What is the recommended dose of vasopressin (Vasopressin) for septic shock?

Vasopressin Dosing in Septic Shock

The recommended starting dose of vasopressin for septic shock is 0.01 units/minute, which can be titrated up by 0.005 units/minute at 10-15 minute intervals to a maximum of 0.07 units/minute. 1

Dosing Protocol

Initial Dosing and Titration

• Start at 0.01 units/minute according to FDA guidelines 1
• Titrate up by 0.005 units/minute every 10-15 minutes until target blood pressure is reached 1
• Maximum recommended dose is 0.07 units/minute for septic shock 1
• After target blood pressure has been maintained for 8 hours without catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated 1

Administration Considerations

• Dilute vasopressin in normal saline (0.9% sodium chloride) or 5% dextrose in water (D5W) prior to intravenous administration 1
• Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration 1
• Administer through a central line whenever possible 2

Clinical Evidence and Rationale

Vasopressin is typically used as an adjunct to norepinephrine in septic shock. The Surviving Sepsis Campaign guidelines note that vasopressin levels are often lower than expected in septic shock, creating a relative vasopressin deficiency 3. This provides the physiological basis for supplementation.

The VASST trial, a landmark randomized controlled trial, studied vasopressin at 0.03 units/minute compared to norepinephrine alone and found no difference in the overall mortality rate 4. However, a predefined subgroup analysis showed potential benefit in patients with less severe septic shock 4.

More recent research has examined whether higher doses might be more effective. A 2022 study compared initial fixed doses of 0.03 units/minute versus 0.04 units/minute and found no significant difference in hemodynamic response between the two dosages (50.0% vs 53.1% response rate) 5. This suggests that higher initial doses may not provide additional benefit.

Role in Septic Shock Management

Vasopressin should be considered as:

• An adjunct to norepinephrine when MAP remains <65 mmHg despite adequate norepinephrine dosing 2
• A means to reduce norepinephrine requirements 2
• A second-line agent in the vasopressor algorithm 2

Monitoring and Safety Considerations

• Arterial catheter placement is recommended for all patients requiring vasopressors 2
• Target MAP of 65 mmHg for most patients 2
• Monitor for adverse effects, as doses above 0.04 units/minute may lead to adverse vasoconstriction-mediated events 6
• Patients who respond to vasopressin (defined as a lowering of the catecholamine dose required to maintain MAP ≥65 mmHg) tend to have better clinical outcomes 7

Practical Approach

1. Start vasopressin at 0.01 units/minute when norepinephrine requirements are increasing or when MAP remains <65 mmHg despite norepinephrine
2. Titrate up by 0.005 units/minute every 10-15 minutes
3. Do not exceed 0.07 units/minute for septic shock
4. Wean vasopressin after hemodynamic stability is achieved for 8 hours without catecholamines

This approach aligns with FDA recommendations and current critical care practice, balancing efficacy with safety concerns related to excessive vasoconstriction.