Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to Fio2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/Fio2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Recombinant human thrombomodulin for pneumonia-induced severe ARDS complicated by DIC in children: a preliminary study.

PURPOSE: Recombinant human soluble thrombomodulin (rTM) has been used to treat disseminated intravascular coagulation (DIC). Recent studies have shown the efficacy of rTM through its anti-inflammatory effects for treatment of adults with acute respiratory distress syndrome (ARDS). However, the safety and efficacy of rTM in children with severe ARDS complicated by DIC have not been reported. In this preliminary study, we reported the feasibility of using rTM for the treatment of pneumonia-induced severe ARDS complicated by DIC in children. METHODS: Six children (age: median 10 months old) with pneumonia-induced severe ARDS complicated by DIC were enrolled in this preliminary study. rTM (380 U/kg) was administered for a maximum of 6 days, in addition to conventional therapies after diagnosis of severe ARDS complicated by DIC. After administration of rTM, we measured changes in the plasma TM concentration and evaluated the clinical course, status of DIC and ARDS, and other laboratory findings, including levels of cytokines, chemokines, and biomarkers. RESULTS: In all six children, the plasma concentration of TM increased and DIC scores decreased after administration of rTM. Four of the six children recovered from the severe ARDS complicated by DIC after treatment, and were discharged from the hospital with no complications. In survived children, levels of soluble receptors for advanced glycation end products, interleukin-6, interleukin-8 and monocyte chemotactic protein-1 decreased after administration of rTM compared to those before rTM. CONCLUSIONS: The rTM administration is feasible as an adjunctive therapeutic strategy for children over 2 months with pneumonia-induced severe ARDS complicated by DIC.

The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS. METHODS: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect. RESULTS: A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS. CONCLUSION: The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.

Parental satisfaction with quality of neonatal care in different level hospitals: evidence from Vietnam.

BACKGROUND: Most health systems provide the most specialized, and presumably also the highest quality of care at a central level. This study assessed parental satisfaction and its determinants in the context of neonatal care in a provincial as well as a national hospital of Vietnam. METHODS: In this cross-sectional quantitative study, parents of 340 preterm infants admitted to neonatal care units of a national and a provincial hospital in 2018 were interviewed using structured questionnaires. Unadjusted and adjusted linear regression models were used to assess the relationship between parental satisfaction and hospital rank. RESULTS: The mean parental satisfaction score was 3.74 at the provincial, and 3.56 at the national hospital. These satisfaction differences persisted when parent and child characteristics were adjusted for in multivariate analysis. Longer length of stay and worsening infant health status were associated with parents reporting lower levels of satisfaction with the quality of care being provided at the healthcare facility. CONCLUSIONS: This study suggests that parents of preterm infants admitted in a provincial hospital were more satisfied with the quality of care received than those in a specialized national hospital. Length of stay and infant health status were the two most important determinants of level of parental satisfaction.

Tuberculous pneumonia-induced severe ARDS complicated with DIC in a female child: a case of successful treatment.

