Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator

Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator

The goal of this observational study is to learn about blood pressure response to the vasopressor drug vasopressin in people with septic shock.

The main questions it aims to answer are:

• Are the levels of molecules showing communication between cells different between people whose blood pressure improves and people whose blood pressure does not improve when given a vasopressor medication?
• Are measurements found on echocardiography (heart ultrasound) different between people whose blood pressure improves and people whose blood pressure does not improve when given a vasopressor medication?
• Are measurements of blood oxygen in tissues just below the skin different between people whose blood pressure improves and people whose blood pressure does not improve when given a vasopressor medication?

Participants will be asked to contribute one or two blood samples. Participants who are ordered the drug vasopressin will contribute two blood samples. Both samples will be about two tablespoons for a total of about four tablespoons. One sample will be drawn before starting vasopressin infusion and the second sample will be drawn between one and six hours after starting the vasopressor drug infusion. At the same time points, advanced echocardiography pictures and measurements of oxygen in tissues from a sensor placed on one of the hands will be taken. Participants who are not ordered the drug vasopressin and only ordered the drug norepinephrine will contribute only one blood sample. At the time the sample is collected, advanced echocardiography pictures and measurements of oxygen in tissues from a sensor placed on one of the hands will be taken. This research also involves analyzing data obtained during the participant's hospital stay.

Septic shock mortality remains high at 33% in North America; current clinical predictors of poor outcomes in septic shock are suboptimal. In addition to antibiotics and intravenous fluids, vasoactive agents are initiated to restore effective tissue perfusion. Norepinephrine (NE) is the recommended first-line vasopressor, but adjunctive arginine vasopressin is used in over one-third of patients to improve blood pressure or decrease NE dosage. However, less than half of vasopressin recipients have a clinically-apparent hemodynamic response (defined as a decrease in NE dosage at 6 hours after vasopressin initiation). Vasopressors, particularly norepinephrine, are known to be immune modulators. Further, each vasopressor has its own unique effect on a patient's hemodynamic profile as assessed by echocardiography and microcirculation measurements. In the current study, the investigators seek to clarify the link between vasopressin, immune response, hemodynamic profile, and microcirculatory measurments. The central goal of this proposal is to identify "vasopressin response" as an easily-identifiable bedside indicator of a distinct septic shock subphenotype.

Inclusion Criteria:

• Adult patients (≥18 years old)
• Septic shock (as defined by Sepsis-3)
• Receiving norepinephrine
• Admitted to a medical, surgical, NeuroSciences, or mixed intensive care unit
• Central venous catheter in place
• Ordered fixed-dose vasopressin as an adjunct to norepinephrine by the primary care team (unless in active control cohort)

Exclusion Criteria:

• Vasopressin ordered for an indication other than septic shock
• Vasopressin initiated at another institution
• Receiving a primary vasopressor other than norepinephrine (eg, phenylephrine)
• Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the preceding 28 days
• Blood hemoglobin concentration <7 g/dL
• Primary treatment team determines that vasopressin initiation is emergent
• Patient or their legal authorized representative opts to not participate in the study