Asystole in 2 Pediatric Patients During Dexmedetomidine Infusion.

INTRODUCTION: Bradycardia is a known side effect of dexmedetomidine. Reports of sinus pauses or asystole, however, are rare. We present 2 cases of pediatric patients who developed asystole on a dexmedetomidine infusion. SUMMARY OF CASES: An 8-week-old male with RSV bronchiolitis and acute hypoxemic respiratory failure was started on dexmedetomidine for sedation at 0.2 mcg/kg/h with a maximum dose of 0.7mcg/kg/h. On Hospital day (HD) 4, on dexmedetomidine at 0.7 mcg/kg/h, he developed intermittent episodes of bradycardia with heart rates in the 60 s. Echocardiogram on HD 6 showed normal function. On HD 7, he began having periods of asystole lasting up to 6 seconds. Dexmedetomidine was discontinued, with the resolution of episodes of asystole after 6 hours. A 27-month-old male with a congenital left diaphragmatic hernia and pulmonary hypertension who had been weaned off sildenafil 6 months earlier underwent re-repair of left diaphragmatic hernia. Postoperatively he remained intubated and paralyzed. Dexmedetomidine was started at 0.3 mcg/kg/h for sedation, with a maximum dose of 1.2 mcg/kg/h. An echocardiogram on HD 3 showed good function with mild to moderate pulmonary hypertension. That evening, with dexmedetomidine at 1.1 mcg/kg/h, he developed a 15 second period of asystole requiring CPR. Dexmedetomidine was discontinued, and he was started on a midazolam infusion with no further episodes. DISCUSSION: Both cases occurred in patients without cardiac conduction defects or on negative chronotropic or sympatholytic medications that have been associated with dexmedetomidine-induced asystole. We hypothesize that both episodes of asystole were due to increased patient-related vagal tone exacerbated by dexmedetomidine.

No es una neumonía, es una hernia diafragmática / It's not pneumonia, it's a diaphragmatic hernia

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Diagnóstico retardado de hernia de Bochdalek. Presentación de caso / Delayed diagnosis of Bochdalek hernia. Case presentation

Fundamento: el defecto congénito en el cierre de la región posterolateral del diafragma se denomina hernia de Bochdalek y solo en el 10 % de los niños el diagnóstico se realiza después del primer mes de vida. Este defecto congénito permite que se desplacen las vísceras abdominales hacia el tórax, lo que a la vez puede ser la causa de una opacidad pulmonar persistente en la radiografía torácica. Objetivo: ilustrar, debido a su infrecuencia, el diagnóstico retardado de hernia de Bochdalek en una paciente con una opacidad pulmonar persistente. Presentación de caso: se describe el caso de una niña de once meses de edad, que ingresó por una opacidad pulmonar persistente en base pulmonar izquierda y signos clínicos de infección. Después de realizar tratamiento con antibióticos durante cinco días tuvo mejoría clínica pero persistía la imagen en la radiografía torácica. En la tomografía computarizada se observó el bazo localizado en el hemitórax izquierdo debido a una hernia de Bochdalek. Conclusiones: el diagnóstico de la hernia de Bochdalek fuera de la etapa de recién nacido es infrecuente, sin embargo esta enfermedad debe tenerse en cuenta en todo paciente con una opacidad pulmonar persistente aun cuando su edad sobrepase la etapa neonatal.

Background: congenital defect in the closure of the posterolateral region of the diaphragm is called Bochdalek hernia and only in 10 % of children the diagnosis is made after the first month of life. This birth defect allows abdominal organs to move into the chest, which in turn can be the cause of persistent pulmonary opacity on chest radiography. Objective: to illustrate the delayed diagnosis of Bochdalek hernia in a patient with a persistent pulmonary opacity, as it is an infrequent case. Case presentation: the case of an eleven months old girl, who was admitted for a left lung base pulmonary opacity and persistent clinical signs of infection is described. The patient had clinical improvement after completing treatment with antibiotics for five days but the image persisted on chest radiography. Computed tomography showed the spleen in the left hemithorax due to Bochdalek hernia. Conclusions: the diagnosis of Bochdalek hernia out of the newborn stage is rare, however this disease should be considered in all patients with persistent pulmonary opacity even when their age exceeds the neonatal stage.

Inhaled nitric oxide use in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To describe the use of inhaled nitric oxide (INO) in newborns with congenital diaphragmatic hernia (CDH). METHODS: Pediatric Health Information System data were queried for newborns with CDH admitted at <8 days of age at tertiary care US pediatric hospitals between 2003 and 2011. INO treatment status and timing in relation to CDH repair were determined for each infant. Hospital-specific rates of INO use, extracorporeal membrane oxygenation (ECMO) use, and mortality were determined. RESULTS: Data were analyzed for 1713 neonates with CDH admitted to 33 hospitals. More than half (57%) received INO during their inpatient stay, and utilization varied dramatically between hospitals (34% to 92%). Neonates treated with INO accumulated >$81 million in pharmacy charges. The proportion of infants receiving INO as well as their duration of therapy increased significantly during the study period. The rate of ECMO utilization and mortality did not change significantly during the study period. Hospital-specific mortality rates did not correlate with INO therapy, ECMO utilization, or case volume. CONCLUSIONS: INO use in neonates with CDH is widespread, and has increased at many US tertiary pediatric hospitals without contemporaneous change in ECMO utilization or mortality. The improvement of evidence-based guidelines for the use of INO in newborns with CDH could lead to a reduction in health care costs for these patients.

Vasopressin improves hemodynamic status in infants with congenital diaphragmatic hernia.

OBJECTIVE: To assess the ability of vasopressin to stabilize hemodynamics in infants with systemic hypotension secondary to congenital diaphragmatic hernia (CDH). STUDY DESIGN: A retrospective chart review was performed to identify 13 patients with CDH treated with vasopressin for refractory hypotension to assess the effect of vasopressin on pulmonary and systemic hemodynamics and gas exchange in this setting. Data collected included demographics, respiratory support, inotropic agents, pulmonary and systemic hemodynamics, urine output, and serum and urine sodium levels during vasopressin therapy. RESULTS: Vasopressin therapy increased mean arterial pressure and decreased pulmonary/systemic pressure ratio, heart rate, and fraction of inspired oxygen. In 6 of 13 patients, extracorporeal membrane oxygenation therapy was no longer indicated after treatment with vasopressin. Improvement in left ventricular function and oxygenation index after vasopressin initiation was associated with a decreased need for extracorporeal membrane oxygenation therapy. Prolonged vasopressin treatment was associated with hyponatremia, increased urine output, and increased urine sodium. CONCLUSIONS: Vasopressin stabilized systemic hemodynamics without adverse effects on pulmonary hemodynamics in a subset of infants with CDH. Our results suggest a potential role for vasopressin therapy in patients with CDH with catecholamine-resistant refractory hypotension.

Doppler parameters of fetal lung hypoplasia and impact of sildenafil.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) is clinically challenging because of associated lung hypoplasia (LH). There have been no validated parameters to evaluate fetal LH severity. Sildenafil has been shown to improve LH mass in nitrofen-induced pulmonary artery (PA) models, but the pulmonary vascular tone has not been evaluated in vivo. The aim of this study was to identify the PA Doppler parameter that best predicts LH severity and to investigate the efficacy of antenatal sildenafil treatment in experimental CDH. STUDY DESIGN: Nitrofen (50-60% CDH in offspring) or vehicle on E9.5 and sildenafil or vehicle on E11.5-20.5 were administrated to pregnant rats. On E20.5, PA Doppler indices were investigated with and without maternal hyperoxia. The presence/absence of CDH, lung/body weight ratio and radial saccular count were assessed at E20.5. RESULTS: At baseline, CDH rats had lower PA Doppler acceleration/ejection time ratios and pulsatility index (PI). Maternal hyperoxia resulted in a significant decrease in the PA/PI suggesting pulmonary vasodilation. In contrast, in CDH fetuses, the ipsilateral PA/PI showed little or no response to hyperoxia (P > .05), and in those with LH, PI response to maternal hyperoxia correlated positively with hernia, lung/body weight ratio (r = 0.70, P = .01). Maternal sildenafil therapy significantly improved PA response to hyperoxia and lung growth in CDH fetuses (P < .01). CONCLUSION: Pulmonary vasodilation that occurs in E20.5 fetal rats in response to maternal hyperoxia is blunted in CDH. Change in PA/PI with hyperoxia is a useful predictor of LH severity. Sildenafil improves pulmonary vascular response and lung growth in fetal CDH.

Sildenafil weaning after discharge in infants with congenital diaphragmatic hernia.

Sildenafil is used to treat pulmonary hypertension (PAH) in infants with congenital diaphragmatic hernia (CDH). However, data to guide sildenafil dosing and weaning are limited. This is concerning in light of a recent report describing increased risk associated with high-dose sildenafil regimens in non-CDH PAH. A retrospective cohort study of sildenafil usage, dosing, and weaning in infants with CDH was conducted at the authors' institution. The findings show that 17 % (19/122) of infants were discharged receiving sildenafil at a median dose of 8 mg/kg/day (range 2.91-5.78 mg/kg/day). The weaning rate was 0.1 mg/kg/week (range 0.01-0.5 mg/kg/week). The infants ceased therapy after a median of 343 days. At the age of 1 year, 29 % were receiving sildenafil at a dose higher than 1.5 mg/kg/day. One infant died of severe PAH. Sildenafil therapy at discharge is common in severe CDH. Variation in dosing and weaning rates highlights the need for standardized assessment and treatment of PAH after discharge to optimize the benefits and minimize the adverse effects of sildenafil.

Manejo perioperatorio de la hernia diafragmática congénita derecha / No disponible

Presentamos el manejo perioperatorio de una RN prematura con HDCD (diagnosticada mediante ecografía en la semana 22) y la posible asociación con el Síndrome de Frías. La Hernia Diafragmática Congénita es una malformación con una incidencia muy baja y generalmente localizada en el lado izquierdo. Pertenece al grupo de las disgenesias diafragmáticas congénitas y se caracteriza por una hipoplasia pulmonar que se define como anatómica y funcional. Una vez conseguida la estabilización del paciente, y nunca antes, el tratamiento definitivo es la corrección quirúrgica, que hoy en día ya no es considerado como una emergencia, teniendo que ser diferido el tiempo necesario para lograr la estabilización hemodinámica y gasométrica del paciente. El grado de hipoplasia pulmonar, la persistencia de hipertensión pulmonar y el grado de prematuridad son los principales factores pronósticos de estos casos, empeorando la supervivencia aquellos pacientes en los que se asocian otras alteraciones cromosómicas (AU)

We present the perioperative management of a premature newborn with HDCD (diagnosed by ultrasound at week 22) and the possible association with Frias Syndrome. Congenital diaphragmatic hernia is a malformation with a very low incidence and generally located on the left side. It belongs to the group of congenital diaphragmatic dysgenesis and it is characterized by pulmonary hypoplasia defined as anatomical and funcional. Once achieved patient stabilization, and never before it, definitive treatment is surgical correction, which today is not considered an emergency and had to be delayed long enough to achieve hemodynamic stabilization of the patient and blood gases. The degree of pulmonary hypoplasia, persistent pulmonary hypertension and the degree of prematurity are major predictors of these cases, worse survival in those patients who associate other chromosomal abnormalities (AU)

Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat.

OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test. RESULTS: CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH. CONCLUSION: Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.

Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia.

