Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections.

OBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. DESIGN: Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration. SETTING: PICUs in 12 high and low/middle-income countries. PATIENTS: Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

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.

Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study.

PURPOSE: We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). METHOD: We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. RESULTS: Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). CONCLUSION: Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.

A multicenter observational study on outcomes of moderate and severe pediatric traumatic brain injuries-time to reappraise thresholds for treatment.

PURPOSE: Children with moderate traumatic brain injury (modTBI) (Glasgow Coma Scale (GCS) 9-13) may benefit from better stratification. We aimed to compare neurocritical care utilization and functional outcomes between children with high GCS modTBI (hmodTBI, GCS 11-13), low GCS modTBI (lmodTBI, GCS 9-10), and severe TBI (sTBI, GCS ≤ 8). We hypothesized that patients with lmodTBI have higher neurocritical care needs and worse outcomes than patients with hmodTBI and are similar to patients with sTBI. METHODS: Prospective observational study from June 2018 to October 2022 in 28 pediatric intensive care units (PICU) in Asia, South America, and Europe. We included children (age < 18 years) with modTBI and sTBI admitted to PICU and measured functional outcomes at 3 months using the Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds, scale 1-8, 1 = upper good recovery, 8 = death). RESULTS: We analyzed 409 patients: 98 (24%) and 311 (76%) with modTBI and sTBI, respectively. Patients with lmodTBI (vs. hmodTBI) were more likely to have invasive ICP monitoring (32.3% vs. 4.5%, p < 0.001), longer PICU stay (days, median [IQR]; 5.00 [4.00, 9.75] vs 4.00 [2.00, 5.00], p = 0.007), and longer hospital stay (days, median [IQR]: 13.00 [8.00, 17.00] vs. 8.00 [5.00, 12, 25], p = 0.015). Median GOS-E Peds scores were significantly different (hmodTBI (1.00 [1.00, 3.00]), lmodTBI (3.00 [IQR 2.00, 5.75]), and sTBI (5.00 [IQR 1.00, 6.00]) (p < 0.001)). After adjusting for age, sex, presence of polytrauma and cerebral edema, lmodTBI, and sTBI remained significantly associated with higher GOS-E scores (adjusted coefficient (standard error): 1.24 (0.52), p = 0.018, and 1.27 (0.33), p < 0.001, respectively) compared with hmodTBI. CONCLUSIONS: Children with lmodTBI have higher rates of neurocritical care utilization and worse functional outcomes than those with hmodTBI but better than those with sTBI. Children with lmodTBI may benefit from guideline-based management similar to what is implemented in children with sTBI. This work was performed in hospitals within the PACCMAN and LARed networks. No reprints will be ordered.

Latin American Consensus on the Management of Sepsis in Children: Sociedad Latinoamericana de Cuidados Intensivos Pediátricos [Latin American Pediatric Intensive Care Society] (SLACIP) Task Force: Executive Summary.

Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

Vaccine apartheid: This is not the way to end the pandemic.

There are many reasons why the international community as a whole should advocate for COVID-19 vaccine equity: global economic recession, uncontrolled outbreaks with higher risk of virus variants and persistent unsafe travelling in an era of now vaccine-preventable cause of death. This inequity is an avoidable threat to global health. Funding agencies, policy makers, drug companies and NGOs among others have the moral duty to end this vaccine apartheid and to make vaccine equity a reality. In this viewpoint, we discuss how inequalities in vaccination access affect a proper control of the pandemic, highlighting specific consequences on child health.

Pediatric Emergency and Critical Care Resources and Infrastructure in Resource-Limited Settings: A Multicountry Survey.

OBJECTIVES: To describe the infrastructure and resources for pediatric emergency and critical care delivery in resource-limited settings worldwide. DESIGN: Cross-sectional survey with survey items developed through literature review and revised following piloting. SETTING: The electronic survey was disseminated internationally in November 2019 via e-mail directories of pediatric intensive care societies and networks and using social media. PATIENTS: Healthcare providers who self-identified as working in resource-limited settings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Results were summarized using descriptive statistics and resource availability was compared across World Bank country income groups. We received 328 responses (238 hospitals, 60 countries), predominantly in Latin America and Sub-Saharan Africa (n = 161, 67.4%). Hospitals were in low-income (28, 11.7%), middle-income (166, 69.5%), and high-income (44, 18.4%) countries. Across 174 PICU and adult ICU admitting children, there were statistically significant differences in the proportion of hospitals reporting consistent resource availability ("often" or "always") between country income groups (p < 0·05). Resources with limited availability in lower income countries included advanced ventilatory support, invasive and noninvasive monitoring, central venous access, renal replacement therapy, advanced imaging, microbiology, biochemistry, blood products, antibiotics, parenteral nutrition, and analgesic/sedative drugs. Seventy-seven ICUs (52.7%) were staffed 24/7 by a pediatric intensivist or anesthetist. The nurse-to-patient ratio was less than 1:2 in 71 ICUs (49.7%). CONCLUSIONS: Contemporary data demonstrate significant disparity in the availability of essential and advanced human and material resources for the care of critically ill children in resource-limited settings. Minimum standards for essential pediatric emergency and critical care in resource-limited settings are needed.

