Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study.

BACKGROUND: Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. METHODS: Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes at 11 time points (from hour 0 up to day 7). Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was the antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin less than or equal to 70%. Data regarding clinical management and heparin dosage were collected. RESULTS: Fifty patients, including 42% postcardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4 to 12) days. Median antithrombin level was 48% (37 to 60%) at baseline. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63% (57 to 73%) and was less than or equal to 70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value less than 70%, and 35 (70%) had at least one antithrombin value less than 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. CONCLUSIONS: Venoarterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 h, that did not correlate with heparin responsiveness.

Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

BACKGROUND: Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. METHODS: For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. RESULTS: Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79-1.26], p = 0.986). CONCLUSIONS: In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020).

Impact of Intraoperative Allogeneic Platelet Transfusion on Healthcare-Associated Infections in Cardiac Surgery: Insights From a Large Single-Center Cohort Study.

OBJECTIVES: Despite significant improvement in patient blood management, cardiac surgery remains a high hemorrhagic risk procedure. Platelet transfusion is used commonly to treat thrombocytopenia-associated perioperative bleeding. Allogeneic platelet transfusion may induce transfusion-related immunomodulation. However, its association with postoperative healthcare-associated infections is still a matter of debate. The objective was to evaluate the impact of allogeneic platelet transfusion during cardiac surgery on postoperative healthcare-associated infection incidence. DESIGN: Retrospective cohort study. SETTING: Tertiary referral academic center. PARTICIPANTS: Patients undergoing cardiac surgery from 2012 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraoperative platelet transfusion was defined as exposure in a causal model. The primary outcome was the incidence of healthcare-associated infections comprised of bloodstream infection, hospital-acquired pneumonia, and surgical-site infection. Among 7,662 included patients, 528 patients (6.8%) were exposed to intraoperative platelet transfusion, and 329 patients (4.3%) developed 454 postoperative infections. Bloodstream infection affected 106 patients (1.4%), hospital-acquired pneumonia affected 174 patients (2.3%), and surgical-site infection affected 148 patients (1.9%). Intraoperative platelet transfusion was associated with an increased risk of bloodstream infection after adjustment by multivariable logistic regression (odds ratio [OR] 2.85; 95% CI 1.40-5.8; p = 0.004; n = 7,662), propensity score matching (OR 3.95; 95% CI 1.57-12.0), p = 0.007; n = 766), and propensity score overlap weighting (OR 3.04; 95% CI 1.51-6.1, p = 0.002; n = 7,762). Surgical-site infection and hospital-acquired pneumonia were not significantly associated with platelet transfusion. CONCLUSIONS: These results suggested that intraoperative allogeneic platelet transfusion is a risk factor for bloodstream infection after cardiac surgery. These results supported the development of patient blood management strategies aimed at minimizing perioperative platelet transfusion in cardiac surgery.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

Combined Platelet and Red Blood Cell Recovery during On-pump Cardiac Surgery Using same™ by i-SEP Autotransfusion Device: A First-in-human Noncomparative Study (i-TRANSEP Study).

BACKGROUND: Centrifugation-based autotransfusion devices only salvage red blood cells while platelets are removed. The same™ device (Smart Autotransfusion for ME; i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage both red blood cells and platelets. The authors tested the hypothesis that this new device could allow a red blood cell recovery exceeding 80% with a posttreatment hematocrit exceeding 40%, and would remove more than 90% of heparin and 75% of free hemoglobin. METHODS: Adults undergoing on-pump elective cardiac surgery were included in a noncomparative multicenter trial. The device was used intraoperatively to treat shed and residual cardiopulmonary bypass blood. The primary outcome was a composite of cell recovery performance, assessed in the device by red blood cell recovery and posttreatment hematocrit, and of biologic safety assessed in the device by the washout of heparin and free hemoglobin expressed as removal ratios. Secondary outcomes included platelet recovery and function and adverse events (clinical and device-related adverse events) up to 30 days after surgery. RESULTS: The study included 50 patients, of whom 18 (35%) underwent isolated coronary artery bypass graft, 26 (52%) valve surgery, and 6 (12%) aortic root surgery. The median red blood cell recovery per cycle was 86.1% (25th percentile to 75th percentile interquartile range, 80.8 to 91.6) with posttreatment hematocrit of 41.8% (39.7 to 44.2). Removal ratios for heparin and free hemoglobin were 98.9% (98.2 to 99.7) and 94.6% (92.7 to 96.6), respectively. No adverse device effect was reported. Median platelet recovery was 52.4% (44.2 to 60.1), with a posttreatment concentration of 116 (93 to 146) · 109/l. Platelet activation state and function, evaluated by flow cytometry, were found to be unaltered by the device. CONCLUSIONS: In this first-in-human study, the same™ device was able to simultaneously recover and wash both platelets and red blood cells. Compared with preclinical evaluations, the device achieved a higher platelet recovery of 52% with minimal platelet activation while maintaining platelet ability to be activated in vitro.

