A secondary analysis of the multicenter Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial found that peripheral administration of vasopressors had a similar 90-day mortality rate with fewer complications compared with central venous catheter administration in the management of sepsis-induced hypotension. Peripheral administration was initiated 2.3 hours earlier than central administration.
“Peripheral administration is clearly safe and clearly gives clinicians tools to more rapidly treat patients appropriately,” said Natalie Achamallah, MD, FCCP, Director of Critical Care Education at Cottage Health. “It took an additional two hours for vasopressors to be initiated by central line, which is especially problematic considering that the central venous catheter group was actually sicker. You saw a sicker group of patients who experienced a delay in care that can be avoided with a different route of administration.”
This secondary analysis compared peripheral vs central administration of vasopressors in a subset of the CLOVERS trial conducted in 60 US hospitals, whereas the main trial compared vasopressors vs fluids for initial resuscitation of patients with septic shock.1
“We had long discussions about whether pressors could be given through a peripheral IV in our [CLOVERS] steering committee,” said Todd W. Rice, MD, MSc, FCCP, Professor of Allergy, Pulmonary, and Critical Care Medicine and Vice President for Clinical Trial Innovation and Operations at Vanderbilt University Medical Center.
“There were a number of sites that were doing this in practice and sites that said they would never do it because of leaks, tissue infiltration, and other safety concerns. We ultimately decided to allow peripheral administration at the study center’s discretion, which provided a great opportunity to collect data on what centers were actually doing and how it played out in practice.”
Peripheral vs central vasopressor administration has been debated in intensive care and emergency departments for years, said Yuri Matusov, MD, Assistant Professor of Medicine at Cedars-Sinai Medical Center. In the absence of robust multicenter data, institutional practice guidelines have been guided by single-center studies, opinion, and personal experience.
“As someone who has worked in a number of different ICUs, there is truly significant institutional variation in comfort between peripheral vs central pressors,” Dr. Matusov said.
Just more than a third (37.2%) of the patient population in the CLOVERS trial who received vasopressors within 24 hours of admission did not have central venous access at enrollment and were included in the secondary analysis. Peripheral vasopressors were initiated via peripheral catheter in 84.2% of patients and via central venous access in 15.8% of patients.
The mean age of patients was 63 years old, 45.9% were female, 16.5% were Black, 71.5% were White, and 12% were another race or race was unreported. The study site was the only factor independently associated with the route of initiation of vasopressor therapy.
Peripheral vs central initiation had statistically similar 90-day mortality outcomes (26.1% vs 37.0%; OR, 3.48 [95% CI, 0.39-1.36]). Complications from peripheral administration were rare and low-grade, occurring in 0.6% of patients, with no reported ulceration or tissue injury. Among patients with a central venous catheter placed in the first 72 hours after admission, 3.7% had complications.
Peripheral access was associated with a shorter time to vasopressor initiation, 4.2 hours vs 6.3 hours, and less fluid administration in 24 hours, 3,280 mL vs 4,050 mL. Peripheral administration was associated with lower rates of intubation (17.8% vs 40.5%; OR, 0.31 [95% CI, 0.18-0.560]) and comparable rates of new kidney replacement therapy, ICU-free days, and other measures. The key takeaway from this analysis is that short-term peripheral vasopressor use in early sepsis resuscitation is safe and may avoid risks associated with central line placement. This trial provided a clear answer to a long-debated clinical question.
“This is one of the larger studies that shows peripheral vasopressor administration is safe and effective,” Dr. Matusov said. “And it suggests that waiting to place a central venous catheter may lead to delay in starting pressors. This suggests that hospitals that have policies against peripheral vasopressor use should reconsider those policies.”
References
1. Munroe ES, Co IN, Douglas I, et al. Peripheral vasopressor use in early sepsis-induced hypotension. JAMA Netw Open. 2025;8(8):e2529148. doi:10.1001/jamanetworkopen.2025.29148