Driving Pressure and Normalized Energy Transmission Calculations in Mechanically Ventilated Children Without Lung Disease and Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To compare the new tools to evaluate the energy dissipated to the lung parenchyma in mechanically ventilated children with and without lung injury. We compared their discrimination capability between both groups when indexed by ideal body weight and driving pressure. DESIGN: Post hoc analysis of individual patient data from two previously published studies describing pulmonary mechanics. SETTING: Two academic hospitals in Latin-America. PATIENTS: Mechanically ventilated patients younger than 15 years old were included. We analyzed two groups, 30 children under general anesthesia (ANESTH group) and 38 children with pediatric acute respiratory distress syndrome. INTERVENTIONS: Respiratory mechanics were measured after intubation in all patients. MEASUREMENTS AND MAIN RESULTS: Mechanical power and derived variables of the equation of motion (dynamic power, driving power, and mechanical energy) were computed and then indexed by ideal body weight. Driving pressure was higher in pediatric acute respiratory distress syndrome group compared with ANESTH group. Receiver operator curve analysis showed that driving pressure had the best discrimination capability compared with all derived variables of the equation of motion indexed by ideal body weight. The same results were observed when the subgroup of patients weighs less than 15 kg. There was no difference in unindexed mechanical power between groups. CONCLUSIONS: Driving pressure is the variable that better discriminates pediatric acute respiratory distress syndrome from nonpediatric acute respiratory distress syndrome in children than the calculations derived from the equation of motion, even when indexed by ideal body weight. Unindexed mechanical power was useless to differentiate against both groups. Future studies should determine the threshold for variables of the energy dissipated by the lungs and their association with clinical outcomes.

How Are Clinicians Treating Children With Sepsis in Emergency Departments in Latin America?: An International Multicenter Survey.

OBJECTIVE: Guidelines adherence in emergency departments (EDs) relies partly on the availability of resources to improve sepsis care and outcomes. Our objective was to assess the management of pediatric septic shock (PSS) in Latin America's EDs and to determine the impact of treatment coordinated by a pediatric emergency specialist (PEMS) versus nonpediatric emergency specialists (NPEMS) on guidelines adherence. METHODS: Prospective, descriptive, and multicenter study using an electronic survey administered to PEMS and NPEMS who treat PSS in EDs in 14 Latin American countries. RESULTS: We distributed 2164 surveys with a response rate of 41.5%, of which 22.5% were PEMS. Overall American College of Critical Care Medicine reported guidelines adherence was as follows: vascular access obtained in 5 minutes, 76%; fluid infusion technique, 60%; administering 40 to 60 mL/kg within 30 minutes, 32%; inotropic infusion by peripheral route, 61%; dopamine or epinephrine in cold shock, 80%; norepinephrine in warm shock, 57%; and antibiotics within 60 minutes, 82%. Between PEMS and NPEMS, the following differences were found: vascular access in 5 minutes, 87.1% versus 72.7% (P < 0.01); fluid infusion technique, 72.3% versus 55.9% (P < 0.01); administering 40 to 60 mL/kg within 30 minutes, 42% versus 29% (P < 0.01); inotropic infusion by peripheral route, 75.7% versus 56.3% (P < 0.01); dopamine or epinephrine in cold shock, 87.1% versus 77.3% (P < 0.05); norepinephrine in warm shock, 67.8% versus 54% (P < 0.01); and antibiotic administration within first 60 minutes, 90.1% versus 79.3% (P < 0.01), respectively. Good adherence criteria were followed by 24%. The main referred barrier for sepsis care was a failure in its recognition, including the lack of triage tools. CONCLUSIONS: In some Latin American countries, there is variability in self-reported adherence to the evidence-based recommendations for the treatment of PSS during the first hour. The coordination by PEMS support greater adherence to these recommendations.

