Monitoring in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: Monitoring is essential to assess changes in the lung condition, to identify heart-lung interactions, and to personalize and improve respiratory support and adjuvant therapies in pediatric acute respiratory distress syndrome (PARDS). The objective of this article is to report the rationale of the revised recommendations/statements on monitoring from the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies focused on respiratory or cardiovascular monitoring of children less than 18 years old with a diagnosis of PARDS. We excluded studies focused on neonates. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. We identified 342 studies for full-text review. Seventeen good practice statements were generated related to respiratory and cardiovascular monitoring. Four research statements were generated related to respiratory mechanics and imaging monitoring, hemodynamics monitoring, and extubation readiness monitoring. CONCLUSIONS: PALICC-2 monitoring good practice and research statements were developed to improve the care of patients with PARDS and were based on new knowledge generated in recent years in patients with PARDS, specifically in topics of general monitoring, respiratory system mechanics, gas exchange, weaning considerations, lung imaging, and hemodynamic monitoring.

Plateau Pressure and Driving Pressure in Volume- and Pressure-Controlled Ventilation: Comparison of Frictional and Viscoelastic Resistive Components in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine frictional, viscoelastic, and elastic resistive components, as well threshold pressures, during volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) in pediatric patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective cohort study. SETTING: Seven-bed PICU, Hospital El Carmen de Maipú, Chile. PATIENTS: Eighteen mechanically ventilated patients less than or equal to 15 years old undergoing neuromuscular blockade as part of management for ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were in VCV mode during measurement of pulmonary mechanics, including: the first pressure drop (P1) upon reaching zero flow during the inspiratory hold, peak inspiratory pressure (PIP), plateau pressure (P PLAT ), and total positive end-expiratory pressure (tPEEP). We calculated the components of the working pressure, as defined by the following: frictional resistive = PIP-P1; viscoelastic resistive = P1-P PLAT ; purely elastic = driving pressure (ΔP) = P PLAT -tPEEP; and threshold = intrinsic PEEP. The procedures and calculations were repeated on PCV, keeping the same tidal volume and inspiratory time. Measurements in VCV were considered the gold standard. We performed Spearman correlation and Bland-Altman analysis. The median (interquartile range [IQR]) for patient age was 5 months (2-17 mo). Tidal volume was 5.7 mL/kg (5.3-6.1 mL/kg), PIP cm H 2 O 26 (23-27 cm H 2 O), P1 23 cm H 2 O (21-26 cm H 2 O), P PLAT 19 cm H 2 O (17-22 cm H 2 O), tPEEP 9 cm H 2 O (8-9 cm H 2 O), and ΔP 11 cm H 2 O (9-13 cm H 2 O) in VCV mode at baseline. There was a robust correlation (rho > 0.8) and agreement between frictional resistive, elastic, and threshold components of working pressure in both modes but not for the viscoelastic resistive component. The purely frictional resistive component was negligible. Median peak inspiratory flow with decelerating-flow was 21 (IQR, 15-26) and squared-shaped flow was 7 L/min (IQR, 6-10 L/min) ( p < 0.001). CONCLUSIONS: P PLAT , ΔP, and tPEEP can guide clinical decisions independent of the ventilatory mode. The modest purely frictional resistive component emphasizes the relevance of maintaining the same safety limits, regardless of the selected ventilatory mode. Therefore, peak inspiratory flow should be studied as a mechanism of ventilator-induced lung injury in pediatric ARDS.

Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. SETTING: One hundred five international PICUs. PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study.

BACKGROUND: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). METHODS: Retrospective analysis of a prospective observational international cohort study. RESULTS: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure-positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min-1·Kg-1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min-1·Kg-1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min-1·Kg-1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min-1·Kg-1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. CONCLUSIONS: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. TAKE HOME MESSAGE: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

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.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

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.

Pediatric Inflammatory Multisystem Syndrome Associated With SARS-CoV-2: A Case Series Quantitative Systematic Review.

ABSTRACT: Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) is infrequent, but children might present as a life-threatening disease. In a systematic quantitative review, we analyzed 11 studies of PIMS-TS, including 468 children reported before July 1, 2020. We found a myriad of clinical features, but we were able to describe common characteristics: previously healthy school-aged children, persistent fever and gastrointestinal symptoms, lymphopenia, and high inflammatory markers. Clinical syndromes such as myocarditis and Kawasaki disease were present in only one third of cases each one. Pediatric intensive care unit admission was frequent, although length of stay was less than 1 week, and mortality was low. Most patients received immunoglobulin or steroids, although the level of evidence for that treatment is low. The PIMS-ST was recently described, and the detailed quantitative pooled data will increase clinicians' awareness, improve diagnosis, and promptly start treatment. This analysis also highlights the necessity of future collaborative studies, given the heterogeneous nature of the PIMS-TS.

Low Spontaneous Breathing Effort during Extracorporeal Membrane Oxygenation in a Porcine Model of Severe Acute Respiratory Distress Syndrome.

BACKGROUND: A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. METHODS: Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. RESULTS: Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. CONCLUSIONS: In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.

A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection.

Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.

Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation.

RATIONALE: There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it. OBJECTIVES: To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO. METHODS: Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period. MEASUREMENTS AND MAIN RESULTS: Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power. CONCLUSIONS: In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers.

Biomarkers of pre-existing risk of Torsade de Pointes under Sotalol treatment.

INTRODUCTION: Antiarrhythmic drugs therapies are currently going through a turning point. The high risk that exists during the treatments has led to an ongoing search for new non-invasive toxicity risk biomarkers. METHODS: We propose the use of spatial biomarkers obtained through the quaternion algebra, evaluating the dynamics of the cardiac electrical vector in a non-invasive way in order to detect abnormal changes in ventricular heterogeneity. In groups of patients with and without history of Torsade de Pointes undergoing a Sotalol challenge, we compute the radius and the linear and angular velocities of QRS complex and T-wave loops. From these signals we extract significant features in order to compute a risk patient classifier. RESULTS: Using machine learning techniques and statistical analysis, the combinations of few indices reach a pair of sensitivity/specificity of 100%/100% when separating patients with arrhythmogenic substrate. Several biomarkers not only measure drug-induced changes significantly but also observe differences in at-risk patients outperforming current standards. DISCUSSION: Alternative biomarkers were able to describe pre-existing risk of patients. Given the high levels of significance and performance, these results could contribute to a better understanding of the torsadogenic substrate and to the safe development of drug therapies.

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.

Effectiveness of Two Targeted Temperature Management Methods After Pediatric Postcardiac Arrest: A Multicenter International Study.

OBJECTIVES: It is currently recommended that after return of spontaneous circulation following cardiac arrest, fever should be prevented using TTM through a servo-controlled system. This technology is not yet available in many global settings, where manual physical measures without servo-control is the only option. Our aim was to compare feasibility, safety and quality assurance of servo-controlled system versus no servo-controlled system cooling, TTM protocols for cooling, maintenance and rewarming following return of spontaneous circulation after cardiac arrest in children. DESIGN: Prospective, multicenter, nonrandomized, study. SETTING: PICUs of 20 hospitals in South America, Spain, and Italy, 2012-2014. PATIENTS: Under 18 years old with a cardiac arrest longer than 2 minutes, in coma and surviving to PICU admission requiring mechanical ventilation were included. METHODS: TTM to 32-34°C was performed by prospectively designed protocol across 20 centers, with either servo-controlled system or no servo-controlled system methods, depending on servo-controlled system availability. We analyzed clinical data, cardiac arrest, temperature, mechanical ventilation duration, length of hospitalization, complications, survival, and neurologic outcomes at 6 months. PRIMARY OUTCOME: feasibility, safety and quality assurance of the cooling technique and secondary outcome: survival and Pediatric Cerebral Performance Category at 6 months. MEASUREMENTS AND MAIN RESULTS: Seventy patients were recruited, 51 of 70 TTM (72.8%) with servo-controlled system. TTM induction, maintenance, and rewarming were feasible in both groups. Servo-controlled system was more effective than no servo-controlled system in maintaining TTM (69 vs 60%; p = 0.004). Servo-controlled system had fewer temperatures above 38.1°C during the 5 days of TTM (0.1% vs 2.9%; p < 0.001). No differences in mortality, complications, length of mechanical ventilation and of stay, or neurologic sequelae were found between the two groups. CONCLUSIONS: TTM protocol (for cooling, maintenance and rewarming) following return of spontaneous circulation after cardiac arrest in children was feasible and safe with both servo-controlled system and no servo-controlled system techniques. Achieving, maintaining, and rewarming within protocol targets were more effective with servo-controlled system versus no servo-controlled system techniques.

Renal Decapsulation Prevents Intrinsic Renal Compartment Syndrome in Ischemia-Reperfusion-Induced Acute Kidney Injury: A Physiologic Approach.

OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high mortality that lacks of specific curative treatment. Therapies focusing on the hydraulic behavior have shown promising results in preventing structural and functional renal impairment, but the underlying mechanisms remain understudied. Our goal is to assess the effects of renal decapsulation on regional hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury experimental model. METHODS: In piglets, intra renal pressure, renal tissue oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion group with intact kidney, an ischemia-reperfusion group where the kidney capsule was removed, and in a sham group. RESULTS: Decapsulated kidneys displayed an effective reduction of intra renal pressure, an increment of renal tissue oxygen pressure, and a better performance in the regional delivery, consumption, and extraction of oxygen after reperfusion, resulting in a marked attenuation of acute kidney injury progression due to reduced structural damage and improved renal function. CONCLUSIONS: Our results strongly suggest that renal decapsulation prevents the onset of an intrinsic renal compartment syndrome after ischemic acute kidney injury.