A common treatment for children in diabetic crisis should be abandoned in most cases because it appears to contribute to a rare but often-fatal complication known as cerebral edema, according to a study by researchers at UC Davis School of Medicine and Medical Center. The study also identifies two simple blood test measurements that can help doctors predict which patients are in greatest danger of developing the potentially deadly complication.
The study, the largest and most statistically rigorous examination yet of risk factors for cerebral edema in children with diabetic ketoacidosis, appears in the Jan. 25 issue of the New England Journal of Medicine.
The researchers found that bicarbonate, a common treatment for diabetic ketoacidosis, appears to increase the risk of cerebral edema, or swelling of the brain, which can be fatal. In ketoacidosis, toxic levels of acids called ketones build up in the blood. Bicarbonate is often given in the emergency department to reduce these acid levels.
"In the past there has been some suspicion that giving bicarbonate can increase risk of cerebral edema, but ours is the first study to show that it can," said Nathan Kuppermann, senior author of the study, a pediatric emergency physician and associate professor of internal medicine at UC Davis. "I imagine doctors in emergency departments and pediatric intensive care units will put this knowledge into effect immediately."
The UC Davis researchers, led by Nicole Glaser, a pediatric endocrinologist and assistant professor of pediatrics, also found that children with diabetic ketoacidosis who have lower initial arterial carbon dioxide measurements and higher serum urea nitrogen concentrations are at increased risk for cerebral edema. When a child shows up at an emergency department with diabetic ketoacidosis, blood tests for carbon dioxide and urea nitrogen levels are routinely ordered.
"Until now, no one really knew who was at greatest risk for developing cerebral edema. We determined which of the tests that doctors routinely order are most predictive of who will go on to develop cerebral edema," Glaser said. "The hope is that by knowing these risk factors, doctors will be able to better monitor the high-risk children, and pick up the initial signs of this complication before it progresses to a more serious stage."
Cerebral edema can lead to coma, neurological damage, and death. While the complication occurs in only about 1 percent of diabetic ketoacidosis cases in children, 40 percent to 90 percent of the children who develop cerebral edema die, and many others are left with permanent brain damage. In all, cerebral edema accounts for 50 percent to 60 percent of diabetes-related deaths in children.
"Children with (low carbon dioxide and high urea nitrogen) should be monitored extensively for signs of neurologic deterioration, and hyperosmolar therapy (to reduce swelling) should be immediately available if early signs of cerebral edema occur," Glaser and her co-authors recommend in their article.
In addition, the authors state that "treatment with bicarbonate is associated with increased risk of cerebral edema and should be avoided in most circumstances."
Caused by too little insulin in the body, diabetic ketoacidosis occurs mainly in patients with type I diabetes mellitus, also known as juvenile diabetes or insulin- dependent diabetes. Symptoms of ketoacidosis include unusual thirst, frequent urination, constant fatigue, dry or flushed skin, nausea and vomiting, labored breathing, confusion, and a fruity odor on the breath. The condition requires immediate emergency medical intervention.
For 25 percent to 40 percent of children with new-onset type I diabetes, ketoacidosis is the first recognized sign of disease. Ketoacidosis also can occur later in the course of the disease if a diabetic patient misses an insulin injection, gets sick or is subjected to some other significant stress.
Kristi Oppold, of Woodland, Calif., is among the 25 percent to 40 percent of children who first found out she had diabetes when she developed ketoacidosis. She is also one of the rare children to develop cerebral edema. Fortunately, she survived without any permanent neurological damage.
"It is the scariest thing I've ever experienced," Terri Oppold says of her daughter's 12-hour coma, brought on by the brain swelling. "No child should have to go through this."
In their study, Glaser and her colleagues reviewed the medical charts of 6,977 children hospitalized for diabetic ketoacidosis over a 15-year period at a ten medical centers. These children were compared with two control groups of children with diabetic ketoacidosis who did not develop cerebral edema. Comparisons among the groups were subjected to a series of sophisticated statistical tests.
Other studies have attempted to identify risk factors for cerebral edema in children with diabetic ketoacidosis. However, the studies were small, lacked control groups for comparison, and reached contradictory findings.
Each year 30,000 Americans are diagnosed with type 1 diabetes, more than 13,000 of them children, according to the Juvenile Diabetes Foundation. In type 1 diabetes, the pancreas produces little or no insulin. Because insulin is necessary for life, sufferers must take multiple insulin injections a day for the rest of their lives.