The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and pulmonary hypertension (PH). We previously reported successful treatment with imatinib of a patient with CDH. This study examines the effect of antenatal imatinib administration on the pulmonary vasculature in a rat model of CDH. Pregnant rats were given nitrofen to induce CDH. Controls were given olive oil. Half of the CDH fetuses and half of the controls were treated with imatinib antenatally E17-E21, rendering four groups: Control, Control+Imatinib, CDH, and CDH+Imatinib. Lung sections were obtained for morphometry and immunohistochemistry, and protein was purified for Western blot. Effects of nitrofen and imatinib on Ki-67, caspase-3, PDGF-B, and PDGF receptors were analyzed. Imatinib significantly reduced medial wall thickness in pulmonary arteries of rats with CDH. It also normalized lumen area and reduced the proportion of fully muscularized arteries. Imatinib also caused medial thinning in the control group. Cell proliferation was increased in CDH, and this proliferation was significantly reduced by imatinib. PDGF-B and PDGFR-ß were upregulated in CDH, and imatinib treatment resulted in a downregulation. PDGFR-α remained unchanged in CDH but was significantly downregulated by imatinib. Antenatal imatinib treatment reduces development of medial wall thickness and restores lumen area in pulmonary arteries in nitrofen-induced CDH. The mechanism is reduced cell proliferation. Imatinib is an interesting candidate for antenatal therapy for PH in CDH, but potential side effects need to be investigated and more specific targeting of PDGF signaling is needed.

Retinoic acid rescues deficient airway innervation and peristalsis of hypoplastic rat lung explants.

BACKGROUND: Bronchial peristalsis modulates lung growth and is deficient in hypoplastic nitrofen-exposed rat lung explants. Retinoic acid (RA) rescues lung hypoplasia. This study examines whether decreased bronchial innervation contributes to this developmental deficiency and if RA is able to recover bronchial innervation and motility. MATERIAL AND METHODS: After IRB approval, pregnant rats received either 100 mg nitrofen or vehicle on gestational day 9.5 (E9.5). Embryonic lung primordia harvested on E13 were cultured for 72 h and RA was added daily to the medium when appropriate. Lung growth was assessed by counting the number of terminal buds and measuring explant surface, total DNA and protein in control, control + RA, nitrofen and nitrofen + RA groups. Peristaltic contractions were recorded for 10 min under an inverted microscope. Lung explants stained for anti-protein gene product 9.5 (PGP 9.5) and smooth muscle α-actin were examined under a confocal microscope for depicting the specific relationship between neural and smooth muscle cells. PGP 9.5 and smooth muscle α-actin levels were quantified by Western blot analysis for assessing the neural and muscle cell expressions. Comparisons between groups were made with non-parametric tests. RESULTS: The number of terminal buds, the explants' surface and the DNA and protein contents were significantly decreased in nitrofen-exposed lungs in comparison with controls. In contrast, these measurements were normal in explants exposed to both nitrofen and RA. Bronchial peristalsis (contractions/min) was significantly decreased in nitrofen-exposed lungs in comparison with controls; in contrast, in nitrofen + RA lungs it was similar to controls. In all study groups, the airways were surrounded by smooth muscle and ensheathed in a plexus of nerve fibers containing ganglia. PGP 9.5 protein levels were decreased in nitrofen-exposed lungs, but they normalized when RA was added. No differences were found in α-actin protein levels. Explants exposed only to RA were similar to control. CONCLUSIONS: Lung growth, bronchial innervation and peristalsis are decreased in nitrofen-exposed lung explants and are rescued by RA. If deficient airway innervation contributing to dysmotility and pulmonary hypoplasia can be pharmacologically rescued, new relatively simple prenatal interventions could be envisioned.

Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia.

Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH.

Exogenous surfactant: intubated present, nebulized future?

