Browsing by Author "Soto, Dagoberto"
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- ItemCapillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study(2024) Hernández, Glenn; Valenzuela, Emilio Daniel; Kattan, Eduardo; Castro, Ricardo; Guzmán, Camila; Kraemer, Alicia Elzo; Sarzosa, Nicolás; Alegria, Leyla; Contreras, Roberto; Oviedo, Vanessa; Bravo, Sebastián; Soto, Dagoberto; Sáez, Claudia; Ait-Oufella, Hafid; Ospina Tascón, Gustavo; Bakker, JanBackground: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. Methods Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80–85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). Results CRT decreased significantly with both tests (from 5 [3.5–7.6] to 4 [2.4–5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3–5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. Conclusions Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.
- ItemDexmedetomidine 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
- ItemEarly 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
- ItemEffect 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.
- ItemEffect of Lactamase Inhibitors on the Biosensor Penp during the Measurement of Lactam Antibiotics Concentration(2019) Soto, Dagoberto; Furtunato Da Silva, Camila; Ugalde, Cristián; Wong, Kwok Yin; Leung, Yun Chung; So, Lok Yan; Andresen Hernández, Max
- ItemEffects 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., GlennAbstract 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)
- ItemEffects 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, GustavoAbstract 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.
- ItemExtended 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.
- ItemHypoxia-related parameters during septic shock resuscitation: Pathophysiological determinants and potential clinical implications(AME PUBL CO, 2020) Pavez, Nicolas; Kattan, Eduardo; Vera, Magdalena; Ferri, Giorgio; Daniel Valenzuela, Emilio; Alegria, Leyla; Bravo, Sebastian; Pairumani, Ronald; Santis, Cesar; Oviedo, Vanessa; Soto, Dagoberto; Ospina Tascon, Gustavo; Bakker, Jan; Hernandez, Glenn; Castro, RicardoBackground: Assessment of tissue hypoxia at the bedside has yet to be translated into daily clinical practice in septic shock patients. Perfusion markers are surrogates of deeper physiological phenomena. Lactate-to-pyruvate ratio ( LPR) and the ratio between veno-arterial PCO2 difference and Ca-vO(2) (Delta PCO2/Ca-vO(2)) have been proposed as markers of tissue hypoxia, but they have not been compared in the clinical scenario. We studied acute septic shock patients under resuscitation. We wanted to evaluate the relationship of these hypoxia markers with clinical and biochemical markers of hypoperfusion during septic shock resuscitation.
- ItemImpairment 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 IgnaciaIntroduction: 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.
- ItemImplementation and design of customized ex vivo machine perfusion. Analysis of its first results(Wiley, 2021) Riveros, Sergio; Marino, Carlo; Ochoa, Gabriela; Morales, Emilio; Soto, Dagoberto; Alegria, Leyla; Josefina Zenteno, Maria; Branes, Alejandro; Achurra, Pablo; Rebolledo, Rolando A.The lack of organs available for transplantation is a global problem. The high mortality rates on the waiting list and the high number of discarded livers are reasons to develop new tools in the preservation and transplantation process. New tools should also be available for low-income countries. This article reports the development of customized normothermic machine perfusion (NMP). An ex vivo dual perfusion machine was designed, composed of a common reservoir organ box (CRO), a centrifugal pump (portal system, low pressure), and a roller pump (arterial system, high pressure). Porcine livers (n = 5) were perfused with an oxygenated normothermic (37celcius) strategy for 3 hours. Hemodynamic variables, metabolic parameters, and bile production during preservation were analyzed. Arterial and portal flow remain stable during perfusion. Total bilirubin production was 11.25 mL (4-14.5) at 180 minutes. The median pH value reached 7.32 (7.25-7.4) at 180 minutes. Lactate values decreased progressively to normalization at 120 minutes. This perfusion setup was stable and able to maintain the metabolic activity of a liver graft in a porcine animal model. Design and initial results from this customized NMP are promising for a future clinical application in low-income countries.
- ItemReduction of Respiratory Rate in COVID-19-Associated ARDS(2022) Damiani, L. Felipe; Oviedo, Vanessa; Alegria, Leyla; Soto, Dagoberto; Basoalto, Roque; Consuelo Bachmann, M.; Jalil Contreras, Yorschua Frederick; Santis, Cesar; Vera, Magdalena; Retamal, Jaime; Bruhn, Alejandro; Bugedo, Guillermo
- ItemTherapeutic monitoring of antibiotics. New methodologies: biosensors(SOC MEDICA SANTIAGO, 2015) Soto, Dagoberto; Silva, Camila; Andresen, Max, V; Soto, Natalia; Wong, Kwok Yin; Andresen, MaxThe pharmacokinetics of antibiotics, especially in severely ill patients, may be profoundly altered due to multiple pathophysiological changes. Recent studies have shown that empiric dosing recommendations for ICU patients are inadequate to effectively treat a broad range of susceptible organisms and need to be reconsidered. Therapeutic drug monitoring (TDM) is an important mean for optimizing drug utilization and doses for the purpose of improving the clinical effectiveness. However, it is very challenging to quantify plasma antibiotic concentrations in clinical situations as a routine practice, because of the high costs and complexities associated with advanced instrumental techniques. Currently there are not routine and low cost methods to determine the presence and concentration of beta-lactam antibiotics in plasma patients in a clinical setup. Indeed, such analytical methods are based on chromatographic techniques mainly used in research. Here we describe and comment different techniques, focusing on our preliminary experience using biosensors.