Peripheral Vasopressor Use for Sepsis-Induced Hypotension

• In Sepsis
• Wed, 10 Sep 2025

Vasopressors are standard therapy for sepsis-induced hypotension and shock, traditionally given via central venous catheters (CVCs) due to concerns about tissue injury from peripheral intravenous catheter (PIV) extravasation. Recent studies, however, suggest that peripheral vasopressors are safe, with low extravasation rates and minimal tissue injury, while offering advantages such as faster initiation and avoidance of CVC-related risks. These findings led the 2021 Surviving Sepsis Campaign to recommend starting vasopressors peripherally to prevent delays, with CVC placement once feasible. Despite growing use, most evidence comes from small, single-centre safety studies, leaving uncertainty about real-world practice patterns and patient outcomes. 

The Crystalloid Liberal vs Early Vasopressors in Sepsis (CLOVERS) trial, which allowed peripheral vasopressors, provides an opportunity to examine factors influencing route choice and the impact of peripheral administration on complications and outcomes.

A secondary analysis of the CLOVERS trial examined patients from 60 US hospitals (March 2018–February 2022) who received vasopressors within 24 hours of enrolment without preexisting central venous access. The study’s primary analysis examined the route of vasopressor initiation, while the secondary analysis evaluated continuation of peripheral vasopressors beyond 6 hours. Factors influencing vasopressor route were assessed using univariable and multivariable analyses, and multivariable models evaluated associations with outcomes, including 90-day mortality. Descriptive statistics summarised 28-day peripheral vasopressor and CVC complications.

Of 1,563 CLOVERS patients, vasopressors were initiated peripherally in 84.2% (490 patients) and via central access in 15.8% (92 patients). The study site was the only factor independently influencing route selection. Adjusted 90-day mortality was similar between peripheral and central initiation (26.1% vs 37.0%). Peripheral vasopressors were continued beyond 6 hours in 68.0% of cases, with rare, low-grade complications (0.6%) and no tissue injury. In contrast, CVC placement complications occurred in 3.7% of patients within the first 72 hours.

In this study of patients with sepsis-induced hypotension, most vasopressors were initiated peripherally, and over half of the patients continued peripheral vasopressors beyond 6 hours. Complication rates were low (0.6%), and the vasopressor route was not associated with 90-day mortality.

Peripheral vasopressor use in CLOVERS aligns with previous studies showing this approach is common in clinical practice and supported by emerging safety data and guidelines. Site-level variation strongly influenced vasopressor route, highlighting the role of institutional culture and the need for standardised protocols. 

Optimal thresholds for transitioning from peripheral to central administration remain unclear, reflecting variability in institutional policies. Adverse events from peripheral vasopressors were rare and low-grade, lower than previous reports, whereas CVC placement carried a 3.7% complication rate, consistent with previous studies.

Although most research has focused on safety, the study also assessed patient outcomes, finding no association between vasopressor route and mortality. Differences in secondary outcomes likely reflected underlying patient severity rather than the effects of the vasopressor route. Overall, these findings support the safe use of early peripheral vasopressors, which may provide practical advantages such as faster initiation without increasing mortality risk.

Future research should clarify the safety of prolonged use, optimal transition thresholds to central access, and the influence of catheter types to inform consistent clinical guidelines.

Source: JAMA
Image Credit: iStock

References:

Munroe ES, Co IN, Douglas I et al. (2025) Peripheral Vasopressor Use in Early Sepsis-Induced Hypotension. JAMA Netw Open. 8(8):e2529148.