Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10 year multicentric study.

BACKGROUND: Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors. METHODS: We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model. RESULTS: Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2-7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3-11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21-8.32]) and total number of TPE sessions (OR 1.14 [1.08-1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010). CONCLUSION: Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.

PURPOSE: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. METHODS: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. RESULTS: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048). CONCLUSION: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

Prediction of esophagogastroduodenoscopy therapeutic usefulness for in-ICU suspected upper gastrointestinal bleeding: the SUGIBI score study.

BACKGROUND: Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB. METHODS: We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort. RESULTS: Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score < 4 had a negative predictive value of 95% (91-99) for hemostatic endotherapy [AUC of 0.81; 0.75-0.91 (p < 0.0001)]. The SUGIBI score for predicting the need for an EGD-guided hemostatic procedure was next validated in a multicenter cohort with an AUC of 0.75 (0.66-0.85) (p < 0.0001), a score < 4 having a negative predictive value of 95% (92-97). CONCLUSIONS: Our study shows that the therapeutic usefulness of bedside emergency EGD for SUGIB in critically ill patients is limited to a minority of patients. The SUGIBI score should help clinicians stratify the probability of a therapeutic EGD.

Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.

BACKGROUND: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known. METHODS: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1. RESULTS: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03). CONCLUSION: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline. CLINICALTRIALS: gov Identifier: NCT05094856.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study.

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? STUDY DESIGN AND METHODS: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Prospective evaluation of bleeding risk among thrombocytopenic patients admitted in intensive care unit.

PURPOSE: Bleeding risk evaluation of thrombocytopenic patients admitted in ICU has been poorly investigated. METHODS: A prospective observational study conducted in an 18-bed medical ICU. Consecutive patients with thrombocytopenia (<150 Giga/L) and no bleeding at admission were included. RESULTS: Over one year, 91 patients were included, mainly men (63%), with an age of 61 [46-68] years and a SOFA score of 6 [3-8]. Twenty-three patients (25%) had an hemorrhagic event during ICU stay, mainly digestive (n = 9; 39%) and urological (n = 6; 26%). The time between ICU admission and bleeding was 8 [2-19] days. Almost half of bleeding events required vasopressor infusion and a hemostatic procedure. At admission, two variables were significantly different between the Bleeding and No-Bleeding groups: plasma urea level was significantly higher in the Bleeding group (9 [5.1; 13] vs. 13 [8.9; 31] mmol/L; p < 0.001) and the presence of skin purpura was associated with a 3-fold higher risk for bleeding during ICU stay (HR: 3.4 [1.3-8.3]; p < 0.05). In contrast, admission platelet count was not significantly different between the 2 groups (90 [32; 128] vs 62 [36; 103] G/L; p = 0.26). CONCLUSION: Plasma urea levels and the presence of skin purpura are helpful in identifying thrombocytopenic patients at high-risk of bleeding during ICU stay.

Permissive Hypotension Has No Deleterious Impact on Fluid Balance or Kidney Function.

OBJECTIVES: Mean arterial hypotension between 55 and 65 mm Hg could be tolerated safely in the absence of tissue hypoperfusion, but the consequences on fluid balance and kidney function remain unknown. DESIGN: During a 1-year period, we retrospectively collected data of consecutive septic patients admitted for sepsis with a mean arterial pressure (MAP) less than 65 mm Hg despite fluid resuscitation. SETTING: Medical 18-bed ICU in a tertiary teaching hospital. PATIENTS: Septic patients with a MAP less than 65 mm Hg despite initial resuscitation. INTERVENTIONS: In our ICU, MAP between 55 and 65 mm Hg was tolerated in the absence of peripheral hypoperfusion (permissive hypotension) or corrected using norepinephrine (septic shock group) when peripheral tissue hypoperfusion was present. MEASUREMENTS AND MAIN RESULTS: Ninety-four consecutive septic patients were included, 15 in the permissive hypotension group and 79 in the septic shock group. Median age was 66 years (57-77 yr) and 42% were women. The main sources of infection were respiratory (45%) and abdominal (18%). Severity was more important in septic shock group with higher Sequential Organ Failure Assessment score (7 [5-10] vs. 4 [1-6]; p < 0.0001), more frequent organ support therapy and ultimately higher mortality (38 vs. 0%; p < 0.01). The total volume of crystalloids infused before ICU admission was not different between groups (1930 ± 250 vs. 1850 ± 150 mL; p = 0.40). Within the 6 first hours of ICU stay, patients in the permissive hypotension group received less fluids (530 ± 170 vs. 1100 ± 110 mL; p = 0.03) and had higher urinary output (1.4 mL [0.88-2.34 mL] vs. 0.47 mL/kg/hr [0.08-1.25 mL/kg/hr]; p < 0.001). In addition, kidney injury evaluated using KDIGO score was lower in the permissive hypotension group at 48 hours (0 hr [0-1 hr] vs. 1 hr [0-2 hr]; p < 0.05). CONCLUSIONS: In septic patients without clinical peripheral hypoperfusion, mean arterial hypotension between 55 and 65 mm Hg could be tolerated safely without vasopressor infusion and was not associated with excessive fluid administration or kidney damage.

Sonometric assessment of cough predicts extubation failure: SonoWean-a proof-of-concept study.

BACKGROUND: Extubation failure is associated with increased mortality. Cough ineffectiveness may be associated with extubation failure, but its quantification for patients undergoing weaning from invasive mechanical ventilation (IMV) remains challenging. METHODS: Patients under IMV for more than 24 h completing a successful spontaneous T-tube breathing trial (SBT) were included. At the end of the SBT, we performed quantitative sonometric assessment of three successive coughing efforts using a sonometer. The mean of the 3-cough volume in decibels was named Sonoscore. RESULTS: During a 1-year period, 106 patients were included. Median age was 65 [51-75] years, mainly men (60%). Main reasons for IMV were acute respiratory failure (43%), coma (25%) and shock (17%). Median duration of IMV at enrollment was 4 [3-7] days. Extubation failure occurred in 15 (14%) patients. Baseline characteristics were similar between success and failure extubation groups, except percentage of simple weaning which was lower and MV duration which was longer in extubation failure patients. Sonoscore was significantly lower in patients who failed extubation (58 [52-64] vs. 75 [70-78] dB, P < 0.001). After adjustment on MV duration and comorbidities, Sonoscore remained associated with extubation failure. Sonoscore was predictive of extubation failure with an area under the ROC curve of 0.91 (IC95% [0.83-0.99], P < 0.001). A threshold of Sonoscore < 67.1 dB predicted extubation failure with a sensitivity of 0.93 IC95% [0.70-0.99] and a specificity of 0.82 IC95% [0.73-0.90]. CONCLUSION: Sonometric assessment of cough strength might be helpful to identify patients at risk of extubation failure in patients undergoing IMV.

Improvement of central vein ultrasound-guided puncture success using a homemade needle guide-a simulation study.

BACKGROUND: Out-of-plane (OOP) approach is frequently used for ultrasound-guided insertion of central venous catheter (CVC) owing to its simplicity but does not avoid mechanical complication. In-plane (IP) approach might improve safety of insertion; however, it is less easy to master. We assessed, a homemade needle guide device aimed to improve CVC insertion using IP approach. METHOD: We evaluated in a randomized simulation trial, the impact of a homemade needle guide on internal jugular, subclavian and femoral vein puncture, using three approaches: out-of-plane free hand (OOP-FH), in-plane free hand (IP-FH), and in-plane needle guided (IP-NG). Success at first pass, the number of needle redirections and arterial punctures was recorded. Time elapsed (i) from skin contact to first skin puncture, (ii) from skin puncture to successful venous puncture and (iii) from skin contact to venous return were measured. RESULTS: Thirty operators performed 270 punctures. IP-NG approach resulted in high success rate at first pass (jugular: 80%, subclavian: 95% and femoral: 100%) which was higher than success rate observed with OOP-FH and IP-FH regardless of the site (p = .01). Compared to IP-FH and OOP-FH, the IP-NG approach decreased the number of needle redirections at each site (p = .009) and arterial punctures (p = .001). Compared to IP-FH, the IP-NG approach decreased the total procedure duration for puncture at each site. CONCLUSION: In this simulation study, IP approach using a homemade needle guide for ultrasound-guided central vein puncture improved success rate at first pass, reduced the number of punctures/redirections and shortened the procedure duration compared to OOP and IP free-hand approaches.

Extracranial anticoagulant related bleedings admitted to intensive care units: a French multicenter retrospective study.

BACKGROUND: Anticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding. METHODS: A retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included. RESULTS: 486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2. CONCLUSION: Anticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs.

Impact of immunosuppressive regimen on ICU acquired pneumonia in critically ill COVID-19.

BACKGROUND: Immunosuppressors (IS) such as Dexamethasone (DXM), Tocilizumab, and high-dose methylprednisolone boli (HDMB), are used in COVID-19-related acute respiratory distress syndrome (ARDS). This study aimed to determine whether COVID-19 ARDS-related combined IS therapy was associated with an increased incidence of ICU-acquired pneumonia (IAP). METHODS: We retrospectively analyzed COVID-19-ARDS admitted to ICU from March 2020 to April 2022. Patients' and IAP characteristics were analyzed according to five IS regimens: No IS, DXM alone, DXM+HDMB, DXM+tocilizumab, and DXM+tocilizumab+HDMB. To investigate the role of IS on IAP incidence, we performed a multivariate logistic regression and built a propensity score. Ultimately, we used a conditional logistic regression after pairing on the propensity score. RESULTS: The study included 496 COVID-19-ARDS. Regarding the IS therapy, 12.7% received no IS, 43% DXM alone, 21.6% DXM+HDMB, 15.5% DXM+tocilizumab and 5.4% DXM+tocilizumab+HDMB. 37% presented at least one IAP, and the IAP incidence was higher with DXM+HDMB (66.4%) compared to no IS (P<0.0001), DXM (P<0.0001) and DXM+tocilizumab (P<0.0001). HDMB and probabilistic antibiotherapy at admission were independent IAP predictors after adjustment on the propensity score (respectively OR:2.44; P<0.0001 and OR:2.85; P<0.001). CONCLUSIONS: In critically ill COVID-19, HDMB significantly increases the risk of IAP whereas DXM alone, nor in combination with tocilizumab, did not.

