Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study)

<div><p>Background</p><p>Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk.</p><p>Methods and Findings</p><p>We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (<2.6 mM) in the first 48 h. Secondary outcomes included admission to a NICU, admission for hypoglycaemia, and breastfeeding at discharge and at 6 wk. Prespecified potential dose limitations were tolerance of gel, time taken to administer, messiness, and acceptability to parents. From August 2013 to November 2014, 416 babies were randomised. Compared to babies randomised to placebo, the risk of hypoglycaemia was lowest in babies randomised to a single dose of 200 mg/kg dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47–0.99, <i>p</i> = 0.04) but was not significantly different between dose groups (<i>p</i> = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64–0.98, <i>p</i> = 0.03; number needed to treat = 10, 95% CI 5–115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33–1.25, <i>p</i> = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21–1.01, <i>p</i> = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups.</p><p>Conclusions</p><p>The incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes.</p><p>Trial Registration</p><p>Australian New Zealand Clinical Trials Registry <a href="https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12613000322730" target="_blank">ACTRN12613000322730</a></p></div

Details of study gel and supplementary dextrose administration for each dosage group.

<p>Details of study gel and supplementary dextrose administration for each dosage group.</p

Median blood glucose concentration at four time intervals for each dose regime of dextrose gel.

<p>Boxplots for blood glucose concentration (mM) at time = 2, 4, 8, and 12 h ± 30 min, for each cumulative dose of prophylactic dextrose gel, where 0 mg/kg is placebo, 200 mg/kg is 0.5 ml/kg dextrose once, 400 mg/kg is 1 ml/kg once, 800 mg/kg is 0.5 ml/kg for four doses, and 1,000 mg/kg is 1 ml/kg once followed by 0.5 ml/kg for a further three doses. The box represents 25th to 75th percentiles. The horizontal bar within the box is the median, and the solid dot within the box is the mean. The whiskers are 1.5 (interquartile range [IQR]) above and below the 25th and 75th percentile. Solid dots beyond the whiskers represent outliers.</p

Primary and secondary outcomes for each dosage group.

<p>Primary and secondary outcomes for each dosage group.</p

Consolidated Standards of Reporting Trials (CONSORT) diagram.

<p>One baby was randomised in error following closure of the trial after randomisation of 415 babies and was excluded from the analysis. All other babies had primary outcome data available and were included in the intention-to-treat analysis.</p

Limitation scores.

<p>Limitation scores.</p

Odds of hypoglycaemia for each cumulative dose of prophylactic dextrose gel.

<p>Odds ratios of blood glucose concentration < 2.6 mM for each cumulative dose of prophylactic dextrose gel, where 0 mg/kg is placebo, 200 mg/kg is 0.5 ml/kg dextrose once, 400 mg/kg is 1 ml/kg once, 800 mg/kg is 0.5 ml/kg for four doses, and 1,000 mg/kg is 1 ml/kg once followed by 0.5 ml/kg for a further three doses. Data are odds ratios +/− 95% CI adjusted for prespecified potential confounders (sex, gestational age, and delivery mode), and the numerals above the figure are the number (%) of babies who experienced hypoglycaemia (blood glucose concentration < 2.6 mM) in each group.</p

Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Background: Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity. Methods: PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545. Findings: Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8\ub71%) of 2396 patients in the CPAP group and 197 (8\ub72%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1\ub701 [95% CI 0\ub781-1\ub724]; p=0\ub795). 200 (8\ub79%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3\ub75%] of 2241 patients), oronasal dryness (43 [1\ub79%]), excessive air leak (36 [1\ub76%]), vomiting (26 [1\ub72%]), and pain (24 [1\ub71%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability. Interpretation: In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended

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