Study comparing early restrictive and liberal fluid therapy for sepsis-induced hypotension

Vanderbilt University Medical Center had a leading role in a large national study designed to compare two early interventions in the treatment of patients with sepsis, the body’s severe response to an uncontrolled infection.

Sepsis can cause dangerously low blood pressure, which is typically treated with intravenous (IV) fluids and/or a vasopressor, a drug that causes blood vessels to constrict. Whether treatment of sepsis-induced hypotension should primarily be treated with IV fluids or vasopressors has been debated for decades with no clear answer.

In the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial, researchers compared these two approaches to treating sepsis. Test results, which were published in New England Journal of Medicineshowed that both a resuscitation strategy that relied on high-volume fluid administration and one that relied on lower fluid volumes with greater use of vasopressors led to nearly identical survival.

Sepsis is one of the most common causes of death worldwide. There has never been good data to inform us how much fluid to give to our sickest septic patients and when to start vasopressors.”

Wesley H. Self, MD, MPH, Senior Vice President for Clinical Research at VUMC and the Study’s Senior Author

“The CLOVERS trial results are important because they provide strong data showing that supporting blood pressure with either IV fluids or vasopressors can result in similar outcomes,” Self said. “To me, these results emphasize that rapid attainment of normal blood pressure and systemic perfusion may be more important than the method used to achieve normal blood pressure.”

According to the Centers for Disease Control and Prevention, at least 1.7 million adults in the United States develop sepsis each year, and at least 350,000 die from the disease. About one in three people who die in US hospitals have sepsis.

The CLOVERS trial was funded by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and enrolled 1,563 adults with septic shock at 60 medical centers across the United States over about three years. The trial was designed and conducted by investigators as part of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network.

In addition to Self, key researchers from VUMC who helped design and run the trial were Matthew Semler, MD, MSc, and Todd Rice, MD, MSc, both in the Department of Medicine’s Division of Allergy, Pulmonary and Critical Care Medicine.

“Prior to this study, clinicians debated whether prioritizing fluid resuscitation or initiating vasopressor therapy earlier was best for patients with septic shock,” Rice said. “This trial shows that both are acceptable treatment options and result in similar clinical outcomes. The CLOVERS trial represents the first trial to address this question in patients with septic shock, and the results are very informative for clinicians caring for these patients, ” he said. .

“The two approaches that we compared in the study are common in current clinical practice, but if you had two doctors treating a patient, they might not agree on the best approach,” Semler said. “The purpose of the trial was to determine whether one of the approaches produced better results than the other.

“It is difficult to make progress in the treatment of sepsis. Studies over the past 30 years have evaluated new drugs to treat sepsis, but none have worked. We believe that optimizing the use of treatments we already have, may be a key to improving outcomes for patients with sepsis.”

VUMC’s Center for Learning Healthcare and others are pushing researchers not just to look at potential new drugs, but to compare existing treatments to understand how best to use them.”

Semler said there are still many unanswered questions about the treatment of patients with sepsis, including:

  • Is it possible to customize the amount of IV fluid given to each patient? Could it be that some patients need more and some need less?
  • There are different types of liquids. Which one should be used?
  • Which vasopressor should be used and when should it be started?
  • What is the target blood pressure to achieve?
  • Which antibiotics give the best results?

Semler said questions like these are the focus of the Center for Learning Healthcare, which brings together clinicians, health system operations managers and researchers to generate evidence throughout the delivery of health care to continuously improve the quality, value and safety of health care. that is offered. to patients.

“Sepsis is just one of hundreds of acute illnesses. We should be doing the same type of research for gastrointestinal bleeding and acute respiratory failure and trauma, and not just in the hospital, but in the clinic,” Semler said. “We can’t recommend and prescribe treatments without knowing for sure how well they work. We need to compare them to see which one is best.”


Vanderbilt University Medical Center

Journal reference:

National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network., (2023) Early restrictive or liberal fluid therapy for sepsis-induced hypotension. New England Journal of Medicine.

Study comparing early restrictive and liberal fluid therapy for sepsis-induced hypotension

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