Examinando por Autor "Cruces, Pablo"

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    Capnometry after an inspiratory breath hold, PLATCO2, as a surrogate for PaCO2 in mild to moderate Pediatric Acute Respiratory Distress Syndrome: A feasibility study
    (Wiley Periodicals, 2023-07-10) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Améstica, Marjorie; Araneda, Patricio; Ramirez, Yennys; Vásquez-Hoyos, Pablo; Díaz, Franco
    Objective: Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end‐tidal PCO2 measured immediately after a 3‐s inspiratory‐hold (PLATCO2) by capnometry and PaCO2 measured by arterial blood gases (ABG) in PARDS. Measurements and Main Results: All patients were in volume‐controlled ventilation mode. The regular end‐tidal P P CO ETCO ( ) 2 2 (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory‐hold of 3 s was performed for lung mechanics measurements, recording PETCO2 in the breath following the inspiratory‐hold. (PLATCO2). End‐tidal alveolar dead space fraction (AVDSf) was calculated as [( – )/ PP P aCO ETCO aCO ] 2 2 2 and its surrogate (S)AVDSf as [( CO – )/ CO PLAT 2 ETCO PLAT 2 P ] 2 . Measurements of PaCO2 were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland–Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2–11) months. Tidal volume was 5.8 (5.7–6.3) mL/kg, PEEP 8 (6–8), driving pressure 10 (8–11), and plateau pressure 17 (17–19) cm H2O. Forty‐one paired measurements were analyzed. PaCO2 was higher than PETCO2 (52 mmHg [48–54] vs. 42 mmHg [38–45], p < 0.01), and there were no significant differences with PLATCO2 (50 mmHg [46–55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between PaCO2 and PLATCO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67–0.90]; and rho = 0.80, p < 0.001.), and for PETCO2 were weak and strong (ρc = 0.27 [95% CI: 0.15–0.38]; and rho = 0.63, p < 0.01). The bias between PLATCO2 and PaCO2 was −0.4 ± 3.5 mmHg (LoA −7.2 to 6.4), and between PETCO2 and PaCO2 was −8.5 ± 4.1 mmHg (LoA −16.6 to −0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was −0.5 ± 5.6% (LoA −11.5 to 10.5) Conclusion: This pilot study showed the feasibility of measuring end‐tidal CO2 after a 3‐s end‐inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.
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    Clinical and organizational framework of repurposing pediatric intensive care unit to adult critical care in a resource-limited setting: Lessons from the response of an urban general hospital to the COVID-19 pandemic
    (Elsevier, 2022) Díaz, Franco; Kehr, Juan; Cores, Camila; Rubilar, Patricia; Medina, Tania; Vargas, Caroline; Cruces, Pablo
    Purpose We aim to describe the action plan and clinical results of a COVID-19 unit for adult patient care in units intended for critically ill children, proposing a clinical/administrative framework. Methods We reviewed the preparedness of the PICU team before the surge of cases of COVID-19 and the organizational/administrative issues to increase critical beds in a six-bed PICU allocated to adult critical care in a government-funded general hospital in Latin America. We analyzed the prospectively collected administrative/clinical data of severe COVID-19 cases admitted to PICU during the peak of the first wave of the pandemic. Results We describe a 6-step preparedness plan: recruitment and education, admission criteria, children diversion, team hierarchy, and general and respiratory equipment. The 6-bed PICU was allocated to adult care for 20 weeks, progressively increasing capacity to a 23-bed dedicated COVID-19 unit managed by the PICU team. A six-block bed organizational units were implemented, and personnel increased from 40 to 125 healthcare workers in 24 h shifts. COVID-19 incidence in personnel was 0.5/1000 workdays. One hundred thirty-six patients were admitted, median age 59 (51,65) years old, 68% were male, and 63% had P/F ≤ 100. In addition, 48% received mechanical ventilation, the median length of stay was 7 (3,17), and in-hospital mortality was 15%. Conclusions We propose an organizational framework for the role of PICU in the hospital action plan to increase adult critical beds. The cohort of patients admitted to a PICU repurposed as a COVID-19 ICU had good outcomes. These data are valuable to plan coordinated actions of the healthcare system for future scenarios.
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    Comparison of Interleukin-6 plasma concentration in multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and pediatric sepsis
    (Frontiers Media S.A., 2021-11-15) Díaz, Franco; Busto B., Raúl; Yagnam, Felipe; J. Karsies, Todd; Vásquez-Hoyos, Pablo; Jaramillo-Bustamante, Juan-Camilo; Gonzalez-Dambrauskas, Sebastián; Drago, Michelle; Cruces, Pablo
    Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy. Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis. Design: A retrospective cohort study from previously collected data. Setting: Individual patient data were gathered from three different international datasets. Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. Exposure: None. Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done. Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock. Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don’t discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.
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    Factores asociados a ventilación mecánica prolongada en niños con fallo respiratorio de causa pulmonar: estudio de cohortes del registro de LARed Network
    (Elsevier, 2023-06-15) Barajas-Romero, Juan Sebastían; Vásquez-Hoyos, Pablo; Pardo, Rosalba; Jaramillo-Bustamante, Juan Camilo; Grigolli, Regina; Monteverde-Fernández, Nicolas; Gonzalez-Dambrauskas, Sebastián; Jabornisky, Roberto; Cruces, Pablo; Wegner, Adriana; Díaz, Franco; Pietroboni, Pietro
    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. 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
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    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
    (SAGE Publications, 2022) Fernández-Sarmiento, Jaime; De Souza, Daniela Carla; Martinez, Anacaona; Nieto, Victor; López-Herce, Jesús; Soares Lanziotti, Vanessa; Arias López, María del Pilar; Brunow De Carvalho, Werther; Oliveira, Claudio F.; Jaramillo-Bustamante, Juan Camilo; Díaz, Franco; Yock-Corrales, Adriana; Ruvinsky, Silvina; Munaico, Manuel; Pavlicich, Viviana; Iramain, Ricardo; Márquez, Marta Patricia; González, Gustavo; Yunge, Mauricio; Tonial, Cristian; Cruces, Pablo; Palacio, Gladys; Grela, Carolina; Slöcker- Barrio, Maria; Campos-Miño, Santiago; González- Dambrauskas, Sebastian; Sánchez-Pinto, Nelson L.; Celiny García, Pedro; Jabornisky, Roberto
    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.
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    Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C: implicaciones para las terapias y los resultados
    (Sociedad Chilena de Pediatría, 2023) Díaz, Franco; Domínguez-Rojas, Jesús; Coronado Muñoz, Álvaro; Luna-Delgado, Yesica; Alvarado-Gamarra, Giancarlo; Quispe Flores, Gaudi; Caqui-Vilca, Patrick; Atamari-Anahui, Noé; Muñoz Ramírez, Cleotilde Mireya; Tello-Pezo, Mariela; Cruces, Pablo; Vásquez-Hoyos, Pablo
    Objetivo: describir la mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico (SDRAP) asociado a COVID-19 aguda y MIS-C con insuficiencia respiratoria. Métodos: se realizó un estudio observacional multicéntrico concurrente, analizando variables clínicas y mecánica pulmonar del SDRAP asociado a COVID-19 en 4 unidades de cuidados intensivos pediátricos (UCIP) del Perú. El análisis de subgrupos incluyó el SDRAP asociado a síndrome inflamatorio multisistémico en niños (MIS-C), MIS-PARDS, y el SDRAP con infección respiratoria primaria por COVID-19, C-PARDS. Además, se realizó un análisis de curva operador receptor (ROC) para mortalidad y mecánica pulmonar. Resultados: Se incluyeron 30 pacientes. La edad fue de 7,5(4-11) años, 60% varones y la mortalidad del 23%. El 47% correspondió al grupo MIS-PARDS y el 53% al grupo C-PARDS. C-PARDS tuvo RT-PCR positiva en el 67% y MIS-PARDS ninguna (p<0,001). El grupo C-PARDS presentaba una hipoxemia más profunda (relación P/F <100, 86% frente a 38%, p<0,01) y una presión de conducción más alta [14(10-22) frente a 10(10-12) cmH2O], así como una menor distensibilidad del sistema respiratorio (CRS) [0,5 (0,3-0,6) frente a 0,7(0,6-0,8) ml/kg/cmH2O] en comparación con MIS-PARDS (todos p<0,05). El análisis ROC para la mortalidad mostró que la presión de conducción tenía el mejor rendimiento [AUC 0,91(IC95%0,81-1,00), con el mejor punto de corte de 15 cmH2O (100% de sensibilidad y 87% de especificidad). La mortalidad en los C-PARDS fue del 38% y del 7% en los MIS-PARDS (p=0,09). Los días sin VM fueron 12(0-23) en la C-PARDS y 23(21-25) en la MIS-PARDS (p=0,02). Conclusiones: Los pacientes con C-PARDS, presentan características de mecánica pulmonar similares al SDRAP clásico de moderado a grave. Esto no se observó en los pacientes con MIS-C. Como se ha visto en otros estudios, una presión de conducción ≥ 15 cmH2O fue el mejor discriminador de mortalidad. Estos hallazgos pueden ayudar a guiar las estrategias de manejo ventilatorio para estas dos presentaciones diferentes.
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    Mechanical power in pediatric acute respiratory distress syndrome: A PARDIE study
    (BMC, 2022-01) Bhalla, Anoopindar K.; Klein, Margaret J.; I Alapont, Vincent Modesto; Emeriaud, Guillaume; Kneyber, Martin C. J.; Medina, Alberto; Cruces, Pablo; Díaz, Franco; Takeuchi, Muneyuki; Maddux, Aline B.; Mourani, Peter M.; Camilo, Cristina; White, Benjamin R.; Yehya, Nadir; Pappachan, John; Di Nardo, Matteo; Shein, Steven; Newth, Christopher; Khemani, Robinder; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
    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 diferences in mechanical ventilation management.
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    Mielitis flácida aguda e infeccion por enterovirus: una enfermedad grave emergente.
    (Sociedad Chilena de Pediatría, 2022) Bustos B, Raúl; Díaz, Franco; Cores, Camila; Castro Z., Francisca; Cruces, Pablo
    La mielitis flácida aguda (MFA) es una enfermedad neuro inflamatoria de la medula espinal caracterizada por la aparición aguda de parálisis flácida asimétrica de predominio proximal y una lesión longitudinal de la sustancia gris de la médula espinal. Afecta principalmente a los niños y se ha descrito desde el año 2014 . Objetivo: Reportar una enfermedad pediátrica neurológica grave emergente en Chile. Casos Clínicos: Tres niños, (2 sexo femenino), rango de edad 4 - 6 años, previamente sanos, que tras infección respiratoria alta febril, presentaron una parálisis aguda asimétrica de predominio proximal en extremidades, que progresó en dos de ellos hacia tetraparesia. En todos se aisló enterovirus en el aspirado nasofaríngeo. En el líquido cefalorraquídeo presentaron pleocitosis, la resonancia magnética demostró hiperintesidad en T2 de la sustancia gris de la médula cervical. Todos ingresaron a cuidados intensivos (UCI) y dos requirieron ventilación mecánica (VM) . La terapia con corticoides, inmunoglobulina y plasmaféresis fue ineficaz. A 12 meses de seguimiento, un paciente permaneció tetrapléjico y dependiente de VM, otro falleció de arritmia ventricular en la UCI, el tercero permanece en rehabilitación con recuperación parcial. Conclusiones: Estos son los primeros reportes de esta enfermedad neurológica emergente en nuestro país. Frente a un niño con una parálisis aguda de extremidades de predominio proximal y asimétrica, los pediatras debemos tener un alto índice de sospecha de una MFA. Dado que puede progresar rápidamente y llevar a una insuficiencia respiratoria, la sospecha de MFA debe ser considerada como una emergencia médica.
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    Noninvasive continuous positive airway pressure is a lung- and diaphragm-protective approach in self-inflicted lung injury
    (The American Thoracis Society, 2024-04-15) Cruces, Pablo; Erranz, Benjamín; Pérez, Agustín; Reveco, Sonia; González, Carlos; Retamal, Jaime; Poblete, Daniela; Hurtado, Daniel E.; Díaz, Franco
    Strenuous spontaneous effort can promote lung and diaphragmatic injury in acute lung injury (ALI), phenomena known as “patient self-inflicted lung injury” (P-SILI) and load-induced diaphragmatic injury, respectively (1–3). Although continuous positive airway pressure (CPAP) can relieve hypoxemia and work of breathing (4), it is controversial if it prevents lung and diaphragmatic injury (5, 6). We aimed to investigate the effects of noninvasive CPAP on lung and diaphragmatic injury in an ALI model compared with unassisted animals.
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    Noninvasive ventilation for Pediatric Acute Respiratory Distress Syndrome: experience from the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study
    (The Society of Critical Care Medicine; The World Federation of Pediatric Intensive and Critical Care Societies, 2023) Díaz, Franco; Emeriaud, Guillaume; Pons-Òdena, Marti; Bhalla, Anoopindar K.; Shein, Steven L.; Killien, Elizabeth Y.; Modesto i Alapont, Vicent; Rowan, Courtney; Baudin, Florent; Lin, John C.; Grégoire, Gabrielle; Napolitano, Natalie; Mayordomo-Colunga, Juan; Cruces, Pablo; Medina, Alberto; Smith, Lincoln; Khemani, Robinder G.
    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
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    Pediatric ARDS phenotypes in critical COVID-19: implications for therapies and outcomes
    (Yale University; Cold Spring Harbor Laboratory (CSHL), 2022-06) Díaz, Franco; Domínguez-Rojas, Jesús; Luna-Delgado, Yesica; Caqui-Vilca, Patrick; Martel-Ramírez, Carlos; Quispe-Chipana, Miguel; Cruz-Arpi, Mario; Atamari-Anahui, Noé; Muñoz Ramírez, Cleotilde Mireya; Quispe Flores, Gaudi; Tello-Pezo, Mariela; Cruces, Pablo; Vásquez-Hoyos, Pablo
    Purpose to describe lung mechanics in Pediatric Acute Respiratory Disease Syndrome (PARDS) associated with COVID-19. We hypothesize two phenotypes according to respiratory system mechanics and clinical diagnosis. Methods a concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICUs) of Perú. Subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operator curve analysis (ROC) for mortality was performed. Results 30 patients were included. Age was 7.5(4-11) years, 60% male, and mortality 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS phenotypes. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p<0.001). C-PARDS group had more profound hypoxemia (P/Fratio<100, 86%vs38%,p<0.01) and higher driving-pressure (DP) [14(10-22)vs10(10-12)cmH2O], and lower compliance of the respiratory system (CRS)[0.5(0.3-0.6)vs 0.7(0.6-0.8)ml/kg/cmH2O] compared to MIS-PARDS (all p<0.05). ROC-analysis for mortality showed that DP had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-point of 15 cmH2O (100% sensitivity and 87% of specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS(p=0.09). MV free-days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS(p=0.02) Conclusion critical pediatric COVID-19 is heterogeneous in children. COVID-19 PARDS had two phenotypes with distinctive pulmonary mechanics features. Characteristics of C-PARDS are like a classic primary PARDS, while a decoupling between compliance and hypoxemia was more frequent in MIS-PARDS. In addition, C-PARDS had fewer MV free-days. DP ≥ 15 cmH2O had the best performance of the quasi-static calculations to discriminate for mortality. Standardized pulmonary mechanics measurements in PARDS might reveal essential information to tailor the ventilatory strategy in pediatric critical COVID-19.
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    Plateau pressure and driving pressure in volume- and pressure- controlled ventilation: comparison of frictional and viscoelastic resistive components in Pediatric Acute Respiratory Distress Syndrome
    (Society of Critical Care Medicine​ and The World Federation of Pediatric Intensive and Critical Care Societies, 2023-09) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Ramirez, Yennys; Díaz, Franco
    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). 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
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    Relationship between national changes in mobility due to non-pharmaceutical interventions and emergency department visits due to pediatric acute respiratory infections during the COVID-19 pandemic
    (Yale University; Cold Spring Harbor Laboratory (CSHL), 2022-01) Díaz, Franco; Carvajal, Cristóbal; Gatica, Sebastián; Vásquez-Hoyos, Pablo; Jabornisky, Roberto; Von Moltke, Richard; Jaramillo-Bustamante, Juan Camilo; Pizarro, Federico; Cruces, Pablo
    Background Strong social distancing measures were quickly implemented in Chile during the SARS-CoV-2 outbreak. One of the aims of non-pharmaceutical interventions (NPI) mandates was to decrease overcrowding, thus is usually measured as mobility changes. Methods we gather data from national health statistics for pediatric emergency (PED) visits for acute respiratory infection (ARI) in children younger than 15. We defined a historical cohort, including data from 2016 to 2019, and compared them with 2020 and 2021 pandemic years. Also, Chile’s national mobility reports from the online google database were downloaded. We tested the correlation between changes in mobility and relative reduction in PED-ARI by Spearman’s Rank Test. Results Historical data showed a mean of 46863 ± 3071 PED-ARI weekly visits with a high seasonal variation, with two peaks in weeks 20 and 28 and weeks 32 to 36. This transient drop was temporally associated with the mid-winter 2-week holiday of schools. The usual PED visits peaks did not occur in 2020 and 2021. Mobility declined from week 9, reaching lower than historical data from week 12 and a minimum of 43% in week 15 of 2020 . The correlation between mobility and PED-ARI visits showed a strong monotonic relationship (quadratic) with a Spearman’s rho of 0.80 (95% CI 0.75 to 0.86) . Conclusion NPI resulting in a decrease in mobility should be considered a robust public health measure to relieve the winter’s collapse of the national health system, decreasing morbimortality in children due to PED-ARI.
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    Reply to Pérez
    (American Thoracic Society, 2023) Cruces, Pablo; Erranz, Benjamín; Díaz, Franco
    Reply to Pérez. Patient self-inflicted and ventilator-induced lung injury: two sides of the same coin?
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    Respiratory system compliance accurately assesses the “Baby Lung” in Pediatric Acute Respiratory Distress Syndrome
    (The American Thoracis Society, 2024-04-01) Cruces, Pablo; Reveco, Sonia; Caviedes, Paola; Díaz, Franco
    The concept of the “baby lung” has gained widespread recognition in acute respiratory distress syndrome (ARDS) and has significantly influenced the principles of protective mechanical ventilation (MV) (1). This concept is rooted in tomographic studies performed in adult patients with ARDS, which revealed the presence of a smaller, normally aerated lung compartment at the end of expiration and normal specific lung elastance. There is a strong correlation between end-expiratory lung volume (EELV) and respiratory system.
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    Spontaneous breathing promotes lung injury in an experimental model of alveolar collapse
    (Springer Nature, 2022) Bachmann, María Consuelo; Cruces, Pablo; Díaz, Franco; Oviedo, Vanessa; Goich, Mariela; Fuenzalida, José; Damiani, Luis Felipe; Basoalto, Roque; Jalil, Yorschua; Carpio, David; Hamidi Vadeghani, Niki; Cornejo, Rodrigo; Rovegno, Maximiliano; Bugedo, Guillermo; Bruhn, Alejandro; Retamal, Jaime
    Vigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as “patient self-inflicted lung injury”. Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB‐group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late
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    Ventilatory load reduction by combined mild hypothermia and ultraprotective mechanical ventilation strategy in severe COVID-19-related acute respiratory distress syndrome: A physiological study.
    (The Emergency Medicine Association of Turkey, 2024-04) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Ramírez, Yenny; Díaz, Franco
    We report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18 years old, severe COVID 19 related ARDS, driving pressure ∆P >15 cmH2 O despite low-VT strategy, and extracorporea therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%–75%). Mixed effects analysis and Dunnett’s test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170–192) to 152 (137–170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31–40) to 29 (26–34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2 O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds.