Outcome of Obstructed Total Anamalous Pulmonary Venous Connection (TAPVC) Repair Patients with Milrinone Versus Milrinone and Inhaled Nitric Oxide (INO): A Prospective Randomized Observational Study

Background: Obstructed total anomalous pulmonary venous connection (TAPVC) typically present with severe cardiovascular decompensation and requires urgent surgical management. Pulmonary arterial hypertension (PAH) is a major risk factor affecting mortality. Perioperative management focuses on providing inotropic support and managing potential pulmonary hypertensive episodes. Milrinone and inhaled nitric oxide (iNO) efficiently reduce pulmonary artery pressure (PAP) and help to improve the outcome. The aim was to determine the outcome of patients with high PAP with milrinone alone and a combination of iNO and milrinone. Material and Method: After ethical committee approval, the study was conducted over a period of 3 years in 80 patients with obstructed TAPVC repair. A total of 80 patients having severe PAH (supra systemic arterial pressure) randomly divided into two groups with 40 patients in each (M & MN). Group M (milrinone) patients received milrinone and Group MN (milrinone & iNO) patients received both milrinone (after opening aortic cross clamp) and iNO (post operative ICU). Ventilation time, hospital stay, ICU stay, complications, in hospital mortality were compared between both groups. Result: Ventilation time, Intensive Care Unit (ICU) stay, hospital stay for group M was 8.02 � 5.74 days, 11.25 � 7.33 day, 14.92 � 8.55 days, respectively, and for group MN was 5.02 � 1.78 days, 8.27 � 3.24 days, 10.3 � 3.18 days, respectively. In hospital mortality for group M and MN was 10% and 2.5%, respectively. P value for each variable was significant < 0.05 (except mortality). Conclusion: Most of the patients with obstructed TAPVC had severe PAH. Management of severe PAH with a combination of milrinone with iNO had a better outcome than milrinone alone.

The early use of iNO in extremely premature neonates with refractory hypoxic respiratory failure / 中国新生儿科杂志

Objective:To study the early use of inhaled nitric oxide (iNO) as a rescue therapy in extremely premature infants (EPIs) with refractory hypoxic respiratory failure (HRF).Methods:Between January 2021 and December 2021, EPIs with refractory HRF receiving iNO within the first week of life in our NICU were enrolled. Their clinical characteristics and outcomes were retrospectively analyzed.Results:A total of 11 EPIs were included with 5 males and 6 females. The median gestational age (GA) was 24(22.6, 25.2) weeks. The median birth weight (BW) was 580(490, 770) g. The most common primary diagnoses were moderate/severe respiratory distress syndrome (RDS) (5/11) and early-onset sepsis (3/11). The median age starting iNO therapy was 6.5(4.5, 34.0)h and the median duration of iNO was 24(12, 36)h. The median iNO starting dose was 5(5, 8) ppm and the therapeutic range was 5-20 ppm. Therapeutic efficacy was defined as ≥30% FiO 2 reduction after 6 h of iNO treatment. The treatment was effective in 8 cases. The oxygenation index (OI) decreased more than 10% from baseline 1 h after initiation in 9 patients and in all 11 patients after 12 h of iNO. The reduction of OI was more prominent in EPIs with a higher OI at baseline. Of the 11 patients, 8 survived, 1 died and 2 abandoned further treatments. Conclusions:As an early rescue therapy for EPIs with refractory HRF, iNO can improve oxygenation without obvious short-term adverse effects.

Revisión Sistemática Exploratoria sobre Uso de Óxido Nítrico Inhalado para Evaluación de Reactividad Vascular Pulmonar en Laboratorio de Hemodinamia en Sujetos Pediátricos con Hipertensión Pulmonar / Exploratory Systematic Review on the Use of Inhaled Nitric Oxide for Evaluation of Pulmonary Vascular Reactivity in Hemodynamics Laboratory in Pediatric Subjects with Pulmonary Hypertension

Introducción. La hipertensión arterial pulmonar (HAP) es una enfermedad que presenta un elevado índice de mortalidad en la población pediátrica. Para su diagnóstico, el gold standard es la prueba de reactividad vascular pulmonar (PRVP), debido a que permite medir la respuesta vasodilatadora del lecho vascular pulmonar frente a la administración de moléculas con acción terapéutica, como el óxido nítrico inhalado (iNO). Esta prueba al ser positiva se asocia a un mejor pronóstico. En la actualidad existe incertidumbre y falta de consenso sobre la indicación y administración de iNO durante la PRVP. Objetivo. Describir el uso reportado en la literatura sobre iNO en PRVP en sujetos pediátricos con HAP. Métodos. Revisión sistemática exploratoria sensible en bases de datos PubMed, Epistemonikos, Cochrane, Scopus, Lilacs y Scielo, que describen el uso de iNO durante la PRVP en sujetos pediátricos con HAP. Resultados. se identificaron 8.906 artículos, de los cuales se seleccionaron 5 para la revisión cualitativa. La PRVP se realizó durante el cateterismo cardiaco derecho (CCD) en sujetosentre 2 semanas y 18 años de edad. Los diagnósticos fueron HAP primaria, idiopática y asociada a patología cardiaca congénita, cardiomiopatía y enfermedad pulmonar. Esta prueba fue realizada en sujetos sólo con soporte de oxígeno o con sedación profunda en ventilación mecánica invasiva, con dosis variables de oxígeno (21 y 100%) e iNO (3 y 80 ppm), o asociado a otras moléculas como iloprostol®, dilitiazem, sildenafil y/o epoprostenol. La administración de iNO disminuyó presión de arteria pulmonar y la resistencia vascular pulmonar, con mantención de presión arterial sistémica y gasto cardiaco y sin complicaciones asociadas a su uso. Conclusiones. Existen escasos estudios sobre iNO en PRVP pediátrica y con calidad metodológica limitada. El iNO se utiliza como método diagnóstico de vaso reactividad en sujetos pediátricos con HAP asociada a cardiopatía congénita, primaria o secundaria. Los protocolos para su uso son variables con dosis entre 20 y 40 ppm, con o sin uso de oxigeno adicional, con tiempos poco precisos y sin consenso en equipos de administración.

Background. Pulmonary arterial hypertension (PAH) is a disease that has a high mortality rate among the pediatric population. For its diagnosis, the pulmonary vascular reactivity test (PVRT) is considered the "Gold Standard", because it allows to measure the vasodilator response of pulmonary vascular circulation with the administration of molecules with therapeutic action, such as inhaled nitric oxide (iNO). This test, when positive, is associated with a better prognosis of the disease. Currently, there's uncertainty and lack of consensus on the indication and administration of iNO during the PVRT. Objetives. to describe use of iNO in PVRT in pediatric users with PAH reported in the literature. Methods. Scoping review of studies published between 1992 and 2021 in PubMed, Epistemonikos, Cochrane, Scopus, Lilacs and Scielo databases, which describe the use of iNO during PVRT in pediatric users with PAH, in English and Spanish. Primary and secondary studies with a sensitive search strategy were considered. Results. 8,906 articles were identified, 40 were selected by title, 8 by full text, and 5 for final qualitative review. Of the total of articles selected, 3 were primary and 2 secondary studies. PVRT was performed during right heart catheterization (RHC) in a population between 2 weeks and 18 years old. Diagnoses were primary PAH, idiopathic PAH and PAH associated with congenital heart disease, cardiomyopathy and pulmonary disease. This test was carried out in subjects on spontaneous ventilation with oxygen support or with deep sedation in invasive mechanical ventilation, with variable oxygen doses between 21 and 100%, with exclusive use of iNO between 3 and 80 ppm, being more used between 20 and 40 ppm, or associated with other molecules such as iloprostol®, dilithiazim, sildenafil and / or epoprostenol. In all selected studies, administration of iNO decreased PAP (pulmonary artery pressure) and PVR (pulmonary vascular resistance), with maintenance of SBP (systemic arterial blood pressure) and cardiac output. The primary studies were made up of pre and post-test of serial or parallel interventions. The selected studies of iNO in PVRT did not report complications associated with its use. Conclusions. studies on iNO in pediatric PVRT are scarce in number of publications and methodological quality. iNO is used as a diagnostic method of vasoreactivity in pediatric users with PAH associated with congenital, primary, or secondary heart disease. The protocols for its use are variable with recommended doses between 20 and 40 ppm, with or without the use of additional O2, with imprecise times and without consensus in administration equipment. The response to PVRT serves as a guide for the treatment and prognosis of pediatric users with PAH.

Efecto del óxido nítrico inhalado en la mecánica ventilatoria y oxigenación de pacientes con hipoxemia grave refractaria a prono prolongado y bloqueo neuromuscular secundario a infección por SARS-CoV-2 / Effect of inhaled nitric oxide on ventilatory mechanics and oxygenation of patients with severe hypoxemia refractory to prolonged prone and neuromuscular blockade secondary to SARS-CoV-2 / Efeito do óxido nítrico inalado na mecânica ventilatória e oxigenação de pacientes com hipoxemia grave refratária a pronação prolongada e bloqueio neuromuscular secundário à infecção por SARS-CoV-2

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Abstract: Introduction: Among the patients infected with SARS-CoV-2, 14.6% were admitted to intensive care unit. this 29 to 75% required invasive mechanical ventilation with an associated mortality of 12 to 81%. Acute respiratory distress syndrome (ARDS) is the most serious form of presentation. The pathophysiology of ARDS secondary to SARS-CoV-2 differs from conventional causes. It presents dysregulation in hypoxic pulmonary vasoconstriction, secondary acute pulmonary hypertension and microthrombotic phenomena. The development of refractory severe hypoxemia (PaO2 < 60 mmHg or PaO2/FiO2 < 100 mmHg, with FiO2 80 to 100%, with PEEP > 10 to 20 cmH2O for at least 10 to 12 hours) constitutes the scenario of maximum severity with an associated mortality of 71 to 94%. The use of rescue strategies that impact on the specific pathophysiology of this entity such as the use of inhaled nitric oxide, neuromuscular blockade and prone ventilation have emerged as therapeutic targets of interest. Protective mechanical ventilation (plateau pressure [Pplat] < 27 cmH2O and driving pressure [DP] < 15 cmH2O) continues to be the cornerstone of the management. Objectives: To determine whether there is an association between the use of inhaled nitric oxide and prone ventilation with ventilatory mechanics in patients with severe refractory hypoxemia secondary to SARS-CoV-2 infection. Material and methods: A historical, retrospective, descriptive, comparative and retrolective cohort study was carried out. Data from the records of patients admitted to the Respiratory ICU of the ABC Medical Center with a diagnosis of ARDS secondary to SARS-CoV-2 infection who required iNO and mechanical ventilation in prone from April 1 to December 31, 2020 were analyzed. A univariate analysis was performed, the statistical analysis was performed in SPSS v 21, measures of trend, dispersion were analyzed as well as the analysis of risk factors with Student's t test and χ2. Results: A total of 108 patients were analyzed, of which 54 received iNO, neuromuscular blockade and prone and 54 only neuromuscular blockade and prone ventilation. 81.5% (n = 88) were men. The most common comorbidity was diabetes mellitus in 51.9% (n = 56). The increase in oxygenation (delta PaO2/FiO2) was with a median of 31.9 ± 15.2 mmHg in the iNO group and 52.9 ± 16.74 mmHg in the control group (p = 0.001). The postintervention Pplat in the iNO group was 26.3 ± 3 and 34.5 ± 1.9 cmH2O in the control group (p = 0.792). The preintervention DP in the iNO group was 17.2 ± 3.9 and 13.4 ± 2.8 cmH2O in control group vs 13.1 ± 1.29 and 12 ± 1.92 cmH2O after the intervention (p = 0.001). Conclusions: The use of iNO in patients with severe hypoxemia refractory to prone ventilation and neuromuscular blockade did not produce a statistically significant improvement in oxygenation, however it allowed to reprogram the ventilatory support to keep the patient in goals of alveolar protection.

Resumo: Introdução: 14.6% dos pacientes infectados com SARS-CoV-2 são internados em terapia intensiva. Destes, 29 a 75% necessitam de ventilação mecânica invasiva com mortalidade associada de 12 a 81%. A síndrome do desconforto respiratório agudo (SDRA) é a forma mais grave de apresentação. A fisiopatologia da SDRA secundária ao SARS-CoV-2 difere das causas convencionais. Apresenta desregulação na vasoconstrição pulmonar hipóxica, hipertensão pulmonar aguda secundária e fenômenos microtrombóticos. O desenvolvimento de hipoxemia grave refratária (PaO2 < 60 mmHg ou PaO2/FiO2 < 100 mmHg, com FiO2 de 80 a 100%, PEEP > 10 a 20 cmH2O por pelo menos 10 a 12 horas) constitui o cenário mais grave com mortalidade associada de 71 a 94%. O uso de estratégias de resgate que impactam na fisiopatologia específica dessa entidade, como o uso de óxido nítrico inalatório (NOi), bloqueio neuromuscular e ventilação prona, surgiram como alvos terapêuticos de interesse. A ventilação mecânica protetora (Pressão de Platô [PPLAT] < 27 cmH2O e Pressão de Condução [CP] < 15 cmH2O) continua sendo a base de seu manejo. Objetivo: Determinar se existe associação entre o uso de óxido nítrico inalatório e ventilação prona prolongada com mecânica ventilatória em pacientes com hipoxemia refratária grave secundária à infecção por SARS-CoV-2. Material e métodos: Realizou-se um estudo de coorte histórico, retrospectivo, descritivo, comparativo e retroletivo. Analisaram-se dados dos prontuários de pacientes internados na UTI Respiratória do Centro Médico ABC com diagnóstico de SDRA secundária à infecção por SARS-CoV-2 que necessitaram de óxido nítrico inalatório e ventilação mecânica prona no período de 1o de abril a 31 de dezembro de 2020. Realizou-se uma análise univariada , a análise estatística foi realizada no SPSS v 21, foram analisadas as medidas de tendência e dispersão, assim como a análise dos fatores de risco com teste t de Student e χ2. Resultados: Analisaram-se 108 pacientes, dos quais 54 receberam NOi, bloqueio neuromuscular e prono e 54 apenas bloqueio neuromuscular e ventilação prona. 81.5% (n = 88) eram homens. A comorbidade mais comum foi diabetes mellitus em 51.9% (n = 56). O aumento da oxigenação (Delta PaO2/FiO2) foi com mediana de 31.9 ± 15.2 mmHg no grupo NOi e 52.9 ± 16.74 mmHg no grupo controle (p = 0.001). A PPLAT após a intervenção no grupo NOi foi de 26.3 ± 3 e 34.5 ± 1.9 cmH2O no grupo controle (p = 0.792). A PC antes da intervenção no grupo NOi foi de 17.2 ± 3.9 e 13.4 ± 2.8 cmH2O no grupo controle vs 13.1 ± 1.29 e 12 ± 1.92 cmH2O após a intervenção (p = 0.001). Conclusões: O uso de NOi em pacientes com hipoxemia grave refratária à ventilação em pronação e bloqueio neuromuscular não produziu melhora estatisticamente significativa na oxigenação, porém permitiu que o suporte ventilatório fosse reprogramado para manter as metas de proteção alveolar do paciente.

TRALI as a Cause of Massive Tracheal Secretions during Cardiac Surgery / 日本心臓血管外科学会雑誌

A 46 year-old man underwent double valve replacement for valve insufficiency due to infective endocarditis. Upon withdrawal from extracorporeal circulation and administration of 8 units of fresh frozen plasma, a large amount of yellow serous secretion was aspirated from the trachea, and rapid and exacerbated oxygenation was observed. We determined that the patient was not congested, based on his hemodynamics; instead, he appeared to have acquired transfusion-related acute lung injury (TRALI). The patient was given a steroid infusion. By the time the patient returned to the intensive care unit, his oxygenation capacity improved and the secretions from his trachea decreased. The patient was weaned off the ventilator on the second post-operative day. Inhaled nitric oxide was very effective in improving oxygenation. We conjectured that TRALI should be recognized as a differential diagnosis for poor oxygenation after withdrawal from extracorporeal circulation.

Drug treatment of neonatal persistent pulmonary hypertension / 中国小儿急救医学

Neonatal persistent pulmonary hypertension refers to the continuous increase of pulmonary artery pressure, right heart pressure, right-to-left shunt at foramen ovale and ductus arteriosus level, severe hypoxemia and even respiratory failure after birth.At present, the drug treatments of neonatal persistent pulmonary hypertension include inhaling nitric oxide, sildenafil, milrinone, endothelin receptor antagonists bosentan, prostaglandins and their analogs.This review briefly summarized the progress on the treatment of neonatal persistent pulmonary hypertension.

Inhaled nitric oxide improves postoperative hemodynamics in patients with cyanotic congenital heart disease combined with decreased pulmonary blood flow / 中国胸心血管外科临床杂志

@#Objective    To explore the hemodynamic effects of inhaled nitric oxide (iNO) on postoperative hemodynamic in patients with cyanotic congenital heart disease (CHD) combined with decreased pulmonary blood flow. Methods    From 2014 to 2018, there were 1 764 patients who received corrective repair of cyanotic CHD with decreased pulmonary blood flow in the Department of Pediatric Cardiac Surgery of Fuwai Hospital. We included 61 patients with the ratio of right ventricular systolic pressure to systolic blood pressure (SBP) ≥75% after weaning from cardiopulmonary bypass. There were 41 males and 20 females, with the age of 20.5 (9.0, 39.0) months and weight of 12.5±7.8 kg. The patients were divided into two groups: a conventional group (33 patients, conventional therapy only) and a combined therapy group (28 patients, iNO combined with conventional therapy). The hemodynamics during the first 24 hours after iNO therapy and the in-hospital outcomes of the two groups were investigated and compared. Results    There was no statistical difference between the two groups in demographic characteristics and surgical parameters (P>0.05). The hemodynamic effects of iNO within 24 hours included the decrease in the vasoactive inotropic score (VIS, 21.6±6.6 vs. 17.3±7.2, P=0.020) along with the increase in blood pressure (SBP: 73.7±9.7 mm Hg vs. 90.8±9.1 mm Hg, P<0.001) , the decrease in central venous pressure (10.0±3.1 mm Hg vs. 7.9±2.1 mm Hg, P=0.020), the decrease in lactate (2.2±1.7 mmol/L vs. 1.2± 0.5 mmol/L, P<0.001) and increase in urine output [2.8±1.7 mL/(kg·h) vs. 4.9±2.2 mL/(kg·h), P<0.001]. The decrease of VIS at 24 h after the surgery in the conventional therapy group was not statistically significant (22.1±7.9 vs. 20.0±8.5, P=0.232). Besides, we discovered that the need for renal replacement therapy (RRT) was less in the combined therapy group than that in the conventional therapy group, especially in the moderate complicated surgery [risk adjustment in congenital heart surgery (RACHS-1) ≤3] subgroup (9.5% vs. 40.7%, P=0.016). Conclusion    In pediatric patients after corrective repair of cyanotic and pulmonary blood follow decreased CHD with increased pulmonary vascular resistance, iNO combined with conventional therapy can improve the hemodynamics effectively. Compared with the conventional therapy, the combined therapy with iNO can decrease the VIS and the need for RRT, which is beneficial to the postoperative recovery of patients.

Progress of inhaled nitric oxide on treatment of persistent pulmonary hypertension of new-born / 中国小儿急救医学

Persistent pulmonary hypertension is a serious disease among new-borns.Despite the variety of causes, similar physiopathologic changes characterize this syndrome: a persistently raised pulmonary vascular resistance after birth, which leads to severe hypoxemia due to extrapulmonary shunting.The fundamental treatment is to reduce pulmonary vascular pressure and improve hemodynamics.Modern treatments such as inhaled nitric oxide, high-frequency oscillation ventilation, extracorporeal membrane oxygenation, and/or other pulmonary vasodilators could reduce mortality in neonatal persisitent pulmonary hypertension(PPHN). Inhaled nitric oxide is the main method for the treatment of PPHN, which can effectively improve oxygenation and reduce the need for extracorporeal membrane oxygenation(ECMO). The effect of inhaled nitric oxide is different with the gestational age changed.This article aims to summarize the clinical research progress of inhaled nitric oxide in the treatment of PPHN.

Effect of inhaled nitric oxide with mechanical ventilation in persistent pulmonary hypertension of newborn / 中国小儿急救医学

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.

Effect of inhaled nitric oxide with mechanical ventilation in persistent pulmonary hypertension of newborn / 中国小儿急救医学

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. Pulmona-ry 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) de-clined from(13. 98 ± 2. 40) cmH2 O(1 cmH2 O＝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 gradu-ally,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.

Analysis of curative effect of high frequent oscillation ventilation combined with inhaled nitric oxide for neonatal hypoxic respiratory failure / 中华实用儿科临床杂志

Objective To compare the curative effect with high frequent oscillation ventilation (HFOV) and with HFOV + inhaled nitric oxide (iNO) in the treatment of neonatal hypoxic respiratory failure (NRHF).Methods Data of 60 NHRF patients in the People's Hospital of Dehong Prefecture from January 2015 to December 2016 were retrospectively analyzed.The patients were divided into HFOV group (32 cases) and HFOV + iNO group (28 cases) according to the treatment methods.The comparison between the 2 groups was established as following:oxygenation index(OI),arterial partial pressure of carbon dioxide [Pa (CO2)] and complications.Results There was no significant difference between the 2 groups in time of birth,gestational age,birth weight,gender ratio and original diseases (all P ＞ 0.05).As for OI there was no significant difference at 0 h between the 2 groups (27.8 ± 3.5 vs.27.6 ± 3.7) (t =0.04,P ＞ 0.05);OI of HFOV + iNO group (11.2 ± 3.4,7.3 ± 3.0,7.0 ± 2.6,respectively) was more significantly decreased than that in the HFOV group (14.5 ± 3.3,9.6 ± 3.0,8.5 ± 2.8,respectively) at 8 h,16 h,24 h,and there were significant differences between the 2 groups (t =3.81,5.16,2.14,all P ＜ 0.05).As for P a (CO2) there was no significant difference at 0 h [(65.14 ± 14.97) mmHg vs.(64.79 ± 13.40) mmHg] (t =0.095,P ＞ 0.05);the changes in Pa (CO2) had no statistically significance difference between HFOV + iNO group and HFOV group at 8 h,16 h,24 h [8 h:(50.71 ± 10.49) mmHg vs.(49.02 ± 11.74) mmHg,16 h:(40.99 ± 12.38) mmHg vs.(40.02 ± 12.04) mmHg,and 24 h:(39.01 ±9.80) mmHg vs.(38.00 ±7.85) mmHg,all P ＞0.05].As for the complications,there was no difference between the 2 groups in pulmonary air leak,pneumorrhagia,intracranial hemorrhage,blood platelet ＜100 × 109/L,methemoglobin concentration ＞ 3％,or dysfunction of blood coagulation (all P ＞ 0.05).Conclusion Both HFOV and HFOV + iNO methods are effective for NRHF.Treatment with HFOV + iNO method is more effective.Treatment for NHRF with HFOV + iNO is safe,effective,without complication increase in a short term.

Analysis of curative effect of high frequent oscillation ventilation combined with inhaled nitric oxide for neonatal hypoxic respiratory failure / 中华实用儿科临床杂志

Objective To compare the curative effect with high frequent oscillation ventilation (HFOV) and with HFOV + inhaled nitric oxide (iNO) in the treatment of neonatal hypoxic respiratory failure (NRHF).Methods Data of 60 NHRF patients in the People's Hospital of Dehong Prefecture from January 2015 to December 2016 were retrospectively analyzed.The patients were divided into HFOV group (32 cases) and HFOV + iNO group (28 cases) according to the treatment methods.The comparison between the 2 groups was established as following:oxygenation index(OI),arterial partial pressure of carbon dioxide [Pa (CO2)] and complications.Results There was no significant difference between the 2 groups in time of birth,gestational age,birth weight,gender ratio and original diseases (all P ＞ 0.05).As for OI there was no significant difference at 0 h between the 2 groups (27.8 ± 3.5 vs.27.6 ± 3.7) (t =0.04,P ＞ 0.05);OI of HFOV + iNO group (11.2 ± 3.4,7.3 ± 3.0,7.0 ± 2.6,respectively) was more significantly decreased than that in the HFOV group (14.5 ± 3.3,9.6 ± 3.0,8.5 ± 2.8,respectively) at 8 h,16 h,24 h,and there were significant differences between the 2 groups (t =3.81,5.16,2.14,all P ＜ 0.05).As for P a (CO2) there was no significant difference at 0 h [(65.14 ± 14.97) mmHg vs.(64.79 ± 13.40) mmHg] (t =0.095,P ＞ 0.05);the changes in Pa (CO2) had no statistically significance difference between HFOV + iNO group and HFOV group at 8 h,16 h,24 h [8 h:(50.71 ± 10.49) mmHg vs.(49.02 ± 11.74) mmHg,16 h:(40.99 ± 12.38) mmHg vs.(40.02 ± 12.04) mmHg,and 24 h:(39.01 ±9.80) mmHg vs.(38.00 ±7.85) mmHg,all P ＞0.05].As for the complications,there was no difference between the 2 groups in pulmonary air leak,pneumorrhagia,intracranial hemorrhage,blood platelet ＜100 × 109/L,methemoglobin concentration ＞ 3％,or dysfunction of blood coagulation (all P ＞ 0.05).Conclusion Both HFOV and HFOV + iNO methods are effective for NRHF.Treatment with HFOV + iNO method is more effective.Treatment for NHRF with HFOV + iNO is safe,effective,without complication increase in a short term.

Inhaled Nitric Oxide Therapy for Acute Respiratory Distress Syndrome in Children.

The aim of this study was to evaluate the effects of inhaled nitric oxide (iNO) therapy on oxygenation and mortality in children with acute respiratory distress syndrome (ARDS). Thirty-three children with ARDS and an arterial SatO2 <88% despite mechanical ventilation were analyzed. Patients in the iNO group were prospectively enrolled and treated with conventional therapy plus iNO. The control group consisted of retrospectively analyzed patients treated only with conventional therapy. A significant increase in PaO2/FiO2 ratio (25.6%) and decrease in oxygenation index (19.5%) was observed after 4 h of iNO treatment, when compared to baseline values. A positive response to iNO was detected in 69% of patients, and there was no difference between pulmonary and extrapulmonary ARDS. There was no difference in mortality and duration of mechanical ventilation between iNO and control group.

The Effect of Inhaled Nitric Oxide in Preterm Infants less than 1,250 g with Respiratory Failure / 대한주산의학회잡지

PURPOSE: Inhaled nitric oxide (iNO) therapy can decrease pulmonary vascular resistance and improve oxygenation through enhanced ventilation-perfusion matching. This study investigated therapeutic response and possible factors affecting the response to iNO in preterm infants with respiratory failure. METHODS: This is a retrospective study of 17 preterm infants with respiratory failure whose birth weight were 1,250 g or less and were treated with iNO, admitted in the neonatal intensive care units at Seoul National University Bundang Hospital between January 2006 and June 2010. Infants were classified as responders if they presented a reduction of FiO2 of more than 20% during 24 hours from the beginning of the treatment, and as non-responder if not. RESULTS: Eight infants (47%) were classified as the responder group and nine infants (53%) as the non-responder group. Mean gestational age was 25.4+/-1.6 weeks in the responder group and 26.0+/-1.6 weeks in the non-responder group. Mean birth weight was 701.9+/-190.1 g in the responder group and 816.1+/-241.6 g in the non-responder group. In the responder group, infants received iNO at postnatal day 12+/-9, in the non-responder group, iNO at postnatal day 35+/-25 (P=0.02). The exposure duration to FiO2 > or =0.5 prior to iNO treatment was significantly shorter in responders than in non-responders (0.1+/-0.4 d vs. 12.6+/-16.3 d, P=0.04). The mechanical ventilation duration was shorter and the postmenstrual age and postnatal age at last extubation were earlier in responders than in non-responders (52+/-25 d vs. 120+/-67 d, P=0.03) (33.1+/-3.0 weeks vs. 45.4+/-9.5 weeks, P=0.01; 55+/-25 d vs. 125+/-59 d, P=0.01). The postmenstrual age and postnatal age at last oxygen treatment were earlier in responders than in non-responders (41.1+/-2.4 weeks vs. 49.0+/-4.5 weeks, P=0.03; 109+/-28 d vs. 158+/-36 d, P=0.03). CONCLUSION: Responders during iNO treatment in preterm infants with respiratory failure had earlier postnatal age and shorter duration of the exposure to hyperoxia. The responder group resulted in good response with early iNO treatment, thus the weaning of mechanical ventilation and oxygen was earlier than the non-responder group. Further studies on effects of beginning time of iNO treatment and long-term effects, especially bronchopulmonary dysplasia, intraventricular hemorrhage and neurodevelopmental outcome are necessary.

Experience with inhaled nitric oxide therapy in patient with neurogenic pulmonary edema: A case report

Neurogenic pulmonary edema is known in patients after head injuries or other cerebral lesions. Typically, this form of pulmonary edema occurs minutes to hours after central nervous system injury and may manifest during the perioperative period. It is always a life-threatening symptom after increased intracranial pressure (ICP), where immediate therapeutic interventions are imperative. Rapid initiation of strategies aimed at ameliorating hypoxia including support of oxygenation and ICP reduction is paramount. We report a case that responded dramatically to inhaled nitric oxide (NO). This therapy, to our experience, seems to provide a way not to reduce pulmonary hypertension, but to improve ventilation-perfusion mismatch for the treatment of refractory hypoxemia in neurogenic pulmonary edema patient.

Survival Rate Changes in Neonates with Congenital Diaphragmatic Hernia and its Contributing Factors

The purpose of this study was to demonstrate survival rate changes after the introduction of inhaled nitric oxide (iNO) therapy, and to identify the factors that influence these changes in neonates with a congenital diaphragmatic hernia (CDH) at a single center. A total of 48 neonates were divided into two groups based on the time of admission, i.e., into period I (P1; n=17; before the introduction of iNO therapy) and period II (P2; n=31; after the introduction of iNO therapy). Survival rates of the 48 neonates showed a tendency to increase from 53% during P1 to 77% during P2, but without a statistical significance, but a significant difference was found between survival rates during the two periods after adjusting for initial clinical characteristics, when the postoperative survival rate increased significantly from 69% for P1 to 100% for P2. The mean duration of preoperative respiratory management was significantly longer for P2 than for P1. Seven of 12 patients who received preoperative iNO therapy due to persistent pulmonary hypertension or refractory preductal hypoxemia in P2 survived after operation. We speculate that a management strategy based on iNO therapy and delayed operation, rather than differences between the initial clinical characteristics of the two study groups, might partially contribute to the observed improvements in postoperative and overall survival rates in neonates with CDH.

Óxido nítrico inalatório para crianças com síndrome do desconforto respiratório agudo: [revisão] / Inhaled nitric oxide for children with acute respiratory distress syndrome: [review]

JUSTIFICATIVA E OBJETIVOS: O objetivo desse estudo foi rever a literatura sobre a utilização de óxido nítrico inalatório em crianças com síndrome do desconforto respiratório agudo. CONTEÚDO: Revisão bibliográfica e seleção de publicações mais relevantes sobre óxido nítrico inalatório, utilizando a base de dados MedLine e Cochrane de Revisões Sistemáticas. A revisão incluiu descrição de aspectos da definição, fisiopatologia e tratamento ventilatório da síndrome do desconforto respiratório agudo, assim como o metabolismo, efeitos biológicos e aplicação clínica do óxido nítrico inalatório, comentando dose, administração e retirada do gás, precações, efeitos adversos e contra-indicações. CONCLUSÕES: O óxido nítrico, vasodilatador pulmonar seletivo, tem efeitos benéficos sobre as trocas gasosas e ventilação em crianças com hipóxia grave. É seguro quando administrado em ambiente de tratamento intensivo sob rigorosa monitorização. Estudos aleatórios e controlados devem enfocar a administração precoce do gás na síndrome do desconforto respiratório agudo, quando essa é potencialmente reversível.

BACKGROUND AND OBJECTIVE: The objective of this study was to review the literature on inhaled nitric oxide to children with acute respiratory distress syndrome. CONTENTS: A review of literature and selection of the most important publications on inhaled nitric oxide, using the MedLine and Cochrane Systematic Review Databases. This review was organized as follows: introduction; metabolism and biological effects; clinical applications; dosage, gas administration and weaning process; warnings and side-effects. Inhaled nitric oxide use was described in acute respiratory distress syndrome. CONCLUSIONS: Inhaled nitric oxide as the first vasodilator to produce selective pulmonary vasodilation has beneficial effects on gas exchange and ventilation, improving outcome in children with severe hypoxia. It is safe when administered in intensive care units under strict surveillance and monitoring. Further studies should be concentrated on early treatment, when acute respiratory distress syndrome is potentially reversible.

Factors Affecting the Response to Inhaled Nitric Oxide Therapy in Persistent Pulmonary Hypertension of the Newborn Infants

Persistent pulmonary hypertension of the newborn infant (PPHN), is a clinical syndrome characterized by elevated pulmonary vascular resistance, resulting from reactive vasoconstriction or structural remodeling of the pulmonary vasculature. Although inhaled nitric oxide (iNO) has emerged as a novel selective treatment of PPHN, responses to iNO are variable according to the etiologies or the clinical situation. A retrospective chart review of 51 newborn infants with PPHN and treated with iNO, was undertaken to evaluate the factors affecting response to iNO. Response to iNO was defined as a reduction in the oxygenation index (OI) of more than 20%, or disappearance of the difference in oxygen saturation between preductal and postductal circulation after iNO therapy. The patients were divided into two groups; the responder group and the non- responder group. Respiratory distress syndrome (RDS) was more commonly associated with PPHN in the responder group than in the non-responder group (p < 0.05), while there were many more patients with congenital diaphragmatic hernia (CDH) in the non-responder group than in the responder group (p < 0.05). Infants with meconium aspiration syndrome (MAS) were similar in both of the two groups. Initial OI, initial mean airway pressure (MAP), and initial and peak NO concentration were significantly lower in the responder group compared to the non-responder group (p < 0.05). Rapid response (response to iNO within the first hour) was shown in 74% of the responder group and 33% of the nonresponder group (p < 0.05). There was no significant differences in the initial chest radiographic findings, such as normal, focal or bilateral diffuse infiltration, with the exception of CDH, between each group. Lower initial OI, lower initial MAP and significant response within the first hour were shown to be favourable factors in response to iNO therapy. Patients with RDS associated with PPHN responded much better to iNO than those with other diseases.

Comparison of Treatment Outcomes in Persistent Pulmonary Hypertension of the Newborn

PURPOSE: To compare the efficacy of conventional strategy versus high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for the treatment of full term neonates with persistent pulmonary hypertension (PPHN). METHODS: Full term infants admitted with diagnosis of PPHN to neonatal intensive care units of Asan Medical Center from a period of 1994 to 2001 were included. The major exclusion criteria included congenital anomalies and pulmonary hypoplasia caused by various etiologies. Demographic, therapeutic responses and outcomes were compared between two study phases depending upon treatment modalities used: phase 1 (January 1994-July 1997) using conventional strategy and phase II (July 1997-December 2001) using either conventional strategy or/with iNO or HFOV with iNO. RESULTS: A total of 16 patients and 32 patients were enrolled in phase I and phase II studies, respectively. The primary diagnosis for PPHN included idiopathic (n=12), hyaline membrane disease (n=16), meconium aspiration syndrome (n=11), and sepsis (n=10). Statistically significant improvements were noted in survival, oxygenation index and alveolar- arterial oxygen tension difference during phase II than phase I study period. 75% of those infants treated with iNO showed good responses. Improvements in duration of ventilator use, oxygen supplementation, hospitalization were noted during phase II study period, however, not statistically significant compared to phase I study period. The impairments in neurodevelopmental outcomes were noted in 1 and 2 patients during phase I and phase II study periods, respectively. CONCLUSION: We conclude that HFOV and iNO are more efficacious and safe rescue mode of treatment than conventional strategy for full term infants with PPHN.

Predictors of Clinical Outcome in the Newborns of Persistent Pulmonary Hypertension Treated with Inhaled Nitric Oxide

PURPOSE: Inhaled nitric oxide (iNO) has been known to improve oxygenation in newborns with persistent pulmonary hypertension (PPHN). This study was performed to evaluate the predictors of clinical outcome in the newborn infants with PPHN treated with iNO. METHODS: Between September 1998 and August 2002, 23 newborn infants with PPHN treated with iNO were enrolled in this study. Reduction of oxygenation index (OI) and AaDO2 to 30% or more were defined as clinical response. Accoding to the response time within or after 12 hours, the clinical response was sub-categorized as early or delayed response, respectively. RESULTS: The mean gestational age and birth weight of 23 newborn infants were 36.7+/-4.4 weeks and 2,644+/-907 g. The mean baseline OI and AaDO2 were 22.20+/-13.63 and 477.16+/-127.96. There were ten non-responsders, eight early responsders and five delayed responders. Eleven neonates showed sustained response for 24 hours. The mean AaDO2, and PaO2 were decreased after 12 hours (P<0.05), while there was no difference in oxygenation index, arteral pH and PaCO2. The mortality rates of non-responders or not- sustained responders were higher than those of responders or sustained responders (P< 0.05). The birth weight of death group was lower than that of survival group and AaDO2, and OI at 12 hours after iNO therapy in survival group were lower than those in death group. CONCLUSION: Predictors of the clinical outcome of iNO therapy were clinical response patterns after iNO therapy, time taken until clinical response, duration of response and change of oxygenation at 12 hours after iNO therapy.