ROX (Respiratory rate-OXygenation) index to predict early response to high-flow nasal cannula therapy in infants with viral bronchiolitis.

INTRODUCTION: High-flow nasal cannula (HFNC) is commonly used as first step respiratory support in infants with moderate-to-severe acute viral bronchiolitis (AVB). This device, however, fails to effectively manage respiratory distress in about a third of patients, and data are limited on determinants of patient response. The respiratory rate-oxygenation (ROX) index is a relevant tool to predict the risk for HFNC failure in adult patients with lower respiratory tract infections. The primary objective of this study was to assess the relationship between ROX indexes collected before and 1 h after HFNC initiation, and HFNC failure occurring in the following 48 h in infants with AVB. METHOD: This is an ancillary study to the multicenter randomized controlled trial TRAMONTANE 2, that included 286 infants of less than 6 months with moderate-to-severe AVB. Collection of physiological variables at baseline (H0), and 1 h after HFNC (H1), included heart rate (HR), respiratory rate (RR), fraction of inspired oxygen (FiO2), respiratory distress score (modified Wood's Clinical Asthma Score [mWCAS]), and pain and discomfort scale (EDIN). ROX and ROX-HR were calculated as SpO 2 FiO 2 RR $\frac{\left(\frac{{\mathrm{SpO}}_{2}}{{\mathrm{FiO}}_{2}}\right)}{\mathrm{RR}}$ and 100 × ROX HR $100\times \frac{\mathrm{ROX}}{\mathrm{HR}}$ , respectively. Predefined HFNC failure criteria included increase in respiratory distress score or RR, increase in discomfort, and severe apnea episodes. The accuracies of ROX, ROX-HR indexes and clinical variable to predict HFNC failure were assessed using receiver operating curve analysis. We analyzed predictive factors of HFNC failure using multivariate logistic regressions. RESULT: HFNC failure occurred in 111 of 286 (39%) infants, and for 56 (50% of the failure) of them within the first 6 h. The area under the curve of ROX indexes at H0 and H1 were, respectively, 0.56 (95% confidence interval [CI] 0.48-0.63, p = 0.14), 0.56 (95% CI 0.49-0.64, p = 0.09). ROX-HR performances were better but remained poorly discriminant. HFNC failure was associated with higher mWCAS score at H1 (p < 0.01) and lower decrease in EDIN scale during the first hour of HFNC delivery (p = 0.02). In the multivariate analyses, age and mWCAS score were were found to be independent factors associated with HFNC failure at H0. At H1, weight and mWCAS were associated factors. CONCLUSION: In this study, neither ROX index, nor physiological variables usually collected in infants with AVB had early discriminatory capacity to predict HFNC failure.

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.

Predictive Value of Optic Nerve Sheath Diameter for Diagnosis of Intracranial Hypertension in Children With Severe Brain Injury.

Background and Aims: Intracranial Hypertension (ICH) is a life-threatening complication of brain injury. The invasive measurement of intracranial pressure (ICP) remains the gold standard to diagnose ICH. Measurement of Optic Nerve Sheath Diameter (ONSD) using ultrasonography is a non-invasive method for detecting ICH. However, data on paediatric brain injury are scarce. The aim of the study was to determine the performance of the initial ONSD measurement to predict ICH occurring in children with severe brain injury and to describe the ONSD values in a control group. Methods: In this cross-sectional study, ONSD was measured in children aged 2 months-17 years old with invasive ICP monitoring: before placement of ICP probe and within the 60 min after, and then daily during 3 days. ONSD was also measured in a control group. Results: Ninety-nine patients were included, of whom 97 were analysed, with a median (IQR) age of 8.7 [2.3-13.6] years. The median (IQR) PIM 2 score was 6.6 [4.4-9.7] and the median (IQR) PELOD score was 21 [12-22]. Aetiologies of brain injury were trauma (n = 72), infection (n = 17) and stroke (n = 8). ICH occurred in 65 children. The median (IQR) ONSD was 5.58 mm [5.05-5.85]. ONSD performed poorly when it came to predicting ICH occurrence within the first 24 h (area under the curve, 0.58). There was no significant difference between the ONSD of children who presented with ICH within the first 24 h and the other children, with a median (IQR) of 5.6 mm [5.1-5.9] and 5.4 mm [4.9-5.8], respectively. Infants aged less than 2 years had a median (IQR) ONSD of 4.9 mm [4.5-5.2], significantly different from children aged more than 2 years, whose median ONSD was 5.6 mm [5.2-5.9]. Age, aetiology or ICP levels did not change the results. Thirty-one controls were included, with a median age of 3.7 (1.2-8.8) years. The median (IQR) of their ONSD measurement was 4.5 mm [4.1-4.8], significantly lower than the patient group. Conclusion: In a paediatric severe brain injury population, ONSD measurement could not predict the 24 h occurrence of ICH. Severity of patients, timing and conditions of measurements may possibly explain these results.

Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

Malignant pertussis in infants: factors associated with mortality in a multicenter cohort study.

BACKGROUND: Malignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands' strategy is associated with survival. METHODS: We reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands' algorithm (indication and timing of specific treatments). RESULTS: Twenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7-28] G/l/day vs 5.9 [3.0-6.8] G/l/day, p = 0.007). WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio < 1 were significantly associated with death (p = 0.001 and p = 0.003, respectively). Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands' strategy was associated with survival (100% vs 0%; p < 0.001, relative risk of death = 0.18, 95%-CI [0.05-0.64]). CONCLUSIONS: A fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands' strategy, with the expectation of a better survival.

Management of severe asthma exacerbation: guidelines from the Société Française de Médecine d'Urgence, the Société de Réanimation de Langue Française and the French Group for Pediatric Intensive Care and Emergencies.

BACKGROUND: The French Emergency Medicine Society, the French Intensive Care Society and the Pediatric Intensive Care and Emergency Medicine French-Speaking Group edited guidelines on severe asthma exacerbation (SAE) in adult and pediatric patients. RESULTS: The guidelines were related to 5 areas: diagnosis, pharmacological treatment, oxygen therapy and ventilation, patients triage, specific considerations regarding pregnant women. The literature analysis and formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Of the 21 formalized guidelines, 4 had a high level of evidence (GRADE 1+/-) and 7 a low level of evidence (GRADE 2+/-). The GRADE method was inapplicable to 10 guidelines, which resulted in expert opinions. A strong agreement was reached for all guidelines. CONCLUSION: The conjunct work of 36 experts from 3 scientific societies resulted in 21 formalized recommendations to help improving the emergency and intensive care management of adult and pediatric patients with SAE.

Nutritional management of young infants presenting with acute bronchiolitis in Belgium, France and Switzerland: survey of current practices and documentary search of national guidelines worldwide.

Feeding difficulties are common in young infants presenting with acute bronchiolitis, but limited data is available to guide clinicians adapting nutritional management. We aimed to assess paediatricians' nutritional practices among Western Europe French speaking countries. A survey was disseminated to describe advice given to parents for at home nutritional support, in hospital nutritional management, and preferred methods for enteral nutrition and for intravenous fluid management. A documentary search of international guidelines was concomitantly conducted. Ninety-three (66%) contacted physicians responded. Feeding difficulties were a common indication for infants' admission. Written protocols were rarely available. Enteral nutrition was favoured most of the time when oral nutrition was insufficient and might be withheld in case of severe dyspnoea to decrease respiratory workload. Half of physicians were aware of hyponatremia risk and pathophysiology, and isotonic intravenous solutions were used in less than 15% of centres. International guideline search (23 countries) showed a lack of detailed nutritional management recommendations in most of them.Conclusion: practices were inconsistent among physicians. Guidelines detailed nutritional management poorly. Awareness of hyponatremia risk in relation to intravenous hypotonic fluids and of the safety of enteral hydration and nutrition is insufficient. New guidelines including detailed nutritional management recommendations are urgently needed. What is Known? • Infants presenting with acute bronchiolitis face feeding difficulties. • Underfeeding may promote undernutrition, and intravenous hydration with hypotonic fluids may induce hyponatremia. What is New? • Physicians' nutritional practices are inconsistent and awareness of hyponatremia risk and pathophysiology is insufficient among physicians. • Awareness of hyponatremia risk and pathophysiology is insufficient among physicians. • The reasons for enteral nutrition withholding in bronchiolitis infants are not evidence based, and national guidelines of acute bronchiolitis across the world are elusive regarding nutritional management. • National guidelines of acute bronchiolitis across the world are elusive regarding nutritional management.

A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2).

PURPOSE: High-flow nasal cannula (HFNC) therapy is increasingly proposed as first-line respiratory support for infants with acute viral bronchiolitis (AVB). Most teams use 2 L/kg/min, but no study compared different flow rates in this setting. We hypothesized that 3 L/kg/min would be more efficient for the initial management of these patients. METHODS: A randomized controlled trial was performed in 16 pediatric intensive care units (PICUs) to compare these two flow rates in infants up to 6 months old with moderate to severe AVB and treated with HFNC. The primary endpoint was the percentage of failure within 48 h of randomization, using prespecified criteria of worsening respiratory distress and discomfort. RESULTS: From November 2016 to March 2017, 142 infants were allocated to the 2-L/kg/min (2L) flow rate and 144 to the 3-L/kg/min (3L) flow rate. Failure rate was comparable between groups: 38.7% (2L) vs. 38.9% (3L; p = 0.98). Worsening respiratory distress was the most common cause of failure in both groups: 49% (2L) vs. 39% (3L; p = 0.45). In the 3L group, discomfort was more frequent (43% vs. 16%, p = 0.002) and PICU stays were longer (6.4 vs. 5.3 days, p = 0.048). The intubation rates [2.8% (2L) vs. 6.9% (3L), p = 0.17] and durations of invasive [0.2 (2L) vs. 0.5 (3L) days, p = 0.10] and noninvasive [1.4 (2L) vs. 1.6 (3L) days, p = 0.97] ventilation were comparable. No patient had air leak syndrome or died. CONCLUSION: In young infants with AVB supported with HFNC, 3 L/kg/min did not reduce the risk of failure compared with 2 L/kg/min. This clinical trial was recorded on the National Library of Medicine registry (NCT02824744).

Nasal high flow in management of children with status asthmaticus: a retrospective observational study.

BACKGROUND: Asthma is the most common obstructive airway disease in children and adults. Nasal high flow (NHF) is a recent device that is now used as a primary support for respiratory distress. Several studies have reported use of NHF as a respiratory support in status asthmaticus; however, there are no data to recommend such practice. We therefore conducted this preliminary study to evaluate NHF therapy for children with status asthmaticus admitted to our PICU in order to prepare a multicentre randomized controlled study. RESULTS: Between November 2009 and January 2014, 73 patients with status asthmaticus were admitted to the PICU, of whom 39 (53%) were treated with NHF and among these 10 (26%) presented severe acidosis at admission (pH < 7.30). Thirty-four less severe children (41%) were treated with standard oxygen. For one child (2.6%) NHF failed and was then switched to non-invasive ventilation. NHF was discontinued in another patient because of the occurrence of pneumothorax after 31 h with NHF; the patient was then switched to standard oxygen therapy. Mean ± SD heart rate (165 ± 21 vs. 141 ± 25/min, p < 0.01) and respiratory rate (40 ± 13 vs. 31 ± 8/min, p < 0.01) decreased significantly, and blood gas improved in the first 24 h. In the subgroup of patients with acidosis, median [IQR] pH increased significantly between hour 0 and 2 (7.25 [7.21-7.26] vs. 7.30 [7.27-7.33], p = 0.009) and median [IQR] pCO2 decreased significantly (7.27 kPa [6.84-7.91 vs. 5.85 kPa [5.56-6.11], p = 0.007). No patient was intubated. CONCLUSION: This retrospective study showed the feasibility and safety of NHF in children with severe asthma. Blood gas and clinical parameters were significantly improved during the first 24 h. NHF failed in only two patients, and none required invasive ventilation.

