Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. Open-label randomized controlled study. Surgical and medical intensive care units of nine university and city hospitals. Sixty-one patients with sepsis. Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7–1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency.

Inflammation in sepsis is associated with hypercoagulation that may lead to thrombosis and disseminated intravascular coagulation. Conventional diagnostic assays are poorly sensitive to procoagulant changes in sepsis. Objectives of the article is to study changes in hemostatic state of septic patients using spatial clot growth assay (currently being developed under the trademark of thrombodynamics) and to compare the sensitivity of this method with the sensitivity of conventional methods. Sixteen patients with hematological malignancies and sepsis were enrolled in the study. All patients had been surveyed for a month following the infection onset. Spatial clot growth assay monitors fibrin clot development in a nonstirred thin layer of platelet-free plasma activated by immobilized tissue factor. Clotting time tests, thromboelastography, D-dimer assays were also performed. Spatial clot growth revealed hypercoagulation in six patients. D-dimer levels increase (with vein thrombosis in one case) was subsequently observed in five of them. D-dimer levels did not increase when spatial clot growth was normal. At the next time point, after spatial clot growth assay showed hypercoagulation, the mean D-dimer concentration was significantly higher than after a normal analysis (457 versus 234 μg/l; P < 0.05); there was no such correlation for other assays. The remaining 10 patients had elevated D-dimer levels on the first day; this either decreased gradually or remained elevated. Spatial clot growth showed normalization in survivors and growing hypocoagulation in nonsurvivors. Measuring spatial clot growth dynamics has potential diagnostic utility for the evaluation of thrombotic risk.

A typical hemolytic uremic syndrome (aHUS) presents similarly to thrombotic thrombocytopenic purpura (TTP) and other causes or conditions with thrombotic microangiopathy (TMA), such as disseminated intravascular coagulation or sepsis. Similarity in clinical presentation may hinder diagnosis and optimal treatment selection in the urgent setting in the ICU. However, there is currently no consensus on the diagnosis or treatment of aHUS for ICU specialists. This review aims to summarize available data on the diagnosis and treatment strategies of aHUS in the ICU to enhance the understanding of aHUS diagnosis and outcomes in patients managed in the ICU. To this end, a review of the recent literature (January 2009-March 2016) was performed to select the most relevant articles for ICU physicians. Based on the paucity of adult aHUS cases overall and within the ICU, no specific recommendations could be formally graded for the critical care setting. However, we recognize a core set of skills required by intensivists for diagnosing and managing patients with aHUS: recognizing thrombotic microangiopathies, differentiating aHUS from related conditions, recognizing involvement of other organ systems, understanding the pathophysiology of aHUS, knowing the diagnostic workup and relevant outcomes in critically ill patients with aHUS, and knowing the standard of care for patients with aHUS based on available data and guidelines. In conclusion, managing critically ill patients with aHUS requires basic skills that, in the absence of sufficient data from patients treated within the ICU, can be gleaned from an increasingly relevant literature outside the ICU. More data on critically ill patients with aHUS are needed to validate these conclusions within the ICU setting.

Hemostatic disorders play an important role in the pathogenesis and clinical manifestations of COVID-19. The purpose of the research was a detailed consideration of the pathogenesis, clinical manifestations, and methods of diagnosing and treatment of coronavirus-induced coagulopathy (CIC). At the onset of COVID-19, hypercoagulability is detected, and consumption coagulopathy and disseminated intravascular coagulation (DIC) syndrome are usually observed at later stages of the disease. In the pathogenesis of hypercoagulation in patients with COVID-19, proinflammatory cytokines, hyperfibrinogenemia, increased blood levels of von Willebrand factor, factor VIII, neutrophilic extracellular traps, platelet activation, production of antiphospholipid antibodies, microvesicles are of importance. Laboratory findings show increased plasma concentrations of D-dimer, fibrinogen, a longer prothrombin time and a decrease in the number of platelets. The cumulative incidence of thrombotic complications ranges from 21 to 31%. Thrombosis risk factors are intensive care unit stay, leukocytosis, and a high plasma D-dimer concentration. Differential diagnosing of CIC should be carried out with disseminated intravascular coagulation, sepsis-induced coagulopathy, antiphospholipid, hemophagocytic syndromes, thrombotic microangiopathy, and heparin-induced thromocytopenia. CIC may be complicated by sepsis, antiphospholipid syndrome, hemophagocytic syndrome, thrombotic microangiopathy, and heparin-induced thrombocytopenia.The main therapy is low molecular weight heparins treatment. Treatment recommendations are provided.

To compare cardiac output (CO) and blood volumes measured by COstatus^® (Transonic Systems Inc., NY, USA) versus PiCCO (Philips IntelliVue MP40 with PiCCO-technology module M3012A#10, Netherlands) in adult ICU patients. This was a prospective single-center study. Each of the 30 patients studied received a 5-Fr Pulsiocath femoral arterial and a standard central venous catheter. Twenty ml of iced 5% dextrose solution was injected for PiCCO measurements. For COstatus measurements, an extracorporeal arteriovenous loop, with two sensors placed on it, was connected between the Pulsiocath femoral arterial and central venous catheters. Blood was circulated through this loop at 12 ml/min for 5–8 min using a pump. Twenty ml of warm saline was injected into the venous side for measurements. For each method, three injections were averaged for comparison. A good agreement for measured CO (range 3.65–16.3 l/min) with a percentage error of 20% was observed, with r = 0.95, bias = −0.037 l/min. PiCCO’s global end-diastolic volume (GEDV) was 2.5 times larger than the analogous COstatus’s total end-diastolic volume (TEDV) [TEDV = 0.28 × GEDV + 176 ml]. PiCCO’s intrathoracic blood volume (ITBV) was larger than the analogous COstatus’s central blood volume (CBV) [CBV = 0.73 × (ITBV) +78 ml]. CO measured by COstatus was found to be equivalent and hence interchangeable with PiCCO in this study population. COstatus blood volumes were found to be within the expected physiological range whilst PiCCO blood volumes were significantly higher, which was also observed in other studies. Future studies using 3D echo/MRI are required to validate these blood volumes.