Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence.

Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.

Pediatric COVID-19 extracorporeal membrane oxygenation transport during the pandemic.

INTRODUCTION: ExtraCorporeal Membrane Oxygenation (ECMO) in pediatric patients with COVID-19 has a survival rate similar to adults. Occasionally, patients may need to be cannulated by an ECMO team in a referring hospital and transported to an ECMO center. The ECMO transport of a COVID-19 patient has additional risks than normal pediatric ECMO transport for the possible COVID-19 transmissibility to the ECMO team and the reduction of the ECMO team performance due to the need of wearing full personal protective equipment. Since pediatric data on ECMO transport of COVID-19 patients are lacking, we explored the outcomes of the pediatric COVID-19 ECMO transports collected in the EuroECMO COVID_Neo/Ped Survey. METHODS: We reported five European consecutive ECMO transports of COVID-19 pediatric patients collected in the EuroECMO COVID_Neo/Ped Survey including 52 European neonatal and/or pediatric ECMO centers and endorsed by the EuroELSO from March 2020 till September 2021. RESULTS: The ECMO transports were performed for two indications, pediatric ARDS and myocarditis associated to the multisystem inflammatory syndrome related to COVID-19. Cannulation strategies differed among patients according to the age of the patients, transport distance varied between 8 and 390 km with a total transport duration between 5 to 15 h. In all five cases, the ECMO transports were successfully performed without major adverse events. One patient reported a harlequin syndrome and another patient a cannula displacement both without major clinical consequences. Hospital survival was 60% with one patient reporting neurological sequelae. No ECMO team member developed COVID-19 symptoms after the transport. CONCLUSION: Five transports of pediatric patients with COVID-19 supported with ECMO were reported in the EuroECMO COVID_Neo/Ped Survey. All transports were performed by an experienced multidisciplinary ECMO team and were feasible and safe for both the patient and the ECMO team. Further experiences are needed to better characterize these transports and draw insightful conclusions.

Increased RSV-A Bronchiolitis Severity in RSV-Infected Children Admitted to a Reference Center in Catalonia (Spain) Between 2014 and 2018.

Between 2014 and 2018, we evaluated the severity of 687 cases of bronchiolitis caused by respiratory syncytial virus (RSV) in Catalonia, Spain. Compared to RSV-B, RSV-A cases required intensive care (adjusted relative risk (aRR) = 1.44, p < 0.01) and respiratory support (aRR = 1.07, p < 0.01) more often; hospital stay was one day longer (p < 0.01). Subgroup identification may aid clinical evaluation and seasonal healthcare planning.

Short- and long-term survival of children treated with ventricular assist devices in Spain, based on 15 years' experience.

OBJECTIVES: To describe the use of ventricular assist devices (VAD) in children in Spain and to identify variables related to survival. METHODS: This is an observational cohort study of all children younger than 18 years of age who underwent an initial implantation of a VAD at any of the 6 paediatric heart transplant centres from May 2006 to December 2020. Subjects were identified retrospectively from each hospital's database. RESULTS: Paracorporeal VADs were implanted in 118 children [pulsatile (63%), continuous (30.5%) or both types (5.9%)]. Small children (<0.7 m2 of body surface area) comprised the majority of this cohort (63.3%). Overall, 67% survived to VAD explantation, and 64.9% survived to hospital discharge. Non-central nervous system haemorrhage (39%) and stroke (38.1%) were the most common complications. Body weight <5 kg, congenital heart disease, pre-implantation bilirubin >34 µmol/l and bridge to decision strategy were associated with a higher mortality at hospital discharge and in the long-term. Interagency registry for mechanically assisted circulatory support (INTERMACS) status 1 and cardiac arrest prior to VAD implantation were related to long-term mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not related to mortality. CONCLUSIONS: In Spain, 67% of the VAD-supported children have been bridged to heart transplantation or to recovery. Body weight lower than 5 kg, congenital heart disease diagnosis, cholestatic liver dysfunction, bridge to decision as VAD strategy, INTERMACS-1 status and cardiac arrest were pre-implantation variables related to mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not.

First surgical experience treating scoliosis using HGT and ECMO: a case report.

CASE PRESENTATION: A 13-year-old female with congenital diaphragmatic hernia-associated pulmonary hypertension presented with severe and rapidly progressing scoliosis. The patient suffered from chronic respiratory failure and high risk of hypertensive crisis with potentially life-threating consequences. The scoliosis was treated with a multidisciplinary approach combining preoperative halo-gravity traction, venoarterial extracorporeal membrane oxygenation support and posterior spinal instrumented fusion. After 2 years of follow-up, results are excellent. CONCLUSIONS: The treatment combination reported here for the first time aims to limit surgical aggressiveness. It could be an effective and safe approach for treating severe spinal deformities in very fragile patients with high surgical risk.

