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.

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.

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.

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.

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.

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.

Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients.

BACKGROUND: Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients. METHODS: Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period. RESULTS: We included 30 patients with septic shock. SOFA score was 11 [8-14], SAPS II was 66 [54-79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430-4246] vs 5362 [1744-10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6-5.5] vs 2.9 [1.9-4.7] s, p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9-7.4] vs 4.6 [3.4-7.0] °C, p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency. CONCLUSION: In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C. ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

BACKGROUND: The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS: In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS: At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2). CONCLUSIONS: Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .).

Exaggerated Microvascular Vasodilating Responses in Cirrhotic Patients With Septic Shock.

OBJECTIVES: Cirrhosis is associated with hemodynamic and vascular disorders. However, microvascular reactivity of cirrhotic patients in the context of sepsis has poorly been investigated. DESIGN: Prospective observational study. SETTING: Medical ICU in a tertiary teaching hospital. PATIENTS: We prospectively included adult patients admitted in the ICU for septic shock with and without cirrhosis. After initial resuscitation, global hemodynamic parameters were recorded and skin microvascular reactivity to local acetylcholine iontophoresis was measured. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty patients with septic shock were included (60% male), 10 with cirrhosis and 20 without, with a median age of 61 years (54-74 yr). Cirrhotic patients were mainly classed as Child-Pugh C (80%) and all of them had ascites. Sequential Organ Failure Assessment score and ICU mortality of cirrhotic patients were higher than the noncirrhotic patients, respectively (6.5 [5.0-8.3] vs 11.5 [9.0-14.0]; p < 0.01; 15% vs 70%; p < 0.01). Peripheral tissue perfusion and global hemodynamic parameters were not different between the cirrhotic and noncirrhotic patients but arterial lactate level was three times higher in patients with cirrhosis (6.0 mmol/L [3.9-8.0 mmol/L] vs 2.0 mmol/L [0.9-3.5 mmol/L]; p < 0.01). Basal skin microvascular blood flow was not statistically different between the groups (4.94 perfusion units [3.45-8.73 perfusion units] vs 6.95 perfusion units [5.24-8.38 perfusion units]; p = 0.29). After acetylcholine simulation, skin microvascular blood flow increased more in cirrhotic patients than in noncirrhotic patients (644% [217-966%] vs 169% [73-505%], p = 0.03). Global microvascular reactivity was seven times higher in cirrhotic patients (area under the curve, 16,412 perfusion units [13,898-19,041 perfusion units] vs 2,664 perfusion units [969-4,604 perfusion units]; p < 0.001). CONCLUSIONS: We identified an exaggerated vasodilating microvascular response in cirrhotic patients with septic shock. Such a result may explain vasopressor resistance and paves the way for future therapeutic trials, targeting nitric oxide pathway specifically in this population.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study.

Haploidentical transplantation has extended the availability of allogeneic hematopoietic stem cell transplant (alloHCT) to almost all patients. Sequential conditioning regimens have been proposed for the treatment of hematological active disease. Whether these new transplantation procedures affect the prognosis of critically ill alloHCT recipients remains unknown. We evaluated this question in a retrospective study including consecutive alloHCT patients admitted to the intensive care unit of a tertiary academic center from 2010 to 2017. During the study period, 412 alloHCTs were performed and 110 (27%) patients-median age 55 (36-64) years-were admitted to ICU in a median time of 58.5 (14-245) days after alloHCT. Twenty-nine (26%) patients had received a haploidentical graft and 34 (31%) a sequential conditioning. Median SOFA score was 9 (6-11). Invasive mechanical ventilation (MV) was required in 61 (55%) patients. Fifty-six (51%) patients died in the hospital. Independent factors associated with in-hospital mortality were as follows: MV (OR=8.44 [95% CI 3.30-23.19], p<0.001), delta SOFA between day 3 and day 1 (OR=1.60 [95% CI 1.31-2.05], p<0.0001), and sequential conditioning (OR=3.7 [95% CI 1.14-12.92], p=0.033). Sequential conditioning was also independently associated with decreased overall survival (HR=1.86 [95% CI 1.05-3.31], p=0.03). Other independent factors associated with reduced overall survival were HCT-specific comorbidity index ≥2 (HR=1.76 [95% CI 1.10-2.84], p=0.02), acute GVHD grade ≥2 (HR=1.88 [95% CI 1.14-3.10], p=0.01), MV (HR=2.37 [95% CI 1.38-4.07, p=0.002), and vasopressors (HR=2.21 [95% CI 1.38-3.54], p=0.001). Haploidentical transplantation did not affect outcome. Larger multicenter studies are warranted to confirm these results.

Characteristics and outcome according to underlying disease in non-AIDS patients with acute respiratory failure due to Pneumocystis pneumonia.

In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).

Epidemiology of infective endocarditis in French intensive care units over the 1997-2014 period-from CUB-Réa Network.

BACKGROUND: Few studies focus only on severe forms of infective endocarditis, for which organ failure requires admission to an intensive care unit (ICU). This study aimed to describe demographical, comorbidities, organ failure, and pathogen-related characteristics in a population of critically ill patients admitted to ICU for infective endocarditis and to identify risk factors of in-ICU mortality. METHODS: Retrospective observational multicenter (N = 34) study of the CUB-Rea register, based on ICD-10 coding rules, between 1997 and 2014 in France including ICU patients managed for infective endocarditis. In-ICU mortality associated factors were assessed by multivariate logistic regression including an interrupted time analysis of three periods (1997-2003, 2004-2009, and 2010-2014). RESULTS: Four thousand four hundred five patients admitted in ICU for infective endocarditis were included. We observed an increase in endocarditis prevalence, as well as an increase in organ failure severity over the three periods. In addition, valve surgery was more frequently performed (27%, 31%, and 42%, P < 0.0001) while in-ICU mortality significantly decreased (28%, 29%, and 23%, P < 0.001). Since 2010, a significant increase in the trends' slope of incidence for Streptococcus sp. and Staphylococcus sp. was observed with no change concerning intracellular bacteria, Enterococcus sp. or Candida sp. slope trends. In multivariate analysis, age, SAPS2, organ failure, stroke, and Staphylococcus sp. were associated with ICU mortality. Conversely, surgery, intracardiac devices, male gender, and Streptococcus sp.-related infective endocarditis were associated with a better outcome. CONCLUSIONS: Our study reveals a shifting landscape of infective endocarditis epidemiology in French ICUs, characterized by reduced in-ICU mortality despite higher severity, more surgery, and substantial changes in microbial epidemiology.

Mottling score is a strong predictor of 14-day mortality in septic patients whatever vasopressor doses and other tissue perfusion parameters.

BACKGROUND: Mottling score, a tissue perfusion parameter, is correlated with outcome in septic shock patients. However, its predictive value on mortality according to prognostic covariates such as vasopressor dose and other tissue perfusion parameters remains unknown. METHODS: Mottling score and tissue perfusion parameters were recorded at ICU admission (H0), H-6, H 12, and H-24 and used to assess the predictive value of mottling score on 14-day mortality in a development cohort. Results were then validated in an independent cohort of septic shock patients in Brazil. RESULTS: Overall, 259 patients with sepsis or septic shock were included, 14-day mortality was 37%. Factors associated with death were mottling score (OR 2.26 [95% CI, 1.72-2.97]), arterial lactate level (OR 1.29 [1.11-1.5]), and urine output < 0.5 ml/Kg/h (OR 3.03 [1.37-6.69]). The C statistic for the model was 0.90 in the development cohort and 0.76 in the validation cohort. The predictive value of mottling score was not affected by vasopressor doses (p for interaction = 0.33): OR for mottling score ranged from 2.34 [1.10-3.15] in patients without vasopressor to 3.84 [1.98-7.43] in patients infused with high doses of vasopressor (> 0.8 µg/kg/min). There was no difference in the effect of mottling score on mortality according to mean arterial pressure, heart rate, cardiac index, and urine output, but we found a significant interaction between arterial lactate level and mottling score (p = 0.04). The predictive value of the mottling score remains significant when using the recent SEPSIS-3 definition of septic shock. Finally, a decrease of mottling score during resuscitation was significantly associated with better outcome after adjustment on SOFA score (p = 0.001). CONCLUSIONS: Our results support the high prognostic value of mottling score for 14-day mortality in septic patients, whatever vasopressor dosage and other perfusion parameters. Mottling score variations during resuscitation are also predictive of mortality.

Exploring the microvascular impact of red blood cell transfusion in intensive care unit patients.

BACKGROUND: Red blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial. METHODS: In a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion. Skin microvascular reactivity was measured before and 30 min after RBC transfusion. Plasma was collected to analyze intravascular hemolysis and draw the lipidomic and cytokine profiles. RESULTS: In a cohort of 59 patients, the median age was 66 [55-81] years and SAPS II was 38 [24-48]. After RBC transfusion, endothelium-dependent microvascular reactivity improved in 35 (59%) patients, but worsened in 24 others (41%). Comparing clinical and biological markers revealed that baseline blood leucokyte counts distinguished improving from worsening patients (10.3 [5.7; 19.7] vs. 4.6 [2.1; 7.3] × 109/L; p = 0.001) and correlated with variations of microvascular reactivity (r = 0.36, p = 0.005). Blood platelet count was also higher in improving patients (200 [97; 280] vs 160 [40; 199] × 103/mL, p = 0.03) but did not correlate with variations of microvascular reactivity. We observed no intravascular hemolysis (HbCO, heme, bilirubin, LDH), but recorded a significant increase in RBC microparticle levels specific to improving patients after transfusion (292 [108; 531] vs. 53 [34; 99] MP/µL; p = 0.03). The improvement in microvascular dilation was positively correlated with RBC microparticle levels (R = 0.83, p < 0.001) and conversion of arachidonic acid into vasodilating eicosanoids. CONCLUSIONS: Patients displaying an improved microvascular reactivity after RBC transfusion had high blood leukocyte counts, increased RBC microparticle formation, and enhanced metabolism of arachidonic acid into vasodilating lipids. Our data suggested a contribution of recipient leukocytes to the vascular impact of RBC transfusion.

Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis.

OBJECTIVES: Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human. DESIGN: Prospective observational study. SETTING: Medical ICU in a tertiary teaching hospital. PATIENTS: To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01). CONCLUSIONS: We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.

Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Adult Patients Requiring Intensive Care.

RATIONALE: Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients. OBJECTIVES: To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis. METHODS: This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (≤8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm3; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome. CONCLUSIONS: The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment.

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.