Early Versus Late Adjunctive Vasopressin in Septic Shock

Sepsis is a highly prevalent and morbid disease estimated to account for up to 20% of annual deaths globally. If not rapidly identified and intervened upon, patients with sepsis may progress to septic shock, which is associated with mortality rates up to 50%. Patients with septic shock have persistent hypotension requiring vasoactive agents to augment blood pressure despite fluid resuscitation. Norepinephrine is recommended first-line by the Surviving Sepsis Campaign (SSC) guidelines for patients with septic shock. If mean arterial pressure (MAP) remains inadequate on norepinephrine, vasopressin is suggested as the second-line adjunctive agent. Over 30% of patients with septic shock in the United States (US) receive adjunctive vasopressin, with use rising over time. Despite increased use over time, ideal patient selection and initiation timing for adjunctive vasopressin in the course of a patient's shock are not well elucidated. The 2021 iteration of the SSC guidelines note that initiating vasopressin when the patient requires between 0.25 and 0.5 mcg/kg/min of norepinephrine "seems sensible". Yet, many questions remain regarding the timing of vasopressin initiation. The goal of this proposal is to evaluate the timing of vasopressin initiation in patients with septic shock based on the norepinephrine requirements at the time of vasopressin initiation. This pilot study will attempt to develop CDS technology in which to answer this clinical question.

• vasopressin - early initiation (Drug), also known as vasopressin: BPA fires to provider prompting vasopressin initiation when the norepinephrine dose is between 10-20 mcg/min
• vasopressin - standard initiation (Drug), also known as vasopressin: BPA fires to provider prompting vasopressin initiation when the norepinephrine dose is between 20-35 mcg/min

Primary outcomes

• Norepinephrine-equivalent dose [Outcome evaluated on day of vasopressin initiation]: The primary outcome is the norepinephrine-equivalent dose (in mcg/min) at the time of vasopressin initiation between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation

Secondary outcomes

• Proportion of patients within goal norepinephrine-equivalent dose range [Outcome evaluated on day of vasopressin initiation]: This outcome will evaluate the overall proportion of patients enrolled in the trial whose norepinephrine dose at the time of vasopressin is within the goal range for the treatment group (< 20 mcg/min for the early vasopressin group and > 20 mcg for the standard of care vasopressin)

Other outcomes

• Hemodynamic Response [6 hours after vasopressin initiation]: Compare rates of hemodynamic response to vasopressin initiation between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation
• ICU mortality [Through hospitalization admission]: Compare ICU mortality between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation
• In-hospital mortality [Through hospitalization admission]: Compare rates of in-hospital mortality between patients who were randomized by CDS to early adjunctive vasopressin initiation compare to late adjunctive vasopressin initiation
• BPA response rates [between the time of study enrollment and vasopressin initiation]: Overall evaluate and describe BPA response: the proportion of patients who were initiated on vasopressin, time to vasopressin initiation after BPA firing, and provider documented rationale for not initiating vasopressin after BPA firing

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 Years
* Diagnosis of Septic Shock
* Admitted to Cleveland Clinic Main Campus Medical ICU
* Receiving continuous infusion of norepinephrine at a dose > 5 mcg/min at time of enrollment

Exclusion Criteria:

* Administration of any other vasoactive agent other than norepinephrine at time of enrollment
* Initiation of vasopressin by provider outside of the context of study when NE < 10 mcg/min (before BPA firing)

• Results publication: Sacha GL, Lam SW, Wang L, Duggal A, Reddy AJ, Bauer SR. Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock. Crit Care Med. 2022 Apr 1;50(4):614-623. doi: 10.1097/CCM.0000000000005317. PMID 34582425

• Gretchen L. Sacha, PharmD, Principal investigator, The Cleveland Clinic