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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Multicenter Study
Pharmacokinetics, Pharmacodynamics and Safety of Nivolumab in Patients With Sepsis-induced immunosuppression: A multicenter, open-label phase 1/2 study.
Sepsis often induces an immunosuppressive state, which is associated with high mortality rates. Immunostimulation may be beneficial for sepsis. We investigated the pharmacokinetics, pharmacodynamics, and safety of nivolumab, a human programmed death-1 immune checkpoint inhibitor approved for the treatment of several cancers. ⋯ A single dose of 960 mg nivolumab appeared to be well tolerated and sufficient to maintain nivolumab blood concentrations. Both 480 mg and 960 mg nivolumab seemed to improve immune system indices over time.
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Multicenter Study Observational Study
Venous-To-Arterial Carbon Dioxide Partial Pressure Difference: Predictor of Septic Patient Prognosis Depending on Central Venous Oxygen Saturation.
This study aimed to assess the viability of using the venous-to-arterial carbon dioxide partial pressure difference (P(v-a)CO2) to predict clinical worsening of septic shock, depending on central venous oxygen saturation (ScvO2). The prospective, observational, multicentric study conducted in three intensive care units (ICUs) included all patients with a septic shock episode during the first 6 h, with 122 patients assessed. Clinical worsening was defined as an increase of sequential organ failure assessment (SOFA) scores ≥1 (ΔSOFA ≥1) within 2 days. ⋯ ROC analysis confirmed that Lac [1-6] and P(v-a)CO2 [1-6] were significantly associated with ΔSOFA at least 1, whereas ScvO2 [1-6] was not. Finally, ΔSOFA at least 1 was associated with higher 28-day (76% vs. 10%, P = 0.001) and ICU (83% vs. 12%, P = 0.001) mortality rates, which were higher in patients with P(v-a)CO2 [1-6] more than 5.8 mmHg (57% vs. 33%; P = 0.012). In conclusion, P(v-a)CO2 may help predict outcomes for septic shock patients regardless of ScvO2 values.
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We evaluated the early hemodynamic profile of patients presenting with acute circulatory failure to the Emergency Department (ED) using focused echocardiography performed by emergency physicians after a dedicated training program. ⋯ Hypovolemia was predominantly identified in patients presenting to the ED with acute circulatory failure. Although vasoplegia was more frequently associated with sepsis, early ventricular dysfunction was also depicted in septic patients. Focused echocardiography seemed reliable when performed by recently trained emergency physicians without previous experience in ultrasound.
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Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis, and treatment. ⋯ Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring.
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Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. ⋯ sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis.