Corrigendum: Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU.

[This corrects the article DOI: 10.3389/fped.2023.1167595.].

Haemodynamic support for paediatric septic shock: a global perspective.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU.

Background: A consensus on the definition of prolonged mechanical ventilation (PMV) for children does not exist. There is still lack of published work presenting the epidemiology, risk factors and outcomes at different cut-points for PMV patients. These are important for planning the goals of treatment and counseling of the prognosis for patient families. We aimed to determine the incidence, baseline characteristics, risk factors and outcomes of PMV in pediatric patients at various cut-points (>14, >21 or >30days). Methods: A retrospective cohort study among children <18-years-old who were PMV > 14 days in the PICU of King Chulalongkorn Memorial Hospital was conducted. The primary outcomes were incidence of PMV with various cut-points. We stratified patients into three groups (Group 1; PMV > 14-21, Group 2; >21-30, Group 3; >30 days) for evaluating the baseline characteristics, risk factors, and outcomes of PMV (extubation success, tracheostomy status and death). Factors associated with PMV and deaths were analyzed using univariate and multivariate logistic regression. Results: From January 2018 to August 2022, 1,050 patients were screened. Of these, 114 patients were enrolled. The incidence of PMV > 14, >21 and >30 days were 10.9%, 7.3% and 5.0% respectively. Extubation success was significantly lower in Group 3 than in Groups 1 & 2 (15.4% vs. 62.2% & 56.0%, P < 0.001). Consequently, the tracheostomy rate (63.5% vs. 16.2% & 12.0%, P < 0.001), VAP rate (98.1% vs. 59.5% & 80.0%, P < 0.001), mortality rate by disease (34.6% vs. 5.4% & 20.0%, P = 0.003), median PICU LOS (50.5 vs. 22.0 & 28.0 days, P < 0.001) and median hospital LOS (124.5 vs. 55.0 & 62.0 days, P < 0.001) were also significantly higher for Group 3 compared with Groups 1 & 2. The factor associated with PMV > 30 days was VAP (aOR: 19.53, 95% CI: 2.38-160.34, P = 0.01). Factors associated with non-surviving patients were 3rd degree PEM (aOR: 5.14, 95% CI: 1.57-16.88, P = 0.01), PIM3 score ≥14 (aOR: 6.75, 95% CI: 2.26-20.15, P < 0.001) and muscle relaxant usage (aOR: 5.58, 95% CI: 1.65-18.86, P = 0.01). Conclusion: Extubation failure, tracheostomy rate, VAP rate, mortality rate by disease, PICU LOS and hospital LOS were significantly higher for PMV >30 days. Consequently, we suggest that a 30-day duration as a cut-point for PMV in PICUs might be more appropriate.

Sepsis-related pediatric acute respiratory distress syndrome: A multicenter prospective cohort study.

OBJECTIVES: This study aimed to compare the risk factors and outcomes for organ dysfunction between sepsis-related Pediatric acute respiratory distress syndrome (PARDS) and nonsepsis PARDS. METHODS: We prospective cohort recruited intubated patients with PARDS at four tertiary care centers in Thailand. The baseline characteristics, mechanical ventilation, fluid balance, and clinical outcomes were collected. The primary outcome was organ dysfunction. RESULTS: One hundred and thirty-two mechanically ventilated children with PARDS were included in the study. The median age was 29 months and 53.8% were male. The mortality rate was 22.7% and organ dysfunction was 45.4%. There were 26 (19.7%) and 106 (80.3%) patients who were classified into sepsis-related PARDS and nonsepsis PARDS, respectively. Sepsis-related PARDS patients had a significantly higher incidence of acute kidney injury (30.8% vs. 13.2%, P = 0.041), septic shock (88.5% vs. 32.1%, P < 0.001), organ dysfunction (84.6% vs. 35.8%, P < 0.001), and death (42.3% vs. 17.9%, P = 0.016) than nonsepsis PARDS group. Multivariate analysis adjusted for clinical variables showed that sepsis-related PARDS and percentage of fluid overload were significantly associated with organ dysfunction (odds ratio [OR] 11.414; 95% confidence interval [CI] 1.40892.557, P = 0.023 and OR 1.169; 95% CI 1.0121.352, P = 0.034). CONCLUSIONS: Sepsis-related PARDS patients had more severe illness, organ dysfunction, and mortality than nonsepsis PARDS patients. The higher percentage of fluid overload and presentation of sepsis was the independent risk factor of organ dysfunction in PARDS patients.

The Role of Blood Purification by HA330 as Adjunctive Treatment in Children with Septic Shock.

INTRODUCTION: Despite advances in supportive care for critically ill patients, sepsis remains an important cause of death worldwide in the PICU. One of the hallmarks of sepsis is hyperinflammation due to the excessive release of inflammatory mediators. Recently, new therapeutic approaches, such as immune modulation and blood purification, have been tried to improve outcomes in patients with septic shock. METHODS: This study is a prospective observational study composed of children with septic shock and the PELOD-2 score ≥10 or the PRISM-3 score ≥15. All received 2-4 h of HA330 treatment on 2 consecutive days, used as adjunctive therapy. The effectiveness of HA330 hemoperfusion was evaluated by improving the PELOD-2 and PRISM-3 scores, the vasoactive inotropic score (VIS), and inflammatory markers from baseline to 72 h after the use of HA330 hemoperfusion. RESULTS: Twelve patients hospitalized in the PICU and diagnosed with septic shock between July 2021 and May 2022 were included in this study and received hemoperfusion with HA330. The average PELOD-2 and PRISM-3 scores decreased significantly from 9.5 (IQR: 6.5-13.0) at baseline to 2.0 (IQR: 0-6.5) at 72 h (p = 0.002) and from 16.5 (IQR: 15.0-20.5) at baseline to 5.5 (IQR: 2.0-9.5) at 72 h (p = 0.002), respectively. The VIS decreased significantly from baseline to 72 h (p = 0.003). IL-6, procalcitonin, and lactate levels also decreased significantly from baseline to 72 h (p = 0.005, 0.03, and 0.03, respectively). Two of 12 patients expired due to their underlying condition (2/12, 16.7%). Device-related adverse events did not occur in this study. CONCLUSIONS: Our observational case series suggests a possible role for HA330 hemoperfusion as an adjunctive treatment of refractory septic shock in children with high severity scores in the context of rapid improvement in organ dysfunction, without serious adverse effects.

Multisystem inflammatory syndrome in children (MIS-C) showing disseminated aspergillosis, cytomegalovirus reactivation and persistent SARS-COV-2: Case report with autopsy review.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging phenomenon associated with SARS-COV-2 infection (COVID-19) occurring in < 1 % of infected children. MIS-C is characterized by a hyperinflammatory state with excessive cytokine release ('storm') leading to hemodynamic compromise and multiorgan failure, with a death rate of ∼2 %. Autopsy examination can play a particularly important role in helping to understand the pathogenesis of MIS-C. Yet, only five autopsy studies have been reported to date. We report a fatal case of MIS-C involving a previously healthy, 5-year-old Thai boy admitted with MIS-C, one month after exposure to SARS-COV-2. While in intensive care, he was found to have a hypertrophic cardiomyopathy, and despite immunosuppressive treatment for MIS-C, developed shock and died. Multiorgan inflammation was not found at autopsy, implying that the MIS-C had responded to treatment. However, there was disseminated aspergillosis and cytomegalovirus reactivation, attributed to the immunosuppression. SARS-COV-2 virus was also found in multiple organs. To the best of our knowledge, this is the first reported autopsy of an MIS-C patient from Asia, and the first report of aspergillosis in MIS-C. This case underscores that the risks of immunosuppression are also a concern in MIS-C. Although MIS-C is generally considered to be a post-infectious hyperimmune reaction, persistence of SARS-COV-2 is a feature in all autopsies of MIS-C patients reported to date, suggesting a possible role in the pathogenesis, at least in fatal cases.

Changes Adopted in Asian Pediatric Hospitals during the COVID-19 Pandemic: A Report from the Pediatric Acute and Critical Care COVID-19 Registry of Asia.

There is wide variation in the overall clinical impact of novel coronavirus disease 2019 (COVID-19) across countries worldwide. Changes adopted pertaining to the management of pediatric patients, in particular, the provision of respiratory support during the COVID-19 pandemic is poorly described in Asia. We performed a multicenter survey of 20 Asian pediatric hospitals to determine workflow changes adopted during the pandemic. Data from centers of high-income (HIC), upper middle income (UMIC), and lower middle income (LMIC) countries were compared. All 20 sites over nine countries (HIC: Japan [4] and Singapore [2]; UMIC: China [3], Malaysia [3] and Thailand [2]; and LMIC: India [1], Indonesia [2], Pakistan [1], and Philippines [2]) responded to this survey. This survey demonstrated substantial outbreak adaptability. The major differences between the three income categories were that HICs were (1) more able/willing to minimize use of noninvasive ventilation or high-flow nasal cannula therapy in favor of early intubation, and (2) had greater availability of negative-pressure rooms and powered air-purifying respirators. Further research into the best practices for respiratory support are warranted. In particular, innovation on cost-effective measures in infection control and respiratory support in the LMIC setting should be considered in preparation for future waves of COVID-19 infection.

Achievement of nutritional goals after a pediatric intensive care unit nutrition support guideline implementation.

BACKGROUND AND AIMS: A nutrition support guideline was developed and implemented in a pediatric intensive care unit (PICU) to improve the nutritional management of patients. This study aimed to evaluate the impact of this guideline on achieving energy and protein delivery goals. METHODS: Medical records of the patients admitted in the PICU from August 2015 to April 2017 were retrospectively reviewed. Patients who stayed in the PICU for less than 24 h or had an inborn error of metabolism were excluded. Achievement of nutritional goals was compared between the patients during the pre-implementation period (August to October 2015) and post-implementation period (November 2015 to April 2017) of the guideline. Subgroup analysis by protocol compliance was conducted in the post-implementation group. RESULTS: A total of 215 patients were included in the study (53 pre-implementation, 162 post-implementation). There were no differences between the two groups in patient characteristics, time to start enteral nutrition, time to reach the energy delivery goal, time to reach the protein delivery goal, and proportion of the patients who reached each goal. In the post-implementation group, parenteral nutrition was delayed to three days compared with one day in pre-implementation (p = 0.027) and the proportion of patients who did not receive nutrition support was lower (3.1% vs 9.4% pre-implementation, p = 0.043). Subgroup analysis in the post-implementation group showed that 69.7% of the patients were protocol compliant, of which the time to reach the energy delivery goal (59 vs 103 h, p < 0.001) and protein delivery goal (64 vs 135 h, p = 0.02) were significantly shorter compared with the non-compliant group. Moreover, the proportion of the patients who reached the energy delivery goal (75.2% vs 24.5%, p < 0.001) and protein delivery goal (56.6% vs 12.2%, p < 0.001) were higher in the compliant group. CONCLUSIONS: Compliance with the nutrition support guideline significantly improved the achievements in delivering energy and protein to patients in PICU. Increasing compliance with the guideline may improve clinical outcomes in PICU patients.

Polymyxin B Hemoperfusion in Pediatric Septic Shock: Single-Center Observational Case Series.

OBJECTIVES: To evaluate the use of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) as adjunctive therapy during pediatric patients with septic shock. DESIGN: Prospective observational study. SETTING: Nine-bed PICUs at university referral hospital. PATIENTS: Children (30 d to 15 yr) with septic shock and Pediatric Logistic Organ Dysfunction (PELOD)-2 score greater than or equal to 10 or Pediatric Risk of Mortality (PRISM) 3 score greater than or equal to 15, who were also receiving at least one inotrope. INTERVENTION: Patients received 2-4 hour treatment with PMX-DHP 20R column on 2 consecutive days. MEASUREMENTS AND MAIN RESULTS: We enrolled six children aged 21-167 months old (median, 99-mo old), with a body weight of 10-50 kg (median, 28 kg). All six patients had both PELOD-2 greater than or equal to 10 and PRISM-3 greater than or equal to 15, required invasive mechanical ventilation, and received standard treatment for septic shock before enrollment. We observed significant improvement in PELOD-2 score from baseline to 72 hours after the start of PMX-DHP (mean [95% CI] from 14.3 [12.2-16.5] to 6.0 [0.3-11.7]; p = 0.006). The vasoactive inotropic score (VIS) and lactate concentration also significantly decreased from baseline to 72 hours (VIS, 60 mmol/L [25-95 mmol/L] to 4.0 mmol/L [44.1-12 mmol/L]; p = 0.003; lactate, 2.4 mmol/L [1.0-3.8 mmol/L] to 1.0 mmol/L [0.5-1.5 mmol/L]; p = 0.01). Five of six patients survived. There was no device-related adverse event in these patients. CONCLUSIONS: In this case series of treatment with PMX-DHP as adjunctive therapy in children with refractory septic shock and high baseline severity, we have shown that patient recruitment is feasible. We have also found that clinical hemodynamic and severity of illness scores at 72 hours may be potential end points for testing in future randomized controlled trials.

Therapeutic Plasma Exchange with Continuous Renal Replacement Therapy for Pediatric Acute Liver Failure: A Case Series from Thailand.

AIM AND OBJECTIVE: Pediatric acute liver failure (PALF) is a life-threatening condition. Extracorporeal support has been applied for toxic metabolite clearance and serves as a bridging therapy to liver transplantation (LT) or to the regeneration of the liver, but evidence for treatment approaches is still lacking in the pediatric population. We aim to report our experience on therapeutic plasma exchange with high-volume continuous renal replacement therapy (TPE + HV-CRRT) as a promising supportive treatment for PALF. MATERIALS AND METHODS: A total of eight PALF cases aged 9 months to 14 years, weighing 10-50 kg., who were admitted to PICU King Chulalongkorn Memorial Hospital, Thailand and treated with TPE + HV-CRRT from January 2016 to September 2019 were reviewed. Patient demographic data, indications, technical aspects, and clinical outcomes were recorded. RESULTS: All patients who underwent TPE + HV-CRRT showed clinical improvement regarding serum bilirubin levels and coagulation studies after the therapy. Complications from the therapy were hemodynamic instability, symptomatic fluid overload, and bleeding from catheter sites. Among these, 6 (75%) patients survived with 4 (50%) successful LTs and 2 (25%) spontaneous recovery. Two children (25%) died while on the transplantation list. CONCLUSION: TPE + HV-CRRT can be used safely as a bridging therapy in children with PALF. As opposed to the adult population, higher volume of TPE or higher blood flow rate in pediatric patients might associate with hemodynamic instability during the procedure. HOW TO CITE THIS ARTICLE: Trepatchayakorn S, Chaijitraruch N, Chongsrisawat V, Chanakul A, Kongkiattikul L, Samransamruajkit R. Therapeutic Plasma Exchange with Continuous Renal Replacement Therapy for Pediatric Acute Liver Failure: A Case Series from Thailand. Indian J Crit Care Med 2021;25(7):812-816.

Balanced Salt Solution Versus Normal Saline in Resuscitation of Pediatric Sepsis: A Randomized, Controlled Trial.

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576.

Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs.

