In septic shock, should vasopressin or noradrenaline (norepinephrine) be weaned first?

From the Guidelines

In septic shock, norepinephrine (noradrenaline) should typically be weaned first before vasopressin. When a patient is stabilizing and ready for vasopressor weaning, the recommended approach is to maintain the vasopressin dose (usually fixed at 0.03-0.04 units/minute) while gradually reducing the norepinephrine infusion 1. Once norepinephrine has been completely weaned off, vasopressin can then be tapered and discontinued. This sequence is preferred because vasopressin is generally used as an adjunctive agent to norepinephrine, helping to restore vascular tone through a different mechanism. Vasopressin works on V1 receptors causing vasoconstriction independent of catecholamine pathways, which is particularly beneficial in septic shock where patients often develop catecholamine resistance.

Key Considerations

• The use of vasopressin in septic shock is recommended as an adjunct to norepinephrine, with the intent of either raising mean arterial pressure or decreasing norepinephrine dosage 1.
• Norepinephrine is recommended as the first-choice vasopressor in septic shock, with a strong recommendation and moderate quality of evidence 1.
• The fixed-dose nature of vasopressin therapy makes it more practical to maintain vasopressin while adjusting the more easily titratable norepinephrine infusion based on blood pressure response.
• Maintaining vasopressin during norepinephrine weaning may help prevent rebound hypotension, as it provides baseline vasomotor support while reducing catecholamine exposure.

Clinical Implications

• Clinicians should prioritize weaning norepinephrine before vasopressin in patients with septic shock, based on the most recent and highest quality evidence available 1.
• The decision to wean vasopressors should be individualized and based on the patient's clinical response, with careful monitoring of blood pressure and other vital signs.
• The use of vasopressin and norepinephrine in septic shock should be guided by established clinical guidelines and protocols, with consideration of the patient's underlying condition and potential risks and benefits of therapy.

From the FDA Drug Label

After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper vasopressin injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure. The FDA drug label does not answer the question.

From the Research

Weaning Vasopressin or Noradrenaline in Septic Shock

There is limited direct evidence on whether to wean vasopressin or noradrenaline first in septic shock. However, the available studies provide some insights into the use of these vasopressors in septic shock:

• The study by 2 discusses the management of septic shock, including the use of vasopressors, but does not specifically address the weaning of vasopressin or noradrenaline.
• The study by 3 found that norepinephrine is the most commonly used first-line vasopressor in septic shock, and its use has increased over time.
• The study by 4 reviews the pharmacology and clinical application of vasoactive therapy in septic shock, including the use of norepinephrine and vasopressin, but does not provide guidance on weaning.
• The study by 5 evaluated the use of closed-loop control based on fuzzy logic to wean norepinephrine in septic shock patients, and found that it reduced the duration of shock and the total amount of norepinephrine infused.
• The study by 6 compared the outcomes of adult patients with septic shock who received vasopressin versus norepinephrine as the first-line vasopressor, and found that vasopressin was associated with a lower requirement for renal replacement therapy.

Considerations for Weaning

When considering weaning vasopressin or noradrenaline in septic shock, the following factors should be taken into account:

• The patient's hemodynamic status and response to vasopressor therapy
• The presence of any underlying conditions that may affect the patient's ability to tolerate weaning, such as cardiac or renal dysfunction
• The potential risks and benefits of weaning, including the risk of hypotension and the potential for improved renal function
• The use of adjunctive therapies, such as corticosteroids or other vasoactive agents, which may affect the patient's response to weaning

Clinical Decision-Making

The decision to wean vasopressin or noradrenaline first in septic shock should be made on a case-by-case basis, taking into account the individual patient's clinical status and response to therapy. The available evidence suggests that norepinephrine is the most commonly used first-line vasopressor in septic shock, and that vasopressin may be associated with a lower requirement for renal replacement therapy. However, the optimal strategy for weaning these agents has not been established, and further research is needed to guide clinical decision-making 2, 3, 4, 5, 6.