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Multicenter Study
. 2025 Aug 1;8(8):e2529148.
doi: 10.1001/jamanetworkopen.2025.29148.

Peripheral Vasopressor Use in Early Sepsis-Induced Hypotension

Elizabeth S Munroe  1 , Ivan N Co  1   2 , Ivor Douglas  3 , Robert Hyzy  1 , Akram Khan  4 , Kristine Nelson  1 , Pauline K Park  5 , Ithan D Peltan  6 , Todd W Rice  7 , Sarah Seelye  8 , Wesley H Self  9 , Nathan I Shapiro  10 , Hallie C Prescott  1   8 ; NHLBI PETAL Network
Collaborators, Affiliations
Multicenter Study

Peripheral Vasopressor Use in Early Sepsis-Induced Hypotension

Elizabeth S Munroe et al. JAMA Netw Open. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Khan reported receiving grants from 4D Medical, Dompe Pharmaceuticals, Direct Biologics, and the Department of Defense outside the submitted work. Dr Peltan reported receiving research payments (paid to institution) from Regeneron, Bluejay Diagnostics, and Novartis outside the submitted work. Dr Rice reported receiving personal fees from Cumberland Pharmaceuticals Inc (Senior Director of Medical Affairs), Cytovale Inc (consulting), and Sanofi Inc (data safety monitoring board) and grants from the Patient-Centered Outcomes Research Institute, Department of Defense, and Centers for Disease Control and Prevention outside the submitted work. Dr Self reported receiving personal fees from Regeneron (consulting) outside the submitted work. Dr Prescott reported receiving grants from the National Institutes of Health, Agency for Healthcare Research and Quality, and the US Department of Veterans Affairs; salary support from the Centers for Disease Control and Prevention and Blue Cross Blue Shield of Michigan; consulting fees from Aurobac Therapeutics; and having worked on the Service on Surviving Sepsis Campaign Guidelines outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
Study flow diagram of patients receiving vasopressors in the Crystalloid Liberal vs Early Vasopressors in Sepsis trial who were included in this study. Route of vasopressor administration is shown with administration through a central venous catheter (CVC; ie, central administration) and administration through a peripheral venous catheter (ie, peripheral administration). Route of vasopressor administration is shown at initiation, continuation beyond 6 hours, and at 72 hours. aOf the 249 individuals with CVC continuation at 6 hours and 333 individuals with peripheral continuation at 6 hours, 49 (8.4%) died within 72 hours.
Figure 2.
Figure 2.. Adjusted Variation in Peripheral Vasopressor Initiation and Continuation Across Sites
Caterpillar plots showing variation in adjusted rates of peripheral vasopressor initiation (A) and continuation beyond 6 hours (B) across study sites (hospitals) in the Crystalloid Liberal vs Early Vasopressors in Sepsis trial. Dots reflects the mean rate and the error bars reflect the 95% CI. The population mean is indicated by the dotted line. Sites with less than 10 observations each were combined. Rates were adjusted for following covariables: age, sex, Charleson comorbidity score, body mass index, on noninvasive or invasive mechanical ventilation at baseline, baseline mean arterial pressure, baseline lactate, baseline creatine, randomization location (emergency department vs intensive care unit), and study group.
See this image and copyright information in PMC

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