Publications by authors named "Sandrine Wiramus"

24 Publications

  • Page 1 of 1

Beta-lactam allergy labeling in intensive care units: An observational, retrospective study.

Medicine (Baltimore) 2021 Jul;100(27):e26494

Aix Marseille Université, School of Medicine - La Timone Medical Campus, EA 3279, CEReSS - Health Service Research and Quality of Life Center.

Abstract: This retrospective study aimed to describe the association between the "β-lactam allergy" labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.Retrospective cohort study.Seven ICU of the Aix Marseille University Hospitals from Marseille in France.We collected the uses of the label "β-lactam allergy" in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3-14] vs 6 [3-14] days, standardized beta -0.09, P = .046; and 18 [10-29] vs 15 [8-28] days, standardized beta -0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64-0.98] P = .032 and 0.79 [0.63-0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.In our cohort, the labeling of a β-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a β-lactam allergy and lower ICU and 28-day mortality rates.Trial registration: Retrospectively registered.
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http://dx.doi.org/10.1097/MD.0000000000026494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270612PMC
July 2021

The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study.

Trials 2020 Nov 25;21(1):973. Epub 2020 Nov 25.

Department of Anaesthesiology, Critical Care Medicine and Burn unit, AP-HP, Saint Louis and Lariboisière University Hospitals, 1 Avenue Claude Vellefaux, 75010, Paris, France.

Background: The indication for antibiotic prophylaxis in burn patients remains highly controversial, with no consensus having been reached. The objective of antibiotic prophylaxis is to reduce the risk of postoperative local and systemic infections. Burn surgery is associated with a high incidence of bacteremia, postoperative infections, and sepsis. However, antibiotic prophylaxis exposes patients to the risk of selecting drug-resistant pathogens as well as to the adverse effects of antibiotics (i.e., Clostridium difficile colitis). The lack of data precludes any strong international recommendations regarding perioperative prophylaxis using systemic antibiotics in this setting. The goal of this project is therefore to determine whether perioperative systemic antibiotic prophylaxis can reduce the incidence of postoperative infections in burn patients.

Methods: The A2B trial is a multicenter (10 centers), prospective, randomized, double-blinded, placebo-controlled study. The trial will involve the recruitment of 506 adult burn patients with a total body surface area (TBSA) burn of between 5 and 40% and requiring at least one excision-graft surgery for deep burn injury. Participants will be randomized to receive antibiotic prophylaxis (antibiotic prophylaxis group) or a placebo (control group) 30 min before the incision of the first two surgeries. The primary outcome will be the occurrence of postoperative infections defined as postoperative sepsis and/or surgical site infection and/or graft lysis requiring a new graft within 7 days after surgery. Secondary outcomes will include mortality at day 90 postrandomization, skin graft lysis requiring a new graft procedure, postoperative bacteremia (within 48 h of surgery), postoperative sepsis, postoperative surgical site infection, number of hospitalizations until complete healing (> 95% TBSA), number of hospitalization days living without antibiotic therapy at day 28 and day 90, and multiresistant bacterial colonization or infection at day 28 and day 90.

Discussion: The trial aims to provide evidence on the efficacy and safety of antibiotic prophylaxis for excision-graft surgery in burn patients.

Trial Registration: ClinicalTrials.gov NCT04292054 . Registered on 2 March 2020.
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http://dx.doi.org/10.1186/s13063-020-04894-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687822PMC
November 2020

Management of severe thermal burns in the acute phase in adults and children.

Anaesth Crit Care Pain Med 2020 04 5;39(2):253-267. Epub 2020 Mar 5.

Department of Anaesthesiology, Critical Care and Burn Centre, Lariboisière-Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, Paris, France; Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, Paris, France; Department of Research, University of Ottawa Heart Institute, Ottawa, ON, Canada.

Objectives: To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children.

Design: A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion.

Results: The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations.

Conclusion: Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.
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http://dx.doi.org/10.1016/j.accpm.2020.03.006DOI Listing
April 2020

Outcome and characteristics of invasive fungal infections in critically ill burn patients: A multicenter retrospective study.

Mycoses 2020 Jun 10;63(6):535-542. Epub 2020 May 10.

