Do excess fluids cause brain injuries in children with diabetic ketoacidosis?

June 13, 2018, UC Davis

For decades, clinicians have worried that giving too much intravenous fluid to children with diabetic ketoacidosis (DKA) may contribute to brain swelling and injury, and even death. Now, after a national study that examined more than a thousand patients with DKA, UC Davis researchers and their colleagues from around the country have shown that fluid infusion does not cause brain injury in children with DKA.

The study is published in the June 14, 2018 issue of the New England Journal of Medicine (NEJM).

"For three decades, we have been giving too little fluids because we've been taught that fluids cause injuries in children with DKA," said Nathan Kuppermann, distinguished professor and chair of emergency medicine and first author on the paper. "It's not about the , it's about something else. It's time we started looking beyond fluids and addressing the other factors that are important."

When insulin is in short supply, cells cannot take in sugar for energy. As a result, the body begins breaking down fat and muscle, releasing fatty acids and generating ketones—the process that causes DKA. The condition is a serious complication of diabetes and can be fatal if not promptly addressed.

In the 1980s, clinicians noticed that children who had suffered brain swelling during DKA had received what appeared to be more fluids than children who had not had this life-threatening complication. They hypothesized that the infused were generating brain swelling and became more cautious when administering these fluids.

Kuppermann and his wife and research partner Nicole Glaser began working on the problem nearly 20 years ago. They noted that early research did not control for the severity of the children's conditions when assessing the impact of fluid therapy during cases of brain injury/swelling.

"The severity of dehydration in the child is strongly linked to the risk of brain injury," said Glaser, professor of pediatrics and senior author on the paper. "Of course, kids who are more dehydrated, receive more fluids. You can erroneously make the conclusion that fluids are causing the brain swelling, when it's just a reflection of the fact that children who are sickest and have the greatest dehydration are the ones at greatest risk."

In a paper published in NEJM in 2001, Glaser, Kuppermann and colleagues showed it was unlikely that fluids were causing brain . However, because it wasn't a randomized prospective study—long considered the gold standard for clinical research—the findings did little to change fluid management choices among clinicians.

The research study described in the current paper takes a more robust approach. Conducted at 13 centers over six years as part of the nationwide Pediatric Emergency Care Applied Research Network (PECARN), the team assessed how fluid administration and other factors influenced neurological outcomes in 1,389 childhood DKA cases. The study was divided into four arms, separating patients by rate of infusion and salinity of fluids.

Statistically, there were no significant differences between any of the groups. While kids who received fluids more rapidly had a lower frequency of brain injuries, these results were not statistically significant. In a subset of cases—the children who were most severely ill (i.e. most acidotic) - rapid fluids did offer statistical improvements in some brain function measures.

Kuppermann and Glaser feel the findings will now enable clinicians to more comfortably use their best professional judgment in fluid management for pediatric patients with DKA.

"We don't consider this a license to give fluids inappropriately," said Kuppermann, who also is a professor of pediatrics. "But it does allow clinicians to give children the fluids they need clinically rather than inappropriately withholding fluids. If they're dehydrated, give them fluids without fear."

Though they are pleased to have delineated the lack of relationship between fluids and neurological damage from DKA, Kuppermann and Glaser want to better understand the true causes. They hope to build on previous research that showed abnormal blood flow to the brain, combined with inflammatory proteins, may be a primary culprit in neurological damage.

"Now we want to stop thinking about fluids, and we're really going after what we think is the pathologic mechanism that's causing ," said Glaser. "These studies might point us towards treating patients with anti-inflammatory medications to protect the brain."

Explore further: Dehydration can lead to serious complications

Related Stories

Dehydration can lead to serious complications

September 16, 2016
Dehydration occurs when you use or lose more fluid than you take in, and your body doesn't have enough water and other fluids to carry out its normal functions. If you don't replace lost fluids, you will get dehydrated.

Saline use on the decline at Vanderbilt following landmark studies

February 27, 2018
Vanderbilt University Medical Center is encouraging its medical providers to stop using saline as intravenous fluid therapy for most patients, a change provoked by two companion landmark studies released today that are anticipated ...

Isotonic fluids safer for pediatric maintenance IV therapy

January 3, 2014
(HealthDay)—For children requiring maintenance intravenous (IV) fluids, isotonic fluids are safer than hypotonic fluids in terms of plasma sodium (pNa) levels, according to a meta-analysis published online Dec. 30 in Pediatrics.

Cooling of dialysis fluids protects against brain damage

September 18, 2014
While dialysis can cause blood pressure changes that damage the brain, cooling dialysis fluids can protect against such effects. The findings come from a study appearing in an upcoming issue of the Journal of the American ...

Diluted apple juice, preferred fluids for treating mild gastroenteritis in kids

April 30, 2016
Children with mild gastroenteritis and minimal dehydration experienced fewer treatment failures such as IV rehydration or hospitalization when offered half-strength apple juice followed by their preferred fluid choice compared ...

Too many heart failure patients are treated with IV fluids, study finds

February 2, 2015
Many patients hospitalized with severe heart failure are receiving potentially harmful treatment with intravenous fluids, a Yale-led study has found.

Recommended for you

Researchers discover abundant source for neuronal cells

December 13, 2018
USC researchers seeking a way to study genetic activity associated with psychiatric disorders have discovered an abundant source of human cells—the nose.

In the developing brain, scientists find roots of neuropsychiatric diseases

December 13, 2018
The most comprehensive genomic analysis of the human brain ever undertaken has revealed new insights into the changes it undergoes through development, how it varies among individuals, and the roots of neuropsychiatric illnesses ...

How the brain tells you to scratch that itch

December 13, 2018
It's a maddening cycle that has affected us all: it starts with an itch that triggers scratching, but scratching only makes the itchiness worse. Now, researchers have revealed the brain mechanism driving this uncontrollable ...

Study confirms role of brain's support cells in Huntington's, points to new therapies

December 13, 2018
New research gives scientists a clearer picture of what is happening in the brains of people with Huntington's disease and lays out a potential path for treatment. The study, which appears today in the journal Cell Stem Cell, ...

Researchers identify pathway that drives sustained pain following injury

December 13, 2018
A toddler puts her hand on a hot stove and swiftly withdraws it. Alas, it's too late—the child's finger has sustained a minor burn. To soothe the pain, she puts the burned finger in her mouth.

Researchers find the cause of and cure for brain injury associated with gut condition

December 13, 2018
Using a mouse model of necrotizing enterocolitis (NEC)—a potentially fatal condition that causes a premature infant's gut to suddenly die—researchers at Johns Hopkins say they have uncovered the molecular causes of the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.