Browsing by Author "Alegría, Leyla"

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    Dexmedetomidine ameliorates gut lactate production and impairment of exogenous lactate clearance in an endotoxic sheep model
    (2015) Hernández P., Glenn; Tapia, Pablo; Bruhn, Alejandro; Soto, Dagoberto; Alegría, Leyla; Jarufe Cassis, Nicolás; Menchaca, Rodrigo; Meissner, Arturo; Vives, María Ignacia; Ospina Tascón, Gustavo A.; Luengo, Cecilia; Bakker, Jan
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    Early and severe impairment of lactate clearance in endotoxic shock is not related to liver hypoperfusion: preliminary report
    (2014) Tapia, Pablo; Soto, Dagoberto; Bruhn, Alejandro; Regueira Heskia, Tomás; Jarufe Cassis, Nicolás; Alegría, Leyla; Bachler, J. P.; Leon, F.; Vicuña, C.; Hernández P., Glenn
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    Effect of a lung rest strategy during ECMO in a porcine acute lung injury model
    (2015) Araos, J.; Tapia, Pablo; Alegría, Leyla; García Cañete, Patricia; Rodríguez, F.; Amthauer, M.; Castro, G.; Soto, Dagoberto; Damiani Rebolledo, L. Felipe; Bugedo Tarraza, Guillermo; Bruhn, Alejandro; Cruces, Pablo; Salomon, Tatiana; Erranz, B.; Carreño, P.; Medina, T.
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    Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock The ANDROMEDA-SHOCK Randomized Clinical Trial
    (2019) Hernández P., Glenn; Ospina Tascón, Gustavo A.; Damiani, Lucas Petri; Estenssoro, Elisa; Dubin, Arnaldo; Hurtado, Javier; Friedman, Gilberto; Castro, Ricardo; Alegría, Leyla; Teboul, Jean Louis; Cecconi, Maurizio; Ferri, Giorgio; Jibaja, Manuel; Pairumani, Ronald; Fernández, Paula; Barahona, Diego; Granda Luna, Vladimir; Biasi Cavalcanti, Alexandre; Bakker, Jan
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    Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial
    (2020) Castro López, Ricardo; Kattan Tala, Eduardo José; Valenzuela, Emilio Daniel; Alegría, Leyla; Oviedo, Vanessa; Soto, Dagoberto; Vera Alarcón, María Magdalena; Bravo Morales, Sebastián; Bakker, Jan; Hernández P., Glenn
    Abstract Background Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. Results Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375–2625] vs. 1500 [1000–2000], p = 0.3), or balances (982[249–2833] vs. 15,800 [740–6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. Conclusions CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)
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    Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock
    (2016) Hernández P., Glenn; Tapia, Pablo; Alegría, Leyla; Soto, Dagoberto; Jarufe Cassis, Nicolás; Achurra Tirado, Pablo; Rebolledo, Rolando; Bruhn, Alejandro; Castro, Ricardo; Kattan Tala, Eduardo José; Bakker, Jan; Luengo, Cecilia; Gomez, Jussara; Ospina Tascón, Gustavo
    Abstract Background Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. Methods Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. Results Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. Conclusions Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.Abstract Background Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. Methods Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. Results Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. Conclusions Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.
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    Extended extracorporeal lung support in a porcine acute lung injury model. Feasibility and preliminary data
    (2014) Bruhn, Alejandro; Cruces, P.; Tapia, Pablo; García Cañete, Patricia; Alegría, Leyla; Araos, J.; Soto, Dagoberto; Rodríguez, F.; Amthauer, M.; Rodríguez, D.
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    Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion
    (2014) Tapia Ossa, Pablo José; Soto, Dagoberto; Bruhn, Alejandro; Alegría, Leyla; Jarufe Cassis, Nicolás; Kattan Tala, Eduardo José; Regueira Heskia, Tomás; Meissner, Arturo; Menchaca, Rodrigo; Vives, María Ignacia
    Introduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock.Methods: After anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method.Results: Significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P <0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P <0.01).Conclusions: Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.
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    Implementación de un modelo porcino de trasplante hepático en Chile
    (Sociedad de Cirujanos de Chile, 2020) Ochoa, Gabriela; Marino, Carlo; Riveros, Sergio; Morales, Emilio; Jarry, Cristian; Viñuela, Macarena; Alegría, Leyla; Zenteno, María Josefina; Martínez Castillo, Jorge; Achurra Tirado, Pablo; Rebolledo Acevedo, Rolando Arturo
    Objetivo: Presentar la implementación del primer modelo porcino de trasplante hepático (TH) en Chile y sus resultados. Material y Método: Se implementó un protocolo quirúrgico y anestésico en el contextode una investigación en perfusión normotérmica hepática financiada por un Fondo Nacional de Desarrollo Científico y Tecnológico. Los cerdos fueron seleccionados por peso (35-40 kilos), en cada experimentose utilizó dos, donante y receptor, sometidos a procura y trasplante respectivamente. El análisis se realizó con estadística descriptiva. Resultados: Se realizaron 26 experimentos (marzo de 2018-octubre de 2019). El protocolo consta de 7 etapas: Preparación, Instrumentalización, Procura o Hepatectomía, Tiempo Anhepático, Etapa de Isquemia-Reperfusión, Monitorización y Eutanasia. Las primeras tres son similares en ambos cerdos, y desde la cuarta en adelante corresponde sólo al receptor. La supervivencia a la cirugíafue de 92,3% (24/26) y al seguimiento de 76,9% (20/26). La mortalidad se produjo por inestabilidad cardiovascular postreperfusión portal. El tiempo quirúrgico promedio fue de 170 min, y el tiempo anhepático de 33 min. La PAM cursó una baja postreperfusión con recuperación al final de la monitorización (67,4 mmHg media) y la tendencia en ph fue a acidosis al final del seguimiento (7,21 media). Se requirió drogas vasoactivas en 12 casos. Discusión: Logramos implementar un modelo experimental simplificado y reproducible de TH sin necesidad de circulación extracorpórea ni puente veno-venoso gracias a la estandarización de la técnica quirúrgica y de los cuidados perioperatorios. Conclusiones: La consolidación de un modelo experimental significa el primer paso en investigación preclínica de nuevas tecnologías asociadas al TH en Chile.
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    Organizational Issues, structure and processes of care in 257 ICUs in Latin America: a study from the latin America Intensiva Care Network
    (2017) Estenssoro, Elisa; Alegría, Leyla; Murias, Gastón; Friedman, Gilberto; Castro López, Ricardo; Nin Vaeza, Nicolas; Loudet, Cecilia; Bruhn, Alejandro; Jibaja, Manuel; Ospina Tascon, Gustavo; Ríos, Fernando; Machado, Flavia R.; Biasi Cavalcanti, Alexandre; Dubin, Arnaldo; Hurtado, F. Javier; Briva, Arturo; Romero, Carlos; Bugedo Tarraza, Guillermo; Bakker, Jan; Cecconi, Maurizio; Azevedo, Luciano; Hernández P., Glenn
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    Statistical analysis plan for early goal-directed therapy using a physiological holistic view - The andromeda-shock: a randomized controlled trial
    (2018) Hernández P., Glenn; Cavalcanti, Alexandre Biasi; Ospina-Tascón, Gustavo; Dubin, Arnaldo; Hurtado, Francisco Javier; Damiani, Lucas Petri; Friedman, Gilberto; Castro López, Ricardo; Alegría, Leyla; Bakker, Jan; Cecconi, Maurizio; Teboul, Jean-Louis