Critically ill infants and children do not gain extra benefit from lower blood-sugar levels, compared to higher levels within the usual care range, according to research from the Children’s Hospital of Philadelphia, the University of Pennsylvania School of Nursing and Boston Children’s Hospital published in the New England Journal of Medicine.

In fact, though both levels were relatively safe, control to lower levels actually increased the risk of hypoglycemia, or very low blood sugar, said Vinay Nadkarni, a CHOP critical care specialist and professor of anesthesiology and critical care in Penn’s Perelman School of Medicine.

“It’s clear that high blood sugars are associated with worse outcomes in children,” said Nadkarni, who was also the paper’s senior author and co-principal investigator of the study. “But controlling blood sugar to lower targets within the usual care range does not appear to provide additional benefit.”  

The research team also included co-principal investigator Michael Agus of Boston Children’s and Martha A.Q. Curley, Penn’s Ellen and Robert Kapito Professor in Nursing Science and a professor of anesthesia and critical care medicine at Perelman. Together, they conducted a national trial called the Heart and Lung Failure Pediatric Insulin Titration Trial, which uses the acronym HALF-PINT.

They enrolled 713 critically ill children ranging in age from 2 weeks to 17 years who came from 35 pediatric centers. Participants, who all had hyperglycemia but were not cardiac-surgery patients, were randomized into two groups: one in which clinicians aimed for lower glucose control targets of 80 to 110 milligrams per deciliter, and another with a higher target of 150 to 180 milligrams per deciliter.

Ruth Lebet, a Penn Nursing doctoral student working with Curley, collected data from nurses responsible for implementing the trial protocol, which included drawing blood glucose, inputting that value and nutrition data into a computer-based algorithm and determining on the spot whether to move forward with the computer’s suggested next steps or take alternative action.

“When the computer made a recommendation, the nurses at the bedside used their clinical judgment to determine, ‘That seems reasonable,’ or ‘No, that does not seem reasonable,” Curley said. “It’s important that new technology supplement, not replace, a nurse’s clinical judgment.”

Quickly, the HALF-PINT study results became clear: The two treatment groups saw no significant differences in ICU-free days, mortality, organ dysfunction or ventilator-free days.

This is the third such trial resulting in similar findings; two recent high-impact pediatric studies in predominantly cardiac-surgical patients found no difference in survival outcomes or infection risk between lower and higher glucose target ranges. Both studies were multicenter trials, one in Europe and the other in the United States, led by Agus.

“The HALF-PINT study represents a third strike against glucose control to a target of 80 to 110 milligrams per deciliter,” Nadkarni said.

Though the trial ended early when it was determined that proceeding was unlikely to offer different results, follow-up research will continue with study patients to evaluate survival and neurological outcomes a year after treatment, he said.

Curley and Lebet plan to assess the data they prospectively collected from the trial about nursing cognitive workload in managing very sick patients.

“Few people have really looked at what it takes for bedside nurses to implement highly technical therapy within a chaotic environment,” Curley said. “It’s about working with nurses to make sure they have the tools to augment — not distract from — their clinical judgment in caring for complex, critically ill infants and children.”

Funding for the research came from the National Heart, Lung and Blood Institute of the National Institutes of Health.