The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain): A long-term, clinical, epidemiologic and economic study.

BACKGROUND: Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. METHODS: From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. RESULTS: A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. CONCLUSIONS: Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.

Parvovirus B19 myocarditis in children: a diagnostic and therapeutic approach.

Parvovirus B19 is one of the most frequent causes of pediatric myocarditis, associating high mortality rates or need for cardiac transplantation. The aim of this study is to describe the clinical course of Parvovirus B19 myocarditis in children with emphasis on the role of endomyocardial biopsy and cardiac magnetic resonance, and the use of an innovative therapeutic strategy. Eleven patients and 12 episodes of polymerase chain reaction (PCR)-confirmed Parvovirus B19 myocarditis were prospectively collected for 14 years. Diagnosis was confirmed either histopathologically or by magnetic resonance. A life-threatening clinical presentation is described, similar to previous series, but with 83.3% overall survival without transplantation. We also present a case of recurrent myocarditis, which is extraordinarily rare. Electrocardiographic patterns presented chiefly peaked p waves, low QRS voltages, and negative T waves on inferior or lateral leads. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance could be a useful diagnostic tool. A good concordance between myocardial and blood PCRs was observed. Seven patients received treatment with corticosteroids and beta interferon and all underwent a significant cardiac function improvement. CONCLUSION: A severe clinical presentation is reported, similar to previous reports but with better outcomes. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance may be used. Both blood and myocardium PCR can be used in children to establish the microbiological etiology. Steroids with IFNß could be a useful therapeutic option, although further multicenter studies are needed to confirm these results. WHAT IS KNOWN: • Parvovirus B19 is one of the most frequent causes of myocarditis in children. It is associated with a fulminant clinical presentation. • Endomyocardial biopsy is the gold standard diagnostic test but it is an invasive procedure. WHAT IS NEW: • Myocarditis may recur in pediatrics, even it is extraordinarily rare. • IFNß with steroids may be a useful therapeutic option to improve the outcomes.

Organización de la atención a pacientes críticos en situación de pandemia: Experiencia del Hospital Vall d’Hebron durante el brote de neumonía por SARS-CoV-2 / Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d’Hebron University Hospital

IntroducciónEn un escenario de circulación comunitaria del virus, el impacto de la pandemia sobre el sistema sanitario y en las unidades de cuidados intensivos (UCI) se preveía devastador. El Hospital Universitario Vall d’Hebron (HUVH) ha desplegado un dispositivo de atención a pacientes críticos sin precedentes.MétodosSe describen las previsiones realizadas, las medidas tomadas y los principales resultados en una cohorte de pacientes críticos durante los primeros dos meses (3 de marzo al 2 de mayo del 2020) de la pandemia por COVID-19 en el HUVH de Barcelona.ResultadosEn el periodo de estudio, ingresaron en las Unidades de Críticos del HUVH 333 pacientes. El porcentaje de los pacientes en VMI o VMI y ECMO se mantuvo constantemente por encima del 78%. La mayoría de pacientes han sido hombres (65%); el grupo de edad más frecuente entre 60 y 70 años. Veintitrés pacientes recibieron ECMO, 18 de los cuales fueron canulados en otro centro y trasladados al HUVH. A fecha de cierre del estudio, 14 pacientes se decanularon satisfactoriamente, tres pacientes fallecieron y el resto siguen en soporte con ECMO. Han sido atendidas en UCI ocho gestantes, con una supervivencia del 100%. La mortalidad en UCI de los pacientes menores de 60 años fue el 3,2%. La estancia media en UCI de las altas y los fallecimientos ha sido de 14 días.ConclusionesLas estrategias de organización de la expansión de recursos para la atención de pacientes críticos, sus principales retos y los resultados obtenidos, pueden servir de clave para futuros escenarios similares.

IntroductionIn the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d́Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources.MethodsWe describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona.In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained.ResultsThree-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days.ConclusionThe adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.

Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d'Hebron University Hospital.

INTRODUCTION: In the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d'Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources. METHODS: We describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona. In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained. RESULTS: Three-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days. CONCLUSION: The adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.

Differences between genetic dilated cardiomyopathy and myocarditis in children presenting with severe cardiac dysfunction.