High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (TRAMONTANE study).

PURPOSE: Nasal continuous positive airway pressure (nCPAP) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (AVB). Although oxygen delivery via high flow nasal cannula (HFNC) is increasingly used, evidence of its efficacy and safety is lacking in infants. METHODS: A randomized controlled trial was performed in five pediatric intensive care units (PICUs) to compare 7 cmH2O nCPAP with 2 L/kg/min oxygen therapy administered with HFNC in infants up to 6 months old with moderate to severe AVB. The primary endpoint was the percentage of failure within 24 h of randomization using prespecified criteria. To satisfy noninferiority, the failure rate of HFNC had to lie within 15% of the failure rate of nCPAP. Secondary outcomes included success rate after crossover, intubation rate, length of stay, and serious adverse events. RESULTS: From November 2014 to March 2015, 142 infants were included and equally distributed into groups. The risk difference of -19% (95% CI -35 to -3%) did not allow the conclusion of HFNC noninferiority (p = 0.707). Superiority analysis suggested a relative risk of success 1.63 (95% CI 1.02-2.63) higher with nCPAP. The success rate with the alternative respiratory support, intubation rate, durations of noninvasive and invasive ventilation, skin lesions, and length of PICU stay were comparable between groups. No patient had air leak syndrome or died. CONCLUSION: In young infants with moderate to severe AVB, initial management with HFNC did not have a failure rate similar to that of nCPAP. This clinical trial was recorded in the National Library of Medicine registry (NCT 02457013).

Neurally adjusted ventilator assist (NAVA) reduces asynchrony during non-invasive ventilation for severe bronchiolitis.

BACKGROUND: To determine the prevalence of main inspiratory asynchrony events during non-invasive intermittent positive-pressure ventilation (NIV) for severe bronchiolitis. Ventilator response time and asynchrony were compared in neurally adjusted ventilator assist (NAVA) and in pressure assist/control (PAC) modes. METHODS: This prospective physiological study was performed in a university hospital's paediatric intensive care unit and included 11 children (aged 35.2 ± 23 days) with respiratory syncytial virus bronchiolitis with failure of nCPAP. Patients received NIV for 2 hr in PAC mode followed by 2 hr in NAVA mode. Electrical activity of the diaphragm and pressure curves were recorded for 10 min. Trigger delay, main asynchronies (auto-triggering, double triggering, or non-triggered breaths) were analyzed, and the asynchrony index was calculated for each period. RESULTS: The asynchrony index was lower during NAVA than during PAC (3 ± 3% vs. 38 ± 21%, P < 0.0001), and the trigger delay was shorter (43.9 ± 7.2 vs. 116.0 ± 38.9 ms, P < 0.0001). Ineffective efforts were significantly less frequent in NAVA mode (0.54 ± 1.5 vs. 21.8 ± 16.5 events/min, P = 0.01). Patient respiratory rates were similar, but the ventilator rate was higher in NAVA than in PAC mode (59.5 ± 17.9 vs. 49.8 ± 8.5/min, P = 0.03). The TcPCO2 baselines values (64 ± 12 mmHg vs. 62 ± 9 mmHg during NAVA, P = 0.30) were the same and their evolution over the 2 hr study period (-6 ± 10 mmHg vs. -12 ± 17 mmHg during NAVA, P = 0.36) did not differ. CONCLUSION: Patient-ventilator inspiratory asynchronies and trigger delay were dramatically lower in NAVA mode than in PAC mode during NIV in infants with severe bronchiolitis.