BACKGROUND: Tuberculous (TB) pneumonia can induce acute respiratory distress syndrome (ARDS). Although TB pneumonia is one of the causes of disease and death among children worldwide, the literature on TB pneumonia-induced ARDS is limited. We report herein on the successful treatment of a two-year-old female child with TB pneumonia-induced severe ARDS complicated with disseminated intravascular coagulation (DIC). CASE PRESENTATION: A two-year-old Vietnamese female child with sustained fever and cough for 20 days was transferred to our hospital. She had severe dyspnea and a chest X-ray showed bilateral infiltration without findings of heart failure. After tracheal intubation, her oxygenation index (OI) and PaO2/FiO2 (PF) ratio were 29 and 60 mmHg, respectively. Mycobacterium tuberculosis was detected by real-time polymerase chain reaction (rPCR) assay of tracheal lavage fluid. She was diagnosed as having severe ARDS that developed from TB pneumonia. Anti-tuberculous therapy and cardiopulmonary support were started. However, her respiratory condition deteriorated despite treatment with high-frequency oscillating ventilation (HFO), vasopressor support, and 1 g/kg of immunoglobulin. On the third day after admission, her International Society on Thrombosis and Hemostasis DIC score had increased to 5. Recombinant human soluble thrombomodulin (rTM) was administered to treat the DIC. After the administration of rTM was completed, OI gradually decreased, after which the mechanical ventilation mode was changed from HFO to synchronized intermittent mandatory ventilation. The DIC score also gradually decreased. Plasma levels of soluble receptor for advanced glycan end products (sRAGE) and high mobility group box 1 (HMGB-1), which are reported to be associated with ARDS severity, also decreased. In addition, inflammatory biomarkers, including interferon-gamma (IFN-γ) and interleukin-6 (IL-6), decreased after the administration of rTM. Although severe ARDS (P/F ratio ≦ 100 mmHg) continued for 19 days, the patient's OI and P/F ratio improved gradually, and she was extubated on the 27th day after admission. The severe ARDS with DIC was successfully treated, and she was discharged from hospital on day 33 post-admission. CONCLUSIONS: We successfully treated a female child suffering from TB pneumonia-induced severe ARDS complicated with DIC using multimodal interventions. (338/350).

High Seroprevalence of Anti-SARS-CoV-2 Antibodies in Children in Vietnam: An Observational, Hospital-Based Study.

Background: The robustness of sero-surveillance has delineated the high burden of SARS-CoV-2 infection in children; however, these existing data showed wide variation. This study aimed to identify the serostatus of antibodies against SARS-CoV-2 and associated factors among children following the fourth pandemic wave in Vietnam. Methods: A cross-sectional study was conducted at Vietnam National Children's Hospital (VNCH) between March 13 and April 3, 2022. Thus, 4032 eligible children seeking medical care for any medical condition not related to acute COVID-19 infection were tested for IgG SARS-CoV-2 antibodies by ADVIA Centaur® SARS-CoV-2 IgG (sCOVG) assay using the residuals of routine blood samples. Results: The median age of enrolled children was 39 (IQR = 14−82) months. The overall seropositive prevalence was 59.2% (95%CI = 57.6−60.7) and the median antibody titer was 4.78 (IQR 2.38−9.57) UI/mL. The risk of seropositivity and the median antibody titer were not related to gender (58.6% versus 60.1%, 4.9 versus 4.6 UI/mL, all p > 0.05). Children aged ≤12 months were likely to be seropositive compared to children aged 36 to <60 months (59.2% versus 57.5%, p = 0.49) and those aged ≥144 months (59.2% versus 65.5%, p = 0.16). Children aged ≥144 months exhibited a significantly higher titer of protective COVID-19 antibodies than other age groups (p < 0.001). In multivariate logistic regression, we observed independent factors associated with SARS-CoV-2 seropositivity, including the age 13 to <36 months (OR = 1.29, 95%CI = 1.06−1.56, p = 0.01), 60 to <144 months (OR = 0.79, 95%CI = 0.67−0.95, p = 0.01), ≥144 months (OR = 1.84, 95%CI = 1.21−2.8, p = 0.005), the presence of infected household members (OR = 2.36, 95%CI = 2.06−2.70, p < 0.001), participants from Hanoi (OR = 1.54, 95%CI = 1.34−1.77, p < 0.001), underlying conditions (OR = 0.71, 95%CI = 0.60−0.85, p ≤ 0.001), and using corticosteroids or immunosuppressants (OR = 0.64, 95%CI = 0.48−0.86, p = 0.003). Conclusions: This study highlights a high seroprevalence of antibodies against SARS-CoV-2 among children seeking medical care for non-acute COVID-19-related conditions in a tertiary children's hospital in Hanoi, Vietnam. In the context of reopening in-person schools and future emerging COVID-19 variants, this point will also be a key message about the necessity of "rush-out" immunization coverage for children, especially those under the age of five years.

Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study.

BACKGROUND: Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions. METHODS: In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete. FINDINGS: Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8-8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04-10·03]), coma on day 2 (2·90 [1·78-4·72]), supplementary oxygen requirement (1·89 [1·25-2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68-5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered. INTERPRETATION: In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region. FUNDING: Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.

Pathogen screening and prognostic factors in children with severe ARDS of pulmonary origin.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal diseases encountered in the pediatric intensive care unit (PICU). The etiological pathogens and prognostic factors of severe ARDS of pulmonary origin in children with respiratory virus infections were prospectively investigated. METHODS: Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory virus infection; and (4) development of severe ARDS within 72 h after PICU admission. Pathogens were detected in the blood and tracheal lavage fluid using molecular techniques and a conventional culture system. The serum levels of inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty-seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus infections, co-infection with bacteria/fungus, and bacteremia/fungemia were observed in 60%, 49%, and 32% of children, respectively. Adenovirus-B, measles virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid. There were no statistically significant differences between non-survivors and survivors regarding the types of pathogen, incidence of multiple virus infection, gender, age, clinical features, and treatment. The serum levels of interferon (IFN)-γ and the IFN-γ/interleukin (IL)-10 ratio were higher in non-survivors. CONCLUSIONS: IFN-γ upregulation as detected on the day of PICU admission was found to be one of the possible prognostic factors affecting a fatal outcome. These results suggest that modulation of inflammatory responses is critical for the clinical management of children with ARDS.

Continuous veno-venous hemofiltration for treatment of enterovirus 71-induced fulminant cardiopulmonary failure: a case report.

INTRODUCTION: Fulminant cardiopulmonary failure is a severe complication of hand, foot and mouth diseases due to enterovirus 71 infection, with a high mortality rate. The treatment is mainly supportive with aggressive cardiopulmonary resuscitation. We report the use of continuous veno-venous hemofiltration in a patient with pulmonary edema and shock due to enterovirus 71 infection. To the best of our knowledge, this is the first report of the use of continuous veno-venous hemofiltration to successfully treat a patient with fulminant cardiopulmonary failure due to enterovirus 71 infection. CASE PRESENTATION: A 36-month-old Asian girl presented to our hospital with pulmonary edema, refractory hypotension and severe cardiac dysfunction due to enterovirus 71 infection. In addition to the standard management and care, we performed continuous veno-venous hemofiltration to overcome refractory shock and our patient eventually made a full recovery. At a three-month follow-up, a full assessment revealed no neurological sequelae. CONCLUSIONS: In the management of patients with enterovirus 71-related fulminant cardiopulmonary failure, early continuous veno-venous hemofiltration may be considered as an alternative treatment to improve patient survival and to prevent severe neurological disabilities.

Risk parameters of fulminant acute respiratory distress syndrome and avian influenza (H5N1) infection in Vietnamese children.

A clinical picture of patients with acute respiratory distress syndrome (ARDS) induced by highly pathogenic avian influenza A (H5N1) has been reported. We reviewed 37 sets of clinical data for pediatric patients with ARDS at the National Hospital of Pediatrics (Hanoi, Vietnam); 12 patients with H5N1-positive and 25 with H5N1-negative ARDS were enrolled. The H5N1-negative patients had a clinical picture and mortality rate similar to that for the pediatric ARDS patients. However, the H5N1-positive patients had ARDS with normal ventilation capacity at the time of hospital admission, then rapidly proceeded to severe respiratory failure. The survival probability and days until final outcome in groups of H5N1-positive (n=12) vs. H5N1-negative (n=25) patients were 17% versus 52% and 12.3+/-5.7 days (median, 11 days) versus 21.5+/-13.8 days (median, 22 days), respectively. Our observations clarified the clinical picture of H5N1-induced fulminant ARDS and also confirmed that relatively older age (approximately 6 years of age), high fever at onset, and leukopenia and/or thrombocytopenia at the time of hospital admission are risk parameters for H5N1-induced fulminant ARDS.