Philip J. Weston

Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants

AIM To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants. METHODS Forty infants were randomly allocated to receive either hydrocortisone (n=21) or dopamine (n=19). RESULTS All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group. CONCLUSION Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.

Incidence of Neonatal Hypoglycemia in Babies Identified as at Risk

OBJECTIVES Routine blood glucose screening is recommended for babies at risk of neonatal hypoglycemia. However, the incidence of hypoglycemia in those screened is not well described. We sought to determine the incidence of hypoglycemia in babies identified as being at risk, and also to determine differences in incidence between at risk groups. STUDY DESIGN Infants (n = 514) were recruited who were born in a tertiary hospital, ≥35 weeks gestation and identified as at risk of hypoglycemia (small, large, infant of a diabetic, late-preterm, and other). Blood glucose screening used a standard protocol and a glucose oxidase method of glucose measurement in the first 48 hours after birth. RESULTS One-half of the babies (260/514, 51%) became hypoglycemic (<2.6 mM), 97 (19%) had severe hypoglycemia (≤2.0 mM), and 98 (19%) had more than 1 episode. The mean duration of an episode was 1.4 hours. Most episodes (315/390, 81%) occurred in the first 24 hours. The median number of blood glucose measurements for each baby was 9 (range 1-22). The incidence and timing of hypoglycemia was similar in all at risk groups, but babies with a total of 3 risk factors were more likely to have severe hypoglycemia. CONCLUSIONS Hypoglycemia is common amongst babies recommended for routine blood glucose screening. We found no evidence that screening protocols should differ in different at risk groups, but multiple risk factors may increase severity. The significance of these hypoglycemic episodes for long-term outcome remains undetermined.

Continuous glucose monitoring in newborn babies at risk of hypoglycemia

OBJECTIVE To determine the usefulness of continuous glucose monitoring in babies at risk of neonatal hypoglycemia. STUDY DESIGN Babies >/=32 weeks old who were at risk of hypoglycemia and admitted to newborn intensive care received routine treatment, including intermittent blood glucose measurement using the glucose oxidase method, and blinded continuous interstitial glucose monitoring. RESULTS Continuous glucose monitoring was well tolerated in 102 infants. There was good agreement between blood and interstitial glucose concentrations (mean difference, 0.0 mmol/L; 95% CI, -1.1-1.1). Low glucose concentrations (<2.6 mmol/L) were detected in 32 babies (32%) with blood sampling and in 45 babies (44%) with continuous monitoring. There were 265 episodes of low interstitial glucose concentrations, 215 (81%) of which were not detected with blood glucose measurement. One hundred seven episodes in 34 babies lasted >30 minutes, 78 (73%) of which were not detected with blood glucose measurement. CONCLUSION Continuous interstitial glucose monitoring detects many more episodes of low glucose concentrations than blood glucose measurement. The physiological significance of these previously undetected episodes is unknown.

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

Background:  Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia.

Continuous Glucose Monitoring in Newborn Infants: How Do Errors in Calibration Measurements Affect Detected Hypoglycemia?

Background: Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. Aim: The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Methods: Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Results: Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Conclusions: Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data.

Cot-Side Electro-Encephalography and Interstitial Glucose Monitoring during Insulin-Induced Hypoglycaemia in Newborn Lambs

Background: The optimal approach to detection and management of neonatal hypoglycaemia remains unclear. Objectives: We sought to demonstrate whether electro-encephalography (EEG) changes could be detected on the amplitude-integrated EEG monitor during induced hypoglycaemia in newborn lambs, and also to determine the accuracy of continuously measured interstitial glucose in this situation. Methods: Needle electrodes were placed in the P3-P4, O1-O2 montages. The interstitial glucose sensor was placed subcutaneously. After 30 min baseline recordings, hypoglycaemia was induced by insulin infusion and blood glucose levels were monitored every 5 min. The infusion was adjusted to reduce blood glucose levels by 0.5 mmol/l every 15 min and then maintain a blood glucose level <1.0 mmol/l for 4 h. EEG parameters analysed included amplitude, continuity and spectral edge frequency. The interstitial and blood glucose levels were compared. Results: All lambs (n = 15, aged 3–11 days) became hypoglycaemic, with median blood glucose levels falling from 6.5 to 1.0 mmol/l, p < 0.0001. There were no detectable changes in any of the measured EEG parameters related to hypoglycaemia, although seizures occurred in 2 lambs. There was moderate agreement between the intermittent blood glucose and continuous interstitial glucose measurements in the baseline, decline, and hypoglycaemia periods (mean difference –0.7 mmol/l, 95% confidence interval, CI, –2.8 to 1.4 mmol/l). However, agreement was poor during reversal of hypoglycaemia (mean difference 4.5 mmol/l, 95% CI –1.1 to 10.7 mmol/l). Conclusions: The cot-side EEG may not be a useful clinical tool in the detection of neurological changes induced by hypoglycaemia. However, continuous interstitial glucose monitoring may be useful in the management of babies at risk of hypoglycaemia.

Cot-Side Electroencephalography Monitoring is Not Clinically Useful in the Detection of Mild Neonatal Hypoglycemia

OBJECTIVES To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modified these patterns. STUDY DESIGN Eligible babies were ≥ 32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia. RESULTS A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twenty-four of the babies had aEEG recordings, and glucose concentrations were low (< 2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia. CONCLUSIONS Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection.

Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns

Objective Alternative cerebral fuels are reputed to provide neuroprotection during hypoglycaemia, particularly in breastfed babies. We measured concentrations of alternative cerebral fuels in hypoglycaemic babies in the first 48 h. Patient and methods Babies were ≥35 weeks, ≤48 h old and at risk of hypoglycaemia (infant of diabetic, preterm, small or large). Plasma glucose, β-hydroxybutyrate, lactate and insulin concentrations were measured in babies who had been hypoglycaemic (<2.6 mM) for >1 h. Results Samples were taken from 35 hypoglycaemic babies at 3.7; 1.8–39.6 (median; range) hours after birth. Concentrations of glucose and β-hydroxybutyrate were low (2.03; 0.19–3.39 mM and 0.06; 0.00–1.20 mM), but lactate concentrations varied widely (3.06; 0.02–7.96 mM). Infants of diabetics had lower β-hydroxybutyrate and higher insulin concentrations, but mode of feeding did not influence plasma concentrations of alternative cerebral fuels. Conclusions Hypoglycaemic babies within the first 48 h after birth are unlikely to receive neuroprotection from ketones. However, lactate may provide an alternative cerebral fuel for many. Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns. Trial registration number ACTRN12608000623392.

Feasibility and safety of early transfer of premature infants from incubators to cots: a pilot study.

Objectives: To document whether medically stable infants can be transferred safely from incubators to unheated, open cots at 1500 g.

What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia

Objective To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. Study design We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. Results The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4‐12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7‐5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8‐6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI −0.3 to 44.2; P = .09) or expressed breast milk (−1.4 mg/dL; 95% CI −3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28‐0.94; P = .03). Conclusions Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first‐line oral treatment of infants with hypoglycemia.