RESUMO

Few data from Latin American centers on clinical outcomes in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome who required extracorporeal membrane oxygenation (ECMO) are published. Moreover, clinical and functional status after hospital discharge remains poorly explored in these patients. We evaluated in-hospital outcomes of severe COVID-19 patients who received ECMO support in two Brazilian hospitals. In one-third of the survivors, post-acute COVID-19 syndrome (PACS), quality of life, anxiety, depression, and return to work were evaluated. Eighty-five patients were included and in-hospital mortality was 47%. Age >65 years (HR: 4.8; 95% confidence interval [CI]: 1.4-16.4), diabetes (HR: 6.0; 95% CI: 1.8-19.6), ECMO support duration (HR: 1.08; 95% CI: 1.05-1.12) and dialysis initiated after ECMO (HR: 3.4; 95% CI: 1.1-10.8) were independently associated with higher in-hospital mortality and mechanical ventilation (MV) duration before ECMO was not (HR: 1.18; 95% CI: 0.71-2.09). PACS-related symptoms were reported by two-thirds and half of patients at 30- and 90-days post-discharge, respectively. The median EQ-5D score was 0.85 (0.70-1.00) and 0.77 (0.66-1.00) at 30 and 90 days. Of the 15 responders, all previously working patients, except one, have returned to work at 90 days. In conclusion, in-hospital mortality in a large Latin American cohort was comparable to the Global extracorporeal life support organization registry.

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RESUMO

Os mecanismos fisiopatológicos associados aos efeitos benéficos da reanimação guiada pela saturação venosa mista de oxigênio (SvO2) durante a sepse não são claros. Nosso objetivo foi avaliar os efeitos de um algoritmo de reanimação guiado pela SvO2 incluindo fluidos, noradrenalina e dobutamina na hemodinâmica, resposta inflamatória e estresse oxidativo cardiovascular durante um modelo experimental que se assemelha clinicamente ao choque séptico. Dezoito porcos anestesiados e cateterizados (35-45 kg) foram submetidos à peritonite por inoculação fecal (0,75 g/Kg). Depois de permanecerem hipotensos, antibióticos foram administrados e os animais foram randomizados em dois grupos: controle (n=9), com suporte hemodinâmico visando pressão venosa central de 8-12 mmHg, débito urinário de 0,5 ml/kg por hora, e pressão arterial média acima de 65 mmHg; e grupo SvO2 (n=9), com os objetivos acima referidos, além de SvO2 acima de 65%. As intervenções duraram 12 hs e incluíram Ringer Lactato e norepinefrina (ambos os grupos) e dobutamina (grupo SvO2). A resposta inflamatória foi avaliada pela concentração plasmática de citocinas, expressão de CD14 de neutrófilos, geração de espécies reativas de oxigênio e apoptose. O estresse oxidativo foi avaliado pelas concentrações de nitratos no miocárdio e no plasma, a atividade miocárdica e vascular de NAD(P)H oxidase, conteúdo de glutationa do miocárdio e expressão de nitrotirosina. A reanimação guiada por SvO2 foi associada com melhor índice sistólico, oferta de oxigênio e diurese. A sepse induziu em ambos os grupos um aumento significativo na concentração de IL-6, nas concentrações de nitrato de plasma e diminuição persistente na expressão de CD14 em neutrófilos. A apoptose e a geração de espécies reativas de oxigênio por neutrófilos não foram diferentes entre os grupos. As estratégias de tratamento não alteraram significativamente os parâmetros de estresse oxidativo. Assim, uma abordagem destinada a otimizar a SvO2...

The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO2)-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO2-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 group SvO2 (n =9), with the goals above, plus SvO2 greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO2 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 NAD(P)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 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 SvO2 during sepsis improves hemoynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects...

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RESUMO

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.

