Recommendations for developing effective and safe paediatric and congenital heart disease services in low-income and middle-income countries: a public health framework.

The global burden of paediatric and congenital heart disease (PCHD) is substantial. We propose a novel public health framework with recommendations for developing effective and safe PCHD services in low-income and middle-income countries (LMICs). This framework was created by the Global Initiative for Children's Surgery Cardiac Surgery working group in collaboration with a group of international rexperts in providing paediatric and congenital cardiac care to patients with CHD and rheumatic heart disease (RHD) in LMICs. Effective and safe PCHD care is inaccessible to many, and there is no consensus on the best approaches to provide meaningful access in resource-limited settings, where it is often needed the most. Considering the high inequity in access to care for CHD and RHD, we aimed to create an actionable framework for health practitioners, policy makers and patients that supports treatment and prevention. It was formulated based on rigorous evaluation of available guidelines and standards of care and builds on a consensus process about the competencies needed at each step of the care continuum. We recommend a tier-based framework for PCHD care integrated within existing health systems. Each level of care is expected to meet minimum benchmarks and ensure high-quality and family centred care. We propose that cardiac surgery capabilities should only be developed at the more advanced levels on hospitals that have an established foundation of cardiology and cardiac surgery services, including screening, diagnostics, inpatient and outpatient care, postoperative care and cardiac catheterisation. This approach requires a quality control system and close collaboration between the different levels of care to facilitate the journey and care of every child with heart disease. This effort was designed to guide readers and leaders in taking action, strengthening capacity, evaluating impact, advancing policy and engaging in partnerships to guide facilities providing PCHD care in LMICs.

Neonates With SARS-CoV-2 Infection and Pulmonary Disease Safely Treated With Remdesivir.

We describe 2 expremature infants presenting with SARS-CoV-2-related pulmonary disease in their second and fifth week of life needing support with mechanical ventilation. Both infants' initial presentation was with repeated apneas. These cases highlight that SARS-CoV-2 infection could present with apneas and has the potential to progress to more severe pulmonary disease in this high-risk age group of patients. Both patients were treated with remdesivir (RDV). We provide the data of 2 high-risk neonates successfully treated with RDV without observation of any described side effects. A recognition that these high-risk neonates could deteriorate and early multidisciplinary team discussion is the mainstay to the compassionate access to RDV. Our experience led us to develop a guideline on the use of RDV below 12 years of age, with particular focus on infants and young children.

Surfactant therapy to facilitate weaning in paediatric patients dependent on extacorporeal membrane oxygenation.

We are reporting two paediatric cases with severe adenoviral acute respiratory distress syndrome with viral counts of 308 and 119 million copies/mL respectively, who required venoarterial extracorporeal membrane oxygenation (ECMO) support for nearly 3 weeks. They were static on ECMO and had shown a complete lack of response to all therapeutic interventions aimed at decreasing ECMO support. To facilitate weaning from ECMO, they received 2-3 doses of surfactant. This led to dramatic improvement in pulmonary compliance, oxygenation and chest X-ray. They were both weaned off ECMO within 24 hours of receiving surfactant. Surfactant was well tolerated, with no adverse effects. In both cases, weaning from ECMO was possible only after surfactant administration. From our experience, we conclude that surfactant administration is a potentially safe and effective treatment modality that helps weaning from ECMO and should be considered in patients who are dependent on ECMO for long duration.

Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia managed with extracorporeal membrane oxygenation: experience and outcome.

OBJECTIVE: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia, an infection that affects predominantly young people, has a mortality rate of > 70% despite aggressive conventional management. Little information is available on the management of patients with Panton-Valentine leukocidin expressing S. aureus pneumonia with extracorporeal membrane oxygenation support. As a large extracorporeal membrane oxygenation center, we reviewed our experience and outcomes with Panton-Valentine Leukocidin expressing S. aureus pneumonia. DATA SOURCES: Locally held register of all extracorporeal membrane oxygenation patients at Glenfield Hospital. STUDY SELECTION: Retrospective study including all patients with sputum-positive Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation support at a single extracorporeal membrane oxygenation center. DATA SYNTHESIS: On review of our database held from September 1989 until date, there were four patients with sputum-confirmed Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation. Refractory hypoxemia and/or uncompensated hypercapnia despite optimal conventional management were the indications for extracorporeal membrane oxygenation. After varying periods on extracorporeal membrane oxygenation with appropriate antibiotic and ancillary care, all four patients were discharged home. CONCLUSIONS: Panton-Valentine leukocidin expressing S. aureus pneumonia can cause severe, necrotizing pneumonia associated with acute respiratory distress syndrome, which can be particularly challenging to manage. Extracorporeal membrane oxygenation support permits low pressure lung ventilation, avoiding barotrauma to lungs made friable by Panton-Valentine leukocidin expressing S. aureus infection. Although this is a small number of patients, the results are encouraging.

Candida peritonitis: a rare complication following early dislodgement of percutaneous endoscopic gastrostomy tube.

