The endothelium takes part in the regulation of numerous physiological functions and lies at the interface of circulating blood and the vessel wall. Under physiological conditions, it is responsible ...for anticoagulant and anti-adhesive properties, and it regulates vasomotor tone and vascular homeostasis. Endothelial dysfunction has been associated with many pathophysiological processes, such as inflammation and oxidative and nitrosative stresses. Endothelial cells are precociously exposed to circulating signaling molecules and physical stresses, like in sepsis and septic shock. Septic shock is associated with hypotension and frequently with disseminated intravascular coagulation contributing to multiple organ failure and a high mortality rate. Impairment of endothelial function leads to phenotypic and physical changes of the endothelium, with deregulated release of potent vasodilators nitric oxide and prostacyclin, reduction of vascular reactivity to vasoconstrictors, associated with leukocytes' and platelets' aggregation, and increase in inducible nitric oxide synthase expression that can exert a negative feedback on endothelial nitric oxide synthase expression, with subsequent deregulation of nitric oxide signaling. Endothelial dysfunction therefore plays a major role in the pathophysiology of septic shock and organ dysfunction, and has been suggested to be a predictor of mortality in sepsis. Thus, early detection of endothelial dysfunction could be of great interest to adapt treatment in initial stage of sepsis. Current therapeutics used in sepsis mostly aim at controlling inflammation, vascular function and coagulation. Fluid administration, vasopressors, vasodilators and recombinant human activated protein C are also part of the treatments with the ultimate goal to exert beneficial effects on organ function and survival.
Ilio-psoas hematoma is a potentially lethal condition that can arise during hospital stay. However, neither the incidence nor the prognosis of patients whose stay in intensive care units (ICU) is ...complicated by a iatrogenic ilio-psoas hematoma is known.
A bicentric retrospective study was conducted to compile the patients who developed an ilio-psoas hematoma while they were hospitalized in ICU between January 2009 and December 2016. Their biometric characteristics, pre-existing conditions, the circumstances in which the hematoma was diagnosed, the treatments they received and their prognosis were recorded.
Forty patients were diagnosed with an ilio-psoas hematoma during their ICU stay. The incidence of this complication was 3.8 cases for 1000 admissions, taking into account only patients who stayed more than three days in ICU. The median age of patients was 74 years old and the median time between admission and the diagnosis of ilio-psoas hematoma was 12.6 days. A large proportion of them was obese (42.5%) and/or under dialysis (50%) prior to developing their hematoma. Ninety-five percent of the patients had heparin at prophylactic or therapeutic doses. Only 10% of them were above the therapeutic range of anticoagulation. The ICU mortality rate was of 50% following this complication (versus a general mortality rate of 22% for the patients without IPH over the same period of time). Patients with IPH that were complicated by disseminated intravascular coagulopathy had a significantly higher mortality rate than those with IPH and no disseminated intravascular coagulopathy (OR 6.91, 95% CI 1.28; 58.8, p = 0.04).
Age, anticoagulation, a high body mass index and dialysis seem to be risk factors of developing an ilio-psoas hematoma in ICU. Iatrogenic ilio-psoas hematomas complicated by disseminated intravascular coagulopathies are more at risk of leading to death. It is noteworthy that activated partial thromboplastin time above the therapeutic range was not a good predictor of developing a hematoma for patients who received unfractioned heparin therapy.
Purpose
Septic shock-induced disseminated intravascular coagulopathy (DIC) contributes to multiple organ failure. Mechanisms governing vascular responses to open occurrence of DIC have not yet been ...established. Circulating plasma microparticles (MPs), released upon cell stress, constitute a catalytic procoagulant surface and are surrogates of vascular cell activation/injury. Herein, MPs were assessed as possible markers of haemostatic and vascular dysfunction in the DIC time course.
Methods
One hundred patients with septic shock from three ICUs were enrolled and their haemostatic status evaluated at admission (D1), D2, D3 and D7. Circulating procoagulant MPs were isolated, quantified by prothrombinase assay and their cellular origin determined. DIC diagnosis was made according to the JAAM 2006 score.
