Study shows different types of crystalloid fluids are equally effective for pediatric sepsis

A major study led by researchers at Children’s Hospital of Philadelphia, Nemours Children’s Health and Children’s National Hospital and involving a broad network of medical centers in the United States and abroad found that different types of crystalloid fluid resuscitation were equally effective in preventing the most serious adverse renal events after treatment of pediatric patients with suspected septic shock. The findings of this large clinical trial are detailed in a study published today The New England Journal of Medicine and is being presented at the Pediatric Academic Society (PAS) meeting in Boston.

Sepsis is a life-threatening response to infection that causes organ failure. The combination of the body’s immune system and infection causes an abnormal response, which can prevent various organ systems from working normally. It is estimated that more than 18,000 children are sent to hospitals across the country every year due to this disease. While several decades of research and improvements in clinical care have greatly improved outcomes for pediatric sepsis patients, nationally about 1 in 10 children with sepsis or septic shock is still at risk of death.

In some previous multi-center studies, researchers found that critically ill adults who received balanced crystalloid fluid — an intravenous (IV) treatment intended to exhibit similar properties to human plasma — had a lower risk of complications and death than the standard 0.9% saline IV solution. This prompted researchers to explore whether a similar study could determine whether a fluid treatment was better for pediatric sepsis patients.

We knew that to answer this question we would need thousands of patients, which would be a challenge. Yet we were excited to move forward because these fluids are cheap and universally available around the world, meaning we won’t have to wait decades to take action after studies are completed; “We can be practical and take immediate action based on the results we get.”

Fran Balamuth, MD, PhD, co-lead author, attending physician and division chief of emergency medicine at CHOP

Because suspected cases of sepsis are uncommon among the general population, Balamuth, along with co-lead author Scott L. Weiss, MD, attending physician and division chief of critical care at Nemours Children’s Hospital, Delaware, and his colleagues needed the collaboration of multiple hospitals to achieve the data standards necessary for meaningful conclusions. To this end, they collaborated with Nathan Kupperman, MD, executive vice president and chief academic officer of Children’s National Hospital and director of the Children’s National Research Institute, who has a history of running successful clinical trials in critically ill children, and served as senior author.

“This trial demonstrates the power of large collaborative research networks to answer important clinical questions for children,” Kupperman said. “By enrolling thousands of patients in multiple countries, we were able to provide the evidence needed for physicians to care for children with suspected septic shock.”

In the United States, the team used the Pediatric Emergency Care Applied Research Network (PECARN), a group of 18 hospitals across the country that form a multi-institutional network for research in pediatric emergency medicine as part of the federal Emergency Medical Services Program for Children. Partner institutions in Canada, Australia, New Zealand and Costa Rica also contributed data. Ultimately, the study represented a total of 47 emergency departments across five countries, enrolling more than 9,000 patients who received either balanced fluids or 0.9% saline.

The primary outcome of the study was major adverse kidney events (MAKE30) up to 30 days, a key outcome measure for kidney injury leading to death, new kidney replacement therapy or persistent kidney dysfunction. The researchers found that MAKE30 occurred in 3.4% of patients enrolled in the balanced fluid group and 3.0% in 0.9% of the saline group. The study found biochemical differences between children treated with the two fluids, including a higher frequency of high blood chloride levels in the 0.9% saline group and higher lactate levels in the balanced fluid group. Both groups had an average of 23 out of 28 hospital-free days, and there was no difference in mortality or other safety outcomes or adverse events.

“This trial confirms that either balanced fluids or 0.9% saline is effective and safe for the initial resuscitation of children with suspected septic shock, and that a fluid strategy that reduces hyperchloremia does not necessarily improve patient outcomes,” said Weiss, MD, attending physician and division chief of critical care at Nemours Children’s Hospital of Delaware. “We also did not identify differences across subgroups. However, despite the large number of participants, it is important to note that we cannot exclude the possibility of a benefit of one fluid or the other in a subgroup of children with the most severe disease.”

“A large trial like this certainly answers a question that has been in our field for many years,” Balamuth said. “In the emergency department of a child with suspected sepsis, you can treat the child with any fluid readily available. And we think that’s great news for children around the world.”