Peripheral IVs are preferable to central lines for most patients with septic shock (Review)

CLOVERS post hoc demonstrates advantages, but don't try this without a protocol

Over the past decade or so, peripheral IVs have become accepted as a reasonably safe, temporary alternative to central venous access for vasopressor administration. But there’s a lingering cultural belief that peripheral IVs are second-best to central venous catheters.

A new post hoc analysis of the CLOVERS randomized trial (Munroe et al, JAMA Network Open 2025) strongly suggests that for a majority of patients with early sepsis-induced hypotension, carefully managed peripheral IVs are preferable overall, and often eliminate any need for central venous access for delivering vasopressors.

Background

Central venous access has been considered the standard of care for administering vasopressors to patients with shock resulting from sepsis or other conditions. Central lines are more secure and reliable, with a lower likelihood of suddenly failing or infiltrating and extravasating vasopressors into soft tissue. Extravasation with severe tissue injury, including limb loss, is the most-feared adverse outcome from infusing vasopressors peripherally.

However, central lines carry risks for pneumothorax and bleeding, as well as infection.

Observational studies have shown the potential safety of peripheral vasopressor infusions, leading sepsis guideline authors to endorse the practice as a temporary measure until central venous access can be obtained.

Of course, “safety” is a relative term in the ICU. All peripheral vasopressor infusions carry an inherent risk for extravasation and tissue damage, which must be promptly recognized and managed to avoid severe injury. These risks are suspected to increase with the dose of vasopressors, the number of agents, their concentration, and the duration of infusions, as well as the location of the peripheral IV.

CLOVERS trial post hoc analysis

CLOVERS was a randomized trial published in NEJM in 2023 testing liberal vs. conservative targets for fluid resuscitation in sepsis with hypotension, among 1,563 patients at 60 U.S. centers. There were no significant differences in outcomes between groups, but patients randomized to a liberal fluid strategy required fewer vasopressors.

Restrictive vs liberal fluid resuscitation in sepsis (CLOVERS trial)

Most patients in both arms of CLOVERS (~84%) had their vasopressors initiated through a peripheral line. This was highly influenced by local practice: a few centers virtually always started pressors through IVs; most did so 75-90% of the time; a few half the time or less.

Patients with peripheral infusions had slightly lower organ failure scores at baseline and were more often described as “White,” but were otherwise similar to those receiving central lines (e.g., they had a similar severity of hypotension).

More than two-thirds of patients whose vasopressors were started through peripheral IVs had them continued peripherally for longer than 6 hours. This was true in both arms of the study. But this practice varied widely by center: one continued peripheral vasopressors after 6 hours ~6% of the time, while another did so 88% of the time. Patients receiving prolonged peripheral vasopressors tended to have less severe disease (organ failure).

Because they were different and were managed somewhat differently from the patients with CVCs, it would be misleading to make direct statistical comparisons. Suffice it to say that patients with peripheral IVs later got CVCs if they needed them, and did just as well (read the paper to draw your own conclusions).

And as these patients were well-distributed through both arms, CLOVERS provides an interesting sort of natural experiment, an “observational-plus” data tranche on the use of peripheral IVs in sepsis-induced hypotension.

Here’s what we can cautiously conclude from the CLOVERS post hoc.

Advantages of Peripheral IVs Over Central Lines