Publications by authors named "Jacques Albanese"

56 Publications

Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock.

Blood 2022 Jan 13. Epub 2022 Jan 13.

AP-HM, France.

Microvesicles (MVs) have previously been shown to exert profibrinolytic capacity, which is increased in patients with septic shock (SS) with a favorable outcome. We therefore hypothesized that the plasmin generation capacity (PGC) could confer to MVs a protective effect supported by their capacity to lyse a thrombus, and we investigated the mechanisms involved. Using a MV-PGC kinetic assay, ELISA and flow cytometry, we found that granulocyte MVs (Gran-MVs) from SS patients display a heterogeneous PGC profile driven by the uPA (urokinase)/uPAR system. In vitro, these MVs lyse a thrombus according to their MV-PGC levels in a uPA/uPAR-dependent manner, as shown in a fluorescent clot lysis test and a lysis front retraction assay. Fibrinolytic activators conveyed by MVs contribute to approximately 30% of the plasma plasminogenolytic capacity of SS patients. In a murine model of SS, the injection of high PGC Gran-MVs significantly improved mouse survival and reduced the number of thrombi in vital organs. This was associated with a modification of the mouse coagulation and fibrinolysis properties toward a more fibrinolytic profile. Interestingly, mouse survival was not improved when soluble uPA was injected. Finally, using a multiplex array on plasma from SS patients, we found that neutrophil elastase correlates with the effect of high-PGC-capacity plasma and modulates the Gran-MV plasmin generation capacity by cleaving uPA-PAI-1 complexes. In conclusion, we show that high PGC level displayed by Gran-MVs reduce thrombus formation and improve survival conferring to Gran-MVs a protective role in a murine model of sepsis.
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http://dx.doi.org/10.1182/blood.2021013328DOI Listing
January 2022

An international survey on aminoglycoside practices in critically ill patients: the AMINO III study.

Ann Intensive Care 2021 Mar 19;11(1):49. Epub 2021 Mar 19.

Department of Intensive Care Medicine, Division of Anesthesiology, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, Place du Professeur Robert Debré, 30 029, Nîmes cedex 9, France.

Background: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock.

Results: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of C and C was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a C/MIC > 8 and 353 (71%) having concentrations above C recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes.

Conclusion: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.
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http://dx.doi.org/10.1186/s13613-021-00834-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979853PMC
March 2021

Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19.

Blood Adv 2021 02;5(3):628-634

Aix Marseille University, INSERM 1263, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Centre de Recherche en CardioVasculaire et Nutrition (C2VN), Marseille, France.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.
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http://dx.doi.org/10.1182/bloodadvances.2020003308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846479PMC
February 2021

Paired acute-baseline serum tryptase levels in perioperative anaphylaxis: An observational study.

Allergy 2019 06 21;74(6):1157-1165. Epub 2019 Mar 21.

Aix-Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, Marseille, France.

Background: Anaphylaxis is recognized mainly through clinical criteria, which may lack specificity or relevance in the perioperative setting. The transient increase in serum tryptase has been proposed since 1989 as a diagnostic tool. Sampling for well-defined acute and baseline determinations has been recommended. We assessed the performance of four proposed algorithms with tightly controlled time frames for tryptase sampling, their robustness with inadequate sampling times, and the possible use of mature tryptase determination.

Methods: A retrospective study was performed on 102 adult patients from the Aix-Marseille University Hospitals who had experienced a perioperative hypersensitivity reaction clinically suggesting anaphylaxis. EAACI and ICON criteria were used to diagnose anaphylaxis. Mature and total serum tryptase levels were measured.

Results: Based on EAACI guidelines, clinical diagnostic criteria for anaphylaxis were found in 76 patients and lacking in 26. The most effective algorithm was the international consensus recommendation of 2012 that acute total tryptase levels should be greater than ([1.2×baseline tryptase] + 2] μg/L to be considered a clinically significant rise. In our cohort, this algorithm achieved 94% positive predictive value (PPV), 53% negative predictive value (NPV), 75% sensitivity, 86% specificity, and a Youden's index value of 0.61. A detectable acute mature tryptase level showed lower sensitivity, particularly in patients with acute total tryptase levels lower than 16 μg/L. Acute tryptase levels varied as a function of the clinical severity of anaphylaxis.

Conclusion: Total tryptase levels in serum discriminated between nonanaphylactic and anaphylactic events in a perioperative setting when acute and baseline levels were collected and analyzed by the consensus algorithm.
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http://dx.doi.org/10.1111/all.13752DOI Listing
June 2019

Clinical value of automated fibrin generation markers in patients with septic shock: a SepsiCoag ancillary study.

Br J Haematol 2018 11 11;183(4):636-647. Epub 2018 Sep 11.

Intensive Care Unit, CHU Nîmes, Univ Montpellier, France.

An ancillary analysis to the SepsiCoag multicentric prospective observational study on patients entering an intensive care unit with septic shock evaluated the prognostic potential of fibrin generation markers (FGMs) tested at inclusion in the study, on survival at day 30. After centralization of samples, three automated FGMs were compared: D-dimers (DDi), fibrin/fibrinogen degradation products (FDP) and fibrin monomers (FM). FM was the single FGM that was significantly higher in non-surviving patients, area under the receiver-operator characteristic curve (AUC ): 0·617, P < 0·0001. Significantly higher International Society on Thrombosis and Haemostasis Disseminated Intravascular Coagulation (ISTH DIC) scores were calculated in non-survivors using each of the three FGMs. A dose-effect relationship was observed between ISTH DIC scores and non-survival, with highest significance obtained using FM as the FGM. An overt DIC diagnosis using the ISTH DIC score calculated using FM was a predictor of non-survival at day 30, independently from overt DIC diagnosis based on scores calculated using FDP or DDi. The AUC values testing the ability of the ISTH DIC score to predict non-survival were 0·650, 0·624 and 0·602 using FM, DDi and FDP, respectively, as the FGM. In patients with septic shock, among the commercially-available automated assays, automated FM is the FGM best related with late prognosis.
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http://dx.doi.org/10.1111/bjh.15576DOI Listing
November 2018

A new assay to evaluate microvesicle plasmin generation capacity: validation in disease with fibrinolysis imbalance.

J Extracell Vesicles 2018 16;7(1):1494482. Epub 2018 Jul 16.

Aix-Marseille Université, C2VN, UMR-1263, INSERM, INRA 1260, UFR de Pharmacie, Marseille, France.

Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance. Using plasma sample spiked with LMVs featuring different levels of PGC, we demonstrated that CD15-beads specifically extracted LMVs. The MV dependency of the test was demonstrated using electron microscopy, high speed centrifugation, nanofiltration and detergent-mediated solubilization and the MV-PGC specificity using plasmin-specific inhibitors, or antibodies blocking elastase or uPA. Thanks to a reaction booster (ε-ACA), we showed that the assay was more sensitive and reproducible than the original method. Moreover, it exhibited a good repeatability, inter-operator and inter-experiment reproducibility. The new immunomagnetic bio-assay was further validated in patients with septic shock. As a result, we showed that MV-PGC values were significantly lower in septic shock patients who died compared to patients who survived, both at inclusion and 24 h later (1.4 [0.8-3.0] 3.1 [1.7-18]  × 10/min,  = 0.02; 1.4 [1-1.6] 5.2 [2.2-16]  × 10/min,  = 0.004). Interestingly, combining both MV-PGC and PAI-1 in a ratio significantly improved the predictive value of PAI-1. This strategy, a hybrid capture bioassay to specifically measure LMV-PGC using for the first time, opens new perspectives for measuring subcellular fibrinolytic potential in clinical settings with fibrinolytic imbalance.
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http://dx.doi.org/10.1080/20013078.2018.1494482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052415PMC
July 2018

Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial.

JAMA 2017 10;318(14):1346-1357

Département Anesthésie et Réanimation B, Centre Hospitalier Universitaire Montpellier, Hôpital Saint-Eloi, and INSERM U-1046, Montpellier, France.

Importance: Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain.

Objective: To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction.

Design, Setting, And Participants: The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016).

Interventions: Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient's resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery.

Main Outcomes And Measures: The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery.

Results: Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, -14%, 95% CI, -25% to -2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality.

Conclusions And Relevance: Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction.

Trial Registration: clinicaltrials.gov Identifier: NCT01536470.
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http://dx.doi.org/10.1001/jama.2017.14172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710560PMC
October 2017

Successful Electroconvulsive Therapy for a Patient With McArdle Disease.

J ECT 2017 12;33(4):e36-e37

Department of Anesthesiology, Sainte Marguerite University Hospital, Marseille, France Department of Psychiatry, Sainte Marguerite University Hospital, Marseille, France Department of Anesthesiology, Sainte Marguerite University Hospital, Marseille, France Department of Psychiatry, Sainte Marguerite University Hospital, Marseille, France

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http://dx.doi.org/10.1097/YCT.0000000000000440DOI Listing
December 2017

Intensive Early Rehabilitation in the Intensive Care Unit for Liver Transplant Recipients: A Randomized Controlled Trial.

Arch Phys Med Rehabil 2017 08 6;98(8):1518-1525. Epub 2017 Mar 6.

Aix-Marseille University, Assistance Publique des Hôpitaux de Marseille, Department of General Surgery and Liver Transplantation, Hôpital de la Conception, Marseille, France. Electronic address:

Objective: To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients.

Design: Prospective randomized study.

Setting: ICU.

Participants: Liver transplant recipients over a period of 1 year (N=40).

Interventions: The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared.

Main Outcome Measures: Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued.

Results: The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group.

Conclusions: The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.
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http://dx.doi.org/10.1016/j.apmr.2017.01.028DOI Listing
August 2017

[Potentially toxic antibiotics concentrations after administration using impregnated dressing in a severe burned patient: A case report].

Therapie 2016 Oct 27;71(5):483-486. Epub 2016 Apr 27.

Service de pharmacologie clinique et pharmacovigilance, laboratoire de pharmacologie clinique, hôpital de la Timone, CHU de la Timone, AP-HM, 13385 Marseille, France.

Severe burned patients present high risk of skins infections, frequently due to Pseudomonas aeruginosa. Impregnated dressings with amikacin or colistin could be a good alternative to obtain effective concentration directly at the infected site. Therapeutic drug monitoring for these antibiotics is currently recommended after an intravenous administration to obtain effective and non-toxic plasmatic concentrations. However, data are lacking about systemic exposition and risk of toxicity after an administration with impregnated dressings. We report the case of a severe burned patient with cutaneous infection treated with amikacin and colistin impregnated dressings, for which plasmatic pharmacokinetic profiles were performed.
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http://dx.doi.org/10.1016/j.therap.2016.03.001DOI Listing
October 2016

About baclofen withdrawal syndrome.

Presse Med 2016 May 23;45(5):547-8. Epub 2016 Mar 23.

CHU Timone, service d'anesthésie-réanimation - réanimation polyvalente et des pathologies du foie (RPPF), 264, rue Saint-Pierre, 13385 Marseille cedex 5, France.

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http://dx.doi.org/10.1016/j.lpm.2016.02.012DOI Listing
May 2016

Two-dimensional-strain echocardiography in intensive care unit patients: A prospective, observational study.

J Clin Ultrasound 2016 Jul 4;44(6):368-74. Epub 2016 Mar 4.

Service d'anesthésie et de réanimation, hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France.

Purpose: Two-dimensional-strain echocardiography (2D-strain) is a promising technique for the early detection of myocardial dysfunction. Our study was aimed to assess its feasibility in the intensive care unit (ICU). Our secondary goal was to determine if 2D-strain could predict the patient's outcome.

Methods: Conventional echocardiography and 2D-strain were performed on 64 consecutive patients admitted to our ICU. Using 2D-strain, the longitudinal deformation of the left ventricle was assessed. Feasibility of 2D-strain, diagnosis performance, and 28-day mortality prediction were determined.

Results: 2D-strain measurements could be performed in 77% of our patients. All 2D-strain variables related to ventricular performance were significantly impaired in the patients who died compared with those who survived. Strain global medium was the only independent echocardiographic variable predictor of 28-day mortality rate (odds ratio 0.60; 95% confidence interval 0.43-0.80, p = 0.002).

Conclusions: 2D-strain measurement is feasible in ICU patients, enabling identifying early left ventricle dysfunction. Strain global medium is an independent predictor of 28-day mortality. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:368-374, 2016.
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http://dx.doi.org/10.1002/jcu.22349DOI Listing
July 2016

[Case report of cardiac tamponade resulting from jugular venous catheterization using ultrasound guidance].

Presse Med 2015 May 2;44(5):556-7. Epub 2015 Mar 2.

Assistance publique-Hôpitaux de Marseille, hôpital Conception, Aix-Marseille université, service d'anesthésie et de réanimation, 13005 Marseille, France.

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http://dx.doi.org/10.1016/j.lpm.2014.11.017DOI Listing
May 2015

Invasive Listeria monocytogenes infection after liver transplantation: a life-threatening condition.

Lancet 2015 Jan;385(9963):200

Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix-Marseille Université, Marseille, France; Comité de Lutte Contre Les Infections Nosocomiales, Hôpital Sainte-Marguerite, Marseille, France.

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http://dx.doi.org/10.1016/S0140-6736(14)61831-6DOI Listing
January 2015

De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial.

Intensive Care Med 2014 Oct 5;40(10):1399-408. Epub 2014 Aug 5.

Service d'anesthésie et de réanimation, Hôpital Nord, Chemin des Bourrely, 13015, Marseille, France,

Background: In patients with severe sepsis, no randomized clinical trial has tested the concept of de-escalation of empirical antimicrobial therapy. This study aimed to compare the de-escalation strategy with the continuation of an appropriate empirical treatment in those patients.

Methods: This was a multicenter non-blinded randomized noninferiority trial of patients with severe sepsis who were randomly assigned to de-escalation or continuation of empirical antimicrobial treatment. Recruitment began in February 2012 and ended in April 2013 in nine intensive care units (ICUs) in France. Patients with severe sepsis were assigned to de-escalation (n = 59) or continuation of empirical antimicrobial treatment (n = 57). The primary outcome was to measure the duration of ICU stay. We defined a noninferiority margin of 2 days. If the lower boundary of the 95 % confidence interval (CI) for the difference in patients assigned to the de-escalation group was less than 2 days, as compared with that of patients assigned to the continuation group, de-escalation was considered to be noninferior to the continuation strategy. Secondary outcomes included mortality at 90 days, occurrence of organ failure, number of superinfections, and number of days with antibiotics during the ICU stay.

Results: The median duration of ICU stay was 9 [interquartile range (IQR) 5-22] days in the de-escalation group and 8 [IQR 4-15] days in the continuation group, respectively (P = 0.71). The mean difference was 3.4 (95 % CI -1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (P = 0.03). The numbers of antibiotic days were 9 [7-15] and 7.5 [6-13] in the de-escalation group and continuation group, respectively (P = 0.03). Mortality was similar in both groups.

Conclusion: As compared to the continuation of the empirical antimicrobial treatment, a strategy based on de-escalation of antibiotics resulted in prolonged duration of ICU stay. However, it did not affect the mortality rate.
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http://dx.doi.org/10.1007/s00134-014-3411-8DOI Listing
October 2014

[Fatal strongyloidiasis following corticosteroid therapy].

Presse Med 2014 Nov 24;43(11):1285-7. Epub 2014 Jul 24.

Aix-Marseille université, AP-HM, hôpital de la Conception, service d'anesthésie et de réanimation, 13385 Marseille, France.

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http://dx.doi.org/10.1016/j.lpm.2014.04.017DOI Listing
November 2014

Sleep disorders among French anaesthesiologists and intensivists working in public hospitals: a self-reported electronic survey.

Eur J Anaesthesiol 2015 Feb;32(2):132-7

From the Department of Anesthesiology and Intensive Care Medicine, Conception Hospital (ER, VB, LR, KH, CN, JA), the Department of Anesthesiology and Intensive Care Medicine, North Hospital (FA, ML) and the Department of Sleep Medicine, Timone Hospital (MR), Aix Marseille University, Marseille, France (AN).

Background: Sleep disorders can affect the health of physicians and patient outcomes.

Objectives: To determine the prevalence of sleep disorders among French anaesthesiologists and intensivists working in a public hospital.

Design: A cross-sectional survey.

Setting: Anaesthesiologists and intensivists working in French public hospitals.

Main Outcome Measures: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) was used to assess the degree of excessive daytime sleepiness.

Results: Among 1504 responders, 677 (45%) physicians reported sleep disorders. The independent factors associated with sleep disorders were reporting of sleep disorders [odds ratio (OR) 12.04, 95% CI (95% confidence interval) 8.89 to 16.46], sleep time less than 7 h (OR 8.86, 95% CI 6.50 to 12.20), work stress (OR 2.04, 95% CI 1.49 to 2.83), stress at home (OR 1.77, 95% CI 1.24 to 2.53), anxiolytic use (OR 3.69, 95% CI 2.23 to 6.25), psychotropic drug use (OR 3.91, 95% CI 1.51 to 11.52) and excessive daytime sleepiness (OR 1.81, 95% CI 1.34 to 2.45). Six hundred and seventy-six (44%) responders reported excessive daytime sleepiness during their professional activity. The independent factors associated with excessive daytime sleepiness were female sex (OR 1.86, 95% CI 1.49 to 2.34), tea consumption (OR 1.47, 95% CI 1.14 to 1.91), regular practice of nap (OR 1.68, 95% CI 1.34 to 2.09), stress at home (OR 1.31, 95% CI 1.02 to 1.68), more than four extended work shifts monthly (OR 1.25, 95% CI 1.01 to 1.56) and sleep disorders (OR 1.73, 95% CI 1.31 to 2.29). Reporting sleep disorder duration and a sleep time less than 7 h were the two major risk factors for sleep disorders. Female sex was the major risk factor for excessive daytime sleepiness.

Conclusion: French anaesthesiologists did not report more sleep disorders than the general population, but their alertness is impaired by a factor of two.
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http://dx.doi.org/10.1097/EJA.0000000000000110DOI Listing
February 2015

An evaluation of the role of gene expression in the prediction and diagnosis of ventilator-associated pneumonia.

Anesthesiology 2011 Aug;115(2):344-52

Service d'Anesthésie et de Réanimation and Centre d'Investigation Clinique, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.

Background: The SepsiChip project explored transcriptional modulation associated with ventilator-associated pneumonia (VAP) in patients admitted to the intensive care unit for trauma. Genome-wide expression analysis may help to identify potential diagnostic markers for diseases. The current study examined the changes in blood transcriptome during VAP.

Methods: The authors prospectively included 165 trauma patients, and 41 developed VAP. Whole blood samples were collected at admission and at VAP. To predict VAP, the admission samples were compared by microarray in patients who did or did not develop VAP. To identify diagnosis markers, paired samples of 35 patients who developed VAP were analyzed. Using NanoString (Seattle, WA), the results were confirmed in the patients who developed VAP. Trauma patients who did not develop VAP served as controls to eliminate a time effect.

Results: The injury severity scores of the patients who did or did not develop VAP were 36 and 29, respectively. No predictive biomarker was identified. For patients who developed VAP, a transcriptional signature was identified between the two sampling times. However, this signature was a generalized pattern related to trauma, independent of the infectious process. Genes involved in the proinflammatory response were down-regulated in the patients who developed VAP, but this difference was not statistically significant.

Conclusions: In contrast to clinical assessment, transcriptional analysis of whole blood samples cannot predict or diagnose VAP in trauma patients. Differentiating infection from inflammation seems challenging.
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http://dx.doi.org/10.1097/ALN.0b013e318225ba26DOI Listing
August 2011

Monitoring of plasma creatinine and urinary γ-glutamyl transpeptidase improves detection of acute kidney injury by more than 20%.

Crit Care Med 2011 Jan;39(1):52-6

Service d'anesthésie et de réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.

Objectives: We sought to determine how early we can detect acute kidney injury inpatients at intensive care unit admission by combining the use of plasma creatinine and urinary γ-glutamyl transpeptidase.

Design: Prospective study including development (n = 100) and validation (n = 56) cohorts.

Settings: Intensive care unit of a university hospital.

Interventions: None.

Measurements And Main Results: To determine acute kidney injury, we subtracted measured creatinine clearance from theoretical creatinine clearance with a 25% reduction signifying acute kidney injury. Its incidence in 100 consecutive patients was 36%. An indexed urinary γ-glutamyl transpeptidase-to-urinary creatinine ratio was significantly increased in the patients with acute kidney injury and did not correlate with plasma creatinine (p = .3). Using a predefined threshold of indexed urinary γ-glutamyl transpeptidase-to-urinary creatinine ratio (>12.4 units/mmol) and plasma creatinine (>89 μmol/L), acute kidney injury detection was significantly improved, making it possible to detect 22 (22%) additional patients with acute kidney injury. This finding was confirmed in the validation group. The rates of false-positive results were 30% and 19% in the data development and internal validation cohorts, respectively.

Conclusions: The use of low-cost, widely available markers (creatinine and urinary γ-glutamyl transpeptidase) increases the detection of acute kidney injury. Further studies are needed to determine the impact on outcome with the use of these biomarkers.
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http://dx.doi.org/10.1097/CCM.0b013e3181fa431aDOI Listing
January 2011

Non-adherence to guidelines: an avoidable cause of failure of empirical antimicrobial therapy in the presence of difficult-to-treat bacteria.

Intensive Care Med 2010 Jan 24;36(1):75-82. Epub 2009 Sep 24.

Service d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Chemin des Bourrely, 13915 Marseille Cedex 20, France.

Purpose: To identify the risk factors of ventilator-associated pneumonia (VAP) due to difficult-to-treat (DTT) bacteria (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii and oxacillin-resistant Staphylococcus aureus), and to assess the rate and the causes of inappropriateness of empirical antimicrobial therapy.

Methods: In an intensive care unit of a university hospital, patients with VAP were empirically treated with antibiotics without activity against DTT bacteria if the patients had no prior hospitalization or prior administration of antibiotics, according to local guidelines.

Results: Overall, the empirical antimicrobial therapy was appropriate in 190 (87%) out of 218 patients with VAP. Fifty (23%) patients developed problems due to DTT bacteria. The risk factors for VAP due to DTT bacteria were shock state, prior antimicrobial therapy, prior stay in long-term care facilities and late-onset VAP. Empirical antimicrobial therapy was inappropriate in 20 (40%) patients with VAP due to DTT bacteria and 8 (5%) patients with VAP due to non-DTT (P = 0.001). Guidelines violations (nine patients), bacteria not included in antibiotic spectrum (eight patients) and bacterial resistance (three patients) were the causes of inappropriateness in case of DTT bacteria.

Conclusion: Despite the abundant information for the treatment of VAP and the establishment of guidelines, too many patients with DTT bacteria received inappropriate antimicrobial therapy. Since 45% of the cases are related to non-adherence to the local protocol, there is room for improvement by implementing educational programs. Also, since DTT bacteria are found in 23% of late-onset VAP, empirical antibiotic treatment should be directed against these pathogens.
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http://dx.doi.org/10.1007/s00134-009-1660-8DOI Listing
January 2010

Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock.

Anesthesiology 2009 Aug;111(2):366-71

Service d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille and Université de la Méditerranée, Marseille, France.

Background: Growing evidence suggests that the microvascular dysfunction is the key element of the pathogenesis of septic shock. This study's purpose was to explore whether the outcome of septic shock patients after early resuscitation using early goal-directed therapy is related to their muscle tissue oxygenation.

Methods: Tissue oxygen saturation (Sto2) was monitored in septic shock patients using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology, Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values were collected at the first measurement done after the macrohemodynamic variables (mean arterial pressure, urine output, central venous saturation in oxygen) were optimized.

Results: After the hemodynamic variables were corrected, no difference was observed between the nonsurvivors and survivors, with the exception of pulse oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values were significantly lower in the nonsurvivors than in the survivors (73% [68-82%] vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2 (P = 0.7).

Conclusions: In septic shock patients, tissue oxygen saturation below 78% is associated with increased mortality at day 28. Further investigations are required to determine whether the correction of an impaired level of tissue oxygen saturation may improve the outcome of these patients.
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http://dx.doi.org/10.1097/ALN.0b013e3181aae72dDOI Listing
August 2009

Long-term outcome in chest trauma.

Anesthesiology 2008 Nov;109(5):864-71

Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Background: Currently, there are limited data available describing the long-term outcomes of chest trauma survivors. Here, the authors sought to describe chest trauma survivor outcomes 6 months and 1 yr after discharge from the intensive care unit, paying special attention to pulmonary outcomes.

Methods: A cohort of 105 multiple trauma patients with blunt chest trauma admitted to the intensive care unit was longitudinally evaluated. After 6 months, a chest computed tomography scan, pulmonary function testing (PFT), and quality of life were collected in 55 of these patients. A subgroup of 38 patients was followed up for 1 yr.

Results: At least one abnormal PFT result was found in 39 patients (71%). Compared with normalized data of the age- and sex-matched population, physical function was decreased in 38 patients (70%). The 6-min walk distance was reduced for 29 patients (72%). Although pathologic images were observed on the chest computed tomography scan from 33 patients (60%), no relation was found between PFT and computed tomography. A ratio of arterial oxygen pressure to inspired oxygen fraction less than 200 at admission to the intensive care unit predicted an abnormal PFT result at 6 months. One year after discharge from the intensive care unit, paired comparisons showed a significant increase in forced vital capacity (P = 0.02) and Karnofsky Performance Status (P < 0.001).

Conclusions: Survivors of multiple traumas including chest trauma demonstrate a persistent decrease in the 6-min walk distance, impairment on PFT, and reduced pulmonary-specific quality of life.
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http://dx.doi.org/10.1097/ALN.0b013e31818a4009DOI Listing
November 2008

Craniocerebral penetrating injury caused by a spear gun through the mouth: case report.

J Neurosurg 2008 May;108(5):1021-3

Department of Intensive Care and Anesthesia, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, France.

The authors report a case of a craniocerebral penetrating injury caused by the shaft of a spear gun. The entry point of the spear was located in the mouth without an obvious exit point. The authors first note the presentation of the patient, whose airway was obstructed by the shaft, and then discuss the surgical procedure, which was focused on removing the shaft in an anterograde direction because of an articulated wishbone located at the tip of the shaft.
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http://dx.doi.org/10.3171/JNS/2008/108/5/1021DOI Listing
May 2008

A novel intravascular rewarming method to treat severe hypothermia.

Eur J Emerg Med 2008 Feb;15(1):56-8

Department of Intensive Care Medicine and Trauma Center, Nord University and Hospital Center, Marseille, France.