UNLABELLED: Candida peritonitis is a rare but potentially fatal complication of early dislodgement of percutaneous endoscopic gastrostomy (PEG) feeding tube. We report the case of 12-year-old boy who developed Candida peritonitis subsequent to early dislodgement of PEG tube. PEG tubes may be prone to accidental dislodgement or removal by patients or carers. This complication has to be recognized early in order to avoid the risk of peritonitis. In our case the patient initially developed coliform peritonitis followed by peritoneal and systemic candidiasis. The patient needed ventilatory support, inotropic support, broad-spectrum antibiotics, total parenteral nutrition and antifungal agents liposomal amphotericin and flucytosine. CONCLUSION: Early dislodged PEG tubes should be recognized early in order to avoid the risk of peritonitis and managed by endoscopic or surgical replacement rather than blind replacement by the appropriately skilled personnel.

Experience with mobile inhaled nitric oxide during transport of neonates and children with respiratory insufficiency to an extracorporeal membrane oxygenation center.

OBJECTIVE: To share our experience with the use of inhaled nitric oxide (iNO) during the transport of ventilated neonates and children to an extracorporeal membrane oxygenation (ECMO) center and to discuss the efficacy and safety of iNO use in this situation. DATA SOURCES: Case note review of 55 consecutive patients transported while receiving iNO to Glenfield Hospital, Leicester, UK, for consideration of ECMO. STUDY SELECTION: Retrospective case note review. DATA EXTRACTION: The clinical condition of each patient recorded at arrival of the transport team at the referring hospital, during transport, and at arrival at Glenfield Hospital. Preclinical and postclinical conditions were compared using the paired Student's t-test. DATA SYNTHESIS: Overall data showed a significant improvement in transcutaneous oximetry measurements (Spo(2): 84.8% preclinical, 90.6% postclinical; p = .006) and Pao(2) (59 torr [7.87 kPa] preclinical, 84 torr [11.23 kPa] postclinical; p = .001) during transport in our patient group. Based on limited safety data, no untoward events or toxic metabolites were observed with iNO therapy during transport. CONCLUSIONS: iNO does appear to improve oxygenation during transfer of patients for ECMO in our series. Based on limited safety data, iNO appears safe to use in transport.

Pneumocephalus in neonatal meningitis: diffuse, necrotizing meningo-encephalitis in Citrobacter meningitis presenting with pneumatosis oculi and pneumocephalus.

UNLABELLED: OBJECTIVE/PATIENT: Gas-containing encephalitis is rarely associated with neonatal meningitis. We report a case of a 19-day-old baby who presented with a rapid onset of septic shock complicated by progressively increasing gas accumulation within the brain and anterior chamber of the eye. We describe the evolution of the clinical picture and the management. INTERVENTIONS: Ventilatory support, fluid resuscitation, and continuous venovenous hemofiltration were provided in view of multiple system failure. Despite effective antibiotic therapy and supportive management, the patient died with worsening accumulation of gas within the brain, resulting in brainstem death. RESULTS: Computed tomographic images were characteristic of diffuse necrotizing meningo-encephalitis. Postmortem examination showed friable brain tissue with venous infarction and extensive gas accumulation. Citrobacter koseri was identified from the blood and cerebrospinal fluid cultures. CONCLUSION: This case re-emphasises the importance of C. koseri as both a community-acquired and nosocomial neonatal pathogen. Radiologic evidence suggestive of diffuse necrotizing meningo-encephalitis in combination with pneumocephalus and pneumatosis oculi in Citrobacter infections has never been described before. Diagnostic imaging with computed tomographic scanning of the brain and initiation of broad-spectrum antibiotics with good penetration into cerebrospinal fluid are indicated as soon as infection with Citrobacter species is suspected clinically, with appearance of pneumatosis oculi as a rare, late finding.

Population pharmacokinetics of theophylline during paediatric extracorporeal membrane oxygenation.

AIMS: To determine the population pharmacokinetics of theophylline during extracorporeal membrane oxygenation (ECMO) from routine monitoring data. METHODS: Retrospective data were collected from 75 term neonates and children (age range 2 days to 17 years) receiving continuous infusions of aminophylline (mean rate 9.2 +/- 2.6 micro g kg-1 min-1) during ECMO. A total of 160 plasma concentrations (range 1-8 per patient), sampled at time intervals ranging from 10 h to 432 h, were included. Population PK analysis and model building were carried out using WinNonMix Professional (Version 2.0.1). Cross-validation was used to evaluate the validity and predictive accuracy of the model. RESULTS: A one-compartment model with first order elimination combined with an additive error model was found to best describe the data. Of the covariables tested, bodyweight significantly influenced clearance and volume of distribution, whereas age was an important determinant of clearance, as adjudged by the differences in the -2 x log likelihood (P < 0.005) and the residual error value. The final model parameters were estimated as: clearance (l h-1) = 0.023 x bodyweight (kg) + 0.000057 x age (days) and volume of distribution (l) = 0.57 x bodyweight (kg). The interindividual variability in clearance and volume of distribution was 38% and 40%, respectively. The residual error corresponded to a standard deviation of 3.6 mg l-1. Cross-validation revealed a median (95% confidence interval) model bias of 9.4% (2.9, 16.5%) and precision of 29.5% (24.8, 36.0%). CONCLUSIONS: The estimated clearance is significantly lower, and volume of distribution higher, than previously reported in non-ECMO patients of similar age. These differences are probably a result of the expanded circulating volume during ECMO and altered renal and hepatic physiology in this critically ill group. Large interindividual variability reflects the heterogeneous nature of patients treated on ECMO.