Total face mask with neurally adjusted ventilatory assist as a rescue therapy in infants with severe bronchiolitis.

Severe bronchiolitis patients are often supported with non-invasive ventilation (NIV). In case of NIV failure, we recently started to use non-invasive neurally adjusted ventilatory assist ventilation (NIV-NAVA) with a total face mask interface (TFM) and report now our experience with this modality of respiratory support. Retrospective study was made from October 2022 to May 2023 at the Geneva University Hospital Paediatric Intensive Care Unit. Inclusion criteria were children, aged from 0 to 6 months, with severe bronchiolitis with initial NIV failure and switch to NIV-NAVA-TFM. From 49 children with respiratory syncytial virus (RSV)-induced bronchiolitis requiring any form of respiratory support, 10 (median age 61 days (IQR 44-73) failing CPAP or NIV underwent rescue treatment with NIV-NAVA using a TFM. Patients were switched to TFM-NIV-NAVA 8 h (IQR 3-22) after admission for 24.5 h (IQR 13-60). After initiation of TFM-NIV-NAVA, oxygenation improved significantly as early as 1 h after initiation, whereas transcutaneous CO2 values remained stable. None of the patients needed to be intubated and there was no episode of TFM discontinuation due to interface discomfort or other unwanted side effects. Sedation was used in all patients with high proportion of intravenous dexmedetomidine. Median ventilatory assistance duration was 2.5 days (IQR 2-4) and median PICU stay was 4.5 (IQR 3-6).   Conclusion: In infants with severe RSV-induced bronchiolitis, respiratory support with TFM-NIV-NAVA seems to be feasible as a rescue therapy and might be considered in selected patients. What is Known: • Bronchiolitic patients with NIV support failure may require invasive mechanical ventilation. • Interface related complications, especially facial sores, can be a cause of NIV failure. What is New: • Total face mask with non-invasive neurally adjusted ventilatory assist (TFM-NIV-NAVA) seems feasible as a rescue therapy in deteriorating patients with CPAP or NIV failure. • TFM-NIV-NAVA can improve oxygenation rapidly in patients with aggravating hypoxemia and seems to be well tolerated.

Clinical practice guidelines: management of severe bronchiolitis in infants under 12 months old admitted to a pediatric critical care unit.

PURPOSE: We present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines. METHODS: Twenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies. The questions were written in the Patient-Intervention-Comparison-Outcome (PICO) format. An extensive Anglophone and Francophone literature search indexed in the MEDLINE database via PubMed, Web of Science, Cochrane and Embase was performed using pre-established keywords. The texts were analyzed and classified according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. When this method did not apply, an expert opinion was given. Each of these recommendations was voted on by all the experts according to the Delphi methodology. RESULTS: This group proposes 40 recommendations. The GRADE methodology could be applied for 17 of them (3 strong, 14 conditional) and an expert opinion was given for the remaining 23. All received strong approval during the first round of voting. CONCLUSION: These guidelines cover the different aspects in the management of severe bronchiolitis in infants admitted to pediatric critical care units. Compared to the different ways to manage patients with severe bronchiolitis described in the literature, our original work proposes an overall less invasive approach in terms of monitoring and treatment.

Early and Late Postoperative Tachyarrhythmias in Children and Young Adults Undergoing Congenital Heart Disease Surgery.

The population of patients with congenital heart disease is constantly growing with an increasing number of individuals reaching adulthood. A significant proportion of these children and young adults will suffer from tachyarrhythmias due to the abnormal anatomy, the hemodynamic burden, or as a sequela of surgical treatment. Depending on the underlying mechanism, arrhythmias may arise in the early postoperative period (hours to days after surgery) or in the late postoperative period (usually years after surgery). A good understanding of the electrophysiological characteristics and pathophysiological mechanisms is therefore crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, risk factors, pathophysiological insights, electrophysiological features, and therapy regarding tachyarrhythmias in children and young adults undergoing reparative surgery for congenital heart disease. The evolution and latest data on treatment options, including pharmacological therapy, ablation procedures, device therapy decision, and thromboprophylaxis, are summarized. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

In situ simulation training for parental presence during critical situations in PICU: an observational study.

Family presence during invasive procedures or cardiopulmonary resuscitation (CPR) is a part of the family-centered approach in pediatric intensive care units (PICUs). We established a simulation program aiming at providing communication tools to healthcare professionals. The goal of this study was to evaluate the impact of this program on the stress of PICU professionals and its acceptance. An observational study of a simulation program, with questionnaire, was used to measure pre- and post-simulation stress and the degree of satisfaction of the participants. PICU of Geneva Children's Hospital, Switzerland. Forty simulations with four different simulation scenarios and various types of parental behavior, as imitated by professional actors, were completed during a 1-year period. Primary outcomes were the difference in perceived stress level before and after the simulation and the degree of satisfaction of healthcare professionals (nursing assistants, nurses, physicians). The impact of previous experience with family members during critical situations or CPR was evaluated by variation in perceived stress level. Overall, 201 questionnaires were analyzed. Perceived stress associated with parental presence decreased from a pre-simulation value of 6 (IQR, 4-7) to 4 (IQR, 2-5) post-simulation on a scale of 1-10. However, in 25.7% of cases, the individually perceived post-simulation stress level was higher than the pre-simulation one. Satisfaction of the participants was high with a median of 10 (IQR, 9-10) out of 10. CONCLUSIONS: A simulation program helps reduce PICU team emotional stress associated with the presence of family members during critical situations or CPR, and is welcomed by PICU team members. WHAT IS KNOWN: • Family presence during cardiopulmonary resuscitation (CPR) or critical situations is a part of the family-centered approach in pediatric intensive care. • The benefits for the family have been already demonstrated. However, this policy is still controversy among healthcare professionals. WHAT IS NEW: • A simulation program seeking to provide skills focused on family presence management in the PICU is useful to reduce stress and was well accepted by participants. • It might become an indispensable training intervention for the implementation of a PICU policy to allow family presence during CPR or other critical situations.

Comparison of inspiratory effort with three variable-flow nasal continuous positive airway pressure devices in preterm infants: a cross-over study.

OBJECTIVE: Patient's work of breathing may vary between different neonatal nasal continuous positive airway pressure (NCPAP) devices. Therefore, we aimed to compare the inspiratory effort of three variable-flow NCPAP delivery systems used in preterm infants. DESIGN: Cross-over study. PATIENTS/SETTING: From June 2015 to August 2016, 20 preterm infants weighing ≤2500 g requiring NCPAP for mild respiratory distress syndrome were enrolled. INTERVENTIONS: Each patient was successively supported by three randomly assigned variable-flow NCPAP systems (MedinCNO, Infant Flow and Servo-i) for 20 min while maintaining the same continuous positive airway pressure level as the patient was on before the study period. MAIN OUTCOME MEASURES: Patients' inspiratory effort was estimated by calculating the sum of the difference between maximal inspiratory and baseline electrical activity of the diaphragm (∆EAdi) for 30 consecutive breaths, and after normalising this obtained value for the timing of the 30 breaths. RESULTS: Physiological parameters (oxygen saturation measured by pulse oximetry, respiratory rate, heart beat, transcutaneous partial pressure CO2) and oxygen requirements remained identical between the three NCPAP systems. Although a wide variability in inspiratory effort could be observed, there were no statistically significant differences between the three systems for the sum of ∆EAdi for 30 breaths: CNO, 262 (±119) µV; IF, 352 (±262) µV; and SERVO-i, 286 (±126) µV, and the ∆EAdi reported on the timing of 30 breaths (sum ∆EAdi/s): CNO, 6.1 (±2.3) µV/s; IF, 7.9 (±4.9) µV/s; SERVO-i, 7.6 (±3.6) µV/s. CONCLUSION: In a neonatal population of preterm infants, inspiratory effort is comparable between the three tested modern variable-flow NCPAP devices.

Immunological Assessment of Pediatric Multisystem Inflammatory Syndrome Related to Coronavirus Disease 2019.

BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) have been reported worldwide. Negative polymerase chain reaction (RT-PCR) testing associated with positive serology in most of the cases suggests a postinfectious syndrome. Because the pathophysiology of this syndrome is still poorly understood, extensive virological and immunological investigations are needed. METHODS: We report a series of 4 pediatric patients admitted to Geneva University Hospitals with persistent fever and laboratory evidence of inflammation meeting the published definition of MIS-C related to COVID-19, to whom an extensive virological and immunological workup was performed. RESULTS: RT-PCRs on multiple anatomical compartments were negative, whereas anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin A (IgA) and immunoglobulin G (IgG) were strongly positive by enzyme-linked immunosorbent assay and immunofluorescence. Both pseudoneutralization and full virus neutralization assays showed the presence of neutralizing antibodies in all children, confirming a recent infection with SARS-CoV-2. The analyses of cytokine profiles revealed an elevation in all cytokines, as reported in adults with severe COVID-19. Although differing in clinical presentation, some features of MIS-C show phenotypic overlap with hemophagocytic lymphohistiocytosis (HLH). In contrast to patients with primary HLH, our patients showed normal perforin expression and natural killer (NK) cell degranulation. The levels of soluble interleukin (IL)-2 receptor (sIL-2R) correlated with the severity of disease, reflecting recent T-cell activation. CONCLUSION: Our findings suggest that MIS-C related to COVID-19 is caused by a postinfectious inflammatory syndrome associated with an elevation in all cytokines, and markers of recent T-cell activation (sIL-2R) occurring despite a strong and specific humoral response to SARS-CoV-2. Further functional and genetic analyses are essential to better understand the mechanisms of host-pathogen interactions.

Imposed Work of Breathing During High-Frequency Oscillatory Ventilation in Spontaneously Breathing Neonatal and Pediatric Models.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) is used in cases of neonatal and pediatric acute respiratory failure, sometimes even as the primary ventilatory mode. Allowing patients (at least neonates) on HFOV to breathe spontaneously soon after intubation has been shown to be feasible, and this is becoming a more generally used approach for infants and small children. However, such an approach may increase the imposed work of breathing (WOB), raising the question of whether the imposed WOB varies with the use of newer-generation HFOV devices, which operate according to different functional principles. METHODS: A bench test was designed to compare the pressure-time product (PTP), a surrogate marker of the imposed WOB, produced with the use of 7 HFOV devices. Scenarios corresponding to various age groups (preterm newborn [1 kg], term newborn [3.5 kg], infant [10 kg], and child [25 kg]) and 2 respiratory system conditions (physiologic and pathologic) were tested. RESULTS: The PTP varied between devices and increased with the oscillation frequency for all devices, independent of the respiratory system condition. Furthermore, the PTP increased with age and was higher for physiologic than for pathologic respiratory system conditions. We considered a change of ≥ 20% as being of clinically relevant; the effect of oscillation frequency was the most important parameter influencing imposed WOB during spontaneous breathing. CONCLUSIONS: Variations in imposed WOB, as expressed by PTP values, during spontaneous breathing depend mainly on the oscillator frequency, respiratory system condition, and, though to a lesser extent, on the device itself.

Serelaxin for infant heart failure in congenital dilated cardiomyopathy.

Serelaxin has been studied in trials in adults with acute heart failure, but not in children. We report the first compassionate use of serelaxin in an infant. A 6-month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane oxygenation following cardiac arrest unresponsive to medical treatment. Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator therapy. During the 48-hour infusion of serelaxin, we observed marked improvement in brain natriuretic peptide, left ventricular systolic function, and dilatation. The patient was successfully weaned from extracorporeal membrane oxygenation 24 hours later. The child died after a second extracorporeal membrane oxygenation run owing to sepsis.

Impact of ventilatory modes on the breathing variability in mechanically ventilated infants.

OBJECTIVES: Reduction of breathing variability is associated with adverse outcome. During mechanical ventilation, the variability of ventilatory pressure is dependent on the ventilatory mode. During neurally adjusted ventilatory assist (NAVA), the support is proportional to electrical activity of the diaphragm (EAdi), which reflects the respiratory center output. The variability of EAdi is, therefore, translated into a similar variability in pressures. Contrastingly, conventional ventilatory modes deliver less variable pressures. The impact of the mode on the patient's own respiratory drive is less clear. This study aims to compare the impact of NAVA, pressure-controlled ventilation (PCV), and pressure support ventilation (PSV) on the respiratory drive patterns in infants. We hypothesized that on NAVA, EAdi variability resembles most of the endogenous respiratory drive pattern seen in a control group. METHODS: Electrical activity of the diaphragm was continuously recorded in 10 infants ventilated successively on NAVA (5 h), PCV (30 min), and PSV (30 min). During the last 10 min of each period, the EAdi variability pattern was assessed using non-rhythmic to rhythmic (NRR) index. These variability profiles were compared to the pattern of a control group of 11 spontaneously breathing and non-intubated infants. RESULTS: In control infants, NRR was higher as compared to mechanically ventilated infants (p < 0.001), and NRR pattern was relatively stable over time. While the temporal stability of NRR was similar in NAVA and controls, the NRR profile was less stable during PCV. PSV exhibited an intermediary pattern. PERSPECTIVES: Mechanical ventilation impacts the breathing variability in infants. NAVA produces EAdi pattern resembling most that of control infants. NRR can be used to characterize respiratory variability in infants. Larger prospective studies are necessary to understand the differential impact of the ventilatory modes on the cardio-respiratory variability and to study their impact on clinical outcomes.

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children.

INTRODUCTION: The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. METHODS: Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. RESULTS: Ep dosing infusions ranged from 0.01 to 0.23 µg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. CONCLUSIONS: According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.

Neurally adjusted ventilatory assist improves patient­ventilator interaction in infants as compared with conventional ventilation.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation controlled by the electrical activity of the diaphragm (Edi). The aim was to evaluate patient-ventilator interaction in infants during NAVA as compared with conventional ventilation. METHODS: Infants were successively ventilated with NAVA, pressure control ventilation (PCV), and pressure support ventilation (PSV). Edi and ventilator pressure (Pvent) waveforms were compared and their variability was assessed by coefficients of variation. RESULTS: Ten patients (mean age 4.3 ± 2.4 mo and weight 5.9 ± 2.2 kg) were studied. In PCV and PSV, 4 ± 4.6% and 6.5 ± 7.7% of the neural efforts failed to trigger the ventilator. This did not occur during NAVA. Trigger delays were shorter with NAVA as compared with PCV and PSV (93 ± 20 ms vs. 193 ± 87 ms and 135 ± 29 ms). During PCV and PSV, the ventilator cycled off before the end of neural inspiration in 12 ± 13% and 21 ± 19% of the breaths (0 ± 0% during NAVA). During PCV and PSV, 24 ± 11% and 25 ± 9% of the neural breath cycle was asynchronous with the ventilator as compared with 11 ± 3% with NAVA. A large variability was observed for Edi in all modes, which was transmitted into Pvent during NAVA (coefficient of variation: 24 ± 8%) and not in PCV (coefficient of variation 2 ± 1%) or PSV (2 ± 2%). CONCLUSION: NAVA improves patient-ventilator interaction and delivers adequate ventilation with variable pressure in infants.

A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase.

INTRODUCTION: The present study is a pilot prospective safety evaluation of a new closed loop computerised protocol on ventilation and oxygenation in stable, spontaneously breathing children weighing more than 7 kg, during the weaning phase of mechanical ventilation. METHODS: Mechanically ventilated children ready to start the weaning process were ventilated for five periods of 60 minutes in the following order: pressure support ventilation, adaptive support ventilation (ASV), ASV plus a ventilation controller (ASV-CO2), ASV-CO2 plus an oxygenation controller (ASV-CO2-O2) and pressure support ventilation again. Based on breath-by-breath analysis, the percentage of time with normal ventilation as defined by a respiratory rate between 10 and 40 breaths/minute, tidal volume > 5 ml/kg predicted body weight and end-tidal CO2 between 25 and 55 mmHg was determined. The number of manipulations and changes on the ventilator were also recorded. RESULTS: Fifteen children, median aged 45 months, were investigated. No adverse event and no premature protocol termination were reported. ASV-CO2 and ASV-CO2-O2 kept the patients within normal ventilation for, respectively, 94% (91 to 96%) and 94% (87 to 96%) of the time. The tidal volume, respiratory rate, peak inspiratory airway pressure and minute ventilation were equivalent for all modalities, although there were more automatic setting changes in ASV-CO2 and ASV-CO2-O2. Positive end-expiratory pressure modifications by ASV-CO2-O2 require further investigation. CONCLUSION: Over the short study period and in this specific population, ASV-CO2 and ASV-CO2-O2 were safe and kept the patient under normal ventilation most of the time. Further research is needed, especially for positive end-expiratory pressure modifications by ASV-CO2-O2. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01095406.