Introduction
Sepsis remains a major global health challenge, characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Vasopressors are cornerstone therapies for early septic shock management, traditionally administered through central venous catheters (CVCs) to mitigate extravasation risks. However, emerging evidence hints at the safety and practicality of peripheral vasopressor infusion during initial resuscitation, especially when rapid intervention is paramount.
Background and Clinical Context
The safe administration of vasopressors via peripheral veins has historically been debated due to concerns about tissue ischemia, ulceration, and other local complications. Nevertheless, single-center studies have suggested that short-term peripheral use may be safe, but their limited scope restricts broad application. Given the urgent need for effective early sepsis management, confirming the safety profile across diverse clinical settings is essential.
Study Design and Methods
This prospective cohort analysis utilizes data from the CLOVERS trial, a large multicenter randomized controlled trial conducted across 60 U.S. hospitals from March 2018 to February 2022. The study included patients with sepsis-induced hypotension within the first 24 hours of enrollment who received vasopressors and lacked initial central venous access. Data analysis was performed from January 2023 to June 2025.
The primary exposure was the route of vasopressor administration—peripheral versus central. Key outcomes included 90-day mortality, continuation of peripheral vasopressors beyond 6 hours, and vascular complications. Statistical methods involved univariable and multivariable models to identify factors influencing route choice and outcome associations.
Major Findings
Out of 1563 patients in the CLOVERS trial, 582 (37.2%) received vasopressors within the first 24 hours, meeting inclusion criteria. The median age was 63 years, and a notable proportion (45.9%) were female. Vasopressors were initiated peripherally in 490 patients (84.2%) and via central access in 92 patients (15.8%).
Analysis revealed that the sole independent factor associated with the route was the study site, with an adjusted median odds ratio of 3.48 (95% CI, 1.57–5.38). This underscores practice variability rather than patient-specific factors influencing route choice.
Remarkably, the 90-day mortality was comparable between peripheral and central initiation groups—26.1% versus 37.0%, respectively (adjusted OR, 0.67; 95% CI, 0.39–1.16)—indicating no statistically significant difference in survival outcomes.
Further, 68% of patients who began peripheral vasopressors continued beyond six hours, highlighting feasibility for ongoing infusion without necessitating early CVC placement. Safety assessments showed that peripheral vasopressor complications were exceedingly rare (0.6%), with no observed tissue ulcerations or injuries. In contrast, CVC placement was associated with a 3.7% complication rate, including infections, bleeding, or mechanical issues.
Implications for Clinical Practice
These findings advocate that short-term peripheral vasopressor use in early sepsis can be both safe and effective, potentially reducing delays to therapy and avoiding the risks associated with central line placement. Practice variability appears driven more by institutional protocols than patient factors, suggesting opportunities for standardization and training.
Limitations and Future Directions
The study’s observational design limits causality assertions. Additionally, while complication rates are low, stringent monitoring and protocols are essential to maintain safety. Future randomized trials are needed to establish definitive guidelines on peripheral vasopressor use and to optimize infusion protocols.
Conclusion
In a diverse, multicenter cohort, peripheral vasopressor administration in early sepsis demonstrated low complication rates and comparable patient outcomes to central administration. These results support broader adoption of peripheral vasopressor infusion, especially during the critical early resuscitation phase, to enhance timely sepsis care.
Reference:
Munroe ES, Co IN, Douglas I, Hyzy R, Khan A, Nelson K, Park PK, Peltan ID, Rice TW, Seelye S, Self WH, Shapiro NI, Prescott HC; NHLBI PETAL Network. Peripheral Vasopressor Use in Early Sepsis-Induced Hypotension. JAMA Netw Open. 2025 Aug 1;8(8):e2529148. doi: 10.1001/jamanetworkopen.2025.29148 . PMID: 40864467 ; PMCID: PMC12391982 .