Quantitation of 10 antibiotics in plasma: Sulfosalicylic acid combined with 2D-LC-MS/MS is a robust assay for beta-lactam therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of antibiotics is particularly important in populations with high pharmacokinetic variabilities, such as critically ill patients, leading to unpredictable plasma concentrations and clinical outcomes. Here, we i) describe an original method for the simultaneous quantification of ten antibiotics (cefepime, ceftazidime, ampicillin, piperacillin/tazobactam, cefotaxime, amoxicillin, cloxacillin, oxacillin, linezolid) using 5-sulfosalicylic acid dihydrate (SSA) solution for protein precipitation together with 2D-LC-MS/MS, and ii) evaluate its impact in a one-year retrospective study. The method involved simple dilution with an aqueous mix of deuterated internal standards and plasma protein precipitation with SSA. Twenty microliters of the supernatant was injected into a C8 SPE online cartridge (30 × 2.1 mm) without any evaporation step and back-flushed onto a C18 UHPLC (100 × 2.1 mm) analytical column. Mass spectrometry detection (Xevo TQD) was performed in positive electrospray, in scheduled MRM mode. Overall analytical runtime was 7 min. Due to analytical constraints and the physicochemical properties of the antibiotics, protein precipitation using organic solvents could not be applied. As an alternative, SSA used with 2D-LC offered various advantages: i) lack of dilution resulting in better assay sensitivity, and ii) good chromatography of hydrophilic compounds. Ten microliters of 30% SSA in water eliminated>90% of plasma proteins, including the most abundant high molecular weight proteins at 55 and 72 kDa. The assay was successfully validated according to FDA and EMA guidelines for all the antibiotics, and the coefficients of variation of the quality control (QC) run during sample analysis over one year were below 10%, whatever the QC levels or the antibiotics. The use of 2D-LC combined with SSA precipitation allowed development of a robust, sensitive and rapid quantification assay. Feedback to clinicians was reduced to 24 h, thus allowing rapid dosage adjustment. During one year, 3,304 determinations were performed in our laboratory: 41% were not in the therapeutic range, 58% of which were sub-therapeutic, underlining the importance of early TDM of antibiotics to limit therapeutic failures and the emergence of bacterial resistance.

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE). METHODS: We conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis. RESULTS: Eighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10-37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity. CONCLUSION: We highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes. CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Impact of corticosteroids on the procoagulant profile of critically ill COVID-19 patients: a before-after study.

BACKGROUND: Several studies have reported an increased risk of thrombotic events in COVID-19 patients, but the pathophysiology of this procoagulant phenotype remains poorly understood. We hypothesized that corticosteroids may attenuate this procoagulant state through their anti-inflammatory effects. The aim of this study was to evaluate the impact of dexamethasone (DXM) on the coagulation profile of severely ill COVID-19 patients. METHODS: We conducted a retrospective, observational before/after bi-centric cohort study among ICU patients hospitalized for severe COVID-19 and receiving therapeutic anticoagulation by unfractionated heparin (UFH). Before and after the standardized use of DXM, we compared inflammatory and coagulation profiles, as well as the kinetics of heparin requirement, adjusted for weight and anti-Xa activity. RESULTS: Eighty-six patients were included, 35 in the no-DXM group, and 51 in the DXM group. At admission, CRP and fibrinogen levels were not different between groups, neither were UFH infusion rates. At day 3 after ICU admission, CRP (178±94 mg/L vs. 99±68 mg/L, P<0.001) and fibrinogen (7.2±1.4 g/L vs. 6.1±1.4 g/L, P=0.001) significantly decreased in the DXM group, but not in the no-DXM group. Over time, UFH infusion rates were lower in the DXM group (P<0.001) without any significant difference in plasma anti-Xa activity. CRP variations correlated with heparin dose variations between Day 0 and Day 3 (r=0.39, P=0.009). Finally, the incidence of venous thromboembolic events during in-ICU stay was significantly reduced in the DXM group (4 vs. 43%, P<0.0001). CONCLUSIONS: In critically ill COVID-19 patients, dexamethasone use was associated with a decrease in both pro-inflammatory and procoagulant profile.

A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. METHODS: We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. RESULTS: Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01). CONCLUSION: In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.