Department of Anesthesiology and Critical Care and Burn Unit, AP-HP, St-Louis Hospital, Paris, France.

Background: Characteristics and outcome of invasive fungal infection (IFI) in critically ill burn patients have been poorly explored.

Objectives: We report the factors associated with 90-day mortality in a multicentre retrospective European study.

Patients/methods: All burn patients with confirmed IFI admitted between 1 January 2010 to 31 December 2015 in 10 centres in France and Belgium were included.

Results: Ninety-four patients were enrolled with 110 cases of IFIs: 79 (71.8%) were yeasts IFI and 31 (28.2%) filamentous IFI. Incidence was 1% among admitted patients. The 90-day mortality was 37.2% for all IFIs combined, 52% for filamentous infection and 31.9% for yeast infection. Patients with more than one IFI had a higher 90-day mortality than patients with only one episode (61.5% vs 33.5% (P = .006)). In multivariate analysis, higher Simplified Acute Physiology Score II (OR = 1.05 (95% CI: 1.02-1.09) P = .003), bacterial co-infection (OR = 3.85 (95% CI: 1.23-12.01), P = .014) and use of skin allografts at the time of IFI diagnosis (OR = 3.87 (95% CI: 1.31-11.42), P = .021) were associated with 90-day mortality.

Conclusions: Although rare, invasive fungal infections remain associated with poor outcome in burn patients. Bacterial co-infection and presence of allograft were potentially modifiable factors independently associated with outcome.
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http://dx.doi.org/10.1111/myc.13068DOI Listing
June 2020

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

Crit Care 2019 Dec 23;23(1):421. Epub 2019 Dec 23.

Department of Anesthesia and perioperative care, University of California San Francisco, San Francisco, USA.

Background: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored.

Methods: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models.

Results: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively.

Conclusion: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation.

Trial Registration: ClinicalTrials.gov, NCT03558646.
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http://dx.doi.org/10.1186/s13054-019-2706-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929494PMC
December 2019

Venovenous extracorporeal membrane oxygenation devices-related colonisations and infections.

Ann Intensive Care 2017 Nov 7;7(1):111. Epub 2017 Nov 7.

Hôpital Nord, Réanimation des Détresses Respiratoires et des Infections Sévères, Assistance Publique-Hôpitaux de Marseille, 13015, Marseille, France.

Background: Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices. This study aims to evaluate the rate of both colonisations and infections related to ECMO devices at the time of ECMO removal.

Results: We included all consecutive adult patients treated with venovenous ECMO (VV-ECMO) for at least 48 h during a 34-month study. At the time of ECMO removal, blood cultures, swab cultures on insertion cannula site and intravascular cannula extremity cultures were systematically performed. Each ECMO device was classified according to the infectious status into three groups: (1) uninfected/uncolonised ECMO device, (2) ECMO device colonisation and (3) ECMO device infection. Ninety-nine patients underwent 103 VV-ECMO, representing 1472 ECMO days. The ECMO device infection rate was 9.7% (10 events), including 7 ECMO device-related bloodstream infections (6.8%). The ECMO device colonisation rate was 32% (33 events). No difference was observed between the three groups, regarding days of mechanical ventilation, ICU length of stay, ICU mortality and in-hospital mortality. We observed a longer ECMO duration in the ECMO device colonisation group as compared to the uninfected/uncolonised ECMO device group [12 (9-20 days) vs. 5 days (5-16 days), respectively, p < 0.05].

Conclusions: At the time of ECMO removal, systematic blood culture and intravascular extremity cannula culture may help to diagnose ECMO device-related infection. We reported a quite low infection rate related to ECMO device. Further studies are needed to evaluate the benefits of systematic strategies of cannula culture at the time of ECMO removal.
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http://dx.doi.org/10.1186/s13613-017-0335-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676570PMC
November 2017

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

Anesthesiology 2017 05;126(5):882-889

From the Réanimation Polyvalente et Surveillance Continue, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, Nice, France (J.-C.O., Y.W., C.I.); Service d'Anesthésie et des Réanimations Chirurgicales, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France (N.M., G.D.); Département d'Anesthésie-Réanimation, Hôpital Edouard-Herriot, Hospices Civils de Lyon, Lyon, France (B.A.); Réanimation Médicale, Hôpital Edouard-Herriot, Hospices Civils de Lyon, Lyon, France (L.A.); Réanimation Chirurgicale, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France (F.A.); Réanimation, Centre Hospitalier Interrégional de Compiègne Noyon, Compiègne, France (G.B.); Réanimation Adultes et Unité de Soins Intensifs, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France (J.-M.C.); Réanimation Polyvalente, Hôpital Sainte-Musse, Centre Hospitalier Interrégional de Toulon-La Seyne sur mer, Toulon, France (J.D.-G., C.G.); Réanimations, Centre Hospitalier Universitaire de Amiens Picardie-Site Sud, Amiens, France (H.D.); Anesthésie et Réanimation Adulte, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Toulouse, France (M.G.); Service de Réanimation, Hôpital Inter-Armées Sainte-Anne, Toulon, France (P.G.); Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France (B.G.); Réanimation Médicale, Hôpital l'Archet 2, Centre Hospitalier Universitaire de Nice, Nice, France (H.H.); Département d'Anesthésie et de Réanimation B, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (S.J.); Division Anesthésie Réanimation Douleur Urgences, Centre Hospitalier Universitaire de Nîmes, Nîmes, France (J.-Y.L.); Réanimation Chirurgicale, Centre Hospitalier Universitaire de Rennes, Rennes, France (Y.M.); Réanimation Polyvalente B, Hôpital Nord, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Priest En Jarez, France (J.M.); Service d'Anesthésie-Réanimation II, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (A.O.); Service de Réanimation Polyvalente, Centre Hospitalier Universitaire Dupuytren, Limoges, France (N.P.); Réanimation Polyvalente, Centre Hospitalier de Beauvais, Beauvais, France (A.-M.G.R.); Réanimation et Surveillance Continue, Centre Hospitalier de Annecy Genevois, Epagny Metz-Tessy, France (M.S.); Service de Réanimation Polyvalente, Centre Hospitalier Princesse Grace, Monaco City, Monaco (A.T.); and Service d'Anesthésie Réanimation, Hôpital de la Conception (S.W.) and Service Anesthésie et Réanimation, Hôpital Nord (L.Z., M.L.), Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Background: Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts.

Methods: An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest).

Results: A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths.

Conclusions: In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.
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http://dx.doi.org/10.1097/ALN.0000000000001612DOI Listing
May 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

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

Night shift decreases cognitive performance of ICU physicians.

Intensive Care Med 2016 Mar 10;42(3):393-400. Epub 2015 Nov 10.

Assistance Publique, Hôpitaux de Marseille, Hôpital Nord, Réanimation des Détresses Respiratoires et des Infections Sévères, Chemin des Bourrely, 13015, Marseille, France.

Background: The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated.

Methods: A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test.

Results: All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift.

Conclusions: The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients' safety and physicians' health should be further evaluated.
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http://dx.doi.org/10.1007/s00134-015-4115-4DOI Listing
March 2016

Cytomegalovirus reactivation in ICU patients.

Intensive Care Med 2016 Jan 30;42(1):28-37. Epub 2015 Sep 30.

Faculté de Médecine, Aix-Marseille Université, URMITE UMR CNRS 7278, 13005, Marseille, France.

Introduction: Approximately 20 years have passed since we reported our results of histologically proven cytomegalovirus (CMV) pneumonia in non-immunocompromised ICU patients. Even if there are more recent reports suggesting that CMV may worsen the outcomes for ICU patients, there is no definite answer to this question: is CMV a potential pathogen for ICU patients or is it simply a bystander?

Methods: We will describe the pathophysiology of active CMV infection and the most recent insights concerning the epidemiological aspects of these reactivations.

Major Findings: Cytomegalovirus can be pathogenic by a direct organ insult (such as for the lung), by decreasing host defences against other microorganisms and/or by enhancing the body's inflammatory response (as in acute respiratory distress syndrome). The incidence of active CMV infection is dependent on the diagnostic method used. Using the most sophisticated available biological tools, the incidence can reach 15-20% of ICU patients (20-40% in ICU patients with positive CMV serology). In adequately powered cohorts of patients, active CMV infection appears to be associated with worse outcomes for mechanically ventilated ICU patients.

