Persistent Pulmonary Hypertension Of Newborn Research Articles

Effectiveness of Bosentan VS Sildenafil for the Treatment of Persistent Pulmonary Hypertension of the Newborn

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious disease among newborns. Pulmonary vasodilators such as Sildenafil, Bosentan and Milrinone are important treatment modalities to treat persistent pulmonary hypertension of the newborn, especially in resource limited centers where inhaled nitric oxide is not available. Objective: To assess and compare the effectiveness of Bosentan and Sildenafil in persistent pulmonary hypertension of the newborn. Method: This randomized controlled trial was done in the NICU, ICMH, Matuail, Dhaka during July 2017 to July 2019. Following echocardiographic diagnosis, a total of 76 patients were randomly assigned into group A and group B (by lottery). Bosentan was given to group A (1mg/kg/body wt) 12 hourly for 7 days and Sildenafil was given to group B (2mg/kg/body wt.) 8 hourly for 7 days via oro-gastric tube/orally. Then heart rate, respiratory rate, cyanotic changes, SPO2 was recorded every day for 7 days and finally on the 8th day echocardiographic findings were obtained. Effects of two groups were compared. Results: The age of presentation of persistent pulmonary hypertension of newborn was < 24 hours and male newborns were predominant in both groups. Almost 100 % newborns had cyanosis, tachypnea and SPO2 <80% on admission. After intervention for 7 days in both groups no newborn had cyanosis or tachypnea. The mean pulmonary artery systolic pressure (PASP) on echocardiography before and after intervention was found (53.16 ± 9.263 and 35.55 ± 6.41) mm of Hg in group A. The mean PASP on echocardiography before and after intervention was found (53.24 ±11.012 and 35.45 ± 7.43) mm of Hg respectively in group B. In both groups the mean PASP was decreased significantly after intervention. But while comparing the PASP between two groups, there was no significant (p>0.05) difference. The mean length of stay in hospital was 13.05 ± 2.96 days for group A and 13.34 ± 2.86 days for group B. The mean length of ......

Nebulized Magnesium Sulfate for Treatment of Persistent Pulmonary Hypertension of Newborn: A Pilot Randomized Controlled Trial.

ObjectivesTo investigate the effectiveness of nebulized magnesium sulfate in treating persistent pulmonary hypertension of newborn (PPHN).MethodsTwenty-eight mechanically ventilated term neonates with severe PPHN were randomized into two groups: NebMag group (n = 14), who receiving nebulized isotonic magnesium (1024 mg/h), and IVMag group (n = 14), who received intravenous magnesium (200 mg/kg over 30 min, followed by 50 mg/kg/h). The study time frame was 24 h. Outcome measures were the changes in oxygenation index (OI), mean arterial blood pressure (MABP), vasoactive inotropic score (VIS), and serum magnesium level.ResultsBaseline demographic, ventilatory, and hemodynamic characteristics were comparable between the two groups. At the end of the study, the OI decreased by 44.3% in the NebMag group compared with 35.3% in the IVMag group (mean difference −3.14; 95%CI −5.08, −1.19; p 0.003). The NebMag group had a higher MABP (mean difference 2.29 mmHg; 95% CI 1.80, 2.77; p 0.000) and lower VIS (mean difference −14.64; 95% CI −16.52, −12.77; p 0.000) at the 24-h study time point. The increase in serum magnesium level, measured at 12-h study time point, was lower in the NebMag group (mean difference −2.26 mmol/L; 95% CI −2.58, −1.96; p 0.000).ConclusionNebulized magnesium sulfate may be an effective therapeutic modality for neonates with severe PPHN on mechanical ventilation, but this should be confirmed by larger studies.Retrospectively registered at www.clinicaltrials.gov (identifier: NCT04328636).

A retrospective study of predisposing factors and outcome of persistant pulmonary hypertension among newborns at rural tertiary care centre

Background: Persistent pulmonary hypertension in newborns (PPHN) remains a significant cause of perinatal morbidity and mortality. Early recognition of factors that increase the risk of PPHN is of great importance in either to prevent or to treat PPHN optimally. Aim was to study the neonatal predisposing factors, profile and outcome of PPHN.Methods: This retrospective study was conducted in level III neonatal care unit, a rural referral centre of North Karnataka, India from January 2018 to April 2020.Results: During the study period a total of 50 infants with PPHN were identified with the incidence of 5.43/1000 live births. Mean gestation age (±SD) was 38.28±2.49 weeks and mean birth weight (±SD) was 2624±512 gm. The most noted risk factors were meconium aspiration syndrome (42%), birth asphyxia (16%), RDS (10%), positive pressure ventilation at birth (52%) and male gender (62%). Out of 50 infants with PPHN, high mortality was seen in low birth weight babies (66.6%). Use of sildenafil showed increased mortality (56.2%) whereas use of surfactant scored better with decreased mortality of 42.8%.Conclusions: Major risk factors for PPHN are MAS, birth asphyxia, RDS and low birth weight. Poor prognosis is seen in male gender, prematurity and CDH with increased risk of mortality. The use of systemic pulmonary vasodilators can be considered with caution and use of surfactant has a role in management of PPHN.

A Presentation of Persistent Pulmonary Hypertension of a Newborn Mimicking Coarctation of Aorta

A male newborn was born to a 18y/o mother at gestational age of 38weeks, birth weight 3295gm via emergent Cesarean section with the indication of fetal distress. The mother was diagnosed with type II DM and pregnancy-induced hypertension. Aspirin was given by a family doctor for prevention of preeclampsia during gestational age of 29 to 36 weeks. After birth, the baby presented persistent desaturation (SpO2 77-85%) and severe respiratory acidosis despite of resuscitation. CXR revealed cardiomegaly. Echocardiography showed remarkable dilatation of right ventricle and a huge Patent Ductus of Arteriosus (PDA) with almost right-toleft shunt. Persistent Pulmonary Hypertension of Newborn (PPHN) was diagnosed. However, the isthmus of aorta was restricted (the narrowest diameter was 0.220cm) (Figure 1).

Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn.

The aim of this study was to use a comprehensive imaging protocol to identify echocardiographic correlations of right and left ventricular size, function, and hemodynamics in neonates with persistent pulmonary hypertension of newborn and describe their relationship with key clinical variables. Retrospective case-control echocardiography-based study of persistent pulmonary hypertension of newborn. A tertiary neonatal ICU in Canada. Forty-nine neonates (gestational age ≥ 35 wk old) diagnosed with persistent pulmonary hypertension of newborn within first 3 days after birth and 50 age-matched controls. None. The echocardiographic measurements comprised of right ventricular and left ventricular functional markers, including tricuspid annular plane systolic excursion, fractional area change, tissue Doppler imaging, and deformation imaging. Sample size was based on detecting an intergroup difference of 10% in tricuspid annular plane systolic excursion, which was considered the primary outcome. Linear correlations between the right and left ventricular indices, as well as their association with the outcome of death or extracorporeal membrane oxygenation were evaluated. Persistent pulmonary hypertension of newborn was associated with lower tricuspid annular plane systolic excursion (6.81 ± 1.92 vs 9.25 ± 1.30 mm), right-ventricular global longitudinal strain (16.9% ± 5.4% vs -21.6% ± 4.6%); left ventricular ejection fraction (49% ± 7% vs 55% ± 6%), left ventricular global longitudinal strain (-16.7% ± 3.3% vs -21.4% ± 2.0%) (all p < 0.01). Right and left ventricular diastolic and global function was also lower in persistent pulmonary hypertension of newborn, with more pronounced changes seen for the right ventricle. Moderate-to-strong linear correlations were observed between the right and left ventricular functional markers, with right ventricular global longitudinal strain and left ventricular global longitudinal strain being the strongest (r = 0.8). Within persistent pulmonary hypertension of newborn group, hypoxic ischemic encephalopathy was associated with lower right and left ventricular systolic and right ventricular diastolic performance. Tricuspid annular plane systolic excursion (p =0.08) and left ventricular systolic velocity (p = 0.09) tended to be lower in patients who subsequently died/needed extracorporeal membrane oxygenation. Persistent pulmonary hypertension of newborn is characterized by global cardiac dysfunction, involving both the right and left ventricles, with significant interventricular functional correlation. Cardiac dysfunction early in disease course may identify patients at highest risk of adverse outcome.

Role of Sildenafil in the Treatment of Persistent Pulmonary Hypertension of Newborn (PPHN) - Should it Be Withdrawn from Market of Bangladesh due to Threat of being Misuses

Background: Recently it has been apprehended that sildenafil, a drug which has been successfully using in the treatment of PPHN and erectile dysfunction in adult, is going to be withdrawn from the market of Bangladesh due to threat of its misuses.&#x0D; Objective: The aim of this study was to see the extent of uses of sildenafil in the treatment of PPHN and importance of availability of this drugs in the market inspite of its probable misuses. Methods: This cross sectional study was conducted in neonatal intensive care unit (NICU), special baby care unit (SCABU) and cardiac intensive care unit (CICU) of Dhaka Shishu (Children) Hospital from June, 2017 to May 2018. Neonates with PPHN were enrolled in the study. All cases were treated with oral sildenefil for PPHN along with others management according to hospital protocol. Data along with other parameters were collected and analyzed.&#x0D; Results: Total 320 patients with suspected PPHN were admitted during the study period. Among them 92 (29%) cases had PPHN. Male were 49(53 %) cases and female were 43(47%) cases. Mean age at hospital admission was 29.7±13.4 hours. Based on echocardiography,13(14%) cases had mild, 38 (41%) cases moderate and 41(45%) cases severe PPHN. Mean duration of sildenafil therapy was 11.9±7.1 days. Improved from PPHN were 83 (90%) cases. Mortality was 10% (9).&#x0D; Conclusion: In this study it was found that the incidence of PPHN is 29% among the suspected newborns. Sildenafil is successfull in improving the oxygenation of PPHN and to decrease the mortality of neonates.&#x0D; DS (Child) H J 2019; 35(2) : 100-104

Persistent Pulmonary Hypertension of Newborn (PPHN)

Abstract not available&#x0D; DS (Child) H J 2019; 35(2) : 90-93

Hex Induced segmental arterial mediolysis superimposed upon idiopathic pulmonary hypertension; Cross-talk of Serotonin with Norepinephrine?

Background: Segmental arterial mediolysis (SAM) is an infrequent arteriopathy initiated by norepinephrine released by the innervating peripheral sympathetic nervous system, that involves the large and medium-sized muscular arteries of the abdomen, retroperitoneum, heart and brain base. It extremely rarely develops in pulmonary arteries. Serotonin (5-HT) is an important vasoconstricting and remodeling agent in the genesis of idiopathic pulmonary hypertension. Methods and findings: Terror stemming from a history of a hex putatively caused a massive release of catecholamines from the adrenal medulla – the norepinephrine representing another stimulus for pulmonary vasoconstriction. Since a presumed low density of alpha-1 adrenoceptor on the medial muscle of pulmonary arteries exists the cross talk of norepinephrine with 5-HT is theorized to have caused the toxic cytoplasmic calcium overload that transformed the norepinephrine induced vasoconstriction to vasospastic SAM. This was identified by the morphologically distinct features of SAM – vacuolization and apoptosis commencing in the outer media, gap formation and granulation tissue developing at the adventitial medial junction alterations superimposed on the morphologic changes of pulmonary hypertension. Cross talk of these two pressor agents also putatively accounted for the genesis of coronary artery SAM in newborn persistent pulmonary hypertension (NPPH) reported in an infant delivered from a pregnancy depressed mother putatively administered a selective serotonin-reuptake inhibitor. Conclusion: Cross talk of norepinephrine with 5-HT accounts for the genesis of SAM in idiopathic pulmonary hypertension and in the coronary arteries in NPPH.

Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension.

Optimal oxygen saturation as measured by pulse oximetry (SpO2) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the SpO2 range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO2) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (FiO2) = 1.0 irrespective of SpO2, and three groups had FiO2 titrated to keep preductal SpO2 between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95-99% SpO2 target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO2 but were exposed to higher FiO2 (0.5 ± 0.21 vs. 0.29 ± 0.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43-0.73] ng/mcg protein vs. 0.1 [IQR, 0.09-0.2] ng/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192-201] mMol nitrite/mg protein vs. 270 [IQR, 227-280] mMol nitrite/mg protein) compared with the 90-94% target group. Brain 3-nitrotyrosine was lower in the 85-89% target group, and brain/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO2 through the first 6 hours are higher with target SpO2 in the 95-99% range. However, the 90-94% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing the 90-94% versus the 95-99% SpO2 target range in term infants with PPHN are warranted.

Use of Magnesium Sulphate in Persistent Pulmonary Hypertension of Newborn

Background: One of the common causes of respiratory distress in neonate is persistent pulmonary hypertension of newborn (PPHN) and has been estimated to occur in 2 per 1000 live born term infants.&#x0D; Objective: To evaluate the effect of injectable Magnesium Sulphate (MgSO4) in the treatment of Persistent Pulmonary Hypertension of Newborn.&#x0D; Methodology: It was a prospective, nonrandomized, clinical study conducted from August 2015 to July 2017 among 25 neonates having moderate to severe PPHN in the Pediatric Cardiac Intensive Care Unit (CICU) of Dhaka Shishu (Children) Hospital. Injectable Magnesium Sulphate was used along with other supportive management. Outcome measures include drop of pulmonary vascular resistance and increase oxygenation. Side effects of Magnesium Sulphate were observed and outcome was recorded. Data were analyzed by using SPSS version 17.&#x0D; Results: There was significant improvement of oxygenation and decrease in pulmonary vascular resistance at 72 hours after use of MgSO4 (p=000). Complications were present in 28% cases which include hypotension in 16% patients, urinary retention in 8% and altered GI function in 8% cases. Mortality was 16% among study population.&#x0D; Conclusion: MgSO4 is effective in improving oxygenation and reduction of pulmonary vascular resistance in PPHN&#x0D; Northern International Medical College Journal Vol.10 (2) Jan 2019: 370-372

A Retrospective study on the profile of persistent pulmonary hypertension of newborn in a tertiary care unit of Eastern India

Context: Persistent pulmonary hypertension of newborn (PPHN) is a common neonatal morbidity. There is a scarcity of data about PPHN from developing countries and the profile of babies with PPHN is different from those reported from developed countries. Aims: The aim is to study the incidence, maternal and infant risk factors, etiologies, treatment modalities, and outcome in babies with PPHN. Setting and Design: This retrospective study was conducted in the Level III neonatal unit of a referral center of Kolkata, India. Methods: This study was conducted by retrospective review of the departmental electronic database and nursing charts of the babies admitted with the diagnosis of PPHN from January 2013 to March 2019. Statistical Analysis: Chi-square test was used for categorical variable and Student's t-test was used for continuous variables to determine statistical significance. P

Status of pulmonary artery pressures on echocardiography among high-risk newborns

Background: There is a paucity of data about the outcome of newborns who have one or more risk factors for persistent pulmonary hypertension of newborn (PPHN) and have some degrees of pulmonary hypertension not significant enough to cause hypoxemia and desaturation to be labeled as PPHN. Objective: Status of pulmonary artery pressures in high risk newborns. Materials and Methods: This was a prospective observational study, in which newborns up to 1 month of age having risk factors for PPHN were included and pulmonary hypertension was identified on echocardiography in neonates more than 48 h of life. Second screening was done at 6 weeks of life independent of subjects having PAH or not at the first screening. Results: Out of 400 cases, 26 patients were lost to follow-up, 2 cases left against medical advice, and 18 patients expired after first screening. Finally, a total of 354 cases came for follow-up at 6 weeks and repeat echocardiography was done in all cases. PAH was found in 54 cases on first screening, 12 neonates had reversal of shunt at the level of patent ductus arteriosus or patent foramen ovale, and only 2 cases had persistence PAH on second screening at 6 weeks. Perinatal asphyxia (43.9%), respiratory distress (31%), and meconium-stained amniotic fluid (30%) have shown a significant association with the development of PAH in these neonates. Development of PAH worsens the prognosis in newborns with asphyxia and sepsis. Conclusion: Newborns with risk factors have some degree of PAH, which can have an adverse impact on outcome.

Use of sildenafil in an infant with persistent pulmonary hypertension secondary to lung and renal hypoplasia \u2013 a case report

BackgroundPremature preterm rupture of membranes (PPROM) is reported to be associated with high rates of neonatal mortality and morbidity. Sildenafil has been used in infants with persistent pulmonary hypertension of newborn (PPHN) due to congenital diaphragmatic hernia (CDH) and bronchopulmonary dysplasia (BPD). Recently, Sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. This case report illustrates the use of early sildenafil for PPHN and right ventricular dysfunction in an unusual setting of lung and renal hypoplasia.Case presentationA male infant was born at 37 weeks with a birth weight of 2840 g. Rupture of membranes developed at approximately 24 weeks of gestational age (GA). Bilateral small kidneys (< 2 standard deviations below average) were detected on ultrasound (US) examination at 30 weeks of gestation. The baby developed pneumothorax and pulmonary hypertensive crisis towards the end of the first day. An echocardiogram showed a dilated right ventricle, moderate right ventricular systolic dysfunction, hypoplastic pulmonary arteries and a large patent ductus arteriosus with bidirectional flow. The patient was sedated, paralyzed, and inhaled nitric oxide was administered to decrease the pulmonary resistance. In anticipation of persistent pulmonary hypertension due to the hypoplastic lungs and small calibre of pulmonary arteries, sildenafil was started on day of life (DOL) 5 at a dosage of 0.25 mg/kg/dose Q8H and gradually increased to 2 mg/kg/dose Q8H on DOL 9. The patient was finally extubated on DOL 7 and weaned off of non-invasive respiratory support on DOL 26. Sildenafil was gradually weaned beginning on DOL 21 and discontinued on DOL 48. Repeat echocardiogram assessment at 3 months showed complete resolution of PHT and right ventricular dilatation.ConclusionsWe describe the early use of sildenafil in treating pulmonary hypertension associated with lung and renal hypoplasia in a non-CDH patient. Following this treatment the patient made a full recovery from right ventricular dysfunction.

Reversed Differential Cyanosis in Two Neonates with Obstructed Supracardiac Total Anomalous Pulmonary Venous Drainage

Generalized cyanosis in newborn can be caused by many pathological conditions and cyanotic congenital heart disease represents one of the important causes. Differential cyanosis refers to the situation where upper limb saturation is higher than lower limb and it is well documented to be caused by persistent pulmonary hypertension in newborn

Effect of Chorioamnionitis on Neonatal Outcome: A Hospital-Based Study

Objective: The aim of this study was to determine the impact of chorioamnionitis on neonatal outcome.&#x0D; Methods: This cross-section descriptive study was conducted in the neonatal intensive care unit (NICU) of the Department of Pediatrics, Liaquat National Hospital Karachi from June 1st, 2016 to December 31st, 2016. Neonates (infants &lt; 28 days of age) with maternal risk factors indicative of chorioamnionitis (maternal febrile illness in last trimester, high WBC count in maternal blood, lower abdominal pain or tenderness, and foul-smelling discharge) were included in the study. The neonates with an inborn error of metabolism and congenital anomalies were excluded from this study. The neonates were further categorized by gestational age as a term (gestational age &gt;37 weeks) and preterm (gestational age &lt;37 weeks). The neonatal outcome is classified into binary categories; dead or alive. Data were recorded by the data collectors in the predesigned proforma. The data were entered and analyzed using SPSS version 22.&#x0D; Results: During the study period, 1200 women delivered a singleton baby, out of which 400 were admitted at NICU. Of 400 infants, a total of 68 neonates of mothers with the indication of chorioamnionitis were enrolled in the study. The mean age of enrolled neonates was 2.55 ± 1.22 days. Out of 68 neonate babies, 33 (48.5%) were males and 35 (51.5%) were females. Only 43 (63%) were delivered, pre-term babies. The morbidities identified were respiratory distress syndrome (33.8%), sepsis (27.9%), intraventricular hemorrhage (10.3%), persistent pulmonary hypertension of newborns (11.8%) and necrotizing enterocolitis (7.4%). A total of 16 (23.5%) neonates died. Out of 16 newborns who died, 32.6% were preterm and 8% were born at term. It was noted that weight, body mass index, fronto-occipital circumference, and gestational age were significant contributors to the mortality.&#x0D; Conclusion: In conclusion, chorioamnionitis is an important contributor to neonatal mortality and morbidity. The neonates of a mother with indications of chorioamnionitis are at an increased risk of respiratory distress syndrome.

P2579Experience of application in Russia pulsoxymetry as screening for detecting critical states in the newborns: critical congenital heart defects and pulmonary hypertension

Abstract Despite the improvement in the last decades of prenatal ultrasound diagnosis and clinical examination of newborns, even in countries with developed health care, up to 28% of newborns with critical congenital heart defects (CHD) are discharged from the hospital without a diagnosis. Early detection of persistent pulmonary hypertension in newborns (PPHN) is often associated with certain difficulties, which leads to a delayed diagnosis of this syndrome and a later start of therapy. Objective To improve the methods of diagnosing the early detection of newborns with hypoxemia due to critical CHD or persistent pulmonary hypertension of the newborn, as well as to achieve a reduction in infant mortality. Materials and methods During the study period – from April 2017 to February 2018 using the developed algorithm for performing screening of critical conditions in newborns using pulse oximetry, 8,358 newborns were examined on the basis of maternity hospitals of the Republic of Tatarstan, which accounted for 88.4% of 9459 births registered. A modified two-band pulse oximetry technique was used, followed by echocardiography of the newborn with a positive screening result. Results The introduction of pulse oximetry screening in the early neonatal period (3rd hour of life) allowed the timely detection of 95 children with a positive test result, whose conditions caused the greatest risk to the health of newborns, which accounted for 1.14% of all children studied. Thanks to the screening, in 13 newborns in the first hours of life, congenital heart defects that were not diagnosed in utero were detected, 5 of them were critical. Persistent pulmonary hypertension was detected in 20 patients. Intrauterine pneumonia was diagnosed in 30 newborns. Among the critical CHDs, the following diagnoses were established: transposition of the great vessels – 2 children, aortic coarctation – 1 child, total abnormal pulmonary vein drainage – 1 child, Taussin-Bing anomaly – 1 child. Evaluation of the effectiveness of the screening showed that a positive result had a decisive role in the timely diagnosis of critical CHD and persistent pulmonary hypertension of the newborn. Conclusions Pulse oximetry helps to identify both systemic hypoxemia and postductal desaturation, which is characteristic of both critical CHD and PPHN, and can be used to screen newborns for these conditions. Pulse oximetry is an easily accessible, non-invasive, painless method that can be included in a regular examination of the newborn. The advantages of pulse oximetry also include simplicity and short procedure time.

Effect of inhaled nitric oxide with mechanical ventilation in persistent pulmonary hypertension of newborn

Objective To study the clinical effect of inhaled nitric oxide(iNO) with mechanical ventilation for the neonates with persistent pulmonary hypertension of newborn(PPHN). Methods A total of 40 neonates with PPHN poorly responding with routine treatment were treated with iNO therapy.Pulmonary artery pressure, blood gas ion analysis and respiratory function changes were observed at different time points before and after iNO. Results Treatment with iNO resulted in a rapid decrease in pulmonary artery pressure from(54.95±17.08) mmHg(1 mmHg=0.133 kPa) to(20.40±14.26) mmHg.Oxygenation of 40 cases improved in the first 0.5~1 hour after iNO therapy, the values of mean airway pressure(MAP)declined from(13.98±2.40)cmH2O(1 cmH2O=0.098 kPa) to(12.44±2.69)cmH2O, oxygenation index(OI)decreased from 26.89±18.62 to 13.84±5.52, PaO2/FiO2 increased from(60.34±23.49) mmHg to(144.46±23.49) mmHg, and the value of pH increased from 7.31±0.14 to 7.37±0.07.Furthermore, within 48 hours after treatment, PaO2/FiO2 and pH increased gradually, while MAP and OI decreased gradually, which all had statistical differences(P<0.01). Conclusion Mechanical ventilation combined with iNO therapy in the treatment of PPHN can rapidly improve the oxygenation status of neonates, reduce pulmonary vascular resistance, and then improve the survival rate and long-term prognosis. Key words: Mechanical ventilation; Inhaled nitric oxide; Persistent pulmonary hypertension of newborn

Role of oral sildenafil in neonates with persistent pulmonary hypertension of newborn

Persistent pulmonary hypertension of newborn is a devastating condition and leads to morbidity and mortality. Even after the increasing use of NO, ECMO and HFO many patients succumb to death. About 50% of the patients either have rebound hypertension or do not respond to the treatment. Hence the role of phosphodiesterase inhibitors (sildenafil) need to be evaluated. Methods is authors report a retrospective case series of 24 patients with PPHN admitted in NICU and treated with oral sildenafil. Results sildenafil was started on all patients on a mean of 1.46 days and stopped on mean of 3.8 days. Initial fio2 was 100%, which after starting sildenafil decreased gradually to 50% on mean of 10 days. Average length of stay in NICU was 20 days. 17(70.8%) patients survived whereas 7 (29%) expired No improvement in oxygen Index after 48 hours (p&lt;0.05) was the independent predicting risk factor for PPHN related mortality in the expired patients.Conclusion are oral sildenafil can be a used in conjunction with other treatment modalities for PPHN especially in resource limited settings.

Cost-benefit analysis of VKA versus NOAC treatment in German patients with atrial fibrillation utilizing patient self-testing.

BackgroundClinical complications of long-term anticoagulation in patients with atrial fibrillation cause significant morbidity and have a substantial economic impact on the healthcare system.ObjectiveTo assess the cost-benefit by implementing patient self-testing (PST) in German patients anticoagulated with vitamin K antagonists (VKA) compared to treatment with the new oral anticoagulant drugs (NOAC) apixaban, dabigatran, edoxaban, and rivaroxaban.MethodsA deterministic decision-analytic model was developed simulating the number of major bleedings, ischemic strokes, and hemorrhagic strokes and their associated costs by utilizing PST compared to those of treatment with NOAC. Data on the rates of these adverse events in both groups during the 1st year of treatment was taken from the NOAC approval studies. Direct costs were evaluated from the perspective of the Statutory Health Insurance (SHI) considering the use of resources directly related to PST testing and costs incurred by hospital treatment of the adverse events. Univariate sensitivity analysis was performed to examine the extent to which our calculations were affected by varying the parameters considered in our model within plausible extremes. To capture the interactions between multiple inputs, we also provided a probabilistic sensitivity analysis (PSA).ResultsWhen achieving an average time in therapeutic range (TTR) of 78%, implementing PST in VKA patients reduces cost per patient compared to NOAC treatment between €603.38 [USD 681.52] (edoxaban) and €762.64 [USD 861.40] (rivaroxaban) during the 1-year observation period. In line with the TTR increase, the initially higher number of adverse events per VKA patient compared to NOACtreated patients in the approval studies becomes largely aligned; the difference in associated hospital costs per patient in the NOAC groups is then only €1.03 [USD 1.16] (in favor of dabigatran), €23.41 [USD 26.44] (in favor of apixaban), €0.53 [USD 0.60] (in favor of edoxaban) and €52.62 [USD 59.43] (in favor of VKA anticoagulation in the rivaroxaban group).In PSA, implementation of self-management results on average in a cost saving between €619.20 [USD 699.39] and €785.24 [USD 886.93] per VKA patient in favor of the SHI. Under all reasonable assumptions, PST remains constantly less expensive irrespective of which NOAC is administered.ConclusionImplementing PST in German VKA patients may significantly reduce SHI expenditures compared to utilizing NOAC.

Identification of genetic factors underlying persistent pulmonary hypertension of newborns in a cohort of Chinese neonates

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is a severe clinical problem among neonatal intensive care unit (NICU) patients. The genetic pathogenesis of PPHN is unclear. Only a few genetic polymorphisms have been identified in infants with PPHN. Our study aimed to investigate the potential genetic etiology of PPHN.MethodsThis study recruited PPHN patients admitted to the NICU of the Children’s Hospital of Fudan University from Jan 2016 to Dec 2017. Exome sequencing was performed for all patients. Variants in reported PPHN/pulmonary arterial hypertension (PAH)-related genes were assessed. Single nucleotide polymorphism (SNP) association and gene-level analyses were carried out in 74 PPHN cases and 115 non-PPHN controls with matched baseline characteristics.ResultsAmong the patient cohort, 74 (64.3%) patients were late preterm and term infants (≥ 34 weeks gestation) and 41 (35.7%) were preterm infants (< 34 weeks gestation). Preterm infants with PPHN exhibited low birth weight and a high frequency of bronchopulmonary dysplasia, respiratory distress syndrome (RDS) and mortality. Nine patients (only one preterm infant) were identified as harboring genetic variants, including three with pathogenic/likely pathogenic variants in TBX4 and BMPR2 and six with variants of unknown significance in BMPR2, SMAD9, TGFB1, KCNA5 and TRPC6. Three SNPs (rs192759073, rs1047883 and rs2229589) in CPS1 and one SNP (rs1044008) in NOTCH3 were significantly associated with PPHN (p < 0.05). CPS1 and SMAD9 were identified as risk genes for PPHN (p < 0.05).ConclusionsIn this study, we identified genetic variants in PPHN patients, and we reported CPS1, NOTCH3 and SMAD9 as risk genes for late preterm and term PPHN in a single-center Chinese cohort. Our findings provide additional genetic evidence of the pathogenesis of PPHN and new insight into potential strategies for disease treatment.