Design and rationale of Heart and Lung Failure – Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children

Abstract

Objectives Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design Multi-center randomized clinical trial. Setting Pediatric ICUs at 35 academic hospitals. Patients Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions Patients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions This trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control.

Tight Glycemic Control in Critically Ill Children

“…Severe hypoglycemia (blood glucose level, <40 mg per deciliter) that was considered by the investigators, according to prospectively defined criteria, 16 to be related to insulin administration occurred in 13 of 349 patients (3.7%) in the lower-target group, as compared with 1 of 349 (0.3%) in the higher-target group (P = 0.01). With the inclusion of instances in which severe hypoglycemia was considered to be unrelated to insulin administration, the total incidence was higher in the lower-target group than in the higher-target group (18 patients [5.2%] vs. 7 [2.0%], P = 0.03).…”

“…16 Patients were randomly assigned, with the use of a central computer, to receive tight glucose control with a target of 80 to 110 mg per deciliter (lower-target group) or 150 to 180 mg per deciliter (higher-target group), with continuous intravenous insulin adjusted to maintain the blood glucose level in the target range. Randomization was performed according to a permuted-block design with stratification according to study site.…”

“…Nutritional intake and indexes of glycemic control were tracked during the period of ICU stay, according to a priori definitions. 16 …”

Tight Glycemic Control in Critically Ill Children

“…16 Patients were randomly assigned, with the use of a central computer, to receive tight glucose control with a target of 80 to 110 mg per deciliter (lower-target group) or 150 to 180 mg per deciliter (higher-target group), with continuous intravenous insulin adjusted to maintain the blood glucose level in the target range. Randomization was performed according to a permutedblock design with stratification according to study site.…”

“…2A and Table 2). The measurements at the start of the intervention were also similar in the lower-target group and the higher-target group ( Severe hypoglycemia (blood glucose level, <40 mg per deciliter) that was considered by the investigators, according to prospectively defined criteria, 16 to be related to insulin administration occurred in 13 of 349 patients (3.7%) in the lower-target group, as compared with 1 of 349 (0.3%) in the higher-target group (P = 0.01). With the inclusion of instances in which severe hypoglycemia was considered to be unrelated to insulin administration, the total incidence was higher in the lower-target group than in the higher-target group (18 patients [5.2%] vs. 7 [2.0%], P = 0.03).…”