Publications by authors named "Ania Nieszkowska"

39 Publications

Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Thromb Haemost 2021 Aug 15;121(8):1031-1042. Epub 2021 Jun 15.

Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2,  < 0.01) and fibrin formation markers (fibrin monomers,  < 0.001) significantly increased, further resulting in significant decreases in platelet count ( < 0.0001) and fibrinogen level ( < 0.001). PAI-1 levels significantly decreased from baseline to day 7 ( < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.
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http://dx.doi.org/10.1055/a-1529-2257DOI Listing
August 2021

Early Bacterial Identification Among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Cohort Study.

Am J Respir Crit Care Med 2021 May 26. Epub 2021 May 26.

Hôpital Pellegrin-Tripode , Service de Reanimation , Bordeaux, France.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines.

Objective: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes.

Methods: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test.

Measurements And Main Results: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients.

Conclusions: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1164/rccm.202101-0030OCDOI Listing
May 2021

Arrhythmia-induced cardiomyopathy: A potentially reversible cause of refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.

Heart Rhythm 2021 Jul 12;18(7):1106-1112. Epub 2021 Mar 12.

Service de Médecine Intensive Réanimation, Institute of Cardiology, Pierre et Marie Curie Sorbonne Université, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; UPMC Université Paris 06, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.

Background: The most severe form of arrhythmia-induced cardiomyopathy in adults- refractory cardiogenic shock requiring mechanical circulatory support-has rarely been reported.

Objective: The purpose of this study was to describe the management of critically ill patients admitted for acute, nonischemic, or worsening of previously known cardiac dysfunction and recent-onset supraventricular arrhythmia who developed refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Methods: This study is a retrospective analysis of prospectively collected data.

Results: Between 2004 and 2018, 35 patients received VA-ECMO for acute, nonischemic cardiogenic shock and recent supraventricular arrhythmia (77% atrial fibrillation [AF]). Cardiogenic shock was the first disease manifestation in 21 patients (60%). Characteristics at ECMO implantation [median (interquartile range)] were Sequential Organ Failure Assessment score 10 (7-13); inotrope score 29 (11-80); left ventricular ejection (LVEF) fraction 10% (10%-15%); and lactate level 8 (4-11) mmol/L. For 12 patients, amiodarone and/or electric cardioversion successfully reduced arrhythmia, improved LVEF, and enabled weaning off VA-ECMO; 11 had long-term survival without transplantation or long-term assist device. Eight patients experiencing arrhythmia-reduction failure underwent ablation procedures (7 atrioventricular node [AVN] with pacing, 1 atrial tachycardia) and were weaned off VA-ECMO; 7 survived. Of the remaining 15 patients without arrhythmia reduction or ablation, only the 6 bridged to heart transplantation or left ventricular (LV) assist device survived.

Conclusion: Arrhythmia-induced cardiomyopathy, mainly AF-related, is an underrecognized cause of refractory cardiogenic shock and should be considered in patients with nonischemic cardiogenic shock and recent-onset supraventricular arrhythmia. VA-ECMO support allowed safe arrhythmia reduction or rate control by AVN ablation while awaiting recovery, even among those with severe LV dilation.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.014DOI Listing
July 2021

Outcomes of severe systemic rheumatic disease patients requiring extracorporeal membrane oxygenation.

Ann Intensive Care 2021 Feb 9;11(1):29. Epub 2021 Feb 9.

Service de Médecine Intensive-Réanimation, Hôpital La Pitié-Salpêtrière, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.

Background: Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can require intensive care unit (ICU) admission because of multiorgan involvement with end-organ failure(s). Critically ill SRD patients requiring extracorporeal membrane oxygenation (ECMO) were studied to gain insight into their characteristics and outcomes.

Methods: This French monocenter, retrospective study included all SRD patients requiring venovenous (VV)- or venoarterial (VA)-ECMO admitted to a 26-bed ECMO-dedicated ICU from January 2006 to February 2020. The primary endpoint was in-hospital mortality.

Results: Ninety patients (male/female ratio: 0.5; mean age at admission: 41.6 ± 15.2 years) admitted to the ICU received VA/VV-ECMO, respectively, for an SRD-related flare (n = 69, n = 38/31) or infection (n = 21, n = 10/11). SRD was diagnosed in-ICU for 31 (34.4%) patients. In-ICU and in-hospital mortality rates were 48.9 and 51.1%, respectively. Nine patients were bridged to cardiac (n = 5) or lung transplantation (n = 4), or left ventricular assist device (n = 2). The Cox multivariable model retained the following independent predictors of in-hospital mortality: in-ICU SRD diagnosis, day-0 Simplified Acute Physiology Score (SAPS) II score ≥ 70 and arterial lactate ≥ 7.5 mmol/L for VA-ECMO-treated patients; diagnosis other than vasculitis, day-0 SAPS II score ≥ 70, ventilator-associated pneumonia and arterial lactate ≥ 7.5 mmol/L for VV-ECMO-treated patients.

Conclusions: ECMO support is a relevant rescue technique for critically ill SRD patients, with 49% survival at hospital discharge. Vasculitis was independently associated with favorable outcomes of VV-ECMO-treated patients. Further studies are needed to specify the role of ECMO for SRD patients.
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http://dx.doi.org/10.1186/s13613-021-00819-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871308PMC
February 2021

Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study.

Ann Intensive Care 2020 Nov 23;10(1):158. Epub 2020 Nov 23.

Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Assistance Publique-Hôpitaux de Paris (APHP), Sorbonne-Université, Groupe Hospitalier Pitié-Salpêtrière, 47-83, Boulevard de L'Hôpital, 75651, Paris Cedex 13, France.

Background: The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons.

