Intensive Insulin Therapy May Be Helpful for Patients in Pediatric Intensive Care

Laurie Barclay, MD
Medscape Medical News 2009. © 2009 Medscape

Targeting blood glucose concentrations to age-adjusted normal fasting concentrations was associated with better short-term outcome of patients in the pediatric intensive care unit (PICU), according to the results of a prospective, randomized controlled study reported online January 27 in The Lancet.

“Critically ill infants and children often develop hyperglycaemia, which is associated with adverse outcome; however, whether lowering blood glucose concentrations to age-adjusted normal fasting values improves outcome is unknown,” write Dirk Vlasselaers, from Catholic University Leuven in Belgium, and colleagues. “We investigated the effect of targeting age-adjusted normoglycaemia with insulin infusion in critically ill infants and children on outcome.”

At the PICU of the University Hospital of Leuven, Belgium, 700 critically ill patients (317 infants aged <1 year and 383 children aged ≥1 year) were enrolled and randomly assigned by blinded envelopes to an intensive group (n = 349) or to a conventional group (n = 351). The intensive group received insulin infusion throughout their PICU stay to target blood glucose concentrations of 2.8 to 4.4 mmol/L in infants and 3.9 to 5.6 mmol/L in children. The conventional group received insulin infusion only to prevent blood glucose from exceeding 11.9 mmol/L.

Patients and laboratory staff were blinded to treatment assignment. The main study outcomes were duration of PICU stay and inflammation, with analysis by intention to treat.

Compared with the conventional group, the intensive group had lower mean blood glucose concentrations (infants, 4.8 ± 1.2 mmol/L vs 6.4 ± 1.2 mmol/L; P < .0001; children, 5.3 ± 1.1 mmol/L vs 8.2 ± 3.3 mmol/L; P < .0001) and more patients who experienced hypoglycemia. When defined as blood glucose levels of 2.2 mmol/L or less, hypoglycemia occurred in 87 patients in the intensive group (25%) compared with 5 patients in the conventional group (1%; P < .0001). When defined as blood glucose levels lower than 1.7 mmol/L, hypoglycemia occurred in 17 (5%) vs 3 (1%) patients, respectively (P = .001).

The intensive group had shorter duration of PICU stay than the conventional group (5.51 days [95% confidence interval (CI), 4.65 – 6.37 days] vs 6.15 days [95% CI, 5.25 – 7.05 days]; P = .017) and a lower percentage of patients with extended (longer than median) PICU stay (132 patients [38%] vs 165 patients [47%]; P = .013). There were also fewer deaths in the intensive group (9 patients [3%] vs 20 patients [6%] in the conventional group; P = .038).

At day 5, the intensive group had an attenuated inflammatory response from baseline, as reflected in lower C-reactive protein (−9.75 mg/L [95% CI, –19.93 to 0.43 mg/L] vs 8.97 mg/L [95% CI, −0.9 to 18.84 mg/L]; P = .007).

“Targeting of blood glucose concentrations to age-adjusted normal fasting concentrations improved short-term outcome of patients in PICU,” the study authors write. “The effect on long-term survival, morbidity, and neurocognitive development needs to be investigated.”

Limitations of this study include lack of blinding; setting in a single center, with three quarters of patients admitted to PICU after cardiac surgery, limiting generalizability; and reliance on nursing expertise with tight blood glucose control.

“This trial was a proof-of-concept study in the [PICU] population, and long-term follow-up and multicentre studies should follow,” the study authors conclude. “Our study, therefore, cannot be considered yet as evidence for general implementation in clinical practice. For future studies, an accurate continuous blood glucose sensor for use in the PICU, which was not available when we undertook our study, would be preferable to keep the risk of hypoglycaemia to a minimum.”

In an accompanying editorial, Mitchell M. Levy, MD, from Rhode Island Hospital in Providence, and Andrew Rhodes, MD, from St. George’s Healthcare National Health Service Trust in London, United Kingdom, note that the optimum target for glycemic control and the best protocol for safe achievement of this target remain unclear. However, recent consensus guidelines recommend a target blood glucose concentration of less than 8.3 mmol/L.

“Ultimately, clinicians must take into account several factors, including the nature of the intensive-care population in their institution and the incidence of hypoglycaemia with local insulin protocols when determining what glucose target is most appropriate for their critically ill patients,” Dr. Levy and Dr. Rhodes write. “Perhaps the results of ongoing large-scale trials will provide greater clarity for this clinical dilemma.”

Research Foundation (Belgium), Research Fund of the University of Leuven (Belgium) and the EU Information Society Technologies Integrated project “CLINICIP,” and Institute for Science and Technology (Belgium) supported this study. The study authors, Dr. Levy, and Dr. Rhodes have disclosed no relevant financial relationships.

Lancet. Published online January 27, 2009.

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