Post-cardiac surgery fungal mediastinitis: clinical features, pathogens and outcome.

OBJECTIVES: The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. METHODS: Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009-2019). RESULTS: Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17-61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43-65] vs. 65 [61-73] yo; p = 0.013), had lower body mass index (24 [20-26] vs. 30 [24-32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28-40] vs. 54 [34-61]; p = 0.012). CONCLUSION: Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.

Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

Outcome of Temporary Circulatory Support As a Bridge-to-Left Ventricular Assist Device Strategy in Cardiogenic Shock Patients.

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.

Diffusion of amoxicillin into heart valves from infective endocarditis patients.

OBJECTIVES: Amoxicillin is the drug of choice in the management of streptococcal and enterococcal infective endocarditis (IE) but little is known regarding amoxicillin diffusion into infected heart valves. Herein, we assessed amoxicillin valvular distribution and related pharmacokinetic/pharmacodynamic (PK/PD) target attainment in IE patients undergoing heart valve surgery. PATIENTS AND METHODS: In this 2-year prospective study, patients with IE treated by continuous infusion of amoxicillin and undergoing a surgical valve replacement were included. Both amoxicillin plasma and tissue concentrations were measured the day of surgery. Amoxicillin concentration in plasma and crushed heart valves were measured by a validated liquid chromatography method coupled with ultra-violet and tandem mass spectrometry, respectively. MIC and MBC of amoxicillin were determined for all available isolates. The rate of achievement of PK/PD efficacy parameters were assessed. RESULTS: Twenty-two heart valves were removed from 20 patients. Bacterial aetiology was streptococcal (n = 17) and enterococcal (n = 3). Amoxicillin mean daily dose was 12 ±â€Š3 g/24 h, mean plasma concentration was 29 ±â€Š21 mg/L (n = 15), mean tissue concentration was 23 ±â€Š15 mg/L (n = 22). Median diffusion rate was 62%. Patients reached a plasma concentration target >4XCMI (n = 13). Tissue concentrations were bactericidal for all streptococcal IE but not for enterococcal IE. CONCLUSIONS: Amoxicillin intravalvular measurements in IE treated patients showed significant penetration into the infectious site. These data are reassuring that in situ bactericidal concentrations can be largely achieved in the management of streptococcal IE and support the need for combination antibiotic therapy for enterococcal IE.

Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. RESULTS: Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.

The impact of iron store on red blood cell transfusion: a multicentre prospective cohort study in cardiac surgery.

BACKGROUND: Anaemia is common prior to cardiac surgery and contributes to perioperative morbidity. Iron deficiency is the main cause of anaemia but its impact remains controversial in the surgical setting. We aimed to estimate the impact of iron deficiency on in-hospital perioperative red blood cell transfusion for patients undergoing elective and urgent cardiac surgery. Secondary objectives were to identify risk factors associated with in-hospital red blood cell transfusion. METHODS: We conducted a prospective multicentre observational study in three university hospitals performing cardiac surgery. We determined iron status prior to surgery and collected all transfusion data to compare iron-deficient and iron-replete patients during hospital stay. We performed a multivariable logistic regression to compare transfusion among groups. RESULTS: Five hundred and two patients were included. A trend of low haemoglobin levels associated with iron deficiency persisted until discharge. Red blood cell transfusion was significantly higher in the group of iron deficient patients during surgery (22% vs 13%, p = 0.017), however the incidence during the whole hospital stay was 31% in the iron-deficient group, not significantly different with the non-deficient group (26%, p = 0.28). Iron deficiency was not independently associated with in-hospital red blood cell transfusion (adjusted OR = 0.85 [0.53-1.36], p = 0.49). CONCLUSIONS: In-hospital red blood cell transfusion was not significantly higher in iron-deficient patients and iron deficiency was not associated with in-hospital red blood cell transfusion in patients undergoing elective and urgent cardiac surgery. Iron deficiency was the main cause of anaemia and anaemia was a strong driver of red blood cell transfusion. Further studies should identify sub-population of iron-deficient patients which may benefit from preoperative iron deficiency management and explore the long-term impact of lower haemoglobin levels at discharge in the iron deficient population.