Results
Ninety-two patients were analysed and 40 had DIC during the first 24 h. Routine clotting times and factor/inhibitor activity did not allow assessing vascular cell involvement. At admission, thrombin generation and fibrinolysis were observed in both groups while impaired fibrin polymerisation was evidenced only in DIC patients. Sustained thrombin generation persisted over time in both groups at D7. While total microparticle concentrations were in the same range regardless of DIC diagnosis, specific phenotypes were already detected at admission in DIC patients. Endothelial- and leucocyte-derived MPs were higher in DIC while an increased soluble glycoprotein V/platelet ratio was delayed, underscoring the first involvement of endothelial cells and leucocytes whereas platelet activation was delayed. Endothelium-derived CD105-MPs (OR 6.55) and CD31-MPs (OR 0.49) were strongly associated with early DIC in multivariate analysis.
Conclusion
Endothelial-derived microparticles are relevant biomarkers of septic shock-induced DIC and could be used to evaluate early vascular injury.
In sepsis, inflammation and thrombosis are both the cause and the result of interactions between circulating (for example, leukocytes and platelets), endothelial and smooth muscle cells. ...Microparticles are proinflammatory and procoagulant fragments originating from plasma membrane generated after cellular activation and released in body fluids. In the vessel, they constitute a pool of bioactive effectors pulled from diverse cellular origins and may act as intercellular messengers. Microparticles expose phosphatidylserine, a procoagulant phospholipid made accessible after membrane remodelling, and tissue factor, the initiator of blood coagulation at the endothelial and leukocyte surface. They constitute a secretion pathway for IL-1β and up-regulate the proinflammatory response of target cells. Microparticles circulate at low levels in healthy individuals, but undergo phenotypic and quantitative changes that could play a pathophysiological role in inflammatory diseases. Microparticles may participate in the pathogenesis of sepsis through multiple ways. They are able to regulate vascular tone and are potent vascular proinflammatory and procoagulant mediators. Microparticles' abilities are of increasing interest in deciphering the mechanisms underlying the multiple organ dysfunction of septic shock.
Abstract
Background
Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex ...explorations may allow to better characterize patients’ respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients.
Methods
All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg
−1
predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH
2
O) within 24 h after intubation.
Results
Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively,
p
= 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%,
p
< 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%,
p
= 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics.
Conclusions
Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH
2
O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients.
Trial registration
NCT03420417 ClinicalTrials.gov (February 5, 2018).
Background
There is no gold standard to diagnose septic shock-induced disseminated intravascular coagulation (DIC). The objective of our multicenter prospective study was to assess the performances ...of the different major scoring systems in terms of mortality prediction and DIC diagnosis. The JAAM-DIC 2016 score, the ISTH overt-DIC 2001 score, the associations of sepsis-induced coagulopathy (SIC) score with JAAM-DIC 2016 or ISTH overt-DIC scores were tested in patients within 12 h of their admission in ICU for septic shock (day 1) and at day 2.
Results
582 patients were enrolled in the study. 182/567 (32.1%) were diagnosed with DIC according to ISTH overt-DIC score, and 193/561 (34.4%) according to JAAM-DIC score; 486/577 patients (84.2%) were diagnosed with a coagulopathy according to SIC score. A moderate concordance was observed between ISTH overt-DIC and JAAM-DIC κ = 0.67 (0.60, 0.73),
p
< 0.001. The delay of positivity of the scores for early DIC patients was not different between JAAM-DIC and ISTH overt-DIC scores. Although it was positive earlier, SIC score had worse diagnosis specificity, as 84.2% of the patients with septic shock were diagnosed with “coagulopathy”. The specificity of SIC score alone to predict mortality was very low 0.18 (0.15; 0.22), compared to the ones of JAAM-DIC score 0.71 (0.67; 0.75), and of ISTH overt-DIC score 0.76 (0.72; 0.80),
p
< 0.001. The sensitivity of SIC score to predict mortality was 0.95 0.89; 0.98, and the ones of JAAM-DIC score and ISTH overt-DIC score were 0.61 0.50; 0.70 and 0.68 0.58; 0.77, respectively. There was no benefit in sensitivity and specificity in combining SIC score to JAAM-DIC score or to ISTH overt-DIC score, compared to JAAM-DIC score or ISTH overt-DIC score alone.
