Characteristics and outcomes of patients with postoperative Candida versus bacterial mediastinitis: a case-matched comparative study.

OBJECTIVES: Postoperative mediastinitis, a feared complication after cardiac surgery, is associated with high mortality, especially of critically ill patients. Candida species infections are rare and severe, with poorly known outcomes. We conducted a case-control study to describe the characteristics, management and outcomes of patients with postoperative Candida mediastinitis. METHODS: This French, monocentre, retrospective study included all patients with postoperative Candida mediastinitis (January 2003-February 2020) requiring intensive care unit admission. Candida mediastinitis patients (henceforth cases) were matched 1:1 with postoperative bacterial mediastinitis (henceforth control), based on 3 factors during mediastinitis management: age >40 years, cardiac transplantation and invasive circulatory device used. The primary end point was the probability of survival within 1 year after intensive care unit (ICU) admission. RESULTS: Forty cases were matched to 40 controls. The global male/female ratio was 2.1, with mean age at admission 47.9 ± 13.8 years. Candida species were: 67.5% albicans, 17.5% glabrata, 15% parapsilosis, 5.0% tropicalis, 2.5% krusei and 2.5% lusitaniae. The median duration of mechanical ventilation was 23, 68.8% of patients received renal replacement therapy and 62.5% extracorporeal membrane oxygenation support. The probability of survival within the first year after ICU admission was 40 ± 5.5% and was significantly lower for cases than for controls (43 ± 8% vs 80 ± 6.3%, respectively; Log-rank test: P < 0.0001). The multivariable Cox proportional hazards model retained only renal replacement therapy [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.1-13.1; P = 0.04] and Candida mediastinitis (HR 2.4, 95% CI 1.1-5.6; P = 0.04) as independently associated with 1-year mortality. CONCLUSIONS: Candida mediastinitis is a serious event after cardiac surgery and independently associated with 1-year mortality. Further studies are needed to determine whether deaths are directly attributable to Candida mediastinitis.

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

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/m2, 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, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 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.

Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 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 compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection 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, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).

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

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.

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

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.

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

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.

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

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-cmH2O driving pressure and EIT-based "optimal PEEP". Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VTdorsal/VTglobal 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/cmH2O 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) cmH2O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH2O after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VTdorsal/VTglobal ratio than patients with compliance ≤ 3 mL/cmH2O (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.

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

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.

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

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.

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

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 CO2-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 CO2 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 CO2 change at ECMO start are associated with intracranial bleeding and high mortality.

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

BACKGROUND: Amikacin infusion requires targeting a peak serum concentration (Cmax) 8-10 times the minimal inhibitory concentration, corresponding to a Cmax 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 Cmax 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 Cmax was measured 30 min after the end of the infusion. Independent predicators of Cmax < 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 < Cmax < 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%. Cmax was < 60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI) < 22 kg/m2 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/m2 or < 22 kg/m2 (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.

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

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 ±â€¯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.

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

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.

Extracorporeal Membrane Oxygenation for Acute Decompensated Heart Failure.

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.

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

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.

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

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 H2O) in 5 cm H2O 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 H2O 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 H2O) were noted, with significantly higher tidal volume and compliance at PEEP10 and PEEP5 than PEEP20. EIT-based best compromise PEEPs were 15, 10, and 5 cm H2O for seven, six, and two patients, respectively, whereas PEEP20 and PEEP0 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.

Brain injury during venovenous extracorporeal membrane oxygenation.

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.

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

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.