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

Combined Platelet and Erythrocyte Salvage: Evaluation of a New Filtration-based Autotransfusion Device.

BACKGROUND: The SAME device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage and wash both red blood cells and platelets. This study evaluated the device performances using human whole blood with the hypothesis that the device will be able to salvage platelets while achieving a erythrocyte yield of 80% and removal ratios of 90% for heparin and 80% for major plasma proteins without inducing signification activation of salvaged cells. METHODS: Thirty healthy human whole blood units (median volume, 478 ml) were diluted, heparinized, and processed by the device in two consecutive treatment cycles. Samples from the collection reservoir and the concentrated blood were analyzed. Complete blood count was performed to measure blood cell recovery rates. Flow cytometry evaluated the activation state and function of platelets and leukocytes. Heparin and plasma proteins were measured to assess washing performance. RESULTS: The global erythrocyte yield was 88.1% (84.1 to 91.1%; median [25th to 75th]) with posttreatment hematocrits of 48.9% (44.8 to 51.4%) and 51.4% (48.4 to 53.2%) for the first and second cycles, respectively. Ektacytometry did not show evidence of erythrocyte alteration. Platelet recovery was 36.8% (26.3 to 43.4%), with posttreatment counts of 88 × 109/l (73 to 101 × 109/l) and 115 × 109/l (95 to 135 × 109/l) for the first and second cycles, respectively. Recovered platelets showed a low basal P-selectin expression at 10.8% (8.1 to 15.2%) and a strong response to thrombin-activating peptide. Leukocyte yield was 93.0% (90.1 to 95.7%) with no activation or cell death. Global removal ratios were 98.3% (97.8 to 98.9%), 98.2% (96.9 to 98.8%), and 88.3% (86.6 to 90.7%) for heparin, albumin, and fibrinogen, respectively. The processing times were 4.4 min (4.2 to 4.6 min) and 4.4 min (4.2 to 4.7 min) for the first and second cycles, respectively. CONCLUSIONS: This study demonstrated the performance of the SAME device. Platelets and red blood cells were salvaged without significant impact on cell integrity and function. In the meantime, leukocytes were not activated, and the washing quality of the device prevented reinfusion of high concentrations of heparin and plasma proteins.

Venoarterial extracorporeal membrane oxygenation induces early immune alterations.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides heart mechanical support in critically ill patients with cardiogenic shock. Despite important progresses in the management of patients under VA-ECMO, acquired infections remain extremely frequent and increase mortality rate. Since immune dysfunctions have been described in both critically ill patients and after surgery with cardiopulmonary bypass, VA-ECMO initiation may be responsible for immune alterations that may expose patients to nosocomial infections (NI). Therefore, in this prospective study, we aimed to study immune alterations induced within the first days by VA-ECMO initiation. METHODS: We studied immune alterations induced by VA-ECMO initiation using cytometry analysis to characterize immune cell changes and enzyme-linked immunosorbent assay (ELISA) to explore plasma cytokine levels. To analyze specific changes induced by VA-ECMO initiation, nine patients under VA-ECMO (VA-ECMO patients) were compared to nine patients with cardiogenic shock (control patients). RESULTS: Baseline immune parameters were similar between the two groups. VA-ECMO was associated with a significant increase in circulating immature neutrophils with a significant decrease in C5a receptor expression. Furthermore, we found that VA-ECMO initiation was followed by lymphocyte dysfunction along with myeloid-derived suppressor cells (MDSC) expansion. ELISA analysis revealed that VA-ECMO initiation was followed by an increase in pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α along with IL-10, a highly immunosuppressive cytokine. CONCLUSION: VA-ECMO is associated with early immune changes that may be responsible for innate and adaptive immune alterations that could confer an increased risk of infection.

The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia.

Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

Association between perioperative normal saline and delayed graft function in deceased-donor kidney transplantation: a retrospective observational study.

PURPOSE: Isotonic 0.9% sodium chloride (normal saline; NS) solution use is common, but its high chloride content has been shown to contribute to acid-base disturbances and acute kidney injury (AKI). As kidney transplant recipients are at high risk of postoperative AKI and renal replacement therapy, we aimed to evaluate the impact of perioperative NS administration on graft function after kidney transplantation. METHODS: All adult patients undergoing deceased-donor kidney transplantation between January 2010 and December 2014 at the Rennes University Hospital were included. Logistic regression models were constructed to evaluate the association of hyperchloremia and hyperchloremic acidosis on delayed graft function (DGF), defined as the need for renal replacement therapy within the first week after transplantation. RESULTS: Three hundred and fifty-nine patients were included, 20% developed DGF. The mean (standard deviation) volume of NS infused in the operating room and in the standard postoperative intensive care unit stay was 4,832 (2,242) mL. In the first 24 postoperative hours, 11% of patients developed hyperchloremia and 11% developed hyperchloremic acidosis. These outcomes were not associated with significantly higher total volumes of NS administration or with DGF. In contrast, multivariable analysis showed that cold ischemia time, donor terminal creatinine, and perioperative NS volume were all independent predictors of DGF. CONCLUSION: Perioperative NS infusion volume was associated with DGF in deceased-donor kidney transplant recipients. Conversely, postoperative hyperchloremia and hyperchloremic acidosis were not associated with an increased risk of DGF, suggesting other mechanisms than a chloride effect.

An odyssey of suturing cardiac wounds: Lessons from the past.

BACKGROUND AND AIM OF THE STUDY: Cardiac wounds have been described for centuries and still remain to be fatal. For a long period of time, the suturing of a myocardial laceration was thought to be absolutely impossible if not sacrilege. METHODS: It is only at the end of the 19th century that pioneers decided to defy such a dogma in desperate cases. RESULTS: Nowadays, it seems obvious that a cardiac stab wound requires emergent surgery whenever possible. CONCLUSIONS: The story of cardiac wounds highlights nicely the change of mind that is required to accept progress and new procedures in medicine.

Impact of age on outcomes of patients assisted by veno-arterial or veno-venous extra-corporeal membrane oxygenation: 403 patients between 2005 and 2015.

INTRODUCTION: To assess the impact of age on early outcomes and mortality in veno-arterial extra-corporeal membrane oxygenation and veno-venous extra-corporeal membrane oxygenation recipients, and to investigate predictors of mortality. METHODS: Single-center retrospective study on prospectively collected data including all patients treated by veno-venous extra-corporeal membrane oxygenation and veno-arterial extra-corporeal membrane oxygenation (January 2005-July 2015). Outcomes were compared among two subgroups: aged less than 65 years (Group 1) versus more than 65 years (Group 2) and by type of support (veno-arterial extra-corporeal membrane oxygenation or veno-venous extra-corporeal membrane oxygenation). RESULTS: Among 403 patients, 20.3% were treated by veno-venous extra-corporeal membrane oxygenation and 79.7% by veno-arterial extra-corporeal membrane oxygenation. Veno-arterial extra-corporeal membrane oxygenation group: 76.6% were included in Group 1 and were more severe (pH 7.30 ± 0.19 vs. 7.35 ± 0.13 in Group 2, p = 0.003; lactates 7.5 ± 5.6 mmol/L vs. 5.8 ± 4.5 mmol/L in Group 2, p = 0.003). Weaning rate was higher in Group 1 (63.8% vs. 45.3%, p = 0.0043). The 30-day survival was higher in Group 1 (52.0% vs. 25.3%, p < 0.001). Univariate analysis identified higher Simplified Acute Physiology Score II (p = 0.02) and noradrenaline (p = 0.04) to be associated with mortality. Veno-venous extra-corporeal membrane oxygenation group: 80.5% were in Group 1. Mean PaO2 was 73.5 ± 42.9 mm Hg versus 100.8 ± 80.3 mm Hg (p = 0.24); FiO2 90.1% ± 18% versus 89.4% ± 16.4% (p = 0.89); and 30-day survival 56.1% versus 25.0% (p = 0.048). CONCLUSION: Patients older than 65 years have higher mortality after veno-arterial extra-corporeal membrane oxygenation or veno-venous extra-corporeal membrane oxygenation. This therapeutic strategy is feasible in the elderly, but comorbidities and clinical presentation have a major impact on prognosis and need to be seriously considered to avoid futile treatment.