Results: Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42-56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8-16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups.

Conclusions: Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.
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http://dx.doi.org/10.1186/s13613-020-00775-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682692PMC
November 2020

Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19-Associated Coagulopathy: Insights From a Prospective, Single-Center Cohort Study.

Circulation 2020 08 17;142(6):611-614. Epub 2020 Jun 17.

Medical Intensive Care Unit (P.M., G.H., J.C., C.D., M.P.D.C., A.N., N.B., M.S., C.E.L., A.C.), Department of Hematology (M.L., I.M.-T., C.F.), and Cardiothoracic Surgery Department (G.L.), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, France. Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France (G.H., G.L., M.S., C.E.L., A.C., C.F.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418760PMC
August 2020

Prone positioning monitored by electrical impedance tomography in patients with severe acute respiratory distress syndrome on veno-venous ECMO.

Ann Intensive Care 2020 Feb 3;10(1):12. Epub 2020 Feb 3.

INSERM, UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Universités, UPMC Univ Paris 06, 75651, Paris Cedex 13, France.

Background: Prone positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated. Our objectives were to describe, through electrical impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level.

Methods: A monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmHO driving pressure and EIT-based "optimal PEEP". Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VT/VT ratio, end-expiratory lung impedance (EELI) and static compliance were collected. Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmHO after 16 h of PP.

Results: For all patients (n = 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP. EIT-based optimal PEEP was significantly lower in PP than in supine position. Median (IQR) optimal PEEP decreased from 14 (12-16) to 10 (8-14) cmHO. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmHO after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VT/VT ratio than patients with compliance ≤ 3 mL/cmHO (P < 0.01).

Conclusion: Although baseline tidal volume distribution on EIT may predict static compliance improvement after PP on ECMO, our results support physiological benefits of PP in all ECMO patients, by modifying lung mechanics and potentially reducing VILI. Further studies, including a randomized-controlled trial, are now warranted to confirm potential PP benefits during ECMO.
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http://dx.doi.org/10.1186/s13613-020-0633-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997307PMC
February 2020

Microcirculation Evolution in Patients on Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock.

Crit Care Med 2020 01;48(1):e9-e17

Sorbonne Universités, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, 75651 Paris Cedex 13, France.

Objectives: Despite the increasing use of venoarterial extracorporeal membrane oxygenation to treat severe cardiogenic shock patients, microcirculation data in this context are scarce. We evaluated the venoarterial extracorporeal membrane oxygenation impact on macrocirculatory hemodynamics and microcirculation in patients with refractory cardiogenic shock and compared the evolutions of those parameters between patients successfully weaned-off extracorporeal membrane oxygenation and those who died on extracorporeal membrane oxygenation.

Design: Prospective study.

Setting: Academic medical ICU.

Patients: Consecutive patients with refractory cardiogenic shock (cardiac arrest excluded) who required venoarterial extracorporeal membrane oxygenation and for whom sublingual microcirculation measurements before cannulation were possible.

Interventions: All patients were followed until death or venoarterial extracorporeal membrane oxygenation removal. Microcirculatory and macrocirculatory evaluations were made before, and 2, 4, 12, 24, and 48 hours after extracorporeal membrane oxygenation initiation, respectively. Patients weaned-off extracorporeal membrane oxygenation were also evaluated 6 hours before and after venoarterial extracorporeal membrane oxygenation removal.

Measurements And Main Results: Fourteen patients (median age, 58 yr [interquartile range, 56-62 yr]; Sequential Organ Failure Assessment score, 14 [12-18]) were included. Acute myocardial infarction (50%) was the main cause of cardiogenic shock. Six patients (33%) were successfully weaned-off extracorporeal membrane oxygenation. Profound microcirculation parameter changes found before venoarterial extracorporeal membrane oxygenation implantation regressed within 12 hours after extracorporeal membrane oxygenation onset. Pre-extracorporeal membrane oxygenation macrocirculation, echocardiography, arterial blood gases, and microcirculation parameters did not differ between patients who died on extracorporeal membrane oxygenation and those successfully weaned. However, perfused small-vessel density, small-vessel density, and percent perfused vessels were consistently higher and then stabilized 48 hours postcannulation for patients successfully weaned-off extracorporeal membrane oxygenation.

Conclusions: Microcirculation is severely impaired in patients with refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. Inability to rapidly restore microcirculation during the first 24 hours, despite normal global/macrocirculatory hemodynamics, was associated with death on extracorporeal membrane oxygenation. Further studies are now warranted to better determine the relevant microcirculation determinants during venoarterial extracorporeal membrane oxygenation support, before future routine use of this promising tool in clinical practice.
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http://dx.doi.org/10.1097/CCM.0000000000004072DOI Listing
January 2020

Transvenous Renal Biopsy of Critically Ill Patients: Safety and Diagnostic Yield.

Crit Care Med 2019 03;47(3):386-392

Service de Médecine Intensive Réanimation, Institut de Cardiométabolisme et Nutrition (iCAN), Hôpital La Pitié-Salpêtrière, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.

Objectives: Transvenous renal biopsy is an alternative way to obtain kidney samples from patients with bleeding risk factors (e.g., antiplatelet therapy and anticoagulation or coagulation disorders). This study was undertaken to determine the safety and diagnostic yield of transvenous renal biopsy of critically ill patients.

Design: Monocenter, retrospective, observational cohort study.

Setting: A 26-bed French tertiary ICU.

Patients: All patients undergoing in-ICU transvenous renal biopsy between January 2002 and February 2018.

Interventions: None.

