Glucose control, organ failure, and mortality in pediatric intensive care* Michael Yung, MD, FRACP, FJFICM; Barry Wilkins, MD, FRCPCH, FRACP, FJFICM; Lynda Norton, RN, MPH; Anthony Slater, FRAPC, FJFICM; for the Paediatric Study Group, Australian and New Zealand Intensive Care Society H yperglycemia is common in critically ill adults and pos- sibly harmful (1, 2). Ran- domized controlled trials in adults outside intensive care units (ICUs) showed a benefit from strict glucose con- trol (3, 4). Van den Berghe and colleagues (5) reduced mortality by maintaining blood glucose between 4.4 and 6.1 mmol/L, using insulin, in adults in the surgical ICU. The benefit might have been from insulin, normoglycemia, or both. However, the authors cautioned against applying their findings to patients not represented in their trial. Subse- quently, they showed a reduction in mor- bidity, but not mortality, by preventing new kidney injury, and they showed earlier weaning and earlier ICU and hospital dis- charge as well in adult medical ICU patients treated similarly (6). All the benefit was in patients staying in ICU 3 days. Australasian (Australian and New Zea- land) adult intensivists have not widely adopted this approach, because of differ- ences in populations and nutritional practices and because of concern about hypoglycemia (7). Hence, the Clinical Trials Group of the Australian and New Zealand Intensive Care Society is con- ducting a randomized controlled trial of intensive glucose control in adults (8). Hyperglycemia also occurs in children in pediatric intensive care units (PICUs) and is associated with harm. The Pediat- ric Risk of Mortality (PRISM) score (9) includes abnormal blood glucose as an independent mortality predictor. Hyper- glycemia independently predicted poor outcome from head injury in children in two studies (10, 11). An earlier study showed no harm from hyperglycemia in head-injured children, but hyperglycemia was defined using a high threshold (15 mmol/L) (12). Hyperglycemic children Objective: In ventilated children, to determine the prevalence of hyperglycemia, establish whether it is associated with organ failure, and document glycemic control practices in Australasian pediatric intensive care units (PICUs). Design: Prospective inception cohort study. Setting: All nine specialist PICUs in Australia and New Zealand. Patients: Children ventilated >12 hrs excluding those with diabetic ketoacidosis, on home ventilation, undergoing active cardiopulmonary resuscitation on admission, or with do-not-re- suscitate orders. Interventions: None. Measurements and Main Results: All blood glucose measure- ments for up to 14 days, clinical and laboratory values needed to calculate Paediatric Logistic Organ Dysfunction (PELOD) scores, and insulin use were recorded in 409 patients. Fifty percent of glucose measurements were >6.1 mmol/L, with 89% of patients having peak values >6.1 mmol/L. The median time to peak blood glucose was 7 hrs. Hyperglycemia was defined by area under the glucose-time curve >6.1 mmol/L above the sample median. Thir- teen percent of hyperglycemic subjects died vs. 3% of nonhyper- glycemic subjects. There was an independent association between hyperglycemia and a PELOD score >10 (odds ratio 3.41, 95% con- fidence interval 1.91– 6.10) and death (odds ratio 3.31, 95% confi- dence interval 1.26 –7.7). Early hyperglycemia, defined using only glucose data in the first 48 hrs, was also associated with these outcomes but not with PELOD >10 after day 2 or with worsening PELOD after day 1. Five percent of patients received insulin. Conclusions: Hyperglycemia is common in PICUs, occurs early, and is independently associated with organ failure and death. However, early hyperglycemia is not associated with later or worsening organ failure. Australasian PICUs seldom use insulin. (Pediatr Crit Care Med 2008; 9:147–152) KEY WORDS: blood glucose; hyperglycemia; insulin; child; inten- sive care; multiple organ failure; severity of illness index; logistic models; mechanical ventilation; mortality *See also p. 231. The Paediatric Study Group (PSG) of the Australian and New Zealand Intensive Care Society (ANZICS) is affiliated with the Clinical Trials Group (CTG) of ANZICS. The members of the writing committee (Michael Yung, MD, FRACP FJFICM; Barry Wilkins, MD, FRCPCH, FRACP, FJFICM; Lynda Norton, RN, MPH; and Anthony Slater, FRAPC, FJFICM) assume responsibility for the overall content and integrity of the article. Members of PSG are from pediatric intensive care units (PICUs) at The Princess Margaret Hospital, Perth, Western Aus- tralia; The Women’s and Children’s Hospital, Adelaide, South Australia (MY, LN); The Royal Children’s Hospi- tal, Melbourne, Victoria; The Children’s Hospital at Westmead, Sydney, NSW (BW); Sydney Children’s Hos- pital, Sydney, NSW; Royal Children’s Hospital, Bris- bane, Queensland (AS); The Mater Misericordiae Hos- pital, Brisbane, Queensland; The Prince Charles Hospital, Brisbane, Queensland; and The Starship Hos- pital, Auckland, New Zealand. Supported, in part, by a grant from the Channel 7 Children’s Research Foundation, Adelaide, South Aus- tralia. The authors have not disclosed any potential con- flicts of interest. For information regarding this article, E-mail: michael.yung@cywhs.sa.gov.au Copyright © 2008 by the Society of Critical Care Medicine and the World Federation of Pediatric Inten- sive and Critical Care Societies DOI: 10.1097/PCC.0b013e3181668c22 147 Pediatr Crit Care Med 2008 Vol. 9, No. 2