Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Role of hemolysis on pulmonary arterial compliance and right ventricular systolic function after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB. METHODS: This is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014-2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB. RESULTS: PAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (-0.28 ml/mmHg, 95%CI -0.49 to -0.01, p = 0.012) and RVFI (0.14 mmHg*L-1*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments. CONCLUSION: PAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB.

A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance-ExSpiron®Xi: a validation study in healthy volunteers.

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the gold standard spirometer technique. This data was not confirmed for MV. The calibration of the device did not improve its performance. Although the accuracy of ExSpiron®Xi was mild and the precision was limited for TV, TV/IBW and MV, the trending ability of the device was strong specifically for TV, TV/IBW and RR. This makes ExSpiron®Xi a non-invasive monitoring system that may detect real-time tidal volume ventilation changes and then suggest the need to better optimize the patient ventilatory support.

Dynamic inflation prevents and standardized lung recruitment reverts volume loss associated with percutaneous tracheostomy during volume control ventilation: results from a Neuro-ICU population.

To determine how percutaneous tracheostomy (PT) impacts on respiratory system compliance (Crs) and end-expiratory lung volume (EELV) during volume control ventilation and to test whether a recruitment maneuver (RM) at the end of PT may reverse lung derecruitment. This is a single center, prospective, applied physiology study. 25 patients with acute brain injury who underwent PT were studied. Patients were ventilated in volume control ventilation. Electrical impedance tomography (EIT) monitoring and respiratory mechanics measurements were performed in three steps: (a) baseline, (b) after PT, and (c) after a standardized RM (10 sighs of 30 cmH2O lasting 3 s each within 1 min). End-expiratory lung impedance (EELI) was used as a surrogate of EELV. PT determined a significant EELI loss (mean reduction of 432 arbitrary units p = 0.049) leading to a reduction in Crs (55 ± 13 vs. 62 ± 13 mL/cmH2O; p < 0.001) as compared to baseline. RM was able to revert EELI loss and restore Crs (68 ± 15 vs. 55 ± 13 mL/cmH2O; p < 0.001). In a subgroup of patients (N = 8, 31%), we observed a gradual but progressive increase in EELI. In this subgroup, patients did not experience a decrease of Crs after PT as compared to patients without dynamic inflation. Dynamic inflation did not cause hemodynamic impairment nor raising of intracranial pressure. We propose a novel and explorative hyperinflation risk index (HRI) formula. Volume control ventilation did not prevent the PT-induced lung derecruitment. RM could restore the baseline lung volume and mechanics. Dynamic inflation is common during PT, it can be monitored real-time by EIT and anticipated by HRI. The presence of dynamic inflation during PT may prevent lung derecruitment.

Algor-ethics: charting the ethical path for AI in critical care.

The integration of Clinical Decision Support Systems (CDSS) based on artificial intelligence (AI) in healthcare is groundbreaking evolution with enormous potential, but its development and ethical implementation, presents unique challenges, particularly in critical care, where physicians often deal with life-threating conditions requiring rapid actions and patients unable to participate in the decisional process. Moreover, development of AI-based CDSS is complex and should address different sources of bias, including data acquisition, health disparities, domain shifts during clinical use, and cognitive biases in decision-making. In this scenario algor-ethics is mandatory and emphasizes the integration of 'Human-in-the-Loop' and 'Algorithmic Stewardship' principles, and the benefits of advanced data engineering. The establishment of Clinical AI Departments (CAID) is necessary to lead AI innovation in healthcare, ensuring ethical integrity and human-centered development in this rapidly evolving field.

Timing of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs). DESIGN: Pooled individual data analysis from five original observational cohort studies. SETTING: European extracorporeal membrane oxygenation (ECMO) centers. PATIENTS: Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87-0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66-3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038). CONCLUSIONS: In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.

Unsupervised segmentation and quantification of COVID-19 lesions on computed Tomography scans using CycleGAN.

BACKGROUND: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. METHODS: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. RESULTS: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. CONCLUSION: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its ability to segment lesions without the need for manual segmentations.

Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies.

BACKGROUND: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic. METHODS: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort. RESULTS: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population. CONCLUSION: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.

A Novel Mask with Selective Ports for Inflow and Outflow Reduces CO2 Rebreathing during Non-Invasive Ventilation: A Physiological Study in Healthy Volunteers.

BACKGROUND: CO2 rebreathing is one of the risks associated with noninvasive ventilation (NIV), possibly contributing to failure. In a bench study, we showed that a novel mask design, with separate limbs for inflow and outflow gases, significantly reduced CO2 rebreathing in different ventilation settings. OBJECTIVES: The study aimed to test whether a new mask design could 1) reduce CO2 rebreathing in healthy volunteers during NIV (phase 1) and 2) reduce minute ventilation (phase 2). MATERIALS AND METHODS: Healthy volunteers were randomly assigned to NIV using two masks in a crossover design: a traditional single-limb mask for inflow and outflow gases and a mask with two separated limbs. In phase 1, six ventilation settings were tested for each mask: CPAP (PEEP 5 cmH2O) and pressure support ventilation (PSV, PS Level 5 cmH2O) using a mechanical ventilator with a bias flow of 8 or 20 L/min; free-flow CPAP (PEEP 5 cmH2O) with 60 or 90 L/min of gas flow. A nasal cannula was inserted in one nostril of the volunteers and connected to a CO2 gas analyzer to measure CO2 during the respiratory cycle. In phase 2, volunteers underwent a prolonged time of ventilation in CPAP 90 L/min and PSV with 20 L/min of bias flow. During free-flow CPAP, electrical impedance tomography was used to record the change in impedance during tidal breathing and then estimate tidal volume. RESULTS: Ten healthy adults were enrolled in phase 1, and 8 volunteers in phase 2. CO2 during inspiration was significantly lower in each setting with the two-limb versus the one-limb mask (p < 0.001). The maximum CO2 reduction was observed in the continuous-flow CPAP settings. EtCO2 was lower with the two-limb mask compared to the one-limb mask (p < 0.001). However, no difference in minute ventilation was observed between the two masks. CONCLUSION: The new mask design with two ports for inhaled and exhaled gases reduced the amount of CO2 rebreathing in all tested ventilation settings. The CO2 rebreathing reduction did not decrease minute ventilation in healthy volunteers.

Nitric oxide: Clinical applications in critically ill patients.

Inhaled nitric oxide (iNO) acts as a selective pulmonary vasodilator and it is currently approved by the FDA for the treatment of persistent pulmonary hypertension of the newborn. iNO has been demonstrated to effectively decrease pulmonary artery pressure and improve oxygenation, while decreasing extracorporeal life support use in hypoxic newborns affected by persistent pulmonary hypertension. Also, iNO seems a safe treatment with limited side effects. Despite the promising beneficial effects of NO in the preclinical literature, there is still a lack of high quality evidence for the use of iNO in clinical settings. A variety of clinical applications have been suggested in and out of the critical care environment, aiming to use iNO in respiratory failure and pulmonary hypertension of adults or as a preventative measure of hemolysis-induced vasoconstriction, ischemia/reperfusion injury and as a potential treatment of renal failure associated with cardiopulmonary bypass. In this narrative review we aim to present a comprehensive summary of the potential use of iNO in several clinical conditions with its suggested benefits, including its recent application in the scenario of the COVID-19 pandemic. Randomized controlled trials, meta-analyses, guidelines, observational studies and case-series were reported and the main findings summarized. Furthermore, we will describe the toxicity profile of NO and discuss an innovative proposed strategy to produce iNO. Overall, iNO exhibits a wide range of potential clinical benefits, that certainly warrants further efforts with randomized clinical trials to determine specific therapeutic roles of iNO.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis.

BACKGROUND: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. METHODS: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to "conventional" ECMO management (Supine group) in patients with severe ARDS. RESULTS: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42-1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). CONCLUSIONS: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Monitoring Lung Injury Severity and Ventilation Intensity during Mechanical Ventilation.

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure burden by high hospital mortality. No specific pharmacologic treatment is currently available and its ventilatory management is a key strategy to allow reparative and regenerative lung tissue processes. Unfortunately, a poor management of mechanical ventilation can induce ventilation induced lung injury (VILI) caused by physical and biological forces which are at play. Different parameters have been described over the years to assess lung injury severity and facilitate optimization of mechanical ventilation. Indices of lung injury severity include variables related to gas exchange abnormalities, ventilatory setting and respiratory mechanics, ventilation intensity, and the presence of lung hyperinflation versus derecruitment. Recently, specific indexes have been proposed to quantify the stress and the strain released over time using more comprehensive algorithms of calculation such as the mechanical power, and the interaction between driving pressure (DP) and respiratory rate (RR) in the novel DP multiplied by four plus RR [(4 × DP) + RR] index. These new parameters introduce the concept of ventilation intensity as contributing factor of VILI. Ventilation intensity should be taken into account to optimize protective mechanical ventilation strategies, with the aim to reduce intensity to the lowest level required to maintain gas exchange to reduce the potential for VILI. This is further gaining relevance in the current era of phenotyping and enrichment strategies in ARDS.

Cardiopulmonary Resuscitation-associated Lung Edema (CRALE). A Translational Study.

Rationale: Cardiopulmonary resuscitation is the cornerstone of cardiac arrest (CA) treatment. However, lung injuries associated with it have been reported.Objectives: To assess 1) the presence and characteristics of lung abnormalities induced by cardiopulmonary resuscitation and 2) the role of mechanical and manual chest compression (CC) in its development.Methods: This translational study included 1) a porcine model of CA and cardiopulmonary resuscitation (n = 12) and 2) a multicenter cohort of patients with out-of-hospital CA undergoing mechanical or manual CC (n = 52). Lung computed tomography performed after resuscitation was assessed qualitatively and quantitatively along with respiratory mechanics and gas exchanges.Measurements and Main Results: The lung weight in the mechanical CC group was higher compared with the manual CC group in the experimental (431 ± 127 vs. 273 ± 66, P = 0.022) and clinical study (1,208 ± 630 vs. 837 ± 306, P = 0.006). The mechanical CC group showed significantly lower oxygenation (P = 0.043) and respiratory system compliance (P < 0.001) compared with the manual CC group in the experimental study. The variation of right atrial pressure was significantly higher in the mechanical compared with the manual CC group (54 ± 11 vs. 31 ± 6 mm Hg, P = 0.001) and significantly correlated with lung weight (r = 0.686, P = 0.026) and respiratory system compliance (r = -0.634, P = 0.027). Incidence of abnormal lung density was higher in patients treated with mechanical compared with manual CC (37% vs. 8%, P = 0.018).Conclusions: This study demonstrated the presence of cardiopulmonary resuscitation-associated lung edema in animals and in patients with out-of-hospital CA, which is more pronounced after mechanical as opposed to manual CC and correlates with higher swings of right atrial pressure during CC.

Arterio-venous fistula causing acute right heart failure: A rare complication of veno-arterial extracorporeal membrane oxygenation.

Introduction: Vascular complications are a major issue in V-A ECMO and can affect long term outcome. Among these, Artero-Venous (AV) fistulas may lead to right heart failure.Case History: A 73-years patient supported with V-A ECMO for post-cardiotomy biventricular failure developed right heart failure after V-A ECMO decannulation, requiring V-A ECMO recannulation. The presence of an AV femoral fistula was incidentally revealed during femoral vein cannulation, from which oxygenated blood was unexpectedly drawn. The angiographic assessment confirmed the presence of a fistula between superficial femoral artery and vein, at the site of the first venous ECMO cannulation. This was caused by the venous cannula that inadvertently passed across the artery and created an AV fistula that was opened by the venous cannula removal. The exclusion of the endovascular fistula allowed the right heart failure resolution.Conclusions: In the presence of right heart failure after recent vascular manipulation, AV fistula should be ruled out.

Incidence Rates and Case-Fatality Rates of Cerebral Vein Thrombosis: A Population-Based Study.

Background and Purpose: Cerebral vein thrombosis (CVT) incidence is estimated to be >10 per 1 000 000 per year. Few population-based studies investigating case-fatality rates (CFRs) and pyogenic/nonpyogenic CVT incidence are available. We assessed trends in CVT incidence between 2002 and 2012, as well as adjusted in-hospital CFRs and incidence of hospital admissions for pyogenic/nonpyogenic CVT in a large Northwestern Italian epidemiological study. Methods: Primary and secondary discharge diagnoses of pyogenic/nonpyogenic CVT were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes 325, 671.5, and 437.6. Age, sex, vital status at discharge, length of hospital stay, and up to 5 secondary discharge diagnoses were collected. Concomitant presence of intracerebral hemorrhage (ICH) was registered, and comorbidities were assessed through the Charlson comorbidity index. Results: A total of 1718 patients were hospitalized for CVT (1147 females­66.8%; 810 pyogenic and 908 nonpyogenic CVT, 47.1% and 52.9%, respectively), with 134 patients (7.8%) experiencing a concomitant ICH. The overall incidence rate for CVT was 11.6 per 1 000 000 inhabitants with a sex-specific rate of 15.1 and 7.8 per 1 000 000 in females and males, respectively. CVT incidence significantly increased in women during time of observation (P=0.007), with the highest incidence being at 40 to 44 years (27.0 cases per 1 000 000). In-hospital CFR was 3%, with no difference between pyogenic/nonpyogenic CVT. Patients with concomitant ICH had a higher in-hospital CFR compared with patients without ICH (7.5% versus 2.7%; odds ratio, 2.96 [95% CI, 1.45­6.04]). In-hospital CFR progressively increased with increasing Charlson comorbidity index (P=0.003). Age (odds ratio, 1.03 [95% CI, 1.02­1.05]), Charlson comorbidity index ≥4 (odds ratio, 4.33 [95% CI, 1.29­14.52]), and ICH (odds ratio, 3.05 [95% CI, 1.40­6.62]) were independent predictors of in-hospital mortality. Conclusions: In a large epidemiological study, CVT incidence was found to be comparable to the one registered in population-based studies reported after the year 2000. CVT incidence increased among women over time. In-hospital CFR was low, but not negligible, in patients with concomitant ICH. Age, ICH, and a high number of comorbidities were independent predictors of in-hospital mortality. Pyogenic CVT was not a predictor of in-hospital CFR, although its high proportion was not confirmed by internal validation.

Death in hospital following ICU discharge: insights from the LUNG SAFE study.

BACKGROUND: To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward. METHODS: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments ('treatment limitations'), and the subpopulations with treatment limitations. RESULTS: 2186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge. CONCLUSIONS: A significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073 .

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-ß-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable. RESULTS: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone. CONCLUSIONS: Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.

Extracorporeal Chloride Removal by Electrodialysis. A Novel Approach to Correct Acidemia.

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.