A Model Analysis of Arterial Oxygen Desaturation during Apnea in Preterm Infants

Rapid arterial O2 desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O2 desaturation during apnea () is complicated by the non-linear O2 dissociation curve, falling pulmonary O2 uptake, and by the fact that O2 desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O2 consumption accelerates throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates during stage 1, and finally, total blood O2 capacity (blood volume and hemoglobin content) alone determines during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia

Sudden deterioration due to intra-tumoral hemorrhage of ependymoma of the fourth ventricle in a child during a flight: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, the association between air travel and intra-tumoral hemorrhage in pediatric populations has never been described previously.</p> <p>Case presentation</p> <p>We report the case of a two-and-a-half-year-old Caucasian, Iranian boy with a hemorrhaging brain tumor. He had a posterior fossa midline mass and severe hydrocephalus. He had been shunted for hydrocephalus four weeks earlier and was subsequently referred to our center for further treatment. The hemorrhage occurred in an infra-tentorial ependymoma, precipitated by an approximately 700-mile air journey at a maximum altitude of 25,000 feet.</p> <p>Conclusions</p> <p>A pre-existing intra-cranial mass lesion diminishes the ability of the brain to accommodate the mild environmental disturbances caused by hypercarbia, increased venous pressure and reduced cerebral blood flow during long air journeys. This is supported by a literature review, based on our current knowledge of physiological changes during air travel.</p

A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS) have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria

Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene

Bronchopulmonary dysplasia (BPD), the main consequence of prematurity, has a significant heritability, but little is known about predisposing genes. The aim of this study was to identify gene loci predisposing infants to BPD. The initial genome-wide association study (GWAS) included 174 Finnish preterm infants of gestational age 24-30 weeks. Thereafter, the most promising single-nucleotide polymorphisms (SNPs) associated with BPD were genotyped in both Finnish (n = 555) and non-Finnish (n = 388) replication cohorts. Finally, plasma CRP levels from the first week of life and the risk of BPD were assessed. SNP rs11265269, flanking the CRP gene, showed the strongest signal in GWAS (odds ratio [ OR] 3.2, p = 3.4 x 10(-6)). This association was nominally replicated in Finnish and French African populations. A number of other SNPs in the CRP region, including rs3093059, had nominal associations with BPD. During the first week of life the elevated plasma levels of CRP predicted the risk of BPD (OR 3.4, p = 2.9 x 10(-4)) and the SNP rs3093059 associated nominally with plasma CRP levels. Finally, SNP rs11265269 was identified as a risk factor of BPD (OR 1.8, p = 5.3 x 10(-5)), independently of the robust antenatal risk factors. As such, in BPD, a potential role for variants near CRP gene is proposed

Early inhaled budesonide for the prevention of bronchopulmonary dysplasia

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P = 0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P = 0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P = 0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P = 0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P = 0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality

Improving manual oxygen titration in preterm infants by training and guideline implementation

To study oxygen saturation (SpO2) targeting before and after training and guideline implementation of manual oxygen titration, two cohorts of preterm infants 21%. ABCs where oxygen therapy was given were identified and analyzed. After training and guideline implementation the %SpO2-wtr increased (median interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p 95% did not decrease (73% vs 64%; ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION: Training and guideline implementation in manual oxygen titration improved SpO2 targeting in preterm infants with more time spent within the target range and less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during ABCs were shorter. What is Known: • Oxygen saturation targeting in preterm infants can be challenging and the compliance is low when oxygen is titrated manually. • Hyperoxaemia often occurs after oxygen therapy for oxygen desaturation during apnoeas. What is New: • Training and implementing guidelines improved oxygen saturation targeting and reduced hyperoxaemia. • Training and implementing guidelines improved manual oxygen titration during ABC

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children

BACKGROUND: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children. METHODS: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P(0.1)) was measured in all conditions. The slope of the relation between P(0.1 )and the partial pressure of end-tidal O(2 )or CO(2 )(P(ET)O(2 )and P(ET)CO(2)) served as the index of hypoxic or hypercapnic ventilatory drive. RESULTS: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting P(ET)CO(2 )was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO(2 )retention. CONCLUSIONS: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting P(ET)CO(2). Whether or not diminished hypoxic drive or resting CO(2 )retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO(2 )retention are associated with sleep-disordered breathing in 6–12 year old children