Abstract
IMPORTANCE: Evidence supporting the safety of infusing vasopressors through peripheral intravenous catheters (peripheral vasopressors) is largely derived from single-center studies, limiting generalizability. OBJECTIVE: To evaluate factors associated with vasopressor route selection and assess safety and clinical outcomes of peripheral vasopressor administration in early sepsis resuscitation. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study is a secondary analysis of the Crystalloid Liberal vs Early Vasopressors in Sepsis (CLOVERS) trial conducted in 60 US hospitals from March 2018 to February 2022. Patients in CLOVERS who received vasopressors within 24 hours of enrollment and did not have central venous access at enrollment were included. Data were analyzed from January 2023 to June 2025. EXPOSURE: Route of vasopressor initiation (central or peripheral). MAIN OUTCOMES AND MEASURES: The primary analysis evaluated the route of vasopressor initiation, while the secondary analysis assessed continuation of peripheral vasopressors beyond 6 hours. Univariable and multivariable analyses of factors associated with vasopressor route were conducted, as was a multivariable analysis to evaluate the association of route with outcomes, including 90-day mortality. Descriptive statistics were used to summarize 28-day peripheral vasopressor and central venous catheter (CVC) complications. RESULTS: Of 1563 patients in CLOVERS, 582 (37.2%) received vasopressors and met study inclusion criteria. Included patients had a median (IQR) age of 63 (52-72) years, and 267 (45.9%) were female, 96 (16.5%) were African American, 416 (71.5%) were White, and 70 (12.0%) were another race or had unreported race. Vasopressors were initiated via peripheral catheter in 490 patients (84.2%) and via central venous access in 92 patients (15.8%). Study site was the only factor independently associated with route of initiation (median odds ratio, 3.48; 95% CI, 1.57-5.38). In adjusted analyses, peripheral vs central initiation was associated with statistically comparable 90-day mortality (128 participants [26.1%] vs 34 participants [37.0%]; adjusted odds ratio, 0.67; 95% CI, 0.39-1.16). Peripheral vasopressors were continued beyond 6 hours in 333 of 490 patients (68.0%). Peripheral vasopressor complications were rare and low-grade (3 of 490 patients [0.6%]), with no cases of ulceration or tissue injury. In contrast, there were 14 complications from CVC placement occurring in 12 of 322 patients (3.7%) who had CVCs placed in the first 72 hours. CONCLUSIONS AND RELEVANCE: In this prospective cohort study of the CLOVERS trial, peripheral administration of vasopressors was common and was associated with low complication rates. These findings support the safety and feasibility of short-term peripheral vasopressor use in early sepsis resuscitation.