephrine 1, 3
Norepinephrine Titration Strategy
- Titrate norepinephrine to maintain MAP ≥65 mmHg (or 70-75 mmHg in patients with chronic hypertension) using continuous arterial blood pressure monitoring 1, 3, 2
- Once vasopressin is added at 0.03 units/minute, you have two options: either raise MAP to target by increasing norepinephrine, OR decrease norepinephrine dosage while maintaining hemodynamic stability 1
- The goal of adding vasopressin is to achieve a norepinephrine-sparing effect, allowing you to reduce norepinephrine requirements while maintaining adequate perfusion 1, 4
Escalation Beyond Dual Therapy
If MAP targets cannot be achieved despite norepinephrine titration with fixed-dose vasopressin:
- Add epinephrine (0.05–2 mcg/kg/min) as a third vasopressor agent rather than increasing vasopressin beyond 0.03–0.04 units/minute 1, 3
- Consider dobutamine (2.5–20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP, particularly when myocardial dysfunction is evident 1, 3
- Add hydrocortisone 200 mg/day IV for refractory shock unresponsive to catecholamines and vasopressin after at least 4 hours 1, 3
Critical Monitoring Parameters
- Arterial catheter placement is mandatory for all patients requiring vasopressors to enable precise titration 1, 3, 2
- Monitor tissue perfusion markers beyond MAP: lactate clearance every 2-4 hours, urine output ≥0.5 mL/kg/h, mental status, skin perfusion, and capillary refill 1, 3
- When using vasopressin, consider measuring cardiac output to ensure adequate tissue perfusion is maintained despite vasoconstriction 2
Common Pitfalls to Avoid
- Do not titrate vasopressin like a catecholamine—it is dosed at a fixed rate, not adjusted based on blood pressure response 1, 2
- Avoid escalating vasopressin beyond 0.03–0.04 units/minute as this creates a "perfect storm" of excessive vasoconstriction, myocardial ischemia, and arrhythmogenic potential without hemodynamic benefit 1
- Do not delay adding a third agent (epinephrine) when norepinephrine requirements remain high despite fixed-dose vasopressin—further vasopressin escalation is contraindicated 1
- Gradual norepinephrine dose reduction is preferred over abrupt discontinuation once hemodynamic stability is achieved, though specific tapering increments are not defined in guidelines 1