Measurements And Main Results: Eighty patients (male/female sex ratio, 0.95; mean ± SD age, 47.3 ± 18.3 yr) were included. A histologic diagnosis was obtained for 77 patients (96.3%), with acute tubular necrosis being the most frequent: 23 (29.9%). A potentially treatable cause was found for 47 patients (58.7%). The numbers of patients with 0, 1, 2, or 3 factors (i.e., antiplatelet therapy, thrombopenia [< 150 G/L], and preventive or curative anticoagulation) at the time of the biopsy were, respectively: seven (8.8%), 37 (46.2%), 31 (38.7%), and five (6.3%). Four (5%) and two (2.5%) patients, respectively, had renal hematoma and macroscopic hematuria; none required any specific treatment. Six patients (7.5%) died in-ICU, and 90-day mortality was 8 of 80 (10%). No death was related to transvenous renal biopsy, and median biopsy-to-death interval was 38 days (interquartile range, 19.7-86 d).

Conclusions: Based on this cohort of ICU patients with acute kidney injury, transvenous renal biopsy was safe and obtained a high diagnostic yield for these selected critically ill patients, even in the presence of multiple bleeding risk factors.
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http://dx.doi.org/10.1097/CCM.0000000000003634DOI Listing
March 2019

Ischemic and hemorrhagic brain injury during venoarterial-extracorporeal membrane oxygenation.

Ann Intensive Care 2018 Dec 20;8(1):129. Epub 2018 Dec 20.

Service de Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47, boulevard de l'Hôpital, 75013, Paris, France.

Background: Structural neurological complications (ischemic stroke and intracranial bleeding) and their risk factors in patients receiving venoarterial-extracorporeal membrane oxygenation (VA-ECMO) are poorly described. Our objective was to describe frequencies, outcomes and risk factors for neurological complications (ischemic stroke and intracranial bleeding) in patients receiving VA-ECMO.

Methods: Retrospective observational study conducted, from 2006 to 2014, in a tertiary referral center on patients who developed a neurological complication(s) on VA-ECMO.

Results: Among 878 VA-ECMO-treated patients, 65 (7.4%) developed an ECMO-related brain injury: 42 (5.3%) ischemic strokes and 20 (2.8%) intracranial bleeding, occurring after a median [25th;75th percentile] of 11 [6;18] and 5 [2;9] days of support, respectively. Intracranial bleeding but not ischemic stroke was associated with higher mortality. Multivariable analysis retained only platelet level > 350 giga/L as being associated with ischemic stroke. Female sex, central VA-ECMO and platelets < 100 giga/L at ECMO start were independently associated with intracranial bleeding with respective odds ratios [95% CI] of 2.9 [1.1-7.5], 3.8 [1.1-10.2] and 3.7 [1.4-9.7]. In a nested case-control study, rapid CO-level change from before-to-after ECMO start also seemed to be associated with intracranial bleeding.

Conclusions: Neurological events are frequent in VA-ECMO-treated patients. Ischemic stroke is the most frequent, occurs after 1 week on ECMO support, has no specific risk factor and is not associated with higher mortality. Intracranial bleeding occurs earlier and is associated with female sex, central VA-ECMO, low platelet count and rapid CO change at ECMO start, and high mortality.

Level Of Evidence: This study provides Class IV evidence that central VA-ECMO, low platelet count and rapid CO change at ECMO start are associated with intracranial bleeding and high mortality.
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http://dx.doi.org/10.1186/s13613-018-0475-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301905PMC
December 2018

Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation.

Crit Care 2018 08 19;22(1):199. Epub 2018 Aug 19.

Medical Intensive Care Unit, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne University , Paris 6, 47, bd de l'Hôpital, 75651, Paris Cedex 13, France.

Background: Amikacin infusion requires targeting a peak serum concentration (C) 8-10 times the minimal inhibitory concentration, corresponding to a C of 60-80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin C in critically ill patients on ECMO and to identify relative risk factors.

Methods: This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and C was measured 30 min after the end of the infusion. Independent predicators of C < 60 mg/L after the first amikacin infusion were identified with mixed-model multivariable analyses. Various dosing simulations were performed to assess the probability of reaching 60 mg/L < C < 80 mg/L.

Results: A total of 106 patients on venoarterial ECMO (VA-ECMO) (68%) or venovenous-ECMO (32%) were included. At inclusion, their median (1st; 3rd quartile) Sequential Organ-Failure Assessment score was 15 (12; 18) and 54 patients (51%) were on renal replacement therapy. Overall ICU mortality was 54%. C was < 60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI) < 22 kg/m and a positive 24-h fluid balance. Using dosing simulation, increasing the amikacin dosing regimen to 30 mg/kg and 35 mg/kg of body weight when the 24-h fluid balance is positive and the BMI is ≥ 22 kg/m or < 22 kg/m (Table 3), respectively, would have potentially led to the therapeutic target being reached in 42% of patients while reducing under-dosing to 23% of patients.

Conclusions: ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated.
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http://dx.doi.org/10.1186/s13054-018-2122-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098833PMC
August 2018

When the heart gets the flu: Fulminant influenza B myocarditis: A case-series report and review of the literature.

J Crit Care 2018 10 9;47:61-64. Epub 2018 Jun 9.

Département de Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Pierre et Marie Curie (UPMC), Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, France.

Purpose: To describe patients with refractory cardiogenic shock related to influenza B virus myocarditis rescued by venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO).

Material And Methods: Consecutive patients hospitalized in our unit for influenza-associated myocarditis were prospectively included. We also conducted a systematic MEDLINE database literature review through the PubMed search engine, between 1946 and 2017.

Results: We report the cases of 4 young patients with fulminant myocarditis requiring VA-ECMO for 6 [5-8] days. Influenza B virus was detected in all patients, either in nasopharyngeal sampling or bronchoalveolar lavage fluid. The 4 patients received oseltamivir. Heart function recovery allowed ECMO device removal without cardiac sequelae in all 4 patients. Systematic review retrieved 184 cases of influenza-associated myocarditis, most cases associated with H1N1 type-A infection during the 2009 pandemic. Forty eight cases of influenza myocarditis-associated cardiogenic shock requiring mechanical circulatory support including 3 cases due to influenza B virus were described. Mean duration of mechanical circulatory support was 8.5 ± 6 days and mortality rate was 33%.

Conclusions: Influenza myocarditis is a rare but reversible cause of cardiogenic shock amenable to VA-ECMO rescue. Early antiviral therapy and ECMO support should be considered for patients with fulminant myocarditis during an influenza epidemic.
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http://dx.doi.org/10.1016/j.jcrc.2018.06.001DOI Listing
October 2018

Co-infection with influenza-associated acute respiratory distress syndrome requiring extracorporeal membrane oxygenation.

Int J Antimicrob Agents 2018 Mar 21;51(3):427-433. Epub 2017 Nov 21.

Service de Réanimation, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS-1166, ICAN Institute of Cardiometabolism and Nutrition, Paris, France. Electronic address:

The co-infection frequency and impact among influenza-associated acute respiratory distress syndrome (ARDS) patients requiring extracorporeal membrane oxygenation (ECMO) are not known. This retrospective observational analysis concerned data prospectively collected from patients admitted to our medical intensive care unit (ICU) who received ECMO support for influenza-associated ARDS between 2009-2016. Co-infection was defined as occurring within 48 h following ICU admission. Among the 77 ARDS patients requiring ECMO support, 39 (51%) developed co-infections, with Staphylococcus aureus [18 (46%) of the co-infected patients] being the most prevalent pathogen. Panton-Valentin leukocidin (PVL)-producing S. aureus was isolated from 10 patients (56% of S. aureus co-infections and 26% of all co-infections). Co-infected patients were comparable with those without co-infection, except for BMI, initial disease severity and antibiotic treatment prior to admission. Co-infection was associated with higher in-ICU mortality (62% vs. 29%; P = 0.006) and with fewer ECMO-free days [median (IQR) 0 (0-19) vs. 23 (0-46); P = 0.004] and fewer mechanical ventilation-free days [0 (0-0) vs. 6 (0-35); P = 0.003] on Day 60. Multivariable analysis retained age >49 years, pre-ECMO Simplified Acute Physiology Score (SAPS) II score >70 and co-infection as independent predictors of hospital mortality. In conclusion, co-infection is frequent in ECMO-treated patients with influenza-associated ARDS, affecting ca. 50%, and is independently associated with poor outcome. Staphylococcus aureus was the most frequently identified pathogen, with a high rate of PVL-positive S. aureus. Whether specific therapy targeting PVL-producing S. aureus should be given remains to be determined.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.11.005DOI Listing
March 2018

Extracorporeal Membrane Oxygenation for Acute Decompensated Heart Failure.

Crit Care Med 2017 Aug;45(8):1359-1366

1Service de Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.2Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, France.3Service de Chirurgie Thoracique et Cardiovasculaire, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objective: Long-term outcomes of patients treated with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure (i.e., cardiogenic shock complicating chronic cardiomyopathy) have not yet been reported. This study was undertaken to describe their outcomes and determine mortality-associated factors.

Design: Retrospective analysis of data prospectively collected.

Setting: Twenty-six-bed tertiary hospital ICU.

Patients: One hundred five patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure.

Intervention: None.

Measurements And Main Results: From March 2007 to January 2015, 105 patients were implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure in our ICU (67% of them had an intraaortic balloon pump to unload the left ventricle). Their 1-year survival rate was 42%; most of the survivors were transplanted either directly or after switching to central bilateral centrifugal pump, ventricular-assist device, or total artificial heart. Most deaths occurred early after multiple organ failure. Multivariable analyses retained (odds ratio [95% CI]) pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment score of more than 11 (3.3 [1.3-8.3]), idiopathic cardiomyopathy (0.4 [0.2-1]), cardiac disease duration greater than 2 years pre-extracorporeal membrane oxygenation (2.8 [1.2-6.9]), and pre-extracorporeal membrane oxygenation blood lactate greater than 4 mmol/L (2.6 [1.03-6.4]) as independent predictors of 1-year mortality. Only 17% of patients with pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of 14 or more survived, whereas 52% of those with scores less than 7 and 60% of those with scores 7 or more and less than 11 were alive 1 year later.

Conclusions: Among this selected cohort of 105 patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure, 1-year survival was 42%, but better for patients with pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of less than 11. Venoarterial-extracorporeal membrane oxygenation should be considered for patients with acute decompensated heart failure, but timing of implantation is crucial.
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http://dx.doi.org/10.1097/CCM.0000000000002485DOI Listing
August 2017

Life-threatening massive pulmonary embolism rescued by venoarterial-extracorporeal membrane oxygenation.

Crit Care 2017 Mar 28;21(1):76. Epub 2017 Mar 28.

Medical Intensive Care Unit, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre-et-Marie-Curie, Paris 6, 47, bd de l'Hôpital, 75651, Paris Cedex 13, France.

Background: Despite quick implementation of reperfusion therapies, a few patients with high-risk, acute, massive, pulmonary embolism (PE) remain highly hemodynamically unstable. Others have absolute contraindication to receive reperfusion therapies. Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) might lower their right ventricular overload, improve hemodynamic status, and restore tissue oxygenation.

Methods: ECMO-related complications and 90-day mortality were analyzed for 17 highly unstable, ECMO-treated, massive PE patients admitted to a tertiary-care center (2006-2015). Hospital- discharge survivors were assessed for long-term health-related quality of life. A systematic review of this topic was also conducted.

Results: Seventeen high-risk PE patients [median age 51 (range 18-70) years, Simplified Acute Physiology Score II (SAPS II) 78 (45-95)] were placed on VA-ECMO for 4 (1-12) days. Among 15 (82%) patients with pre-ECMO cardiac arrest, seven (41%) were cannulated during cardiopulmonary resuscitation, and eight (47%) underwent pre-ECMO thrombolysis. Pre-ECMO median blood pressure, pH, and blood lactate were, respectively: 42 (0-106) mmHg, 6.99 (6.54-7.37) and 13 (4-19) mmol/L. Ninety-day survival was 47%. Fifteen (88%) patients suffered in-ICU severe hemorrhages with no impact on survival. Like other ECMO-treated patients, ours reported limitations of all physical domains but preserved mental health 19 (4-69) months post-ICU discharge.

Conclusions: VA-ECMO could be a lifesaving rescue therapy for patients with high-risk, acute, massive PE when thrombolytic therapy fails or the patient is too sick to benefit from surgical thrombectomy. Because heparin-induced clot dissolution and spontaneous fibrinolysis allows ECMO weaning within several days, future studies should investigate whether VA-ECMO should be the sole therapy or completed by additional mechanical clot-removal therapies in this setting.
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http://dx.doi.org/10.1186/s13054-017-1655-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369216PMC
March 2017

Bedside Contribution of Electrical Impedance Tomography to Setting Positive End-Expiratory Pressure for Extracorporeal Membrane Oxygenation-treated Patients with Severe Acute Respiratory Distress Syndrome.

Am J Respir Crit Care Med 2017 08;196(4):447-457

1 INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Université Pierre et Marie Curie Univ Paris 06, Paris, France; and.

Rationale: Optimal positive end-expiratory pressure (PEEP) is unknown in patients with severe acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation receiving mechanical ventilation with very low tidal volume.

Objectives: To evaluate the ability of electrical impedance tomography (EIT) to monitor a PEEP trial and to derive from EIT the best compromise PEEP in this setting.

Methods: A decremental PEEP trial (20-0 cm HO) in 5 cm HO steps was monitored by EIT, with lung images divided into four ventral-to-dorsal horizontal regions of interest. The EIT-based PEEP providing the best compromise between overdistention and collapsed zones was arbitrarily defined as the lowest pressure able to limit EIT-assessed collapse to less than or equal to 15% with the least overdistention. Driving pressure was maintained constant at 14 cm HO in pressure controlled mode.

Measurements And Main Results: Tidal volume, static compliance, tidal impedance variation, end-expiratory lung impedance, and their respective regional distributions were visualized at each PEEP level in 15 patients on extracorporeal membrane oxygenation. Low tidal volume (2.9-4 ml/kg ideal body weight) and poor compliance (12.1-18.7 ml/cm HO) were noted, with significantly higher tidal volume and compliance at PEEP and PEEP than PEEP. EIT-based best compromise PEEPs were 15, 10, and 5 cm HO for seven, six, and two patients, respectively, whereas PEEP and PEEP were never selected.

Conclusions: The broad variability in optimal PEEP observed in these patients with severe ARDS under extracorporeal membrane oxygenation reinforces the need for personalized titration of ventilation settings. EIT may be an interesting noninvasive bedside tool to provide real-time monitoring of the PEEP impact in these patients.
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http://dx.doi.org/10.1164/rccm.201605-1055OCDOI Listing
August 2017

Brain injury during venovenous extracorporeal membrane oxygenation.

Intensive Care Med 2016 May 23;42(5):897-907. Epub 2016 Mar 23.

Service de Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.

Purpose: The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk factors, and impact of cerebral complications occurring in VV-ECMO patients.

Methods: Observational study conducted in a tertiary referral center (2006-2012) on patients developing a neurological complication (ischemic stroke or intracranial bleeding) while on VV-ECMO versus those who did not, and a systematic review on this topic.

Results: Among 135 consecutive patients who had received VV-ECMO, 18 (15 assessable) developed cerebral complications on ECMO: cerebral bleeding in 10 (7.5 %), ischemic stroke in 3 (2 %), or diffuse microbleeds in 2 (2 %), occurring after respective medians (IQR) of 3 (1-11), 21 (10-26), and 36 (8-63) days post-ECMO onset. Intracranial bleeding was independently associated with renal failure at intensive care unit admission and rapid PaCO2 decrease at ECMO initiation, but not with age, comorbidities, or hemostasis disorders. Seven (70 %) patients with intracranial bleeding and one (33 %) with ischemic stroke died versus 40 % of patients without neurological event. A systematic review found comparable intracranial bleeding rates (5 %).

Conclusions: Neurological events occurred frequently in patients on VV-ECMO. Intracranial bleeding, the most frequent, occurred early and was associated with higher mortality. Because it was independently associated with rapid hypercapnia decrease, the latter should be avoided at ECMO onset, but its exact role remains to be determined. These findings may have major implications for the care of patients requiring VV-ECMO.
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http://dx.doi.org/10.1007/s00134-016-4318-3DOI Listing
May 2016

Mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study.

Crit Care Med 2015 Mar;43(3):654-64

1Department of Epidemiology and Preventive Medicine, Australian and New Zealand Intensive Care Research Centre, School of Public Health, Monash University, Melbourne, VIC, Australia. 2Medical-Surgical Intensive Care Unit, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 3Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, Australia. 4Sydney University Medical School, The University of Sydney, Sydney, NSW, Australia. 5Intensive Care Department, Alfred Hospital, Melbourne, VIC, Australia.

Objective: To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality.

Design: Retrospective observational study.

Setting: Three international high-volume extracorporeal membrane oxygenation centers.

Patients: A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013.

Interventions: We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model.

Measurement And Main Results: We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6-18 d) and 28 days (16-42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64-0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support.

Conclusions: Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.
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http://dx.doi.org/10.1097/CCM.0000000000000753DOI Listing
March 2015

The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.

Intensive Care Med 2013 Oct 2;39(10):1704-13. Epub 2013 Aug 2.

Medical-Surgical Intensive Care Unit, iCAN, Institute of Cardiometabolism and Nutrition, Service de Réanimation Médicale, Groupe Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris 6, 47, bd de l'Hôpital, 75651, Paris CEDEX 13, France.

Purpose: This study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors' health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.

Methods: Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008-2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.

Results: Main ARDS etiologies were bacterial (45%), influenza A[H₁N₁] (26%) and post-operative (17%) pneumonias. Six months post-ICU discharge, 84 (60%) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0-14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16% for PRESERVE classes 0-2, 3-4, 5-6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80% of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16%, respectively.

Conclusions: The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.
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http://dx.doi.org/10.1007/s00134-013-3037-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094902PMC
October 2013

Growth-arrest-specific 6 (GAS6) protein in ARDS patients: determination of plasma levels and influence of PEEP setting.

Respir Care 2013 Nov 9;58(11):1886-91. Epub 2013 Apr 9.

Service de Réanimation Médicale, Hôpital Européen Georges Pompidou, Paris, France.

Background: Growth-arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein expressed by endothelial cells and leukocytes participating in cell survival, migration and proliferation and involved in many pathological situations. The aim of our study was to assess its implication in ARDS and its variation according to PEEP setting, considering that different cyclic stresses could alter GAS6 plasma levels.

Methods: Our subjects were enrolled in the ExPress study comparing a minimal alveolar distention (low-PEEP) ventilatory strategy to a maximal alveolar recruitment (high-PEEP) strategy in ARDS. Plasma GAS6, interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) levels were measured at day 0 and day 3 by enzyme-linked immunosorbent assay in blood samples prospectively collected during the study for a subset of 52 subjects included in 8 centers during year 2005.

Results: We found that GAS6 plasma level was elevated in the whole population at day 0: median 106 ng/mL IQR 77-139 ng/mL, with significant correlations with IL-8, the Simplified Acute Physiology Score II and the Organ Dysfunction and Infection scores. Statistically significant decreases in GAS6 and IL-8 plasma levels were observed between day 0 and day 3 in the high-PEEP group (P = .02); while there were no differences between day 0 and day 3 in the low-PEEP group.

Conclusions: GAS6 plasma level is elevated in ARDS patients. The high-PEEP strategy is associated with a decrease in GAS6 and IL-8 plasma levels at day 3, without significant differences in day 28 mortality between the 2 groups. (Clinicaltrials.gov NCT00188058).
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http://dx.doi.org/10.4187/respcare.02129DOI Listing
November 2013

Impact of extracorporeal membrane oxygenation and continuous venovenous hemodiafiltration on the pharmacokinetics of oseltamivir carboxylate in critically ill patients with pandemic (H1N1) influenza.

Ther Drug Monit 2012 Apr;34(2):171-5

Pharmacy Department, Pitie-Salpetriere Hospital, Assistance Publique des Hôpitaux de Paris, AP-HP, Paris, France.

Purpose: The neuraminidase inhibitor oseltamivir is a recommended treatment for influenza A (H1N1) infection. In rare cases, some patients develop influenza-associated multiple organ failures, requiring rescue therapies such as extracorporeal membrane oxygenation (ECMO) or continuous venovenous hemodiafiltration (CVVHDF). This study was designed to evaluate the impact of ECMO and CVVHDF on the pharmacokinetics of oseltamivir carboxylate (OC) in critically ill patients with pandemic (H1N1) influenza treated with oseltamivir.

Patients And Methods: Seven critically ill patients on venovenous ECMO for severe pandemic (H1N1) influenza associated with acute respiratory distress syndrome were treated with various doses of oseltamivir (75 or 150 mg twice daily). Because of acute kidney injury, 3 of them also received CVVHDF. OC, the active form of oseltamivir, was quantified in plasma, and main pharmacokinetic parameters were determined.

Results: OC Cmax (1029 ± 478 ng/mL) and area under the curve (9.00 ± 4.52 mcg·h/mL) for patients on ECMO with preserved renal function were comparable with those of healthy volunteers or noncritically ill patients. Patients both on ECMO and CVVHDF had 4-to 5-fold higher OC Cmax and area under the curve.

Conclusions: ECMO by itself did not impact on the pharmacokinetics of OC. However, the drug accumulated in the plasma of patients on ECMO who also received CVVHDF for renal failure. Based on these results, we recommend that oseltamivir dosage should be decreased and plasma levels of OC be monitored in patients receiving CVVHDF because of acute kidney injury.
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http://dx.doi.org/10.1097/FTD.0b013e318248672cDOI Listing
April 2012

Virus-induced acute respiratory distress syndrome: epidemiology, management and outcome.

Presse Med 2011 Dec 16;40(12 Pt 2):e561-8. Epub 2011 Nov 16.

Assistance publique-Hôpitaux de Paris, université Paris-6-Pierre-et-Marie-Curie, institut de cardiologie, groupe hospitalier Pitié-Salpêtrière, service de réanimation médicale, 75651 Paris cedex 13, France.

The acute respiratory distress syndrome (ARDS) can be induced by viral diseases, with two virus types being responsible: respiratory viruses that cause community-acquired viral pneumonia and Herpesviridae that cause nosocomial viral pneumonia. Among the respiratory viruses that can affect the lung and cause ARDS, pandemic viruses head the list, with influenza viruses H5N1 and H1N1 2009 being the most recently identified. However, other viruses can cause severe ARDS. Notably, a novel coronavirus was responsible for the severe acute respiratory syndrome outbreak in 2003. Apart from these pandemic viruses, respiratory viruses are rarely responsible for viral pneumonia and ARDS. Other than antiviral drug (mainly oseltamivir) administration and avoidance of corticosteroids, management of ARDS due to these viruses does not differ from that for ARDS caused by other diseases. Among Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) are the two viruses causing nosocomial viral pneumonia that can evolve into ARDS. HSV is frequently recovered in the respiratory tract of mechanically ventilated patients and can sometimes be responsible for HSV bronchopneumonitis. Although not evaluated for this indication, acyclovir can be a therapeutic option for patients with HSV bronchopneumonitis and ARDS. CMV pneumonia can also occur in mechanically ventilated patients, but is difficult to diagnose because virus recovery does not necessarily mean viral disease. Ganciclovir can be considered for patients with ARDS and histology- or cytology-proven CMV pneumonia.
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http://dx.doi.org/10.1016/j.lpm.2011.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125714PMC
December 2011

Early percutaneous tracheotomy versus prolonged intubation of mechanically ventilated patients after cardiac surgery: a randomized trial.

Ann Intern Med 2011 Mar;154(6):373-83

Institut de Cardiologie, Hôpital de la Pitié-Salpêtriére, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale, Paris, France.

Background: Whether early percutaneous tracheotomy in patients who require prolonged mechanical ventilation can shorten mechanical ventilation duration and lower mortality remains controversial.

Objective: To compare the outcomes of severely ill patients who require prolonged mechanical ventilation randomly assigned to early percutaneous tracheotomy or prolonged intubation.

Design: Prospective, randomized, controlled, single-center trial (ClinicalTrials.gov registration number: NCT00347321).

Setting: Academic center.

Patients: 216 adults requiring mechanical ventilation 4 or more days after cardiac surgery.

Intervention: Immediate early percutaneous tracheotomy or prolonged intubation with tracheotomy 15 days after randomization.

Measurements: The primary end point was the number of ventilator-free days during the first 60 days after randomization. Secondary outcomes included 28-, 60-, or 90-day mortality rates; durations of mechanical ventilation, intensive care unit stay, and hospitalization; sedative, analgesic, and neuroleptic use; ventilator-associated pneumonia rate; unscheduled extubations; comfort and ease of care; and long-term health-related quality of life (HRQoL) and psychosocial evaluations.

Results: There was no difference in ventilator-free days during the first 60 days after randomization between early percutaneous tracheotomy and prolonged intubation groups (mean, 30.4 days [SD, 22.4] vs. 28.3 days [SD, 23.7], respectively; absolute difference, 2.1 days [95% CI, -4.1 to 8.3 days]) nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, and 30% vs. 30%, respectively). The durations of mechanical ventilation and hospitalization, as well as frequencies of ventilator-associated pneumonia and other severe infections, were also similar. However, early percutaneous tracheotomy was associated with less intravenous sedation; less time of heavy sedation; less haloperidol use for agitation, delirium, or both; fewer unscheduled extubations; better comfort and ease of care; and earlier resumption of oral nutrition. After a median follow-up of 873 days, between-group survival, psychosocial evaluations, and HRQoL were similar.

Limitation: The prolonged intubation group had more ventilator-free days during days 1 to 60 than what was hypothesized (mean, 23.0 days [SD, 17.0]).

Conclusion: Early tracheotomy provided no benefit in terms of mechanical ventilation and length of hospital stay, rates of mortality or infectious complications, and long-term HRQoL for patients who require prolonged mechanical ventilation after cardiac surgery. However, the well-tolerated procedure was associated with less sedation, better comfort, and earlier resumption of autonomy.

Primary Funding Source: French Ministry of Health.
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http://dx.doi.org/10.7326/0003-4819-154-6-201103150-00002DOI Listing
March 2011

Gender impact on the outcomes of critically ill patients with nosocomial infections.

Crit Care Med 2009 Sep;37(9):2506-11

Service de Réanimation Médicale, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.

Objectives: : To investigate gender impact on the outcomes of severe nosocomial infections (pneumonia, bacteremia, catheter-related bloodstream infections, poststernotomy mediastinitis, urinary infections) occurring in a large cohort of patients hospitalized in a medical-surgical intensive care unit. Highly controversial data exist regarding gender-related differences in outcomes of severe nosocomial infections, reflecting potential confounders related to case-mixes or heterogeneity of populations evaluated.

Design: : Retrospective study of patients admitted to our intensive care unit. Multivariable logistic regression-analysis was used to control for confounders in the evaluation of gender impact on intensive care unit death post nosocomial infections.

Setting: : An 18-bed tertiary referral medical-surgical intensive care unit in a teaching hospital.

Patients: : Mixed population of patients who developed nosocomial infections in the intensive care unit.

Measurements And Main Results: : Among the 5081 patients admitted to our intensive care unit from 1995 to 2004, 1341 (34% women) developed nosocomial infections. Pneumonia and mediastinitis were more frequent in men (51% vs. 44%, p = .01 and 29% vs. 22%, p = .01, respectively) whereas urinary infections predominated for women (46% vs. 24%, p < .001). Durations of mechanical ventilation and intensive care unit stays and treatment intensity did not differ between genders. However, intensive care unit mortality was higher for women (37% vs. 32%, p = .06) and this excess mortality was statistically significant (odds ratio = 1.50, 95% Confidence Interval = 1.11-2.03), after controlling for other independent risk factors of intensive care unit death. Compared with those observed for men of the same subgroup, crude ICU death rates were significantly higher for women who developed pneumonia, who were <50 yrs old or had undergone heart surgery before intensive care unit admission. However, multivariable analyses retained feminine gender as significantly associated with mortality only for the last subgroup.

Conclusions: : Female intensive care unit patients developing nosocomial infections seem to be at increased risk of intensive care unit mortality, after carefully controlling for other prognostic factors. Further studies are needed to elucidate the pathophysiology underlying this gender-related difference, to devise tailored gender-specific therapies that might improve outcomes.
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http://dx.doi.org/10.1097/CCM.0b013e3181a569dfDOI Listing
September 2009

Aerosolized antibiotics to treat ventilator-associated pneumonia.

Curr Opin Infect Dis 2009 Apr;22(2):154-8

Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, Paris Cedex 13, France.

Purpose Of Review: This review summarizes the recent data on antibiotic aerosolization to treat ventilator-associated pneumonia.

Recent Findings: Most studies on antibiotic aerosolization have been case reports or descriptive studies. The results of a recent randomized, placebo-controlled trial indicated that adjunctive use of nebulized antibiotic with intravenous antibiotics to treat purulent tracheobronchitis was associated with a better outcome than placebo aerosolization. A randomized study, so far published only as an abstract, showed that amikacin aerosolized with a vibrating-mesh nebulizer--a new-generation device--was well distributed in the lung parenchyma and might lead to less intravenous antibiotic use. Several thorough reviews on nebulization devices, techniques and drawbacks have been published recently.

Summary: Despite recent promising findings, the widespread use of aerosolized antibiotics to treat ventilator-associated pneumonia cannot be recommended. It should be restricted to the treatment of multidrug-resistant Gram-negative ventilator-associated pneumonia.
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http://dx.doi.org/10.1097/QCO.0b013e328322a006DOI Listing
April 2009

Viral infections in the ICU.

Curr Opin Crit Care 2008 Oct;14(5):605-8

Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, and Université Paris 6-Pierre et Marie Curie, France.

Purpose Of Review: The present study reviews the precise role of viruses as causes of pneumonia in mechanically ventilated patients.

Recent Findings: In patients requiring mechanical ventilation, Herpesviridae, mostly herpes simplex virus and cytomegalovirus, are commonly recovered from the respiratory tract. However, viral detection does not necessarily mean viral disease, and the exact role of viruses recovered in the respiratory tract is still being debated. Are they only benign colonizers activated in proportion to the severity of the underlying illness, or are they infectious agents with true attributable morbidity or mortality or both?

Summary: Respiratory viruses are responsible for 10% of community-acquired pneumonia cases but do not cause nosocomial pneumonia. Herpesviridae, mainly herpes simplex virus and cytomegalovirus, are commonly detected in the respiratory tract of nonimmunocompromised, mechanically ventilated patients. Although their detection usually reflects viral reactivation without lung parenchymal involvement, in a particular subset of patients, viral lung disease (bronchopneumonitis) occurs. This bronchopneumonitis seems to have a true impact on outcome, but only interventional studies will be able to determine its real impact. Whether other viruses, such as mimivirus, are responsible for nosocomial pneumonia in mechanically ventilated patients requires additional studies.
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http://dx.doi.org/10.1097/MCC.0b013e32830f1e12DOI Listing
October 2008

Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia.

Intensive Care Med 2008 Aug 18;34(8):1434-40. Epub 2008 Apr 18.

Service de Réanimation Médicale, Groupe Hospitalier Pitié Salpêtrière, Université Paris 6, 75651, Paris Cedex 13, France.

Objective: To assess the predictive capacity for the diagnosis of ventilator-associated pneumonia (VAP) of serum procalcitonin levels before and on the day it is suspected.

Design And Setting: Single-center observational study in the intensive care unit of a teaching hospital.

Patients And Participants: Consecutive patients whose serum procalcitonin levels were available on the day that VAP was clinically suspected (day 1) and at some time within the preceding 5 days ("before").

Measurements And Results: Serum procalcitonin levels were determined on day 1 and "before". Among the 73 suspected episodes VAP was confirmed by quantitative bronchoalveolar lavage cultures in 32 and refuted in 41. Respective median "before" procalcitonin levels were 1.89 ng/ml (interquartile range 0.18-6.01) and 2.14 (0.76-5.75) in patients with and without VAP, but their respective median day-1 procalcitonin levels did not differ: 1.07 ng/ml (0.39-6.57) vs. 1.40 (0.67-3.39). On day 1 a 0.5 ng/ml procalcitonin threshold had 72% sensitivity but only 24% specificity for diagnosing VAP. Between "before" and day 1, procalcitonin increased in 41% and 15% of patients with and without VAP, respectively. Thus a procalcitonin rise on day 1, compared to its "before" level, had 41% sensitivity and 85% specificity for diagnosing VAP, with respective positive and negative predictive values of 68% and 65%.

Conclusions: Crude values and procalcitonin rise had poor diagnostic value for VAP in this particular setting and thus should not be used to initiate antibiotics when VAP is clinically suspected.
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http://dx.doi.org/10.1007/s00134-008-1112-xDOI Listing
August 2008

Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.

JAMA 2008 Feb;299(6):646-55

Département de Réanimation Médicale et Médecine Hyperbare, CHU d'Angers, Angers, France.

Context: The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.

Objective: To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.

Design, Setting, And Patients: A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.

Intervention: Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385).

Main Outcome Measures: The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days.

Results: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.

Conclusions: A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.

Trial Registration: clinicaltrials.gov Identifier: NCT00188058.
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http://dx.doi.org/10.1001/jama.299.6.646DOI Listing
February 2008
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