Electrical Impedance Tomography to Monitor Hypoxemic Respiratory Failure.

Hypoxemic respiratory failure is one of the leading causes of mortality in intensive care. Frequent assessment of individual physiological characteristics and delivery of personalized mechanical ventilation (MV) settings is a constant challenge for clinicians caring for these patients. Electrical impedance tomography (EIT) is a radiation-free bedside monitoring device that is able to assess regional lung ventilation and changes in aeration. With real-time tomographic functional images of the lungs obtained through a thoracic belt, clinicians can visualize and estimate the distribution of ventilation at different ventilation settings or following procedures such as prone positioning. Several studies have evaluated the performance of EIT to monitor the effects of different MV settings in patients with acute respiratory distress syndrome, allowing more personalized MV. For instance, EIT could help clinicians find the positive end-expiratory pressure that represents a compromise between recruitment and overdistension and assess the effect of prone positioning on ventilation distribution. The clinical impact of the personalization of MV remains to be explored. Despite inherent limitations such as limited spatial resolution, EIT also offers a unique noninvasive bedside assessment of regional ventilation changes in the ICU. This technology offers the possibility of a continuous, operator-free diagnosis and real-time detection of common problems during MV. This review provides an overview of the functioning of EIT, its main indices, and its performance in monitoring patients with acute respiratory failure. Future perspectives for use in intensive care are also addressed.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Prone-Positioning for Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated with improved respiratory system static compliance after that intervention. DESIGN: Retrospective, single-center study over 8 years. SETTINGS: Twenty-six bed ICU in a tertiary center. MEASUREMENTS AND MAIN RESULTS: A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio [95% CI], 1.54 [1.05-2.58]) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047). CONCLUSIONS: Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.

Electrical Impedance Tomography Monitoring of Bronchoalveolar Lavage in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: The impact of bronchoalveolar lavage on regional ventilation in mechanically ventilated patients with acute respiratory distress syndrome has rarely been described. Our objectives were use electrical impedance tomography to describe lung impedance variation post bronchoalveolar lavage and identify morphologic patterns according to respiratory failure severity. DESIGN: Monocenter physiologic study on mechanically ventilated patients. SETTING: University medical ICU. INTERVENTIONS: After a recruitment maneuver, tidal impedance variation distributions (a surrogate for impact of bronchoalveolar lavage on tidal volume distribution), end-expiratory lung impedance (correlated with end-expiratory lung volume and used to quantify postbronchoalveolar lavage derecruitment), respiratory mechanics, and blood gases were recorded before and over 6 hours post bronchoalveolar lavage with Pao2 to the Fio2 ratio. Patients were grouped according to their prebronchoalveolar lavage, that is, Pao2 to the Fio2 ratio less than 200 or greater than or equal to 200. RESULTS: Twenty-one patients (median [interquartile range] age 55 yr [50-58 yr]; 13 males), 13 with Pao2 to the Fio2 ratio less than 200, were included. Unlike that latter group, bronchoalveolar lavage significantly impacted tidal impedance variation distribution in patients with Pao2 to the Fio2 ratio greater than or equal to 200, with a ventilation shift to the contralateral lung (from 54% to 42% in the bronchoalveolar lavage side), which persisted up to 6 hours post bronchoalveolar lavage. Similarly, end-expiratory lung impedance was less distributed in the bronchoalveolar lavage side post procedure of patients with Pao2 to the Fio2 ratio greater than or equal to 200, but the difference did not reach statistical significance (p = 0.09). As reported for tidal impedance variation, end-expiratory lung impedance distribution in patients with severe or moderate acute respiratory distress syndrome did not change significantly during the 6 hours post bronchoalveolar lavage. Although bronchoalveolar lavage effects on gas exchanges were minor in all patients, static compliance in patients with Pao2 to the Fio2 ratio greater than or equal to 200 was significantly lower post bronchoalveolar lavage (p = 0.04). CONCLUSIONS: The negative impact of bronchoalveolar lavage on regional ventilation, which persisted at least 6 hours, appeared to be more profound in patients with normal lung function or mild acute respiratory distress syndrome. In contrast, regional ventilation, lung recruitment, respiratory mechanics, and gas exchanges were modestly impacted by the bronchoalveolar lavage in patients with severe or moderate acute respiratory distress syndrome. That finding is reassuring and supports not summarily proscribing bronchoalveolar lavage for the most severely ill with acute respiratory distress syndrome.

Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation.

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU. DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020). SETTING: Two academic hospital ICUs, Paris, France. PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge. INTERVENTIONS: Follow-up by face-to-face neurologic consultation. MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome. CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

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.

Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

INTRODUCTION: Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated. DESIGN: Randomized clinical trial. SETTINGS: Nine-month monocentric study. PATIENTS: Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation. INTERVENTIONS: After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory pressure-very low driving pressure); 2) high pressure 24 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-high driving pressure); and 3) high pressure 17 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure-low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step. MEASUREMENTS AND MAIN RESULTS: Sixteen patients on ECMO after 7 days (1-11 d) of mechanical ventilation were included. "Ultra-protective" mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure. CONCLUSIONS: ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. (Crit Care Med 2019; 47:1505-1512).

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.

Recent advances in venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.