We report here a patient with severe hypothermia (27 degrees C), who was successfully rewarmed by using a novel intravascular rewarming method (in combination with an airways rewarming method) through endotracheal tube.
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http://dx.doi.org/10.1097/MEJ.0b013e3282861d40DOI Listing
February 2008

[Coma following ethanol sclerotherapy].

Presse Med 2008 Apr 4;37(4 Pt 1):614-7. Epub 2008 Jan 4.

Département d'anesthésie et de réanimation, CHU de Nord, F-13915 Marseille Cedex 20, France.

Introduction: Simple serous renal cysts are an often asymptomatic benign disease, sometimes treated with ethanol sclerotherapy. We report a case of iatrogenic acute alcohol intoxication following percutaneous injection of alcohol into a renal cyst under local anesthesia.

Case: The percutaneous injection was guided by computed tomography. At the end of the procedure, the patient went into a coma due to alcohol intoxication: the cyst ruptured and ethanol was resorbed into the systemic circulation.

Discussion: Alcohol injection for sclerotherapy is used for several indications. This rare event has not previous been described, but should be known so that physicians can be prepared to manage it correctly.
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http://dx.doi.org/10.1016/j.lpm.2007.05.041DOI Listing
April 2008

Impact of terlipressin on renal graft function.

Shock 2008 Jun;29(6):667-9

Département d'Anesthésie et de Réanimation, Hôpital Nord, Marseille, France.

To assess the effect of a bolus of terlipressin in brain-dead donors with shock refractory to norepinephrine, a retrospective study was conducted in a 16-bed intensive care unit of a university hospital. Twenty brain-dead donors were treated with norepinephrine within the study period. Nine of these donors developed persisting hypotension (MAP < 65 mmHg) not responding to fluid loading and high dose of norepinephrine. They were then treated with a single bolus of terlipressin (1 mg). This resulted in a MAP rise from 58 +/- 10 to 93 +/- 20 mmHg (P = 0.009). One month after transplantation, no differences were observed in serum creatinine levels of the recipients who received a renal transplant extracted from donors responding or not to norepinephrine (138 +/- 43 vs. 137 +/- 43 microM; P = 0.95). The liver function was similar in both groups. Within the limitations of this study, a single bolus of terlipressin in norepinephrine-resistant vasodilatory shock donors does not affect the renal and liver graft quality in the recipients.
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http://dx.doi.org/10.1097/shk.0b013e31815d0ae7DOI Listing
June 2008

Impact of intensive care on renal function before graft harvest: results of a monocentric study.

Crit Care 2007 ;11(5):R103

Département d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Chemin des Bourrely, 13915 Marseille cedex 20, Université de la Méditerranée, Faculté de Médecine, 13005 Marseille, France.

Background: The aim of life-support measures in brain-dead donors is to preserve the functional value of their organs. In renal transplantation, serum creatinine level is one of the criteria for graft harvest. The aim of this study was to assess the impact of intensive care on donor renal function through two criteria: preharvesting serum creatinine level above 120 micromol/L and the elevation of serum creatinine level above 20% between intensive care unit (ICU) admission and graft harvest.

Methods: Between 1 January 1999 and 31 December 2005, we performed an observational study on 143 brain-dead donors. ICU chronology, hemodynamic, hematosis, and treatment data were collected for each patient from ICU admission to kidney removal.

Results: Twenty-two percent of the 143 patients had a serum creatinine level above 120 micromol/L before graft harvest. The independent factors revealed by multivariate analysis were the administration of epinephrine (odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.33 to 14.32; p = 0.015), oliguria (OR: 3.73, 95% CI: 1.22 to 11.36; p = 0.021), acidosis (OR: 3.26, 95% CI: 1.07 to 9.95; p = 0.038), the occurrence of disseminated intravascular coagulation (OR: 3.97, 95% CI: 1.05 to 15.02; p = 0.042), female gender (OR: 0.13, 95% CI: 0.03 to 0.50; p = 0.003), and the administration of desmopressin (OR: 0.12, 95% CI: 0.03 to 0.44; p = 0.002). The incidence of elevated serum creatinine level above 20% between admission and graft harvest was 41%. The independent risk factors were the duration of brain death greater than 24 hours (OR: 2.64, 95% CI: 1.25 to 5.59; p = 0.011) and the volume of mannitol (OR: 2.08, 95% CI: 1.03 to 4.21; p = 0.041).

Conclusion: This study shows that the resuscitation of brain-dead donors impacts on their renal function. The uses of epinephrine and mannitol are associated with impairment of kidney function. It seems that graft harvest should be performed less than 24 hours after brain death diagnosis.
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http://dx.doi.org/10.1186/cc6120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556746PMC
May 2008

A randomized trial of catheter change and short course of antibiotics for asymptomatic bacteriuria in catheterized ICU patients.

Intensive Care Med 2007 Apr 9;33(4):726-9. Epub 2007 Feb 9.

Département d'Anesthésie et de Réanimation, Assistance Publique Hôpitaux de Marseille, CHU Nord, 13915, Marseille cedex 20, France.

Objective: To determine the effect on the occurrence of urosepsis of a treatment with a short course of antibiotics and indwelling urethral catheter replacement in clinically asymptomatic intensive care unit (ICU) patients with a positive urine culture occurring at least 48 h after catheterization.

Methods: A prospective randomized clinical trial was conducted in the medico-surgical ICU of a tertiary care centre. Sixty patients hospitalized in the ICU with an indwelling urethral catheter for longer than 48 h developing an asymptomatic positive urine culture were randomized to receive either a 3-day course of antibiotics associated with the replacement of the indwelling urethral catheter 4 h after first antibiotic administration or no antibiotics, no catheter replacement (standard of care).

Results: Three patients in each group developed urosepsis (P=0.1). There were no significant differences in duration of mechanical ventilation between the study group and the standard of care group (9 [4-20] days vs 5 [2-15] days, P=0.2), in duration of urinary catheterization (22 [11-40] days vs 18 [14-33] days, P=0.8), or in length of ICU stay (28 [13-46] vs 19 [15-34], P=0.6). The recurrence of positive urine culture at days 7 and 15 was not affected by the randomization (P=0.1). The profile of bacterial resistance was similar in the two groups.

Conclusions: Treating a positive urine culture in an asymptomatic patient with an indwelling urethral catheter does not reduce the occurrence of urosepsis in the medico-surgical ICU.
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http://dx.doi.org/10.1007/s00134-007-0534-1DOI Listing
April 2007

Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse.

Crit Care Med 2007 Feb;35(2):379-85; quizz 386

Intensive Care Unit, Département d'Anesthésie et de Réanimation, Assistance Publique-Hôpitaux de Marseille, Public Hospitals of Marseille, Marseille Medicine University, France.

Objective: To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia.

Design: Prospective observational study during a 36-month period.

Setting: Medical-surgical intensive care unit of a university hospital.

Patients: One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy.

Interventions: None.

Measurements And Main Results: A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p=.04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria.

Conclusions: A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.
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http://dx.doi.org/10.1097/01.CCM.0000253404.69418.AADOI Listing
February 2007

A reappraisal of isoproterenol in goal-directed therapy of septic shock.

Shock 2006 Oct;26(4):353-7

Département d'Anesthésie et de Réanimation, UPRES Equipe d'Accueil 3784, Centre Hospitalier Universitaire Nord, 13915 Marseille cedex 20, France.

The goal of the study was to evaluate the effect of isoproterenol prescribed in goal-directed therapy for septic shock. Out of a cohort of 89 patients with septic shock, 14 patients treated with fluid and norepinephrine had inappropriate mixed venous oxygen saturation (SvO2<70%) not responding to correction of hypoxemia and anemia (>8 g.dL-1). Isoproterenol administration was started at a dose of 0.04 microg.kg-1.minute-1 with 0.025 microg.kg-1.minute-1 increments every 30 minutes until SvO2 was greater than 70%. Mean arterial pressure was maintained>or=65 mm.Hg by adjusting the norepinephrine infusion. Hemodynamic, oxygen, and renal variables were collected during a 12-h period. Patients with a known prior history of coronary disease were not eligible. Isoproterenol administration increased significantly SvO2 (62%+/-10% to 71%+/-9%), cardiac index (3.1+/-0.6 to 4.4+/-1.4 L.min-1.m-2), stroke index (27+/-3.4 to 38+/-6.1 mL.m-2), and left ventricular stroke work index (24+/-3.4 to 40+/-5.0 g.m-1.m-2). Heart rate rise did not reach a significant level. Arterial lactate concentration decreased significantly during the study period (5.7+/-2.8 to 3.4+/-1.6 mmol.L-1). No cardiac adverse events occurred with any electrocardiographic aspects of myocardial ischemia. This study suggests that isoproterenol is efficient to improve hemodynamics and oxygen variables in septic shock patients. There is a need for future investigations in larger groups of patients to determine whether isoproterenol can be an alternative to dobutamine.
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http://dx.doi.org/10.1097/01.shk.0000226345.55657.66DOI Listing
October 2006
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