Researchers find way to detect dangerous brain swelling in diabetic children

A rare swelling of the brain that is nonetheless the most common diabetes-related cause of death for children with the disease could be caught earlier — potentially saving lives — if practitioners learn to recognize key signs, researchers at the University of Florida report.

Although doctors have long been familiar with major symptoms associated with the deadly complication, they may be missing subtler clues that could tip them off to a problem much sooner, when treatment is most likely to work, says UF pediatric endocrinologist Dr. Arlan Rosenbloom. And now, after poring over dozens of medical records on a hunt for crucial patterns, the researchers have devised a standardized way to screen for these signals at a child’s bedside.

“It’s a frightening problem that all pediatricians, pediatric endocrinologists and intensivists are aware of and very much concerned about,” said Rosenbloom, senior author of a paper describing the findings in a recent issue of Diabetes Care. “It’s a serious and important problem that affects children who otherwise can live a long and productive life.”

Children with diabetes risk developing a metabolic imbalance that occurs when the body, lacking adequate insulin, is unable to process glucose and acidic substances called ketones and begins breaking down fats for energy. These substances accumulate in the circulation, leading to the life-threatening condition known as ketoacidosis, Rosenbloom said. The body’s attempt to rid itself of excess glucose and ketones through the kidneys causes increased urination and thirst, with eventual dehydration, drowsiness and stupor, and is the leading cause of hospitalization for youngsters with diabetes. In about one of every 100 episodes of ketoacidosis the potentially devastating complication cerebral edema develops, a swelling of the brain that can rapidly cause severe brain damage or death.

Despite advances in the chronic management of diabetes, not much has changed in the treatment or incidence of cerebral edema over the years, said former UF pediatric endocrinologist Andrew Muir, now chief of pediatric endocrinology at the Medical College of Georgia and the paper’s lead author. Early detection — hours instead of minutes before irreversible damage occurs — could change that, he said. The finding comes at an important time, as the incidence of diabetes is poised to skyrocket.

“Kids with diabetes generally don’t die, but when they do, it is primarily because of cerebral edema, and the traditional thinking has been physicians can’t do a lot if this occurs,” Muir said. “We don’t know as much as we’d like to know about what causes this and the best way to treat it. Our study suggests it’s a complication that often progresses slowly at first. The rate of deterioration, however, becomes more rapid with time. In later stages, it’s very hard to arrest.

“Our main message is if we look carefully we can actually spot the onset of cerebral edema earlier than we realized,” he said. “If there is early recognition, the condition can be treated and lives will be saved, because treatment will be rendered in time. If we wait until children are having a medical emergency and stop breathing, it’s very rare they survive with a normal neurological picture. Timing is everything.”

The research team reviewed medical records from 24 patients ages 1 to 15 who developed cerebral edema due to diabetic ketoacidosis and were cared for at various U.S. hospitals. All the patients had poor outcomes, and their cases were sent to Rosenbloom for his expert review because they were involved in litigation. Records from an additional two patients seen at Shands at UF medical center were added to the review. The researchers also analyzed 69 consecutive episodes of diabetic ketoacidosis in children treated at Shands who were not thought to have developed cerebral edema.

They then applied statistical methods to identify the combinations of symptoms most likely to accurately identify the earliest onset of cerebral edema. These signs were incorporated into a bedside evaluation protocol that researchers then used to evaluate patients. They included a slowing of heart rate, altered level of consciousness and age-inappropriate incontinence, along with vomiting, headache or lethargy.

The screening method was 96 percent accurate in detecting cerebral edema. In addition, the approach identified four cases of cerebral edema among the 69 patients not recognized to have a problem. All had recovered spontaneously.

“One thing that struck us was that the nursing notes really clearly documented changes in these kids’ neurologic state, but nobody recognized the importance of it,” Muir said. “A major goal with this paper was to alert people that you’ve got to specifically tell nurses, tell parents, tell anyone standing by that child’s bedside to watch for these things.

“For example, when kids first present with diabetic ketoacidosis, they often are vomiting, so if a child starts vomiting again (once they are in the hospital) people think that’s OK,” he added. “When we looked through the cases, once a child starts on treatment, the vomiting stops, he said. “If they start vomiting again six or seven hours later, that’s not OK.”

The study also confirmed Rosenbloom’s previous research that showed many youngsters with cerebral edema at first have no apparent changes on computed tomography scans of the brain. Therefore, the diagnosis of cerebral edema needs to be made at the bedside, and CT scans should be postponed until after treatment begins, Rosenbloom said.

“No one ever forgets their cerebral edema cases, whether it’s the ones you’ve succeeded in saving or the ones you’ve lost,” Rosenbloom said. “You just don’t forget them because it’s so frustrating, and that frustration has been in part because of trying to deal with not having specific criteria for intervention. We should be able to save 90 percent of these kids.”

Dr. Mark Sperling, a professor of pediatrics and chairman emeritus of the department of pediatrics at the University of Pittsburgh School of Medicine, said, “Regrettably, we still see cases of missed cerebral edema, not so much in academic medical centers but in community hospitals. When these catastrophes happen, they have their onset in smaller hospitals where there isn’t quite as much awareness. So this paper by Muir and Rosenbloom serves as a wake-up call for the many small community hospitals and nonacademic medical centers where probably a considerable number of these patients may be treated and where practitioners may not be as attuned to the possibility of this devastating complication. There’s that adage that constant vigilance is the eternal price of freedom, and constant vigilance for this particular complication is the eternal price of making sure we save as many children as we can.”

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