Conclusions
Our data suggest that the added value of SIC score alone or combined with other scores is limited, and that both JAAM-DIC score and ISTH overt-DIC score can be used in septic shock patients.
Trial registration
clinicaltrial; Trial registration number: NCT02391792; Date of registration: 18/03/2015; URL of trial registry record:
https://clinicaltrials.gov/ct2/show/NCT02391792?term=meziani&draw=4&rank=1
Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that ...endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification.
Prospective observational study in septic shock patients.
Four medical ICUs in university hospitals.
Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7.
None.
Two hundred fifty-nine patients were analyzed. Sixty-one had disseminated intravascular coagulation at admission, and 32 developed disseminated intravascular coagulation during the first 24 hours after admission. Multiple logistic regression model confirmed that endothelial cell-derived microparticles were associated with disseminated intravascular coagulation: CD105-microparticles (odds ratio, 2.13) and CD31-microparticles (odds ratio, 0.65) (p < 0.05). Furthermore, CD11a-microparticles to leukocyte ratio evidenced leukocyte activation (odds ratio, 1.59; p < 0.05). Prediction of disseminated intravascular coagulation was also analyzed after exclusion of patients with disseminated intravascular coagulation at admission. A new multiple logistic regression analysis demonstrated the association of CD105-microparticles (> 0.60 nM eq. PhtdSer; odds ratio, 1.67; p < 0.01), platelets count (≤ 127 g/L; odds ratio, 0.99; p < 0.01), and prothrombin time (≤ 58%; odds ratio, 0.98; p < 0.05) with disseminated intravascular coagulation. A combining score at admission is predictive of the absence of disseminated intravascular coagulation (area under the curve, 72.9%; specificity, 71.2%; sensitivity, 71.0%, with a negative predictive value of 93.1% and a positive predictive value of 31.0%).
Procoagulant microparticles from endothelial cells and leukocytes reflect a vascular injury during sepsis-induced disseminated intravascular coagulation that precedes obvious activation of coagulation. A combination of prothrombin time, endothelium-derived CD105-microparticles, and platelet count at admission could predict the absence of disseminated intravascular coagulation and allow a better stratification in future randomized clinical trials.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is the leading cause of death within intensive care units (ICUs) ....
During COVID-19 pandemic, visits have been prohibited in most French ICUs. Psychological effects, for reference persons (RPs), of remote-only communication have been assessed.
All RPs of patients ...referred to ICU for COVID-19 were included. HADS, IES-R, and satisfaction were evaluated at admission, discharge/death, and 3 months. At 3 months, a psychologist provided a qualitative description of RPs' psychological distress.
Eighty-eight RPs were included. Prevalence of anxiety and depression was 83% and 73% respectively. At 3 months, lower HADS decrease was associated with patient death/continued hospitalization, and/or sleeping disorders in RPs (p < 0.01). Ninety-nine percent RPs felt the patient was safe (9 7; 10/10 points, Likert-type scale), confident with caregivers (10 9; 10/10 points), and satisfied with information provided (10 9; 10/10 points). All RPs stressed the specific-type of "responsibility" associated with being an RP in a remote-only context, leading RPs to develop narrow diffusion strategies (67%) and restrict the array of contacted relatives to a very few and/or only contacting them rarely. 10 RPs (30%) related the situation to a prior traumatic experience.
RPs experienced psychological distress and reported that being an RP in a remote-only communication context was a specific responsibility and qualified it as an overall negative experience.
NCT04385121 . Registered 12 May 2020. https://clinicaltrials.gov/ .
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