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.c onventional modes of mechanical ventilation are clearly limited in their ability to provide synchrony between the patient and the assist delivered, as demonstrated repeatedly in adults (1,2) and more recently in children (3). Patientventilator asynchrony has been associated with poor clinical outcome (1,2,4). Despite the attempt to improve synchrony with "patient-triggered" modes such as pressure control ventilation (PCV) or pressure support ventilation (PSV), 25% of adult patients show more than 10% asynchrony with the ventilator (1,2,5). In pediatric patients, synchrony is particularly difficult to achieve because of the small tidal volumes, high respiratory rates, and weak airway flows and pressures. Ironically, during synchronized intermittent mandatory ventilation, more than half of the patient's breathing cycle is spent in asynchrony (3) with the ventilator.Besides the poor timing between the patient and the ventilator, patient-ventilator asynchrony also includes the inability of the ventilator to respond to patient demand and the natural breath-to-breath variability. Respiratory variability is a sign of a well functioning respiratory system (6). By definition, PCV and PSV deliver fixed levels of assist, thereby offering no possibility to respond to the patient's respiratory demand and variability.Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers assist in time and in proportion to the electrical activity of the diaphragm (Edi) on a breath-by-breath basis (7). Numerous studies have shown that NAVA efficiently unloads the respirat...

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.

Background Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been reported worldwide. Negative RT-PCR testing associated with positive serology in most cases suggests a post-infectious syndrome. Because the pathophysiology of this syndrome is still poorly understood, extensive virological and immunological investigations are needed. Methods We report a series of four pediatric patients admitted to Geneva University Hospitals with persistent fever and laboratory evidence of inflammation meeting 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-SARS-CoV-2 IgA and IgG were strongly positive by ELISA and immunofluorescence. Both pseudo- and full virus neutralization assays showed the presence of neutralizing antibodies in all children, confirming a recent infection with SARS-CoV-2. 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 haemophagocytic lymphohistiocytosis (HLH). In contrast to patients with primary HLH, our patients showed normal perforin expression and NK cell degranulation. The levels of soluble 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 post-infectious inflammatory syndrome associated with elevation in all cytokines, and markers of recent T-cell activation (sIL-2R) occurring despite a strong and specific humoral response to SARS-CoV2. Further functional and genetic analyses are essential to better understand the mechanisms of host-pathogen interactions.

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