How to manage hyperglycemia in preterm infants with Necrotizing Enterocolitis (NEC)?

Management of Hyperglycemia in Preterm Infants with NEC

In preterm infants with NEC, first reduce the glucose infusion rate to acute illness levels (4-8 mg/kg/min for preterm infants <28 days old), and only initiate insulin therapy if blood glucose remains repetitively >10 mmol/L (180 mg/dL) despite reasonable glucose adjustment. 1, 2

Initial Assessment and Monitoring

• Measure blood glucose using blood gas analyzers rather than handheld glucometers, as the latter are unreliable in neonates due to interference from high hemoglobin and bilirubin levels 3, 2
• Monitor blood glucose every 30 minutes to 2 hours during acute illness and after any glucose infusion rate adjustments 3
• Target blood glucose <8 mmol/L (145 mg/dL) as hyperglycemia above this threshold is associated with increased morbidity and mortality in neonatal ICU patients 1, 4

Step 1: Reduce Glucose Infusion Rate (Primary Intervention)

NEC represents an acute illness requiring immediate reduction in glucose delivery to Day 1 rates, regardless of the infant's postnatal age. 1

Specific glucose infusion targets for preterm infants with acute illness (NEC):

• Reduce to 4-8 mg/kg/min (5.8-11.5 g/kg/day) for preterm newborns <28 days of age 1, 3
• For infants 28 days to 10 kg in the acute phase: 2-4 mg/kg/min (2.9-5.8 g/kg/day) 1

Rationale for glucose reduction:

• Acute critical illness like NEC causes insulin resistance and beta-cell dysfunction, making infants unable to handle normal glucose loads 1, 5, 6
• Endogenous glucose production increases during acute illness, so reducing exogenous glucose is physiologically appropriate 1
• Excessive glucose during acute illness increases lipogenesis, hepatic steatosis, VLDL production, and CO2 production 1

Step 2: Optimize Other Nutritional Components

• Maintain amino acid delivery as higher amino acid intake is associated with reduced hyperglycemia risk in preterm infants 5, 7
• Consider arginine supplementation (may be used for NEC prevention and is associated with better glucose control when plasma levels >57 µmol/L) 1, 7
• Do not reduce lipid emulsions unless triglycerides exceed 3 mmol/L (265 mg/dL), as hypertriglyceridemia may result from excessive glucose-induced lipogenesis rather than lipid infusion 1

Step 3: Insulin Therapy (Only After Glucose Adjustment Fails)

Initiate insulin therapy only when blood glucose remains repetitively >10 mmol/L (180 mg/dL) despite reasonable adaptation of glucose infusion rate. 1, 2

Insulin administration guidelines:

• Use continuous intravenous insulin infusion starting at low doses to minimize hypoglycemia risk 2, 4
• Insulin treatment in hyperglycemic extremely preterm infants is associated with lower mortality in observational data 8
• Hypoglycemia risk increases significantly with insulin therapy, requiring glucose monitoring every 30 minutes to 2 hours 4, 5
• Subcutaneous insulin infusion is feasible but requires higher doses and has less predictable glucose control compared to IV insulin 4

Critical Pitfalls to Avoid

• Never use aggressive insulin therapy without first optimizing glucose infusion rate - this increases hypoglycemia risk without addressing the underlying problem of glucose overload 2, 5
• Avoid maintaining high glucose infusion rates during acute NEC - the acute phase of critical illness renders glucose intake ineffective at lowering protein catabolism 1
• Do not allow repetitive or prolonged hypoglycemia ≤2.5 mmol/L (45 mg/dL) as this causes neurological injury comparable to hyperglycemia 1, 9
• Never reduce glucose infusion rate below minimum thresholds (4 mg/kg/min for preterm infants) as this risks hypoglycemia 1, 3
• Recognize that hyperglycemia >8 mmol/L (145 mg/dL) is independently associated with increased mortality and morbidities including NEC, bronchopulmonary dysplasia, and intraventricular hemorrhage 1, 4

Monitoring During Recovery

• As the infant stabilizes and NEC resolves, gradually increase glucose infusion rate toward stable phase targets: 4-6 mg/kg/min (5.8-8.6 g/kg/day) 1
• During recovery phase when mobilizing, advance to 6-10 mg/kg/min (8.6-14 g/kg/day) with maximum 12 mg/kg/min 1, 3
• Continue frequent blood glucose monitoring during transitions between illness phases 3, 2