BACKGROUND: exogenous surfactant is currently administered via intra-tracheal instillation, a method which can increase the possibility of clinical instability in the peri-surfactant administration period. Since its introduction, there has been an increase in understanding of the pathology of respiratory distress syndrome and surfactant biology. This includes development of a potential nebulized surfactant which has the potential to increase the number, safety and timely administration of the medication in preterm infants. DATA SOURCES: based on recent original publications in the field of surfactant biology, we reviewed our experience with surfactant administration and discussed the available evidence on nebulized surfactant and outlined potential barriers toward widespread introduction of this therapy. RESULTS: surfactant has revolutionized modern neonatal management and nebulized surfactant is attractive and a vector for administration. However, issues regarding costeffectiveness, development of nebulizer devices capable of administration, deposition of medication in the airway and dosing strategies remain unresolved. CONCLUSIONS: nebulized surfactant has the potential to be a therapeutic breakthrough by eliminating the potent volu-and-baro-traumatic effects of mechanical ventilation in the peri-surfactant period. Nebulization would likely lead to increased administration immediately after birth and more emphasis on noninvasive ventilator strategies. These features will aid clinical implementation of nebulized surfactant as a standard of treatment after introduction.

Effects of estrogen on lung development in a rat model of diaphragmatic hernia.

PURPOSE: The study aimed to observe the influence of estradiol on rat models with congenital diaphragmatic hernia (CDH) and understand the potential mechanism. METHODS: Eleven pregnant female Sprague-Dawley rats were randomly divided into 3 groups on day 9.5 of gestation: group C (n = 2) was administered 2 mL of olive oil, whereas group N (n = 3) and group E (n = 6) were administered 200 mg of nitrofen. Antenatal estradiol was given subcutaneously to group E on days 18.5, 19.5, and 20.5 of gestation. Histologic evaluations, incidence of CDH, and the immunoreactivity of transforming growth factor (TGF)-ß1 in lung were observed. In addition, the mRNA levels of TGF-ß1, type I TGF-ß receptor (TßRI), and type II TGF-ß receptor (TßRII) were determined. RESULTS: Histologically, the lungs of group N fetuses were hypoplastic compared with those of group C and had thick-walled septa with poorly developed saccules. Group E showed improved mesenchymal differentiation with well-developed saccules. There was no significant difference between the incidence of CDH in group N and that in group E. The expression of TGF-ß1 in lung tissue and arterioles in group N were significantly higher than those in group C and E. Moreover, relative mRNA expression levels of TGF-ß1 and TßRI in group N were markedly higher than those in group C, whereas those in group E were significantly decreased compared with group N. CONCLUSIONS: Estradiol can promote lung development in rats with CDH. The down-regulation of TGF-ß1 and its signaling pathway may play a role in this effect.

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes.

Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely 'endogenous studies', which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely 'exogenous studies', which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

The outcome in newborns with congenital diaphragmatic hernia in a Norwegian region.

AIM: To evaluate the therapeutic strategies used in neonates with congenital diaphragmatic hernia (CDH) during the last 15 years in our department. METHOD: A retrospective study of 27 neonates with CDH treated at the Neonatal Intensive Care Unit at Ullevaal University Hospital between 1992 and 2006. Since 1992 we have used delayed operative repair and high-frequency ventilation (HFV). Because surfactant replacement and inhaled nitric oxide (iNO) therapy have been used since 1997, we divided the patients into two groups; group 1 from 1992 to 1996 (9 patients) and group 2 from 1997 to 2006 (18 patients). RESULTS: The overall survival was 70%. Group 1 had an exceptionally good outcome, 100% survival versus 56% in the last group. CONCLUSION: Pulmonary hypoplasia and pulmonary hypertension are still the most challenging factors in treatment of neonates with CDH, despite novel therapeutic modalities, such as HFV, surfactant and iNO. Delayed surgery in CDH allows pre-operative stabilization. Extracorporeal membrane oxygenation must be considered in the most severe cases.

Inhaled NO in the experimental setting.

Nitric oxide, a gas molecule, is a unique pharmaceutical agent that can be inhaled and thus delivered directly to the lung. More than a decade of intensive laboratory and clinical investigation has culminated in the current role for inhaled NO as the only selective pulmonary vasodilator for the treatment of persistent pulmonary hypertension of the newborn (PPHN). Not surprisingly, this potent and successful therapy continues to be studied intensively to better define its mechanism of action and role in PPHN treatment. In addition, there remains intense interest in possible new applications for newborns, as well as strategies that may enhance its efficacy. This review describes several areas of current research on amplification of NO signaling in the neonatal pulmonary vasculature, and reviews our current knowledge about the role of iNO in other conditions such as congenital diaphragmatic hernia and congenital heart disease. In addition, laboratory and clinical studies addressing a potential role for iNO as a therapeutic modality for the preterm infant are reviewed.

Early outcome of congenital diaphragmatic hernia in a Malaysian tertiary centre.

INTRODUCTION: This prospective observational study was conducted to determine the outcome of newborns with congenital diaphragmatic hernia (CDH). They were managed with a protocol of gentle ventilation to avoid barotraumas, and inhaled nitric oxide (iNO) or intravenous magnesium sulphate for treatment of persistent pulmonary hypertension of newborns (PPHN). METHODS: All newborns with CDH admitted to neonatal intensive care unit of this hospital during the six-year study period were recruited. High frequency oscillatory ventilation was used when infants required peak inspiratory pressure of more than 25 mmHg. iNO at 20 ppm or intravenous magnesium sulphate was used when PPHN developed. Arterial blood pH was maintained between 7.35 and 7.45, and partial pressure of arterial carbon dioxide was kept above 35 mmHg. Surgery was performed when the infants' general condition and blood gases were stabilised for at least 24 hours. RESULTS: Of 21 infants recruited (15 males and six females, median gestational age 39.0 weeks, median birth weight 2,800 grams), 52.4 percent had PPHN. 12 (57.1 percent) underwent surgery at a median age of 4.9 days. One died postoperatively due to PPHN. Out of the 21 subjects, 11 (52.4 percent) survived to discharge. There was no significant difference in the demographic characteristics, side and size of CDH defects, presence of PPHN, or type of treatment received, between infants who survived and died. However, infants who died had significantly lower mean Apgar scores at five minutes of life (p-value is 0.02), and higher mean oxygenation indexes (OI) (p-value is 0.01) than those of survivors. Two (18.2 percent) of the 11 survivors developed chronic lung disease. CONCLUSION: Low Apgar scores and high OI were associated with poor outcome in infants with CDH.

[Effect of tetrandrine on lung development: experiment of nitrofen-induced congenital diaphragmatic hernia fetal rat model].

OBJECTIVE: To assess the efficacy of prenatal administration of tetrandrine (TET) on pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia (CDH) fetal rat model. METHODS: Six timed-pregnant female Sprague-Dawley rats were randomly divided into 3 equal groups: CDH group (receiving gavage of nitrofen 125 mg dissolved in seed fat on day 9.5), and TET group (receiving gavage of nitrofen 125 mg on day 9.5 and then gavage of TET 30 mg/kg on days 11.5 - 14.5), and control group (given the same dose of peanut oil on day 9.5 and the same dose of normal saline on days 11.5 - 14.5). The fetuses were delivered by cesarean section on day 21 to undergo light microscopy and electron microscopy. The numbers of type II pneumocytes were recorded and compared. RESULTS: CDH were detected in 32 of the 41 fetuses from the CDH and TET groups with a teratogenic rate of 78%, however, without a significant difference between the CDH and TET groups (P = 0.645). Microscopy showed significant lung hypoplasia in both histologic structure and cellular structure in the CDH group; however the lung development of the TET group was improved in comparison to the CDH group. There was no significant difference in numbers of type II pneumocytes among the 3 groups (P = 0.779). CONCLUSION: Prenatal administration of TET can improve the lung development of CDH rats in both histological structure and cellular structure. This may provide a new idea for the clinical treatment of CDH.