When to add vasopressin in patients with septic shock who are hypotensive despite adequate fluid resuscitation and norepinephrine infusion?

When to Add Vasopressin in Septic Shock

Vasopressin should be added to norepinephrine when patients with septic shock remain hypotensive despite adequate fluid resuscitation and norepinephrine infusion, with the goal of either raising mean arterial pressure to target or decreasing norepinephrine dosage. 1

Initial Management of Septic Shock

1. First-line therapy:

   • Norepinephrine is the first-choice vasopressor for septic shock 1
   • Initial fluid resuscitation with crystalloids (at least 30 mL/kg) 2
   • Target mean arterial pressure (MAP) ≥65 mmHg 2

2. When to add vasopressin:

   • When target MAP cannot be maintained with norepinephrine alone
   • When high doses of norepinephrine are required
   • FDA-approved indication: "to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines" 3

Vasopressin Dosing and Administration

• Recommended dose: Up to 0.03 U/min 1
• For septic shock: 0.01 to 0.07 U/min 3
• Preparation: Dilute 20 units/mL with normal saline or D5W to either 0.1 units/mL or 1 unit/mL 3
• Administration: Continuous intravenous infusion
• Duration: Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration 3

Clinical Benefits of Adding Vasopressin

• Allows reduction in norepinephrine requirements 4
• May decrease the risk of rebound hypotension 4
• Works through a different mechanism (V1 receptors) than catecholamines 3
• May be particularly beneficial in less severe septic shock 5
• May reduce the need for renal replacement therapy compared to norepinephrine alone 6

Monitoring During Vasopressin Therapy

• Blood pressure and heart rate
• Urine output (target ≥0.5 mL/kg/h)
• Skin perfusion and mental status
• Lactate clearance
• Renal and liver function tests 2
• Platelet count (may decrease with terlipressin) 4

Potential Adverse Effects

• Decreased cardiac output
• Bradycardia
• Tachyarrhythmias
• Hyponatremia
• Ischemia (coronary, mesenteric, skin, digital) 3
• Bilirubin elevation 4

Special Considerations

• Avoid excessive vasoconstriction by careful titration
• Consider adding dobutamine (2.5-20 μg/kg/min) if there is evidence of myocardial dysfunction or persistent hypoperfusion despite adequate blood pressure 2
• Consider hydrocortisone (up to 200 mg/day) in patients requiring escalating vasopressor doses 1
• Vasopressin reaches peak effect within 15 minutes and effects fade within 20 minutes after stopping infusion 3

Clinical Pearls

• Vasopressin is not recommended as a first-line agent but as an adjunct to norepinephrine
• The pharmacodynamic effect is proportional to the infusion rate 3
• There is no evidence for tachyphylaxis or tolerance to the pressor effect of vasopressin in patients with septic shock 3
• Push-dose vasopressin may be considered as a temporizing measure while preparing continuous infusion 7

By following these guidelines, clinicians can appropriately incorporate vasopressin into the management of patients with septic shock who remain hypotensive despite adequate fluid resuscitation and norepinephrine infusion.