OBJECTIVES: Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries. DESIGN: A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality. SETTING: Nine multidisciplinary PICUs in three Asian countries. PATIENTS: Children with severe sepsis or septic shock admitted to the PICU from January to December 2017. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3-10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10-20 mL/kg] over 20 min [15-30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality. CONCLUSIONS: Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

BACKGROUND: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. METHODS: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-ß-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. RESULTS: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. CONCLUSIONS: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

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.

Non-Invasive Ventilation in Children with Paediatric Acute Respiratory Distress Syndrome.

INTRODUCTION: Evidence supporting non-invasive ventilation (NIV) in paediatric acute respiratory distress syndrome (PARDS) remains sparse. We aimed to describe characteristics of patients with PARDS supported with NIV and risk factors for NIV failure. MATERIALS AND METHODS: This is a multicentre retrospective study. Only patients supported on NIV with PARDS were included. Data on epidemiology and clinical outcomes were collected. Primary outcome was NIV failure which was defined as escalation to invasive mechanical ventilation within the first 7 days of PARDS. Patients in the NIV success and failure groups were compared. RESULTS: There were 303 patients with PARDS; 53/303 (17.5%) patients were supported with NIV. The median age was 50.7 (interquartile range: 15.7-111.9) months. The Paediatric Logistic Organ Dysfunction score and oxygen saturation/fraction of inspired oxygen (SF) ratio were 2.0 (1.0-10.0) and 155.0 (119.4- 187.3), respectively. Indications for NIV use were increased work of breathing (26/53 [49.1%]) and hypoxia (22/53 [41.5%]). Overall NIV failure rate was 77.4% (41/53). All patients with sepsis who developed PARDS experienced NIV failure. NIV failure was associated with an increased median paediatric intensive care unit stay (15.0 [9.5-26.5] vs 4.5 [3.0-6.8] days; P <0.001) and hospital length of stay (26.0 [17.0-39.0] days vs 10.5 [5.5-22.3] days; P = 0.004). Overall mortality rate was 32.1% (17/53). CONCLUSION: The use of NIV in children with PARDS was associated with high failure rate. As such, future studies should examine the optimal selection criteria for NIV use in these children.

Assessment of early goal-directed therapy guideline adherence: Balancing clinical importance and feasibility.

BACKGROUND: Assessing adherence to Early goal-directed therapy (EGDT) is challenging and might account for the negative findings and generalisability of the major trials to a real-life setting. This study was aimed (1) to extract key components of pediatric EGDT guidelines potentially becoming adherence criteria; (2) to classify adherence criteria into complete, clinically important, and feasible; and (3) to compare percent adherence to selected guidelines using the three approaches. METHODS: This study started with review of existing evidence to extract key components of pediatric EGDT guidelines. Modified Delphi method was then conducted in two rounds among national experts to identify feasible and/or clinically important criteria. Data from the national prospective multicenter study "Clinical Effectiveness of the Utilization of Bundled Care for Severe Sepsis and Septicemia Children" at King Chulalongkorn Memorial Hospital (KCMH) during 1 June 2012 and 28 February 2014 was used to compare percentage of adherence across the three approaches. RESULTS: Of 28 components extracted from the review, 10 were identified by the national experts through the Modified Delphi as feasible whereas 8 were identified as clinically important. Thirty-one severe sepsis patients (48.39% male, median age 3.4 years) were reviewed. Sepsis mortality was 9.7%, a significant reduction from 19% and 42% in 2010 and 2007, respectively. Based on the complete adherence criteria, the percent adherence varied from 60.71% to 89.29% (overall mean 76.84%), with lower adherence in the dead than the survived cases (73.81% vs 77.17%; p = 0.55). The percent adherence varied by criteria used: 69.35%, 76.84%, and 84.52% for clinical importance, complete, and feasibility criteria, respectively. CONCLUSION: Adherence determination based on selected clinical importance alone might result in an incorrectly estimated clinical benefit of EGDT guidelines, especially in a resource-limited setting. Both clinical importance and feasibility should be integrated into the development of adherence assessment criteria.

