title: SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress.
abstract: The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). After hypotension, antibiotics were administered, and the animals were randomized to two groups: control (n = 9), with hemodynamic support aiming central venous pressure 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg; and SvO(2) (n = 9), with the goals above, plus SvO(2) greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO(2) group) were administered. Inflammatory response was evaluated by plasma concentration of cytokines, neutrophil CD14 expression, oxidant generation, and apoptosis. Oxidative stress was evaluated by plasma and myocardial nitrate concentrations, myocardial and vascular NADP(H) oxidase activity, myocardial glutathione content, and nitrotyrosine expression. Mixed venous oxygen saturation-driven resuscitation was associated with improved systolic index, oxygen delivery, and diuresis. Sepsis induced in both groups a significant increase on IL-6 concentrations and plasma nitrate concentrations and a persistent decrease in neutrophil CD14 expression. Apoptosis rate and neutrophil oxidant generation were not different between groups. Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated with this strategy may be related to other mechanisms.
authors.affiliation: Intensive Care and Anesthesiology Laboratory, Research and Education Institute, Hospital Sírio-Libanês, São Paulo, Brazil.
authors.forename: André Loureiro
authors.initials: AL
authors.lastname: Rosário
authors.forename: Marcelo
authors.initials: M
authors.lastname: Park
authors.forename: Milena Karina
authors.initials: MK
authors.lastname: Brunialti
authors.forename: Marialice
authors.initials: M
authors.lastname: Mendes
authors.forename: Marjorie
authors.initials: M
authors.lastname: Rapozo
authors.forename: Denise
authors.initials: D
authors.lastname: Fernandes
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Salomão
authors.forename: Francisco Rafael
authors.initials: FR
authors.lastname: Laurindo
authors.forename: Guilherme Paula
authors.initials: GP
authors.lastname: Schettino
authors.forename: Luciano Cesar P
authors.initials: LC
authors.lastname: Azevedo
mesh_terms: D000818:Animals; D004280:Dobutamine / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D009638:Norepinephrine / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000188:drug therapy* / Q000628:therapy*; D013552:Swine
chemical_list: D004280:Dobutamine; D009638:Norepinephrine