Strict glycaemic control in very low birthweight infants using a continuous glucose monitoring system: a randomised controlled trial

Abstract

ObjectiveTo evaluate the efficacy of a strict glycaemic control protocol using a continuous glucose monitoring (CGM) in infants at high risk of dysglycaemia with the aim of reducing the number of dysglycaemic episodes.DesignRandomised controlled trial.SettingNeonatal intensive care unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome.PatientsAll infants <1500 g fed on parental nutrition (PN) since birth were eligible. A total of 63 infants were eligible and 48 were randomised.InterventionAll participants wore a CGM sensor and were randomised in two arms with alarms set at different cut-off values (2.61–10 mmol/L (47–180 mg/dL) vs 3.44–7.78 mmol/L (62–140 mg/dL)), representing the operative threshold requiring modulation of glucose infusion rate according to an innovative protocol.Main outcome measuresThe primary outcome was the number of severe dysglycaemic episodes (<2.61 mmol/L (47 mg/dL) or >10 mmol/L (180 mg/dL)) in the intervention group versus the control group, during the monitoring time.ResultsWe enrolled 47 infants, with similar characteristics between the two arms. The number of dysglycaemic episodes and of infants with at least one episode of dysglycaemia was significantly lower in the intervention group (strict group): respectively, 1 (IQR 0–2) vs 3 (IQR 1–7); (p=0.005) and 12 (52%) vs 20 (83%); p=0.047. Infants managed using the strict protocol had a higher probability of having normal glycaemic values: relative risk 2.87 (95% CI 1.1 to 7.3). They spent more time in euglycaemia: 100% (IQR 97–100) vs 98% (IQR 94–99), p=0.036. The number needed to treat to avoid dysglycaemia episodes is 3.2 (95% CI 1.8 to 16.6).ConclusionWe provide evidence that CGM, combined with a protocol for adjusting glucose infusion, can effectively reduce the episodes of dysglycaemia and increase the percentage of time spent in euglycaemia in very low birthweight infants receiving PN in the first week of life.

Should continuous glucose monitoring be used to manage neonates at risk of hypoglycaemia?

“…The study by Thomson et al showed per cent time in the target range (sensor glucose 2.6-10 mmol/L, 47-180 mg.dl) was greater with CGM than intermittent blood glucose measurement (77% vs. 59%, respectively) and it was highlighted that the CGM also detected clinically unsuspected episodes of hypoglycaemia (23). In the Galderisi study neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, (24). This highlights the role of CGM in providing clinical teams with the information to allow them to be proactive in management and potentially prevent hypoglycaemia.…”

“…The study by Thomson et al showed per cent time in the target range (sensor glucose 2.6–10 mmol/L, 47–180 mg.dl) was greater with CGM than intermittent blood glucose measurement (77% vs. 59%, respectively) and it was highlighted that the CGM also detected clinically unsuspected episodes of hypoglycaemia ( 23 ). In the Galderisi study neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs. 68%, p < .001) and decreased time spent in mild ( p = .04) and severe ( p = .007) hypoglycaemia compared with the blinded CGM group ( 24 ). The study by Perri et al, showed that using CGM alarms for stricter target thresholds of glucose control (3.44–7.78 mmol/L, 62–140 mg/dl) combined with 33% dextrose infusion, as needed, compared to the use of CGM set to more conventional glucose thresholds (2.61–10 mmol/L, 47–180 mg/dl) resulted in significantly less dysglycaemia ( 24 ).…”

“…In the Galderisi study neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs. 68%, p < .001) and decreased time spent in mild ( p = .04) and severe ( p = .007) hypoglycaemia compared with the blinded CGM group ( 24 ). The study by Perri et al, showed that using CGM alarms for stricter target thresholds of glucose control (3.44–7.78 mmol/L, 62–140 mg/dl) combined with 33% dextrose infusion, as needed, compared to the use of CGM set to more conventional glucose thresholds (2.61–10 mmol/L, 47–180 mg/dl) resulted in significantly less dysglycaemia ( 24 ). This highlights the role of CGM in providing clinical teams with the information to allow them to be proactive in management and potentially prevent hypoglycaemia.…”

“…Galderisi et al showed that real-time CGM alarms can be coupled with a computer-based, proportional-integrative-derivative control algorithm to calculate the glucose infusion required. Use of CGM plus the glucose infusion algorithm allowed for tighter control of the glucose concentration ( p < 0.001), without affecting the neonates' growth ( 24 ). In contrast Beardsall et al ( 19 ) reported the use of a closed-loop CGM-insulin delivery system in preterm neonates between 48 and 72 h of life.…”

It is high time we reduce “routine” blood work in neonatal units

“…Lastly, although preterm infants experience a greater number of skin breaks than the average term infant, newborns with hypoglycemia are often exposed to many skin breaks a day from repeated point of care glucose measurements. Recent literature has demonstrated that continuous glucose measurement through subcutaneously implanted devices is both accurate and can help reduce such testing to a couple occurrences a day for calibration in both the preterm and term populations with hypoglycemia ( 11 , 12 ).…”