2026 Southeastern Residency Conference

TITLE: Impact of Vasopressin Initiation Timing on Outcomes of Septic Shock Patients Receiving Norepinephrine 

AUTHORS: Somer Pye, Steven Robinette, Jacquelyn Bryant, Logan Doriety 

OBJECTIVE: Assess the timing of vasopressin addition to norepinephrine in intensive care unit patients experiencing septic shock and the potential impact it has on patient outcomes. 

SELF-ASSESSMENT QUESTION: According to the 2026 Surviving Sepsis Guidelines, which vasopressor is recommended second line to norepinephrine in septic shock?

BACKGROUND: According to the 2021 Surviving Sepsis Guidelines, norepinephrine is recommended as the first-line vasopressor, with the addition of vasopressin as a second-line agent when mean arterial pressure cannot be maintained above 65 mmHg. However, the optimal timing for vasopressin initiation remains undefined.

METHODS: This is a retrospective, single-center cohort study of adult patients in the ICU at McLeod Regional Medical Center that received norepinephrine and vasopressin for at least 8 hours with an electronic diagnosis grouper (EDG) coded diagnosis of severe sepsis with septic shock between August 1, 2023 and July 31, 2025. The primary outcome of this evaluation includes length of time to achieving and maintaining a MAP of 65 mmHg for at least 4 hours without the need for additional vasoactive agents. Secondary outcomes included norepinephrine dose at 3 hours after vasopressin was initiated, incidence of in-hospital mortality, and ICU length of stay.  

RESULTS: A total of 170 patients were screened with 120 patients meeting the inclusion criteria. Of these, 33 were included in the vasopressin <3 hours group, and 87 belonged to the vasopressin ≥3 hours group. All baseline characteristics were similar across the two groups including age, sex, comorbidities, and initial resuscitation strategies with borderline differences in SOFA scores. The primary outcome was achieved in 4.5 hours ([IQR] 4-5) in the vasopressin <3 hours group and 4.3 hours ([IQR] 4-5) in the vasopressin ≥3 hours group (p= 0.55). Secondary outcomes in both groups are as follows: norepinephrine dose at 3 hours (mcg/kg/min) (0.45 [IQR] 0.24-0.5 vs. 0.3 [IQR] ) 0.2-0.5, p=0.33), in-hospital mortality (63.6% vs. 66.6%, p= 0.75), ICU length of stay (days) (5 [IQR] 3-7 vs. 7 [2-13], p=0.12). A subgroup analysis was performed to analyze patients that survived through vasopressor discontinuation. The primary outcome was achieved in 4.5 hours ([IQR] 4-4.7) in the early vasopressin group and 4.2 hours ([IQR] 4-4.7) in the late vasopressin group (p= 0.65).Secondary outcomes for both groups were as follows: norepinephrine dose at 3 hours (mcg/kg/min) (0.3 [IQR] 0.21-0.5 vs. 0.3 [IQR] 0.18-0.4, p=0.40), in-hospital mortality (42.1% vs. 34%, p= 0.26), ICU length of stay (days) (6 [IQR] 4.5-8.5 vs. 11.5 [IQR] 7-16, p=<0.001). Exploratory outcomes of renal dysfunction were as follows: improvement in Scr over 72 hours (57.9% vs. 41.7% p= 0.22), total UOP over 72 hours (mL/kg/hr) (1.80 [IQR] 1.30-2.50 vs. 1.35 [IQR] 0.37-2.5, p=0.59), and new requirement of renal replacement (25.9% vs 34.7%, p= 0.41). Additionally, average time to vasopressin initiation once norepinephrine dose reached 0.15 mcg/kg/min was analyzed between the two groups and was 1.5 hours ([IQR] 0.73-2) and 8 hours ([IQR] 4.46-25.32), respectively.   

CONCLUSION: In this retrospective cohort study, early vasopressin initiation (< 3 hours) was not associated with a statistically significant difference in time to achieving goal MAP or in-hospital mortality compared to later initiation (≥ 3 hours). A shorter ICU length of stay was observed in the subgroup analysis but should be interpreted cautiously. These findings contribute to the existing body of evidence suggesting that vasopressin timing alone may not significantly impact clinical outcomes. Future studies with larger sample sizes should further evaluate optimal timing of vasopressin initiation while accounting for patient severity and dynamic clinical factors.