Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.

IMPORTANCE Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. OBJECTIVE To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. INTERVENTIONS Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. RESULTS Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. CONCLUSIONS AND RELEVANCE Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.

This consensus describes 25 statements regarding the acquisition and interpretation of microcirculatory images needed to guide the assessment of the microcirculation in critically ill patients.

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BackgroundVasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use.MethodsFrom November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14).ResultsA total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60–65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg.ConclusionReported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

A single session of HVHF as salvage therapy in the setting of a goal-directed hemodynamic management algorithm may be beneficial in severe refractory hyperdynamic septic-shock patients. This approach may improve hemodynamics and perfusion parameters, acid-base status, and ultimately hospital survival. Moreover, it is feasible, and safe.

PurposeTo evaluate the prognostic value of the Cv-aCO2/Da-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock.MethodsProspective observational study in a 60-bed mixed ICU. One hundred and thirty-five patients with septic shock were included. The resuscitation protocol targeted mean arterial pressure, pulse pressure variations or central venous pressure, mixed venous oxygen saturation, and lactate levels. Patients were classified into four groups according to lactate levels and Cv-aCO2/Da-vO2 ratio at 6 h of resuscitation (T6): group 1, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; group 2, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0; group 3, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; and group 4, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0.ResultsCombination of hyperlactatemia and high Cv-aCO2/Da-vO2 ratio was associated with the worst SOFA scores and lower survival rates at day 28 [log rank (Mantel–Cox) = 31.39, p < 0.0001]. Normalization of both variables was associated with the best outcomes. Patients with a high Cv-aCO2/Da-vO2 ratio and lactate <2.0 mmol/L had similar outcomes to hyperlactatemic patients with low Cv-aCO2/Da-vO2 ratio. The multivariate analysis revealed that Cv-aCO2/Da-vO2 ratio at both T0 (RR 3.85; 95 % CI 1.60–9.27) and T6 (RR 3.97; 95 % CI 1.54–10.24) was an independent predictor for mortality at day 28, as well as lactate levels at T6 (RR 1.58; 95 % CI 1.13–2.22).ConclusionComplementing lactate assessment with Cv-aCO2/Da-vO2 ratio during early stages of resuscitation of septic shock can better identify patients at high risk of adverse outcomes. The Cv-aCO2/Da-vO2 ratio may become a potential resuscitation goal in patients with septic shock.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-3720-6) contains supplementary material, which is available to authorized users.

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