Prognostic value of continuous electroencephalography in children undergoing therapeutic hypothermia after cardiac arrest: A pilot study.

OBJECTIVE: To determine the prognostic value of continuous electroencephalography (EEG) in children undergoing therapeutic hypothermia after cardiac arrest. METHOD: We retrospectively reviewed medical records and continuous EEG of all patients undergoing therapeutic hypothermia after cardiac arrest from November 2013 to September 2016. Demographic, clinical data and immediate complications were collected. Characteristics of continuous EEG including EEG background, time to normal trace (TTNT) and electrographic seizures were reviewed by investigators. Cerebral performance category scales at 6 months' follow up were evaluated and divided into good (grade 1-2) and poor (grade 3-5) outcome groups. RESULT: Six patients were included (two boys and four girls) with median age of 19.5 months (range13-128 months). Five patients (83.3%) presented with cardiac arrest from near-drowning and one patient with underlying acute lymphocytic leukemia presented an in-hospital cardiac arrest. Initial EKG rhythm was asystole in 3 patients (50%), pulseless activity in 1 patient (16.7%) and initially unknown in 2 patients (33.3%). Two patients (33.3%) who had EEG reactivity and TTNT within 5minutes and 2.5hours had good neurological outcome (CPC1). Four patients (66.7%) with absent EEG reactivity had poor neurological outcome (CPC4, 5 in 3 and 1 children respectively). Three patients from the poor outcome group had electrographic seizures, of whom 2/3 progressed to status epilepticus. Three out of four patients in the poor outcome group had the following complications: pneumonia, bleeding and pancreatitis. CONCLUSION: Early TTNT and EEG reactivity help to predict good neurological outcome in children undergoing therapeutic hypothermia after cardiac arrest. Seizures and status epilepticus may predict poor neurological outcome.

Differences Between Pulmonary and Extrapulmonary Pediatric Acute Respiratory Distress Syndrome: A Multicenter Analysis.

OBJECTIVES: Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome. DESIGN: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality. SETTING: Ten multidisciplinary PICUs in Asia. PATIENTS: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]). CONCLUSIONS: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.

High-Flow Nasal Cannula versus Conventional Oxygen Therapy in Children with Respiratory Distress.

PURPOSE: The aim of this study is to determine the clinical efficacy of high-flow nasal cannula (HFNC) therapy compared with conventional oxygen therapy in children presented with respiratory distress. STUDY DESIGN: This was a randomized controlled study. MATERIALS AND METHODS: Infants and children aged between 1 month to 5 years who were admitted to our tertiary referral center for respiratory distress (July 1, 2014 to March 31, 2015) and met the inclusion criteria were recruited. INTERVENTIONS: Infants and children hospitalized with respiratory distress were randomized into two groups of interventions. All clinical data, for example, respiratory score, pulse rate, and respiratory rate were recorded. The results were subsequently analyzed. RESULTS: A total of 98 respiratory distress children were enrolled during the study period. Only 4 children (8.2%) failed in HFNC therapy, compared with 10 children (20.4%) in conventional oxygen therapy group (P = 0.09). After adjusted for body weight, underlying diseases, and respiratory distress score, there was an 85% reduction in the odds of treatment failure in HFNC therapy group (adjusted odds ratio 0.15, 95% confidence interval 0.03-0.66, P = 0.01). Most children in HFNC therapy group had significant improvement in clinical respiratory score, heart rate, and respiratory rate at 240, 360, and 120 min compared with conventional oxygen therapy (P = 0.03, 0.04, and 0.03). CONCLUSION: HFNC therapy revealed a potential clinical advantage in management children hospitalized with respiratory distress compared with conventional respiratory therapy. The early use of HFNC in children with moderate-to-severe respiratory distress may prevent endotracheal tube intubation. TRIAL REGISTER: TCTR 20170222007.