Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

Treatment of pulmonary surfactant deficiency. A clinical and experimental study.

The background of the present study is of clinical origin: the newborn baby with respiratory insufficiency due to surfactant deficiency (hyaline membrane disease). Until the beginning of this decade only supportive treatment was possible for these patients. The report on surfactant replacement therapy of Fujiwara et al. (1) initiated a new era in treatment of patients with hyaline membrane disease. Although the first results of this new approach of hyaline membrane disease are promising, it is also clear that the disease can not be treated successfully in all patients. ... Zie: Introduction

Heart rate measuring device

The invention relates to a heart rate measuring apparatus and a method, adapted for measuring a subject's (6) heart rate and/or heart rate variation. The heart rate measuring apparatus (1) comprises a holder (2) adapted for carrying a portion of a body part of the subject (6) lying on or resting against the holder (2), a motion sensor (4) operatively connected to the holder (2), wherein the holder (2) is adapted for being at least partly moveable in a horizontal direction relative to the ground (7), the motion sensor (4) being adapted for measuring a signal generated by a movement of the subject (6) at least partly in the horizontal direction. In this way, a reliable signal is obtained adapted for measuring the heart rate and/or heart rate variation of a subject while keeping the implementation costs low

Surfactant nebulisation prevents the adverse effects of surfactant therapy on blood pressure and cerebral blood flow in rabbits with severe respiratory failure

Objective: Surfactant replacement therapy for the neonatal respiratory distress syndrome has shown beneficial effects on lung function and survival. Recently, rapid fluctuations of haemodynamics and cerebral perfusion following surfactant instillation have beer, described and an association with the development of intraventricular haemorrhage has been proposed. Therefore, alternative methods of surfactant therapy that reduce the effects on cerebral perfusion have to be explored. Does instillation of surfactant influence blood pressure and cerebral blood flow in rabbits with severe respiratory failure? Can nebulisation of surfactant prevent these adverse effects on blood pressure and cerebral blood flow? Interventions: Surfactant (Alveofact, 100 mg/kg body weight) was nebulised using the MiniNEB nebuliser, or instilled, in 12 rabbits with severe respiratory failure induced by lung lavage. Assessed were blood gasses, mean arterial blood pressure (MABP) and cerebral blood flow over the left carotid artery, using ultrasonic transit-time flow probes. Results: Partial pressure of oxygen in arterial blood increased quickly after instillation, from 8.7 +/- 1.3 to 24.9 +/- 6.4 kPa after 15 min, and increased gradually during nebulisation from 8.0 +/- 0.5 to 24.5 +/- 4.6 after 120 min. After instillation, MABP decreased 22 +/- 5 % (in 8 min) and cerebral blood flow dropped even more: 64 +/- 9 % within 8 min. During nebulisation, MABP did not change significantly and cerebral blood flow decreased gradually, 31 +/- 14 % over 90 min. Conclusions: Surfactant instillation was followed by a rapid decrease in MABP and an even more pronounced drop in cerebral blood flow, while during nebulisation MABP did not change and cerebral blood flow decreased less and more gradually

Unobtrusive monitoring of neonatal brain temperature using a zero-heat-flux sensor matrix

The temperature of preterm neonates must be maintained within a narrow window to ensure their survival. Continuously measuring their core temperature provides an optimal means of monitoring their thermoregulation and their response to environmental changes. However, existing methods of measuring core temperature can be very obtrusive, such as rectal probes, or inaccurate/lagging, such as skin temperature sensors and spotchecks using tympanic temperature sensors. This study investigates an unobtrusive method of measuring brain temperature continuously using an embedded zero-heat-flux (ZHF) sensor matrix placed under the head of the neonate. The measured temperature profile is used to segment areas of motion and incorrect positioning, where the neonate's head is not above the sensors. We compare our measurements during low motion/stable periods to esophageal temperatures for 12 preterm neonates, measured for an average of 5 h per neonate. The method we propose shows good correlation with the reference temperature for most of the neonates. The unobtrusive embedding of the matrix in the neonate's environment poses no harm or disturbance to the care work-flow, while measuring core temperature. To address the effect of motion on the ZHF measurements in the current embodiment, we recommend a more ergonomic embedding ensuring the sensors are continuously placed under the neonate's head