Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Skeletal Muscle Changes, Function, and Health-Related Quality of Life in Survivors of Pediatric Critical Illness.

OBJECTIVES: To describe functional and skeletal muscle changes observed during pediatric critical illness and recovery and their association with health-related quality of life. DESIGN: Prospective cohort study. SETTING: Single multidisciplinary PICU. PATIENTS: Children with greater than or equal to 1 organ dysfunction, expected PICU stay greater than or equal to 48 hours, expected survival to discharge, and without progressive neuromuscular disease or malignancies were followed from admission to approximately 6.7 months postdischarge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional status was measured using the Functional Status Scale score and Pediatric Evaluation of Disability Inventory-Computer Adaptive Test. Patient and parental health-related quality of life were measured using the Pediatric Quality of Life Inventory and Short Form-36 questionnaires, respectively. Quadriceps muscle size, echogenicity, and fat thickness were measured using ultrasonography during PICU stay, at hospital discharge, and follow-up. Factors affecting change in muscle were explored. Associations between functional, muscle, and health-related quality of life changes were compared using regression analysis. Seventy-three survivors were recruited, of which 44 completed follow-ups. Functional impairment persisted in four of 44 (9.1%) at 6.7 months (interquartile range, 6-7.7 mo) after discharge. Muscle size decreased during PICU stay and was associated with inadequate energy intake (adjusted ß, 0.15; 95% CI, 0.02-0.28; p = 0.030). No change in echogenicity or fat thickness was observed. Muscle growth postdischarge correlated with mobility function scores (adjusted ß, 0.05; 95% CI, 0.01-0.09; p = 0.046). Improvements in mobility scores were associated with improved physical health-related quality of life at follow-up (adjusted ß, 1.02; 95% CI, 0.23-1.81; p = 0.013). Child physical health-related quality of life at hospital discharge was associated with parental physical health-related quality of life (adjusted ß, 0.09; 95% CI, 0.01-0.17; p = 0.027). CONCLUSIONS: Muscle decreased in critically ill children, which was associated with energy inadequacy and impaired muscle growth postdischarge. Muscle changes correlated with change in mobility, which was associated with child health-related quality of life. Mobility, child health-related quality of life, and parental health-related quality of life appeared to be interlinked.

A Cross-Sectional Study of the Clinical Metrics of Functional Status Tools in Pediatric Critical Illness.

OBJECTIVES: To determine the clinical metrics of functional assessments in pediatric critical illness survivors. DESIGN: Cross-sectional observational study. SETTING: PICU follow-up clinic. PATIENTS: Forty-four PICU survivors 6-12 months post PICU stay, and 52 healthy controls 0-18 years old. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: Function was assessed using the Pediatric Quality of Life Inventory 4.0 generic scales and infant scales, the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test, and the Functional Status Scale. Muscle strength was assessed by hand grip strength in children greater than or equal to 6 years. Clinical metrics assessed included floor and ceiling effects, known-group, and convergent validity. Floor and ceiling effects were present if the participants achieving the worst or best scores exceeded 15%, respectively. Known-group validity was assessed by comparing scores between those with and without complex chronic conditions and abnormal versus good baseline function. Convergent validity was assessed using partial correlation between two tools. Functional Status Scale and Pediatric Quality of Life Inventory physical domain scores showed significant ceiling effects in PICU survivors (69.2% and 15.4%, respectively, achieved the highest possible score). Functional scores were not significantly different between children with or without complex chronic conditions or children with good versus abnormal baseline function. In healthy children, Pediatric Quality of Life Inventory physical correlated moderately with hand grip strength (partial r = 0.66; p < 0.001), whereas Pediatric Quality of Life Inventory psychosocial correlated moderately with Pediatric Evaluation of Disability Inventory-Computer Adaptive Test social/cognitive score (partial r = 0.53; p < 0.001). In PICU survivors, only Pediatric Quality of Life Inventory physical and Pediatric Evaluation of Disability Inventory-Computer Adaptive Test mobility scores were correlated (partial r = 0.55; p < 0.001). CONCLUSIONS: PICU functional assessment tools have varying clinical metrics. Considering ceiling effects, Pediatric Evaluation of Disability Inventory-Computer Adaptive Test may be more suitable in survivors than Functional Status Scale. Differences in scores between children with or without complex chronic conditions, and with or without baseline functional impairment, were not observed. Functional assessments likely require a combination of tools to measure the spectrum of pediatric critical illness and recovery.

