Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We sought to review the pharmacology of vasoactive therapy and fluid administration in sepsis and septic shock, with specific insight into the physiologic interplay of these agents. A PubMed/MEDLINE search was conducted using the following terms (vasopressor OR vasoactive OR inotrope) AND (crystalloid OR colloid OR fluid) AND (sepsis) AND (shock OR septic shock) from 1965 to October 2020. ⋯ Current guidelines are not in alignment with the data available, which suggests a potential benefit from low-dose fluid administration and early vasopressor exposure. Future data must account for the impact of both of these pharmacotherapies when assessing clinical outcomes and should assess personalization of therapy based on the possible interaction.
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Recent data suggests improved outcomes among cardiac intensive care unit (CICU) patients treated with norepinephrine, especially patients with severe shock. We aimed to describe the association between norepinephrine and mortality in CICU patients with severe shock, defined as those requiring high-dose vasopressors (HDV). ⋯ Mortality is high among CICU patients requiring HDV, and rises with increasing vasopressor requirements. Use of NE was associated with lower mortality among patients requiring HDV, but not among those without HDV, implying that patients with more severe shock may benefit from preferential use of NE.
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Cardiac arrest (CA) is recognized as a life-threatening disease; however, the initial resuscitation success rate has increased due to advances in clinical treatment. Levosimendan has shown potential benefits in CA patients. However, its exact function on intestinal and systemic circulation in CA or post-cardiac arrest syndrome (PCAS) remained unclear. This study preliminarily investigated the link between dynamic changes in intestine and systemic hemodynamics post-resuscitation after levosimendan administration. ⋯ Levosimendan significantly reduced the cardiac injury and corrected the metabolic status in an experimental rat model of ventricular fibrillation induced CA and cardiopulmonary resuscitation. Levosimendan may ameliorate PCAS-induced intestinal microcirculation dysfunction, partly independent of its effects on macrocirculation.
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Sepsis-associated acute kidney injury (SA-AKI) is a common problem in critically ill patients and is associated with high morbidity and mortality. Early prediction of the survival of hospitalized patients with SA-AKI is necessary, but a reliable and valid prediction model is still lacking. ⋯ Our SAKI model has predictive value for in-hospital mortality of SA-AKI in critically ill patients and outperforms generic scores.
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Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Genetic deletion of myosin light chain kinase (MLCK) reverses intestinal hyperpermeability and improves survival in a murine model of intra-abdominal sepsis. In an attempt to determine whether these findings could be translated using a more clinically relevant strategy, this study aimed to determine if pharmacologic inhibition of MLCK using the membrane permeant inhibitor of MLCK (PIK) improved gut barrier function and survival following sepsis. ⋯ Examination of jejunal tight junctions for potential mechanisms underlying increased leak permeability revealed that mice that received PIK had increased phosphorylated MLC without alterations in occludin, ZO-1, or JAM-A. PIK administration was not associated with significant differences in systemic or peritoneal bacterial burden, cytokines, splenic or Peyer's Patches immune cells or intestinal integrity. These results demonstrate that pharmacologic inhibition of MLCK unexpectedly increases mortality, associated with worsened intestinal permeability through the leak pathway, and suggest caution is required in targeting the gut barrier as a potential therapy in sepsis.