PURPOSE OF REVIEW: To summarize results of the most recent trials on venovenous extracorporeal membrane oxygenation (VV-ECMO) in severe acute respiratory distress syndrome (ARDS) and to elaborate on the unmet needs regarding VV-ECMO management in this setting. RECENT FINDINGS: Although it was terminated early for futility (i.e., failure to demonstrate a difference in 60-day mortality of 20%), the ECMO to Rescue Lung Injury in Severe ARDS trial of VV-ECMO for severe ARDS reported a nonsignificant, but clinically important, reduction in mortality (35 vs. 46%; relative risk 0.76; 95% confidence interval 0.55-1.04, P = 0.09). Refractory hypoxemia led to rescue ECMO in 28% of controls, who had more severe ARDS at inclusion, were extremely sick at the time of ECMO cannulation and for whom mortality was 57%. Beyond the rescue of patients dying of refractory hypoxemia, ECMO may now be used early in severe ARDS patients to reduce the intensity of mechanical ventilation and to minimize ventilator-induced lung injury. Future research in the field should focus on identification of patients who are more likely to benefit from this technique and the right timing for its initiation, optimization of daily management of patients under ECMO to further reduce complications, and selection of optimal ventilator management on ECMO. SUMMARY: VV-ECMO is a reasonable therapeutic option for patients with severe ARDS and major hypoxemia or excessive pressures. Future trials should be designed to optimize patients' management while on VV-ECMO support.

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.

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.

Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA-ECMO flows in a cardiogenic shock population and determine the risk factors of 'high-ECMO flow'. METHODS AND RESULTS: A 7 year database of patients supported with VA-ECMO was used. Based on the median flow during the first 48 h of the VA-ECMO run, patients were classified as 'high-flow' or 'low-flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator-associated pneumonia, ECMO-related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in-hospital and 60 day mortality. Risk factors of high-ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA-ECMO, median age was 51 (40-59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end-stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high-flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26-58) vs. 56 (42-74), P < 0.001], higher lactate [3.6 (2.2-5.8) mmol/L vs. 5.2 (3-9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41-375) U/L vs. 309 (85-939) U/L, P < 0.001], among others. The 'low-flow' group had less ventilator-associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5-7.5) vs. 6 (3-12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high-flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1-7.1] and pre-ECMO lactate (OR 1.1, 95% CI 1.0-1.2). CONCLUSIONS: In patients with refractory cardiogenic shock supported with VA-ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator-associated pneumonia but similar survival compared with patients with lower flows.

Venoarterial extracorporeal membrane oxygenation flow or dobutamine to improve microcirculation during ECMO for refractory cardiogenic shock.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA ECMO) effectively supports refractory cardiogenic shock (rCS), and sustains macro- and microcirculations. We investigated the respective impact of increasing VA ECMO flow or dobutamine dose on microcirculation in stabilized VA ECMO-treated patients with rCS. METHODS: In this prospective interventional study, we included consecutive intubated patients, with ECMO-supported rCS and hemodynamic stability, able to tolerate stepwise incremental dobutamine doses (from 5 to 20 gamma/kg/min) or ECMO flows (progressive increase by 25% above baseline ECMO flow. Baseline was defined as the lowest VA ECMO flow and dobutamine 5 µg/kg/min (DOBU5) to maintain mean arterial pressure (MAP) ≥ 65 mmHg. Macro- and microcirculations were evaluated after 30 min at each level. RESULTS: Fourteen patients were included. Macro- and microcirculations were assessed 2 [2-5] days post-ECMO onset. Dobutamine-dose increments did not modify any microcirculation parameters. Only the De Backer score tended to be reduced (p = 0.08) by ECMO-flow increments whereas other microcirculation parameters were not affected. These findings did not differ between patients successfully weaned-off ECMO (n = 6) or not. CONCLUSIONS: When macrocirculation has already been restored in patients with ECMO-supported rCS, increasing dobutamine (above 5 µg/kg/min) or ECMO flow did not further improve microcirculation.

Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock.

BACKGROUND: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is currently one of the first-line therapies for refractory cardiogenic shock (CS), but its applicability is undermined by the high morbidity associated with its complications, especially those related to mechanical ventilation (MV). We aimed to assess the prognostic impact of keeping patients in refractory CS awake at cannulation and during the VA-ECMO run. METHODS: A 7-year database of patients given peripheral VA-ECMO support was used to conduct a propensity-score (PS)-matched analysis to balance their clinical profiles. Patients were classified as 'awake ECMO' or 'non-awake ECMO', respectively, if invasive MV was used during ≤50% or >50% of the VA-ECMO run. Primary outcomes included ventilator-associated pneumonia and ECMO-related complication rates, and secondary outcomes were 60-day and 1-year mortality. A multivariate logistic-regression analysis was used to identify whether MV at cannulation was independently associated with 60-day mortality. RESULTS: Among 231 patients included, 91 (39%) were 'awake' and 140 (61%) 'non-awake'. After PS-matching adjustment, the 'awake ECMO' group had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, and less antibiotic and sedative consumption. This strategy was also associated with reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021) compared to the 'non-awake' group, respectively. Lastly, MV at ECMO cannulation was independently associated with 60-day mortality. CONCLUSION: An 'awake ECMO' management in VA-ECMO-supported CS patients is feasible, safe, and associated with improved short- and long-term outcomes.

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.

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.