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OBJETIVOS: Apesar da ressuscitação volêmica guiada por saturação venosa central de oxigênio (SvcO2) ser considerada atualmente padrão ouro no tratamento da sepse, poucos estudos caracterizaram o perfil evolutivo de variáveis hemodinâmicas e perfusionais durante esta abordagem terapêutica. Este estudo teve por objetivo descrever evolutivamente estes parâmetros durante o choque séptico experimental sem ressuscitação e após 12 horas de ressuscitação guiada por metas. MÉTODOS: Treze porcos (35-45 kg) anestesiados foram submetidos a peritonite por inoculação fecal (0,75g/kg). Após desenvolverem hipotensão persistente, ambos os grupos receberam antibióticos e foram randomizados em dois grupos: controle (n=7), com suporte hemodinâmico otimizado para pressão venosa central entre 8-12mmHg, diurese acima de 0,5ml/kg/h e pressão arterial média maior que 65mmHg; e SvO2 (n=6), com os objetivos acima e SvO2 acima de 65 por cento. As intervenções incluíram ringer lactato e noradrenalina nos 2 grupos e dobutamina no grupo SvO2. Os animais foram tratados durante doze horas ou óbito. RESULTADOS: A sepse não tratada associou-se a uma significante redução da SvO2, PvO2, débito cardíaco e pressão venosa central e aumento da diferença arterio-venosa da saturação de oxigênio e veno-arterial de CO2. Após ressuscitação, esses parâmetros foram corrigidos em ambos os grupos. A ressuscitação guiada por metas associou-se a um melhor perfil hemodinâmico caracterizado por maiores SvO2, débito cardíaco e pressão venosa central. CONCLUSÕES: A sepse não ressuscitada apresenta um perfil hemodinâmico sugestivo de hipovolemia, com piora perfusional e hemodinâmica revertida após ressuscitação volêmica. A ressuscitação guiada por metas associa-se a uma significante melhora dos parâmetros hemodinâmicos e perfusionais.

OBJECTIVES: Although fluid resuscitation guided by central venous oxygen saturation (SvcO2) is currently considered the gold standard in sepsis therapy, few studies have described hemodynamic and perfusion parameters during this procedure. This study aims to describe these parameters during septic shock without resuscitation and after 12 hours of goal-directed resuscitation. METHODS: Thirteen anesthetized pigs (35-45 kg) had peritonitis caused by fecal inoculation (0.75 g/kg). After developing persistent hypotension, both groups were given antibiotics and randomized either to the control group (n=7) or the experimental group (n=6). In the control group, hemodynamic control was optimized to maintain a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and a mean arterial blood pressure above 65 mmHg. The experimental group received the above target therapy in addition to maintaining a SvO2 above 65 percent. The interventions included lactated Ringer's solution and norepinephrine for both groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or until death. RESULTS: Untreated sepsis was associated with significant reductions in SvO2, PvO2, cardiac output and central venous pressure in addition to increased arteriovenous oxygen saturation and veno-arterial CO2 differences. Following resuscitation, these parameters were corrected in both groups. Goal-directed resuscitation was associated with a better hemodynamic profile, characterized by higher SvO2, cardiac output and central venous pressure. CONCLUSIONS: Non-resuscitated sepsis showed a hemodynamic profile suggesting hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon fluid resuscitation. Goal-directed resuscitation is associated with significantly improved hemodynamic and perfusion parameters.

RESUMO

OBJECTIVES: Although fluid resuscitation guided by central venous oxygen saturation (SvcO2) is currently considered the gold standard in sepsis therapy, few studies have described hemodynamic and perfusion parameters during this procedure. This study aims to describe these parameters during septic shock without resuscitation and after 12 hours of goal-directed resuscitation. METHODS: Thirteen anesthetized pigs (35-45 kg) had peritonitis caused by fecal inoculation (0.75 g/kg). After developing persistent hypotension, both groups were given antibiotics and randomized either to the control group (n=7) or the experimental group (n=6). In the control group, hemodynamic control was optimized to maintain a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and a mean arterial blood pressure above 65 mmHg. The experimental group received the above target therapy in addition to maintaining a SvO2 above 65%. The interventions included lactated Ringer's solution and norepinephrine for both groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or until death. RESULTS: Untreated sepsis was associated with significant reductions in SvO2, PvO2, cardiac output and central venous pressure in addition to increased arteriovenous oxygen saturation and veno-arterial CO2 differences. Following resuscitation, these parameters were corrected in both groups. Goal-directed resuscitation was associated with a better hemodynamic profile, characterized by higher SvO2, cardiac output and central venous pressure. CONCLUSIONS: Non-resuscitated sepsis showed a hemodynamic profile suggesting hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon fluid resuscitation. Goal-directed resuscitation is associated with significantly improved hemodynamic and perfusion parameters.