Discussion: There is no absolute direct proof of a negative impact of active CMV infection on the health outcomes of mechanically ventilated patients. Prospective randomized trials are lacking. Future trials should examine the potential benefits for health outcomes of using antiviral treatments. Such treatments could be prophylactic, pre-emptive or used only when there is an end-organ disease.

Conclusion: Cytomegalovirus infection may affect health outcomes for ICU patients. Additional prospective trials are necessary to confirm this hypothesis.
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http://dx.doi.org/10.1007/s00134-015-4066-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095171PMC
January 2016

Early sex-specific modulation of the molecular clock in trauma.

J Trauma Acute Care Surg 2014 Jan;76(1):241-4

From the Equipe Infection (V.M., C.C., M.L., J.-L.M., J.T.), Genre et Grossesse, URMITE CNRS UMR7278, INSERM U1095, Aix- Marseille Université; Service d'anesthésie et de reanimation (S.W., M.L., J.T.), Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Aix Marseille Université; and Service d'anesthésie et de reanimation (S.W.), Réanimation du centre des brûlés inter-régional de Méditerranée, Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Marseille, France.

Background: Immune system biology and most physiologic functions are tightly linked to circadian rhythms. Time of day-dependent variations in many biologic parameters also play a fundamental role in the disease process. We previously showed that the genes encoding the peripheral molecular clock were modulated in a sex-dependent manner in Q fever.

Methods: Here, we examined severe trauma patients at admission to the intensive care unit. Using quantitative real-time polymerase chain reaction, the whole-blood expression of the molecular clock components ARNTL, CLOCK, and PER2 was assessed in male and female trauma patients. Healthy volunteers of both sexes were used as controls.

Results: We observed a significant overexpression of both ARNTL and CLOCK in male trauma patients.

Conclusion: We report, for the first time, the sex-related modulation of the molecular clock genes in the blood following severe trauma. These results emphasize the role of circadian rhythms in the immune response in trauma patients.

Level Of Evidence: Epidemiologic study, level IV.
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http://dx.doi.org/10.1097/TA.0b013e3182a90014DOI Listing
January 2014

Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial.

JAMA 2013 Oct;310(16):1692-700

Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Réanimation des Détresses Respiratoires et des Infections Sévères UMR-CNRS 7278, Aix-Marseile Université, Marseille, France.

Importance: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality.

Objective: To determine whether statin therapy can decrease day-28 mortality in patients with VAP.

Design, Setting, And Participants: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients.

Interventions: Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first.

Main Outcomes And Measures: Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14.

Results: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score.

Conclusions And Relevance: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes.

Trial Registration: clinicaltrials.gov Identifier: NCT01057758.
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http://dx.doi.org/10.1001/jama.2013.280031DOI Listing
October 2013

Occult pulmonary embolism in intensive care unit patients undergoing chest computed tomography scan: incidence and effect on outcomes.

J Cardiothorac Vasc Anesth 2013 Jun 3;27(3):474-8. Epub 2013 Apr 3.

Service d'Anesthésie et de Réanimation, Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Aix Marseille Université, Marseille, France.

Objective: To determine the incidence of occult pulmonary embolism (PE) and the associated morbidity in an intensive care unit (ICU).

Design: Retrospective study.

Setting: Fifteen-bed ICU of a university hospital.

Participants: Two hundred patients who underwent chest computed tomography (CT) scans with administration of contrast.

Interventions: The patients were classified into 3 groups: (1) Occult PE if the chest CT scan was not taken, specifically for elucidating the diagnosis of PE, but it confirmed this diagnosis; (2) non-occult PE if the chest CT scan was taken to elucidate a suspected diagnosis of PE and confirmed this diagnosis; and (3) the chest CT scan did not confirm this diagnosis. The analysis was conducted to identify the effect of a diagnosis of occult PE on the outcomes of patients.