Body Composition and Acquired Functional Impairment in Survivors of Pediatric Critical Illness.

OBJECTIVES: To identify whether body mass and composition is associated with acquired functional impairment in PICU survivors. DESIGN: Retrospective dual-cohort study. SETTING: Single multidisciplinary PICU. PATIENTS: Two distinct PICU survivor cohorts: 432 unselected admissions from April 2015 to March 2016, and separately 92 patients with abdominal CT imaging at admission from January 2010 to December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission body mass index and Functional Status Scale scores at admission, PICU discharge, and hospital discharge were obtained for all patients. Acquired functional impairment was defined as increase greater than or equal to 3 in Functional Status Scale from baseline. Patients were classified as having: "temporary acquired impairment" (acquired impairment at PICU discharge recovering by hospital discharge), "persistent acquired impairment" (acquired impairment at PICU discharge persisting to hospital discharge), and "no acquired impairment." CT scans were analyzed for skeletal muscle and fat area using National Institute of Health ImageJ software (Bethesda, MD). Multinomial logistic regression analyses were conducted to identify associations between body mass index, muscle and fat indices, and acquired functional impairment. High baseline body mass index was consistently predictive of persistent acquired impairment in both cohorts. In the second cohort, when body mass index was replaced with radiologic anthropometric measurements, greater skeletal muscle, and visceral adipose tissue indices were independently associated with persistent acquired impairment at hospital discharge (adjusted odds ratio, 1.29; 95% CI, 1.03-1.61; p = 0.024 and adjusted odds ratio, 1.13; 95% CI, 1.01-1.28; p = 0.042, respectively). However, this relationship was no longer significant in children with PICU stay greater than 2 days. CONCLUSIONS: In PICU survivors, baseline body mass and composition may play a role in the persistence of acquired functional impairment at hospital discharge. Characterization and quantification of skeletal muscle and fat deserves further study in larger cohorts of PICU children.

Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

Tests and Indices Predicting Extubation Failure in Children: A Systematic Review and Meta-analysis.

INTRODUCTION: There is lack of consensus on what constitutes best practice when assessing extubation readiness in children. This systematic review aims to synthesize data from existing literature on pre-extubation assessments and evaluate their diagnostic accuracies in predicting extubation failure (EF) in children. METHODS: A systematic search in PubMed, EMBASE, Web of Science, CINAHL, and Cochrane was performed from inception of each database to 15 July 2021. Randomized controlled trials or observational studies that studied the association between pre-extubation assessments and extubation outcome in the pediatric intensive care unit population were included. Meta-analysis was performed for studies that report diagnostic tests results of a combination of parameters. RESULTS: In total, 41 of 11,663 publications screened were included (total patients, n = 8111). Definition of EF across studies was heterogeneous. Fifty-five unique pre-extubation assessments were identified. Parameters most studied were: respiratory rate (RR) (13/41, n = 1945), partial pressure of arterial carbon dioxide (10/41, n = 1379), tidal volume (13/41, n = 1945), rapid shallow breathing index (RBSI) (9/41, n = 1400), and spontaneous breathing trials (SBT) (13/41, n = 5652). Meta-analysis shows that RSBI, compliance rate oxygenation pressure (CROP) index, and SBT had sensitivities ranging from 0.14 to 0.57. CROP index had the highest sensitivity [0.57, 95% confidence interval (CI) 0.4-0.73] and area under curve (AUC, 0.98). SBT had the highest specificity (0.93, 95% CI 0.92-0.94). CONCLUSIONS: Pre-extubation assessments studied thus far remain poor predictors of EF. CROP index, having the highest AUC, should be further explored as a predictor of EF. Standardizing the EF definition will allow better comparison of pre-extubation assessments.

Fluid overload in children with pediatric acute respiratory distress syndrome: A retrospective cohort study.

OBJECTIVES: To assess the association of cumulative fluid overload (FO) up to 14 days from the diagnosis of pediatric acute respiratory syndrome (PARDS) with pediatric intensive care unit (PICU) mortality, 28-day mechanical ventilation free days (VFD), and 28-day intensive care unit free days (IFD). We hypothesized that fluid overload, even beyond the acute period, would be associated with increased morbidity and mortality. METHODS: We conducted a retrospective cohort study of PARDS patients admitted to PICU from 2009 to 2015. For repeated admissions, we considered the admission with the highest oxygenation index (OI). Daily FO (%) was calculated as (intake - output)/weight at PICU admission × 100. Peak cumulative FO (CFO) was the highest CFO from the diagnosis of PARDS to Day 14 or to PICU discharge or mortality, whichever was earliest. Rate to peak CFO was the peak CFO divided by the number of days to reach that highest CFO. The association of FO with mortality, VFD and IFD were analyzed with logistic and linear regression models, with the following covariates: Pediatric Index of Mortality 2 score, PARDS severity, and the presence of acute kidney injury (AKI). RESULTS: There were 165 patients included in this study, with a mortality rate of 45.5% (75/165), median age 3.2 years (interquartile range [IQR] 0.7-9.9) and OI 15.8 (IQR 9.5-27.9). Seventy-three (44.2%) patients had severe PARDS and 64 (38.8%) had AKI. AKI (aOR [adjusted odds ratio] 3.19, 95% CI [confidence interval] 1.43-7.09, p = 0.004) and rate to peak cumulative FO (aOR 1.23, 95% CI 1.07-1.42, p = 0.004) were associated with mortality. AKI and peak cumulative FO were associated with decreased VFD and IFD. CONCLUSION: The rate to peak CFO over the first 14 days of PARDS was associated with mortality and peak CFO was associated with decreased VFD and IFD.

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.

Psychosocial impact of the COVID-19 pandemic on paediatric healthcare workers.

INTRODUCTION: Frontline healthcare workers (HCWs) exposed to coronavirus disease 2019 (COVID-19) are at risk of psychological distress. This study evaluates the psychological impact of COVID-19 pandemic on HCWs in a national paediatric referral centre. METHODS: This was a survey-based study that collected demographic, work environment and mental health data from paediatric HCWs in the emergency, intensive care and infectious disease units. Psychological impact was measured using the Depression, Anxiety, Stress Scale-21. Multivariate regression analysis was performed to identify risk factors associated with psychological distress. RESULTS: The survey achieved a response rate of 93.9% (430 of 458). Of the 430 respondents, symptoms of depression, anxiety and stress were reported in 168 (39.1%), 205 (47.7%) and 106 (24.7%), respectively. Depression was reported in the mild (47, 10.9%), moderate (76, 17.7%), severe (23, 5.3%) and extremely severe (22, 5.1%) categories. Anxiety (205, 47.7%) and stress (106, 24.7%) were reported in the mild category only. Collectively, regression analysis identified female sex, a perceived lack of choice in work scope/environment, lack of protection from COVID-19, lack of access to physical activities and rest, the need to perform additional tasks, and the experience of stigma from the community as risk factors for poor psychological outcome. CONCLUSION: A high prevalence of depression, anxiety and stress was reported among frontline paediatric HCWs during the COVID-19 pandemic. Personal psychoneuroimmunity and organisational prevention measures can be implemented to lessen psychiatric symptoms. At the national level, involving mental health professionals to plan and coordinate psychological intervention for the country should be considered.

Nutritional status, intake, and outcomes in critically ill children with bronchiolitis.

BACKGROUND: Optimal nutrition in children with severe bronchiolitis remains poorly described. We aimed to describe nutritional status and practices in children with severe bronchiolitis requiring admission to the pediatric intensive care unit (PICU), and explore their associations with outcomes. METHODS: We conducted a retrospective study on patients with bronchiolitis requiring PICU stay from 2009 to 2014. Demographics, medical data, and baseline weight-for-length Z-scores (WLZ) were collected. In patients requiring more than 48 hours of PICU stay, nutritional intake data in the first 3 days of PICU stay were collected. Underfeeding and overfeeding were defined as the median energy intake of less than 80% and more than 120% of requirements, respectively. Protein adequacy was defined as intake of more than 1.5 g/kg/d. Primary and secondary outcomes of interest were the duration of PICU stay and mechanical ventilation (MV), respectively. RESULTS: Seventy-four patients were included, with a median PICU stay of 4.9 days (interquartile range 2.0-8.2). Low WLZ at baseline was associated with longer duration of PICU stay (adjusted ß: 4.33 [95% confidence interval [CI], 0.49-8.18]; P = .028) and MV days (adjusted ß: 4.87 [95% CI, 1.56-8.18]; P = .008) compared to appropriate WLZ. In patients with ≥48 hours PICU stay, protein adequacy was significantly associated with greater PICU (adjusted ß coefficient, 6.35 [95% CI, 1.66-11.0]; P = .009) and MV days (adjusted ß coefficient, 5.22 [95% CI, 1.06-9.38]; P = .015). CONCLUSION: Among bronchiolitis patients admitted to the PICU, low WLZ at admission was associated with a longer duration of PICU stay and MV. Protein adequacy was associated with longer PICU and MV days in children with ≥48 hours of PICU stay.

Survey of contemporary feeding practices in critically ill children in the Asia-Pacific and the Middle East.

BACKGROUND AND OBJECTIVES: Nutrition is a fundamental component of care of critically ill children. Determining variation in nutritional practices within paediatric intensive care units (PICUs) allows for review and improvement of nutrition practices. METHODS AND STUDY DESIGN: The aim was to survey the nutrition practices and perspectives of paediatric intensivists and dieticians in Asia-Pacific and the Middle East. A questionnaire was developed to collect data on (1) the respondent's and institution's characteristics, (2) nutritional assessments and nutrient delivery practices, and (3) the perceived importance and barriers to optimal enteral feeding in the PICU. RESULTS: We analysed 47 responses from 35 centres in 18 different countries. Dedicated dietetic services were only present in 13 (37%) centres and regular nutrition assessments were conducted in only 12 (34%) centres. In centres with dedicated dieticians, we found greater use of carbohydrate, fat additives and special formulas. Two thirds [31 (66%)] of respondents used total fluids to estimate energy requirements. Only 11 (31%) centres utilized feeding protocols. These centres had higher use of small bowel feeding, acid suppressants, laxatives and gastric residual volume thresholds. When dealing with feed intolerance, they were also more likely to start a motility agent. There was also a lack of consensus on when feeding should start and the use of adjuncts. CONCLUSIONS: Nutrition practices and barriers are unique in Asia-Pacific and the Middle East and strongly reflect a lack of dietetic services. Future effort should focus on developing a uniform approach on nutrition practices to drive paediatric critical care nutrition research in these regions.

Nutrition Support for Children Undergoing Congenital Heart Surgeries: A Narrative Review.

Energy imbalance in infants and children with congenital heart disease (CHD) is common and influenced by age, underlying cardiac diagnoses, and presence or absence of congestive heart failure. During the surgical hospitalization period, these children are prone to nutritional deterioration due to stress of surgery, anesthetic/perfusion techniques, and postoperative care. Poor nutrition is associated with increased perioperative morbidity and mortality. This review aims to examine various aspects of nutrition in critically ill children with CHD, including (1) energy expenditure, (2) perioperative factors that contribute to energy metabolism, (3) bedside practices that are potentially able to optimize nutrient delivery, and (4) medium- to long-term impact of energy balance on clinical outcomes. We propose a nutrition algorithm to optimize nutrition of these children in the perioperative period where improvements in nutrition status will likely impact surgical outcomes.

A review of the use of adjunctive therapies in severe acute asthma exacerbation in critically ill children.

Asthma is a common and potentially life threatening childhood condition. Asthma involves not only chronic airway remodeling, but may also include frequent exacerbations resulting from bronchospasm, edema, and mucus production. In children with severe exacerbations, standard therapy with ß2-agonists, anti-cholinergic agents, oxygen, and systemic steroids may fail to reverse the severe airflow obstruction and necessitate use of adjunctive therapies. These therapies include intravenous or inhaled magnesium, inhaled helium-oxygen mixtures, intravenous methylxanthines, intravenous ß2-agonists, and intravenous ketamine. Rarely, these measures are not successful and following the initiation of invasive mechanical ventilation, inhaled anesthetics or extracorporeal life support may be required. In this review, we discuss the mechanisms and evidence for adjunctive therapies in the setting of severe acute asthma exacerbations in children.