Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in the Recovery Phase of Septic Shock

Study objectives: Patients with septic shock often require vasoactive agents for hemodynamic support; however, the optimal approach to discontinuing these agents once patients reach the recovery phase is currently unknown. The objective of this evaluation was to compare the incidence of hypotension within 24 hours based on the discontinuation order of norepinephrine (NE) and vasopressin (AVP) in patients in the recovery phase of septic shock.

Design: Retrospective cohort study.

Setting: The medical, surgical, and neurosciences intensive care units (ICUs) at a large tertiary care academic medical center.

Patients: A total of 585 adults in the recovery phase of septic shock who received fixed-dose AVP for at least 6 hours as an adjunct to NE between September 2011 and August 2015 were included. Of these patients, 155 had AVP discontinued first, and 430 had NE discontinued first.

Measurements and main results: Hypotension was evaluated during the 24-hour period after discontinuation of the first vasoactive agent and was defined as mean arterial pressure less than 60 mm Hg with one or more of the following interventions: increased remaining vasoactive agent dose by 25%, reinstitution of the discontinued agent, or administration of at least 1 L of fluid bolus. Time to hypotension was evaluated with survival analysis, and risk of hypotension was evaluated with multivariable Cox proportional hazards regression. No significant difference between groups was noted in the incidence of hypotension within 24 hours (55% in the AVP discontinued first group vs 50% in the NE discontinued first group, p=0.28) or ICU mortality (45.2% vs 40.0%, p=0.26). After adjustment for baseline factors with multivariable Cox proportional hazards regression, having AVP discontinued first was independently associated with an increased risk of hypotension with a time-varying effect that decreased over time (HR(t) = e^{[1.16-0.08*t]} , p<0.001).

Conclusion: In patients recovering from septic shock treated with concomitant AVP and NE, no significant difference was noted in the incidence of hypotension based on discontinuation order of these agents.