Measurements And Main Results: Among the 200 patients who underwent chest CT scan, 27 (13%) patients had PE, in whom 18 (9%) were classified as occult PE and 9 (4.5%) as non-occult PE. The duration of ICU stay was increased in patients with PE, as compared with the controls (23 [18-48] days v 17 [10-20] days v 14 [7-29] days; p = 0.02 for occult PE, non-occult PE, and controls, respectively). No difference was observed in mortality rate among the 3 groups.

Conclusion: Occult PE was found in 9% of the cohort. This emphasized the need for developing diagnostic strategies in high-risk patients. Future studies should aim at assessing interventions for preventing this event.
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http://dx.doi.org/10.1053/j.jvca.2012.10.015DOI Listing
June 2013

[Infections in burn patients].

Soins 2012 Jul-Aug(767):36-9

Centre de brûlés interrégional Méditerranée, hôpital La Conception, Marseille.

Infection in patients with serious burns is usually linked to care procedures. It occurs beyond the 48th hour and is the leading cause of mortality. The risk of infection is higher in certain elderly patients or those in a precarious situation. Its frequency can be controlled by high quality and well-organised care.
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September 2012

Hypoxia-inducible factor (HIF1α) gene expression in human shock states.

Crit Care 2012 10;16(4):R120. Epub 2012 Jul 10.

Service d’anesthésie et de réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Chemin des bourrely, 13915, Marseille, France.

Introduction: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients with shock.

Methods: 50 consecutive adult patients with shock and 11 healthy volunteers were prospectively included. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first 4 hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28.

Results: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). The HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 [72-168] vs. 48 [38-54] normalized copies, p < 0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 [range 84-183] vs. 121 [range 72-185] normalized copies, p = 0.92), and did not significantly change within the study period.

Conclusions: The present study is the first to demonstrate the increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.
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http://dx.doi.org/10.1186/cc11414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580697PMC
August 2013

High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality.

Crit Care 2011 Jul 26;15(4):R176. Epub 2011 Jul 26.

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.

Introduction: Current guidelines recommend maintaining central venous oxygen saturation (ScvO2) higher than 70% in patients with severe sepsis and septic shock. As high levels of ScvO2 may reflect an inadequate use of oxygen, our aim was to evaluate the relation between maximal ScvO2 levels (ScvO2max) and survival among intensive care unit (ICU) patients with septic shock.

Methods: We retrospectively analyzed data from all admissions to our ICU between January 2008 and December 2009. All septic shock patients in whom the ScvO2 was measured were included. The measures of ScvO2max within the first 72 hours after the onset of shock were collected.

Results: A total of 1,976 patients were screened and 152 (7.7%) patients met the inclusion criteria. The level of ScvO2max was 85% (78 to 89) in the non-survivors, compared with 79% (72 to 87) in the survivors (P = 0.009).

Conclusions: Our findings raise concerns about high levels of ScvO2 in patients with septic shock. This may reflect the severity of the shock with an impaired oxygen use. Future strategies may target an optimization of tissue perfusion in this specific subgroup of patients.
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http://dx.doi.org/10.1186/cc10325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387619PMC
July 2011

Antibiotic therapy in patients with septic shock.

Eur J Anaesthesiol 2011 May;28(5):318-24

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

The management of a patient with severe sepsis is first to diagnose the infection, to collect samples immediately after diagnosis and to initiate promptly broad-spectrum antibiotic treatment. The choice of empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology and the pharmacokinetics and pharmacodynamics of the antibiotics. In severe infection, guidelines recommend the use of a combination of antibiotics. After results of cultures are obtained, treatment should be re-evaluated to either de-escalate or escalate the antibiotics. This is associated with optimal costs, decreased incidence of superinfection and reduced development of antimicrobial resistance. All these steps should be based on written protocols, and compliance to these protocols should be monitored continuously in order to detect violations and implement corrective procedures.
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http://dx.doi.org/10.1097/EJA.0b013e328346c0deDOI Listing
May 2011

Long-term outcome in medical patients aged 80 or over following admission to an intensive care unit.

Crit Care 2011 24;15(1):R36. Epub 2011 Jan 24.

Medical Intensive Care Unit, Hôpital Nord, Chemin des Bourrely, Marseille 13015, France.

Introduction: The aim of this study was to evaluate factors influencing short- and long-term survival in medical patients aged 80 and over following admission to an intensive care unit.

Methods: All patients aged 80 years or over and admitted between 2001 and 2006 were included in this study. Survival was evaluated between the time of admission and June 2009; factors associated with mortality were determined. Health-related quality of life was evaluated using Short Form (SF)-36 in long-term survivors.

Results: For the 299 patients included (mean age, 84 ± 4 y), hospital mortality was 55%. Factors independently associated with hospital mortality were a higher SAPS II score at ICU admission; the existence of a fatal disease as reflected by the McCabe score and a cardiac diagnosis at admission. In the 133 hospital survivors, median survival time was 710 days (95% CI, 499-921). Two-year mortality rates were 79% of the initial cohort and 53% of hospital survivors. The standardized ratio of mortality at 2 years after hospital discharge was 2.56 (95% CI, 2.08-3.12) when compared with age- and gender-adjusted mortality of the general population. Factors independently associated with mortality at 2 years after hospital discharge were SAPS II score at ICU admission and the McCabe score. Conversely, functional status prior to admission as assessed by Knaus or Karnofsky scores was not associated with long-term mortality. In long-term survivors, SF-36 physical function scores were poor but scores for pain, emotional well-being and social function were not much affected.

Conclusions: The severity of acute disease at admission influences mortality at the hospital and following discharge in patients aged 80 or over. Although up to 50% of patients discharged from the hospital were still alive at 2 years, mortality was increased when compared with the general population. Physical function of long-term hospital survivors was greatly altered.
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http://dx.doi.org/10.1186/cc9984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222073PMC
December 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

Overview of antimicrobial therapy in intensive care units.

Expert Rev Anti Infect Ther 2011 Jan;9(1):97-109

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

In the management of a patient with severe sepsis, it is important to suspect the infection early, to collect samples immediately after diagnosis and to promptly initiate a broad-spectrum antibiotic treatment. The choice of this empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology and pharmacokinetics/pharmacodynamics of antibiotics. In severe infection, guidelines recommend the use of a combination of antibiotics. After results of cultures are obtained, treatment should be re-evaluated to either de-escalate or escalate the antibiotic prescription. This is associated with optimal costs, decreased incidence of superinfection and minimal development of antimicrobial resistance. All these steps should rely on written protocols, and the compliance to these protocols should be continuously monitored in order to detect violations and implement corrective procedures.
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http://dx.doi.org/10.1586/eri.10.147DOI Listing
January 2011

Emerging drugs in sepsis.

Expert Opin Emerg Drugs 2010 Mar;15(1):41-52

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.

Importance Of The Field: Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited.

Areas Covered In This Review: The literature was analyzed with Pubmed() during the 2008 - 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on 'sepsis' were first assessed. Next, relevant experimental data in this field were reported.

What The Reader Will Gain: The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts.

Take Home Message: New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.
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http://dx.doi.org/10.1517/14728210903559860DOI Listing
March 2010

Successful management of Influenza A associated fulminant myocarditis: mobile circulatory support in intensive care unit: a case report.

Cases J 2008 Jul 18;1(1):46. Epub 2008 Jul 18.

Department of anesthesia and intensive care unit, La Timone Hospital, Saint Pierre street 264, 13885, Marseille, Cedex 5, France.

A 26-year-old woman was referred to an Emergency Department because of common flu-like syndrome with hemodynamic collapse. In Intensive Care Unit (ICU), she was diagnosed as a probable septic shock. But despite treatment her condition rapidly deteriorated during the subsequent hours. Diagnosis of cardiogenic shock was established. Mechanical circulatory support was inserted into the patient. She was transferred in a Cardio-Vascular Surgical ICU where at the 5th day of mechanical circulatory support, echocardiography showed heart recovery which allowed weaning of mechanical circulatory support and progressive withdrawal of inotropic support. She was discharged at the 26th day. During her hospitalization, presence of Influenza A RNA was shown in myocardial biopsy.
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http://dx.doi.org/10.1186/1757-1626-1-46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494987PMC
July 2008
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