Septic shock is a syndrome associated with severe infection and a mortality rate of approximately 45%. In line with current recommendations, norepinephrine is the first-line vasopressor used in patients with septic shock. In a previous study, norepinephrine doses above 1 µg/kg/min were associated with mortality rates over 90%. In the same study, doses above 0.3 µg/kg/min were associated with a mortality rate of 40%. An increased mortality compared to the general 40% mortality of septic shock appears to be associated with norepinephrine doses as low as 0.3 µg/kg/min.

Vasopressin stimulates V1 receptors, primarily located on vascular smooth muscle cells. When V1a receptors are stimulated, they induce vasoconstriction by activating protein kinase C via a Gq protein and various second messengers.

Its use is validated in refractory shock states by international guidelines as a second-line vasopressor. This indication was further reinforced in the 2021 update of the septic shock management recommendations.

The VASST study, a randomized controlled trial, assessed the effects of vasopressin versus norepinephrine in septic shock. It found no overall difference in mortality between the two groups. However, in less severe cases where norepinephrine doses were below 14 µg/min before randomization, vasopressin was associated with significantly lower mortality, suggesting potential benefits from early introduction of a second vasopressor.

The VANISH trial failed to confirm this hypothesis, possibly due to broad inclusion criteria and unclear protocol regarding the combined use of both agents. Our hypothesis is that (1) vasopressin is beneficial when used synergistically with norepinephrine; (2) due to its negative effect on cardiac output (as shown in previous studies), vasopressin should only be administered to patients in the hyperdynamic phase of septic shock.

The hypothesis is that the systematic addition of vasopressin to norepinephrine therapy in a hyperdynamic septic shock subpopulation would improve patient outcomes.

Inclusion Criteria:

• Patient aged 18 or over
• Patient who has consented to take part in the research or patient whose close relative has consented to take part in the research or, failing that, patient being included in an emergency situation
• Patient in septic shock with adapted cardiac output
• Patient in whom noradrenaline dosage has been greater than 0.3μg/kg/min for less than 12 hours
• Patients benefiting from or affiliated to social security

Exclusion Criteria:

• Patient with acute coronary syndrome
• Patient with known history of acute coronary syndrome
• Patient with suspected mesenteric ischemia
• Patient with hyponatremia < 130mmol/L,
• Known allergy to vasopressin or its excipients
• Minors
• Pregnant women
• Patients under legal guardianship or curatorship
• Patients under judicial protection.