Acute myocarditis is an inflammatory disease of the myocardium, and it can present as severe heart failure in children. Differential diagnosis with genetic cardiomyopathy can be difficult. The objective of this study is to identify patterns of clinical presentation and to assess invasive and non-invasive measures to differentiate patients with acute myocarditis from patients with dilated genetic cardiomyopathy. We performed a retrospective descriptive study of all paediatric patients (0-16 years old) that presented with new-onset heart failure with left ventricle ejection fraction < 35% in whom we performed an endomyocardial biopsy (EMB) during the period from April 2007 to December 2020. The patients were classified into two groups: Group 1 included 18 patients with myocarditis. Group 2 included 9 patients with genetic cardiomyopathy. Findings favouring a diagnosis of myocarditis included a fulminant or acute presentation (77.8% vs 33.3%, p = 0.01), higher degree of cardiac enzyme elevation (p = 0.011), lower left ventricular dimension z-score (2.2 vs 5.4, p = 0.03) increase of ventricular wall thickness (88.8% vs 33.3%, p = 0.03) and oedema in the EMB. Seven (77.8%) patients with genetic cardiomyopathy had inflammation in the endomyocardial biopsy fulfilling the diagnostic criteria of inflammatory cardiomyopathy.Conclusion: Differentiating patients with a myocarditis from those with genetic cardiomyopathy can be challenging, even performing an EMB. Some patients with genetic cardiomyopathy fulfil the diagnostic criteria of inflammatory cardiomyopathy. Using invasive and non-invasive measures may be useful to develop a predictive model to differentiate myocarditis from genetic cardiomyopathy. What is Known: • Acute myocarditis could present with cardiogenic shock in paediatric patients. • Parvovirus B19 is the main cause of myocarditis in this population. What is New: • Current diagnostic criteria for myocarditis have limited use in paediatric patients presenting with new-onset heart failure. • Some patients with a genetic cardiomyopathy and a new-onset heart failure fulfill the diagnostic criteria of inflammatory cardiomyopathy.

Influenza myocarditis in paediatric patients.

Acute myocarditis is a rare but potentially fatal disease. Endomyocardial biopsy and histologic examination are key to an accurate diagnosis. Despite being an uncommon cause, Influenza A and B viruses are a well-documented aetiology. Myocarditis may complicate about 0 to 10% of influenza virus infections (0.4 to 5% in paediatric cases). The clinical presentation varies widely, from ischemic-like chest pain to fulminant myocarditis with acute hemodynamic compromise, requiring mechanical circulatory support, with high mortality in the acute phase. We report a series of paediatric patients with myocarditis due to Influenza virus, to emphasize the importance of considering this uncommon aetiology.

Miocardiopatía restrictiva: la importancia de su diagnóstico precoz / Restrictive cardiomyopathy: Importance of early diagnosis

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Influenza-Associated Disseminated Aspergillosis in a 9-Year-Old Girl Requiring ECMO Support.

A previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly developed anisocoria. Computed tomography (CT) of the head showed fungal brain lesions. Urgent decompressive craniectomy with lesion drainage was performed; histopathology found hyphae in surgical samples, culture-positive for Aspergillus fumigatus (susceptible to azoles, echinocandins, and amphotericin B). Extension workup showed disseminated aspergillosis. After multiple surgeries and combined antifungal therapy (isavuconazole plus liposomal amphotericin B), her clinical course was favorable. Isavuconazole therapeutic drug monitoring was performed weekly. Extensive immunological study ruled out primary immunodeficiencies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) follow-up showed a gradual decrease in fungal lesions. Influenza-associated pulmonary aspergillosis is well-recognized in critically ill adult patients, but pediatric data are scant. Clinical features described in adults concur with those of our case. Isavuconazole, an off-label drug in children, was chosen because our patient had severe renal failure. To conclude, influenza-associated pulmonary aspergillosis is uncommon in children admitted to intensive care for severe influenza, but pediatricians should be highly aware of this condition to enable prompt diagnosis and treatment.

Transient upper limb ischaemia during veno-arterial extracorporeal membrane oxygenation in a child.

Neck cannulation is the most common cannulation strategy performed to provide veno-arterial extracorporeal membrane oxygenation support in paediatric patients, especially in small children. Upper limb ischaemia is a rare complication of neck cannulation and is likely caused by arterial cannula malposition. We describe a case of right arm ischaemia caused by extrinsic compression of the right subclavian artery by the venous drainage cannula inserted through the right internal jugular vein. Upper limb hypoperfusion was resolved immediately after changing the venous drainage cannula from the right jugular vein to the right femoral vein.

Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d'Hebron University Hospital. / Organización de la atención a pacientes críticos en situación de pandemia: Experiencia del Hospital Vall d'Hebron durante el brote de neumonía por SARS-CoV-2.

INTRODUCTION: In the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d́Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources. METHODS: We describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona. In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained. RESULTS: Three-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days. CONCLUSION: The adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.