Browsing by Author "Garcia-Gallardo, Gustavo"

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    Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow*
    (2023) Ospina-Tascon, Gustavo A.; Aldana, Jose L.; Marin, Alberto Garcia F.; Calderon-Tapia, Luis E.; Marulanda, Angela; Escobar, Elena P.; Garcia-Gallardo, Gustavo; Orozco, Nicolas; Velasco, Maria I.; Rios, Edwin; De Backer, Daniel; Hernandez, Glenn; Bakker, Jan
    OBJECTIVES:To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN:Animal experimental study. SETTING:University translational research laboratory. SUBJECTS:Fifteen Landrace pigs. INTERVENTIONS:Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) (n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) (n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) (n = 3). Time x group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS:Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy (p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group (p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels (p = 0.01) and venous-to-arterial carbon dioxide differences (p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes (p = 0.015) and required significantly less resuscitation fluids (p < 0.001) and lower doses of norepinephrine (p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group (p = 0.021 and p = 0.004, respectively). CONCLUSIONS:In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
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    Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial
    (Associacao de Medicina Intensiva Brasileira - AMIB, 2025) Orozco, Nicolás; Garcia-Gallardo, Gustavo; Cavalcanti, Alexandre Biasi; Dos Santos, Tiago Mendonça; Ospina-Tascón, Gustavo; Bakker, Jan; Morales Ahumada, Sebastián Alonso; Ramos, Karla; Alegría Vargas, Leyla; Teboul, Jean Louis; De Backer, Daniel; Vieillard-Baron, Antoine; Hernández, Liliana Vallecilla; de Lima, Lucas Martins; Damiani, Lucas Petri; Sady, Erica Ribeiro; Santucci, Eliana Vieira; Hernández P., Glenn; Kattan Tala, Eduardo José
    Background: ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes. Objective: To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial. Methods: We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes. Conclusion: According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.