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Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children

Faustino, Edward Vincent S. MD, MHS1; Hirshberg, Eliotte L. MD, MS2; Asaro, Lisa A. MS3; Biagas, Katherine V. MD4; Pinto, Neethi MD, MS5; Srinivasan, Vijay MD6,7; Bagdure, Dayanand N. MD8; Steil, Garry M. PhD9; Coughlin-Wells, Kerry BSN, MPH9; Wypij, David PhD3,10,11; Nadkarni, Vinay M. MD, MSCE6,7; Agus, Michael S. D. MD9,11; for the Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT) Study Investigators

doi: 10.1097/CCM.0000000000003699
Pediatric Critical Care

Objectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children.

Design: Nested case-control study.

Setting: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia.

Patients: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness.

Interventions: None.

Measurements and Main Results: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia.

Conclusions: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

1Department of Pediatrics, Yale School of Medicine, New Haven, CT.

2Division of Pulmonary and Critical Care, Department of Medicine, Intermountain Medical Center, University of Utah, Murray, UT.

3Department of Cardiology, Boston Children’s Hospital, Boston, MA.

4Department of Pediatrics, Columbia University Medical Center and the Morgan Stanley Children’s Hospital, New York, NY.

5Department of Pediatrics, The UChicago Medicine Comer Children’s Hospital, The University of Chicago, Chicago, IL.

6Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA.

7Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

8Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.

9Division of Medical Critical Care, Department of Pediatrics, Boston Children’s Hospital, Boston, MA.

10Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.

11Department of Pediatrics, Harvard Medical School, Boston, MA.

Members of the Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT) Study Investigators are listed in Appendix 1.

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Supported, in part, by the National Institutes of Health (U01 HL107681 and U01 HL108028).

Drs. Faustino’s and Pinto’s institutions received funding from the National Institutes of Health (NIH). Drs. Faustino and Hirshberg, Ms. Asaro, and Drs. Biagas, Srinivasan, Bagdure, Wypij, and Agus received support for article research from the NIH. Dr. Wypij’s and Ms. Asaro’s institutions received funding from the National Heart, Lung, and Blood Institute. Dr. Steil received funding from Eli Lilly and Company and Profusa, and he disclosed off-label product use of DexCom Continuous Glucose Monitors. Drs. Wypij, Nadkarni, and Agus received funding from the NIH to conduct the Heart And Lung Failure-Pediatric INsulin Titration trial. Ms. Coughlin-Wells has disclosed that she does not have any potential conflicts of interest.

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