A.D. Shearman

High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial

Objective: To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects. Design: A multicentre, randomised, double blind, clinical trial. Setting: Four tertiary neonatal units within Australia. Patients: Infants born less than 30 weeks gestation ventilated for more than 48 hours. Interventions: Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management. Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation. Main outcome measure: Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or doxapram within seven days of caffeine loading. Results: A total of 234 neonates were enrolled. A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7 (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p u200a=u200a 0.01). No difference in adverse effects was detected in terms of mortality, major neonatal morbidity, death, or severe disability or general quotient at 12 months. Conclusions: This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life.

Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity

To study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea.

Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring.

The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age <30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. Serum caffeine was assayed by enzyme-multiplied immunoassay technique. Concentration data (431 samples, median: 4 per subject) were obtained from 110 (52 male) infants of mean birth weight of 1009 g, current mean weight (WT) of 992 g, mean gestational age of 27.6 weeks, and mean postnatal age (PNA) of 12 days. Of 1022 doses given, 145 were orogastric, permitting estimation of absolute bioavailability. A 1-compartment model with first-order absorption was fitted to the data in NONMEM. Patient characteristics were screened (P < 0.01) in nested models for pharmacokinetic influence. Model stability was assessed by nonparametric bootstrapping. Clearance (CL) increased nonlinearly with increasing PNA, whereas volume of distribution (Vd) increased linearly with WT, according to the following allometric models: CL (L/h) = 0.167 (WT/70)0.75 (PNA/12)0.358; Vd (L) = 58.7 (WT/70)0.75. The mean elimination half-life was 101. Interindividual variability (IIV) of CL and Vd was 18.8 % and 22.3 %, respectively. Interoccasion variability (IOV) of CL and Vd was 35.1% and 11.1%, respectively. This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted.

Humidified high flow nasal cannulae: Current practice in Australasian nurseries, a survey

Aim:u2003 Humidified High Flow Nasal Cannula (HHFNC) has been increasingly adopted as a new means of respiratory support throughout the world. However, evidence to support its safety and efficacy is limited. The aim of the present survey was to determine current practices regarding the usage of HHFNC by neonatologists in Australia and New Zealand.

Periextubation caffeine in preterm neonates: A randomized dose response trial

Objective:u2003 To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period.

Routine neonatal postextubation chest physiotherapy: A randomized controlled trial

Objective:u2003To test the effects of a neonatal postextubation programme on the incidence of postextubation collapse and adverse outcomes.

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography.

Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end‐expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome.

Heating of gases during neonatal resuscitation: A bench study

AIMnStandard practice within the neonatal unit is to use heated humidified gas as it decreases respiratory complications in neonates requiring respiratory support. Using cold unhumidified gases during resuscitation could potentially cool the baby as well as exacerbate potential lung injury. We aimed to study the temperature and humidity aspects of using heated, humidified gas for neonatal resuscitation.nnnMETHODSnA heated patient circuit was connected to a T-piece resuscitator via a humidifier. An oxygen flowmeter was set at 10 L/min. Temperature recordings at the humidifier chamber (T1), distal temperature probe (T2) and T-piece (T3) were taken over 20 min at 30s intervals. A humidity sensor was placed at T3.nnnRESULTSnTarget temperatures were not reached. Time to 36°C (mean (sd)): T1 11.1 min (1.71); T3 11.6 min (1.77). T2 took 13.6 min (1.07) to reach 39°C. T1 and T3 were within ±1°C at 5.1 min (0.6). A biphasic relationship demonstrated the time lag between the temperatures of the heated patient circuit and the humidifier chamber. T3 strongly correlated to T1 when T1 is ≥28°C (r(2)=0.85). Humidity was difficult to measure and results were inferred from temperature recordings.nnnCONCLUSIONnThis in vitro test showed that heated, humidified gas is possible during neonatal resuscitation. Adequate time must be allowed for the humidifier chamber to warm to near optimal temperature. The patient circuit is initially heated faster than the humidifier chamber. The displayed T1 temperature correlates to the temperature at T3 at ≥28°C.

Effect of flow rate, humidifier dome and water volume on maximising heated, humidified gas use for neonatal resuscitation ☆

AIMnDry, cold gas is used for neonatal resuscitation, contributing to low admission temperatures and exacerbation of lung injury. Recently, a method of heating and humidifying neonatal resuscitation gases has become available. We aimed to determine the optimal flow rate, humidifier chamber and water volume needed to reach 36°C, and near 100% humidity at the patient T-piece in the shortest possible time.nnnMETHODnA T-piece resuscitator was connected via a heated patient circuit to a humidifier chamber. Trials were performed using different gas flow rates (6, 8 and 10L/min), humidification chambers (MR290, MR225) and water volumes (30g, 108g). Temperature was recorded at the humidifier chamber (T1), distal temperature probe (T2) and the T-piece (T3) over a 20min period at 30s intervals. A test lung was added during one trial.nnnRESULTSnNo significant difference existed between flow rates 8L/min and 10L/min (p=0.091, p=0.631). T3 reached 36°C and remained stable at 360s (8L/min, MR225, 30mL); near 100% RH was reached at 107s (10L/min, MR225, 30mL). T3 and humidity reached and remained stable at 480s (10L/min, MR290, 30mL). Target temperature and humidity was not reached with the test lung.nnnCONCLUSIONSnIt is possible to deliver heated, humidified gases in neonatal resuscitation in a clinically acceptable timeframe. We suggest the set-up to achieve optimal temperature and humidity for resuscitation purposes is 10L/min of gas flow, a MR290 humidification chamber, and 30mL of water.

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography: Lung recruitment & endotracheal suction

Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end‐expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome.