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OBJECTIVE: The use of vasopressin as an adjunctive therapy in pulmonary hypertension associated with refractory systemic hypotension has increased. The objective of our study is to describe its effects on term infants. STUDY DESIGN: Retrospective observational study. Setting in a referral level IV neonatal intensive care unit from a middle-income region. The patients are term neonates admitted to our NICU who required vasopressin due to severe Pulmonary Hypertension and refractory hypotension during a 49-month period (December 2019 and December 2023). RESULTS: We identified 68 term infants, all in mechanical ventilation, receiving inhaled nitric oxide (iNO), and a phased protocol management for hypotension. Vasopressin was a started at a mean of 2 days with a mean duration of 80 h. Regarding hemodynamic outcome: diastolic, systolic, and median systemic pressure significantly increased during the first 4 h of treatment, as well as arterial pH and urine output. Accordingly, lactate and Vasoactive Inotropic Score (VIS) score decreased after 4 and 8 h, respectively, after vasopressin was started. Regarding oxygenation markers: oxygen requirements and mean airway pressure decreased significantly (and therefore the oxygenation index decreased in concordance) after 4 h of vasopressin. Echocardiographic indices of pulmonary hypertension progressively improved after vasopressin infusion with a significant decrease of tricuspid ingurgitation velocities and the rate of right-to- left ductal shunt through the ductus arteriosus. In the same way, left and right ventricular output increased after the initiation of vasopressin. CONCLUSION: This study showed that the use of vasopressin in neonates with persistent pulmonary hypertension was associated with a rapid and significant improvement in oxygenation and hemodynamic markers of perfusion, including blood pressure. Its effects begin early during the first hours of treatment.
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INTRODUCTION: Mortality related to CDH is high, but with great variability among centers. There are few studies on patients with this condition born in South America which show poor outcomes. The goal of this study is to present the outcome of CDH in several high-volume quaternary centers in South America, ascertain the factors associated with lower mortality in our population, and compare our outcomes to those of the CDH Study Group (CDHSG). METHODS: The data from two South American centers were retrospectively analyzed and compared with contemporary data from other CDHSG participating centers. Patient demographic and clinical characteristics were also evaluated and compared. RESULTS: Between 2013 and 2018, the two South American centers saw 335 patients with CDH with an overall survival rate of 73.1%. Survival for the high, intermediate, and low-risk groups as determined by the Brindle score was 50%, 70%, and 87%, respectively. In our cohort the strongest predictors of mortality were ECMO use and early PaCO2. There were no significant differences in mortality between the two South American centers and the other CDHSG centers when adjusted by risk score, however, the South American centers had higher use of ECMO in the intermediate-risk group. DISCUSSION: Quaternary South American centers had similar outcomes to CDHSG centers worldwide. The availability and coordination of centralized dedicated care allow more efficient use of scarce technical and professional resources in patients with CDH. LEVEL OF EVIDENCE: III.
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Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Humanos , Hérnias Diafragmáticas Congênitas/terapia , Estudos Retrospectivos , Fatores de Risco , América do Sul/epidemiologiaRESUMO
BACKGROUND: Severe pulmonary hypoplasia related to congenital diaphragmatic hernia (CDH) continues to be a potentially fatal condition despite advanced postnatal management strategies. OBJECTIVE: To evaluate the effect of the antenatal sildenafil and 2(S)-amino-6-boronohexanoic acid (ABH-Arginase inhibitor) on lung volume, pulmonary vascular development, and nitric oxide (NO) synthesis in a Nitrofen-induced CDH rat model. METHODS: Nitrofen-induced CDH rat model was used. Nitrofen was administrated on embryonic day(E) 9,5. At E14, five intervention groups were treated separately: Nitrofen, Nitrofen+Sildenafil, Nitrofen+ABH, Nitrofen+Sildenafil+ABH and Control. At term, offspring's lungs were weighed, some paraffin-embedded for histology, others snap-frozen to analyze eNOS, Arginase I-II expression, and activity. RESULTS: In CDH-bearing offsprings, ABH or Sildenafil+ABH preserved the total lung/body-weight index (p < 0.001), preventing pulmonary vascular smooth muscle cell hyperproliferation and improving lung morphometry. Sildenafil+ABH increased 1.7-fold the lung nitrite levels (p < 0.01) without changes in eNOS expression. Sildenafil and ABH improved the number of pulmonary vessels. CONCLUSION: These results suggest that in this CDH rat model, the basal activity of Arginase participates in the lung volume and, together with phosphodiesterase-5, regulates NOS activity in the term fetal lung. The combined treatment (Sildenafil+ABH) could revert some of the pulmonary features in CDH by improving the local NO synthesis and preventing smooth muscle cell hyperproliferation. IMPACT: This study presents Arginase inhibition as a new therapeutic target and the importance of the combined antenatal treatment to improve pulmonary vascular development in a congenital diaphragmatic hernia (CDH) rat model. This study shows that the action of an Arginase inhibitor (ABH) enhances the effects already described for sildenafil in this model. These results reinforce the importance of prenatal treatments' synergy in recovering the hypoplastic lung in the Nitrofen-induced CDH rat model.
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OBJECTIVE: To evaluate whether combined surfactant with inhaled nitric oxide (iNO) use will prevent newborns with hypoxemic respiratory failure (HRF) from developing an Oxygenation Index (OI) > 40. METHODS: 100 term newborns with acute HRF (OI ≥ 20) were randomized to: Surfactant+iNO: received iNO plus up to two doses of surfactant or iNO-Controls: received iNO+placebo. Main outcome was the development of severe HRF (OI > 40) despite iNO use. RESULTS: Baseline mean ± SD OI was 37.4 ± 14 for the Surfactant+iNO group and 38.2 ± 16 for the controls. Infants receiving surfactant+iNO improved their oxygenation faster, resulting in lower OI at 24 h: 12.9 ± 9 vs 18.7 ± 11 of controls, p < 0.05; and a lower proportion developing OI > 40: 24%(12/50) vs 50%(25/50) of controls, p < 0.02. Fewer infants receiving surfactant+iNO presented the combined outcome of death or ECMO: 16%(8/50) compared to 36%(18/50) of controls, p < 0.05. CONCLUSIONS: Early use of combined surfactant+iNO improves oxygenation preventing the progression to severe HRF. This may reduce mortality and ECMO need. TRIAL REGISTRATION NUMBER: ISRCTN13727958.
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Hipertensão Pulmonar , Insuficiência Respiratória , Administração por Inalação , Humanos , Recém-Nascido , Óxido Nítrico/uso terapêutico , Insuficiência Respiratória/tratamento farmacológico , Tensoativos/uso terapêutico , Falha de TratamentoRESUMO
OBJECTIVES: To describe risk factors for acquired infection during neonatal extracorporeal membrane oxygenation and to examine the predictive value of inflammatory markers in the diagnosis of infection. METHODS: A retrospective study was conducted with data for patients under 30 days supported with extracorporeal membrane oxygenation from 2003 to April 2016, in a neonatal intensive care unit. RESULTS: Our study included 160 neonatal patients, the average age of connection was 8.5 days and the duration of extracorporeal membrane oxygenation support was 9.7 days. The incidence of confirmed infection was 23%. Patients with confirmed infection present more frequently: vaginal delivery, lower birth weight, female sex, diagnosis of congenital diaphragmatic hernia, and longer duration of extracorporeal membrane oxygenation. When comparing the group of patients with confirmed infection and suspicion of infection, there were no significant differences in the inflammatory markers. When calculating the slope for each one, the difference in white blood cell count slope 72 h before the infection is significant; in patients with confirmed infection, the count of white blood cell increases (slope: 0.25), versus the group of patients with suspected infection in whom the count decreases (slope: -0.39). No differences were found in other variables. CONCLUSION: Our study describes that the factors that increase the risk of infection are lower birth weight, vaginal birth, duration of extracorporeal membrane oxygenation, and a positive trend of white blood cell 72 h prior to infection/suspicion. Further studies are necessary to include or definitively rule out the use of these factors and the biomarkers as predictors of infection in neonatal patients supported with extracorporeal membrane oxygenation.
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Abstract Objective: To review the principles of neonatal-pediatric extracorporeal membrane oxygenation therapy, prognosis, and its establishment in limited resource-limited countries in Latino America. Sources: The PubMed database was explored from 1985 up to the present, selecting from highly-indexed and leading Latin American journals, and Extracorporeal Life Support Organization reports. Summary of the findings: Extracorporeal membrane oxygenation provides “time” for pulmonary and cardiac rest and for recovery. It is used in the neonatal-pediatric field as a rescue therapy for more than 1300 patients with respiratory failure and around 1000 patients with cardiac diseases per year. The best results in short- and long-term survival are among patients with isolated respiratory diseases, currently established as a standard therapy in referral centers for high-risk patients. The first neonatal/pediatric extracorporeal membrane oxygenation Program in Latin America was established in Chile in 2003, which was also the first program in Latin America to affiliate with the Extracorporeal Life Support Organization. New extracorporeal membrane oxygenation programs have been developed in recent years in referral centers in Argentina, Colombia, Brazil, Mexico, Perú, Costa Rica, and Chile, which are currently funding the Latin American Extracorporeal Life Support Organization chapter. Conclusions: The best results in short- and long-term survival are in patients with isolated respiratory diseases. Today extracorporeal membrane oxygenation therapy is a standard therapy in some Latin American referral centers. It is hoped that these new extracorporeal membrane oxygenation centers will have a positive impact on the survival of newborns and children with respiratory or cardiac failure, and that they will be available for an increasing number of patients from this region in the near future.
Resumo Objetivo: Analisar os fundamentos, o prognóstico e o estabelecimento da terapia de oxigenação por membrana extracorpórea ECMO neonatal-pediátrica em países da América Latina com recursos limitados. Fontes: A base de dados PubMed foi explorada de 1985 até hoje, selecionamos os principais periódicos da América Latina e relatos da Organização de Suporte de Vida Extracorpóreo. Resumo dos achados: A oxigenação por membrana extracorpórea proporciona “tempo” para descanso pulmonar e cardíaco e para recuperação. Ela é usada no campo neonatal-pediátrico como terapia de resgate, com mais de 1.300 pacientes com insuficiência respiratória e cerca de 1.000 pacientes com cardiopatias por ano. Os melhores resultados de sobrevida de curto e longo prazo são de pacientes com doenças respiratórias isoladas, o que estabelece uma terapia padrão em centros de encaminhamento para pacientes de alto risco. O primeiro programa de oxigenação por membrana extracorpórea neonatal/pediátrico na América Latina foi estabelecido no Chile em 2003, que também foi o primeiro programa na América Latina a se afiliar à Organização de Suporte de Vida Extracorpóreo. Novos programas de oxigenação por membrana extracorpórea foram desenvolvidos nos últimos anos em centros de encaminhamento em Argentina, Colômbia, Brasil, México, Peru, Costa Rica e Chile, que atualmente fundam a seção da América Latina da Organização de Suporte de Vida Extracorpóreo. Conclusões: Os melhores resultados de sobrevida de curto e longo prazo são de pacientes com doenças respiratórias isoladas. Atualmente, a terapia de oxigenação por membrana extracorpórea é uma terapia padrão em alguns centros de encaminhamento da América Latina. Esperamos que esses novos centros de oxigenação por membrana extracorpórea tenham um impacto positivo sobre a sobrevida de neonatos e crianças com insuficiência respiratória ou cardíaca e que estejam disponíveis para um número cada vez maior de pacientes de nossa região no futuro próximo.
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Humanos , Recém-Nascido , Criança , Insuficiência Respiratória/terapia , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Prognóstico , Análise de Sobrevida , América LatinaRESUMO
OBJECTIVE: To review the principles of neonatal-pediatric extracorporeal membrane oxygenation therapy, prognosis, and its establishment in limited resource-limited countries in Latino America. SOURCES: The PubMed database was explored from 1985 up to the present, selecting from highly-indexed and leading Latin American journals, and Extracorporeal Life Support Organization reports. SUMMARY OF THE FINDINGS: Extracorporeal membrane oxygenation provides "time" for pulmonary and cardiac rest and for recovery. It is used in the neonatal-pediatric field as a rescue therapy for more than 1300 patients with respiratory failure and around 1000 patients with cardiac diseases per year. The best results in short- and long-term survival are among patients with isolated respiratory diseases, currently established as a standard therapy in referral centers for high-risk patients. The first neonatal/pediatric extracorporeal membrane oxygenation Program in Latin America was established in Chile in 2003, which was also the first program in Latin America to affiliate with the Extracorporeal Life Support Organization. New extracorporeal membrane oxygenation programs have been developed in recent years in referral centers in Argentina, Colombia, Brazil, Mexico, Perú, Costa Rica, and Chile, which are currently funding the Latin American Extracorporeal Life Support Organization chapter. CONCLUSIONS: The best results in short- and long-term survival are in patients with isolated respiratory diseases. Today extracorporeal membrane oxygenation therapy is a standard therapy in some Latin American referral centers. It is hoped that these new extracorporeal membrane oxygenation centers will have a positive impact on the survival of newborns and children with respiratory or cardiac failure, and that they will be available for an increasing number of patients from this region in the near future.
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Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Insuficiência Respiratória/terapia , Criança , Humanos , Recém-Nascido , América Latina , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension. OBJECTIVE: To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs. METHODS: We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT). RESULTS: We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT. CONCLUSIONS: PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.
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Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hérnias Diafragmáticas Congênitas/tratamento farmacológico , Hipertensão Pulmonar/prevenção & controle , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Sulfonamidas/farmacologia , Actinas/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/fisiopatologia , Hipertensão Pulmonar/etiologia , Imuno-Histoquímica , Neovascularização Fisiológica/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/ultraestrutura , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Citrato de Sildenafila , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Túnica Íntima/ultraestruturaRESUMO
BACKGROUND/AIMS: Hemorrhagic complications during ECMO may affect a large proportion of the patients depending on the clinical setting. To guarantee optimal delivery of blood products to these patients, blood banks require updated information on the transfusion requirements. Few studies to date provide this information. This work assesses transfusion requirements in neonates and children during ECMO during the past 9 years. METHODS: We reviewed blood bank and hospital records of patients who underwent ECMO at our institution between May 2003 and May 2012. Data obtained included age, weight, diagnosis, type, length of ECMO, and daily transfusion requirements during ECMO. Descriptive and non-parametric inferential statistic analyses were performed. Our series included 98 patients. RESULTS: Mean time of patients on ECMO was 9.2 days, with the longest treatment spanning 22 days. Mean daily transfusion requirements were 39.5 ml/kg of RBC, 12.9 ml/kg of plasma, 34.3 ml/kg of platelets and 1.4 ml/kg of cryoprecipitate. Patients who underwent ECMO due to cardiac disease or congenital diaphragmatic hernia (CDH) required significantly higher transfusion volumes of plasma (p<0.05), platelets (p< 0.05) and cryoprecipitate (p<0.05) when compared to patients underwent ECMO due to respiratory disease. Concomitant with the aging of ECMO circuits, patients showed increased requirements of RBC, plasma, and CRYO around the seventh day of the ECMO run. This effect was not observed for platelets, which remained nearly consistent around 2.2 transfusions/day. CONCLUSIONS: ECMO patients required significant transfusion support, which was particularly higher among patients who underwent ECMO due to cardiac disease or congenital diaphragmatic hernia.