Protecting children from iatrogenic harm during COVID19 pandemic.

Critical care management of patients with COVID-19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence-based medicine and encouraged the widespread use of non-tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID-19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.

Therapeutic variability in infants admitted to Latin-American pediatric intensive units due to acute bronchiolitis. / Variabilidad terapéutica en lactantes con bronquiolitis hospitalizados en unidades de cuidados intensivos latinoamericanas.

The objective of this study was to describe the management of infants with acute bronchiolitis admit ted to 20 pediatric intensive care units (PICU) members of LARed in 5 Latin American countries. Pa tients and Method: Retrospective, multicenter, observational study of data from the Latin American Registry of Acute Pediatric Respiratory Failure. We included children under 2 years of age admitted to the PICU due to community-based acute bronchiolitis between May and September 2017. Demo graphic and clinical data, respiratory support, therapies used, and clinical results were collected. A subgroup analysis was carried out according to geographical location (Atlantic v/s Pacific), type of insurance (Public v/s Private), and Academic v/s non-Academic centers. Results: 1,155 patients were included in the registry which present acute respiratory failure and 6 were excluded due to the lack of information in their record form. Out of the 1,147 patients, 908 were under 2 years of age, and out of those, 467 (51.4%) were diagnosed with acute bronchiolitis, which was the main cause of admission to the PICU due to acute respiratory failure. The demographic and severity characteristics among the centers were similar. The most frequent maximum ventilatory support was the high-flow nasal can nula (47%), followed by non-invasive ventilation (26%) and invasive mechanical ventilation (17%), with a wide coefficient of variation (CV) between centers. There was a great dispersion in the use of treatments, where the use of bronchodilators, antibiotics, and corticosteroids, representing a CV up to 400%. There were significant differences in subgroup analysis regarding respiratory support and treatments used. One patient of this cohort passed away. Conclusion: we detected wide variability in respiratory support and treatments among Latin American PICUs. This variability was not explained by demographic or clinical differences. The heterogeneity of treatments should encourage collabora tive initiatives to reduce the gap between scientific evidence and practice.

Positive end-expiratory pressure improves elastic working pressure in anesthetized children.

BACKGROUND: Positive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children. METHODS: Patients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman's analysis were used. Significance was set at P < 0.05. RESULTS: We included 30 patients, median age 39 (15-61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg- 1·cmH2O- 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min- 1 (all P < 0.01). There were no significant changes in resistance and QI. CONCLUSIONS: Analysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.

Respiratory mechanics in infants with severe bronchiolitis on controlled mechanical ventilation.

BACKGROUND: Analysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system. Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU's. METHODS: Infants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV. Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured. Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (KTI and KTE) were calculated. RESULTS: We included 16 patients, of median age 2.5 (1-5.8) months. Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities. Measured respiratory pressures were PIP 29 (26-31), PPL 24 (20-26), tPEEP 9 [8-11] cmH2O. Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP - PEEP) (P < 0.01). QI was significantly lower than QE [5 (4.27-6.75) v/s 16.5 (12-23.8) L/min. RawI and RawE were 38.8 (32-53) and 40.5 (22-55) cmH2O/L/s; KTI and KTE [0.18 (0.12-0.30) v/s 0.18 (0.13-0.22) s], and KTI:KTE ratio was 1:1.04 (1:0.59-1.42). CONCLUSIONS: Analysis of respiratory mechanics of infants with severe bronchiolitis receiving MV shows that the elastic component of the working pressure of the respiratory system is the most important. The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases. A better understanding of lung mechanics in this group of patients may lead to change the traditional ventilatory approach to severe bronchiolitis.

Factors associated with prolonged mechanical ventilation in children with pulmonary failure: Cohort study from the LARed Network registry.

OBJECTIVES: To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). DESIGN: Secondary analysis of a prospective cohort. SETTING: PICUs in centers that are part of the LARed Network between April 2017 and January 2022. PARTICIPANTS: Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. RESULTS: 1698 children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17-2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87-7.36), and fungal infections (OR 6.66, 95% CI 1.87-23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12-0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79-10.20), need for tracheostomy (OR 2.91, 95% CI 1.89-4.48), transfusions (OR 2.94, 95% CI 2.18-3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48-2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89-4.48), and longer PICU stay (OR 1.13, 95% CI 1.10-1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12-2.21). CONCLUSIONS: Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay.