DENISE AYA OTSUKI
Projetos de Pesquisa
Unidades Organizacionais
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
3 resultados
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- Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration-induced Lung Injury(2012) AMBROSIO, Aline M.; LUO, Rubin; FANTONI, Denise T.; GUTIERRES, Claudia; LU, Qin; GU, Wen-Jie; OTSUKI, Denise A.; MALBOUISSON, Luiz M. S.; AULER JR., Jose O. C.; ROUBY, Jean-JacquesBackground: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.
- Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis(2022) CARNICELLI, Paulo; OTSUKI, Denise Aya; MONTEIRO FILHO, Adalberto; KAHVEGIAN, Marcia Aparecida Portela; IDA, Keila Kazue; AULER-JR, Jose Otavio Costa; ROUBY, Jean-Jacques; FANTONI, Denise TabacchiPurpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 x 10(9) cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 +/- 9.7 vs. 32.5 +/- 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 +/- 1 vs. 9.61 +/- 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 +/- 9.6 vs. 63.5 +/- 9.2%, P = 0.026), and increased plasma lactate (3.7 +/- 0.5 vs. 5.5 +/- 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 +/- 0.4 vs. 14.4 +/- 0.3 mL/m(2); P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 +/- 0.2 vs. 2.4 +/- 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.
- Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs(2020) MORAIS, Cristiane Luchesi de Mello; NASCIMENTO, Jorge Willian Leandro; RIBEIRO, Aline Correa; CORTINEZ, Luis Ignacio; CARMONA, Maria Jose Carvalho; MAIA, Debora Rothstein Ramos; MONSEL, Antoine; AULER JR., Jose Otavio Costa; ROUBY, Jean-Jacques; OTSUKI, Denise AyaBackground: Intravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets. Methods: Twelve female piglets received a single intravenous dose of vancomycin (15mg/kg) and were killed 1 (n = 6) or 12h (n = 6) after the end of administration. Twelve piglets received a single nebulized dose of vancomycin (37.5mg/kg) and were killed 1 (n = 6) or 12h (n = 6) after the end of the aerosol administration. In each group, vancomycin lung tissue concentrations were assessed on postmortem lung specimens using high-performance liquid chromatography. Blood samples were collected for serum vancomycin concentration measurement 30min and 1, 2, 4, 6, 8, and 12h after the end of vancomycin administration. Pharmacokinetics was analyzed by nonlinear mixed effect modeling. Results: One hour after vancomycin administration, lung tissue concentrations in the aerosol group were 13 times the concentrations in the intravenous group (median and interquartile range: 161 [71, 301] mu g/g versus 12 [4, 42] mu g/g; P < 0.0001). Twelve hours after vancomycin administration, lung tissue concentrations in the aerosol group were 63 (23, 119) mu g/g and 0 (0, 19) mu g/g in the intravenous group (P < 0.0001). A two-compartment weight-scaled allometric model with first-order absorption and elimination best fit serum pharmacokinetics after both routes of administration. Area under the time-concentration curve from 0 to 12 h was lower in the aerosol group in comparison to the intravenous group (56 [8, 70] mg . h . l(-1)vs. 121 [103, 149] mg . h . l(-1), P = 0.002). Using a population model, vancomycin bioavailability was 13% (95% CI, 6 to 69; coefficient of variation = 85%) and absorption rate was slow (absorption half life = 0.3h). Conclusions: Administration of vancomycin by nebulization resulted in higher lung tissue concentrations than the intravenous route.