Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. METHODS: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. RESULTS: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28-1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. CONCLUSIONS: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 ( https://covid19.cochrane.org/studies/crs-13513201 ).

Sex-Related Differences in Utilization and Outcomes of Extracorporeal Cardio-Pulmonary Resuscitation for Refractory Cardiac Arrest.

Sparse data exist on sex-related differences in extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest (rCA). We explored the role of sex on the utilization and outcomes of ECPR for rCA by retrospective analysis of the Extracorporeal Life Support Organization (ELSO) International Registry. The primary outcome was in-hospital mortality. Exploratory outcomes were discharge disposition and occurrence of any specific extracorporeal membrane oxygenation (ECMO) complications. From 1992 to 2020, a total of 7,460 adults with ECPR were identified: 30.5% women; 69.5% men; 55.9% Whites, 23.7% Asians, 8.9% Blacks, and 3.8% Hispanics. Women's age was 50.4 ± 16.9 years (mean ± standard deviation) and men's 54.7 ± 14.1 (p < 0.001). Ischemic heart disease occurred in 14.6% women vs. 18.5% men (p < 0.001). Overall, 28.5% survived at discharge, 30% women vs. 27.8% men (p = 0.138). In the adjusted analysis, sex was not associated with in-hospital mortality (odds ratio [OR] = 0.93 [confidence interval {CI} = 0.80-1.08]; p = 0.374). Female sex was associated with decreased odds of neurologic, cardiovascular, and renal complications. Despite being younger and having fewer complications during ECMO, women had in-hospital mortality similar to men. Whether these findings are driven by biologic factors or disparities in health care warrants further investigation.

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry.

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings.

Validation of extracorporeal membrane oxygenation mortality prediction and severity of illness scores in an international COVID-19 cohort.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a lifesaving support modality for severe respiratory failure, but its resource-intensive nature led to significant controversy surrounding its use during the COVID-19 pandemic. We report the performance of several ECMO mortality prediction and severity of illness scores at discriminating survival in a large COVID-19 V-V ECMO cohort. METHODS: We validated ECMOnet, PRESET (PREdiction of Survival on ECMO Therapy-Score), Roch, SOFA (Sequential Organ Failure Assessment), APACHE II (acute physiology and chronic health evaluation), 4C (Coronavirus Clinical Characterisation Consortium), and CURB-65 (Confusion, Urea nitrogen, Respiratory Rate, Blood Pressure, age >65 years) scores on the ISARIC (International Severe Acute Respiratory and emerging Infection Consortium) database. We report discrimination via Area Under the Receiver Operative Curve (AUROC) and Area under the Precision Recall Curve (AURPC) and calibration via Brier score. RESULTS: We included 1147 patients and scores were calculated on patients with sufficient variables. ECMO mortality scores had AUROC (0.58-0.62), AUPRC (0.62-0.74), and Brier score (0.286-0.303). Roch score had the highest accuracy (AUROC 0.62), precision (AUPRC 0.74) yet worst calibration (Brier score of 0.3) despite being calculated on the fewest patients (144). Severity of illness scores had AUROC (0.52-0.57), AURPC (0.59-0.64), and Brier Score (0.265-0.471). APACHE II had the highest accuracy (AUROC 0.58), precision (AUPRC 0.64), and best calibration (Brier score 0.26). CONCLUSION: Within a large international multicenter COVID-19 cohort, the evaluated ECMO mortality prediction and severity of illness scores demonstrated inconsistent discrimination and calibration highlighting the need for better clinically applicable decision support tools.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Association Between Mortality and Ventilator Parameters in Children With Respiratory Failure on ECMO.

BACKGROUND: In refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) is a rescue therapy to prevent ventilator-induced lung injury. Optimal ventilator parameters during ECMO remain unknown. Our objective was to describe the association between mortality and ventilator parameters during ECMO for neonatal and pediatric respiratory failure. METHODS: We performed a secondary analysis of the Bleeding and Thrombosis on ECMO dataset. Ventilator parameters included breathing frequency, tidal volume, peak inspiratory pressure, PEEP, dynamic driving pressure, pressure support, mean airway pressure, and FIO2 . Parameters were evaluated before cannulation, on the calendar day of ECMO initiation (ECMO day 1), and the day before ECMO separation. RESULTS: Of 237 included subjects analyzed, 64% were neonates, of whom 36% had a congenital diaphragmatic hernia. Of all the subjects, 67% were supported on venoarterial ECMO. Overall in-hospital mortality was 35% (n = 83). The median (interquartile range) PEEP on ECMO day 1 was 8 (5.0-10.0) cm H2O for neonates and 10 (8.0-10.0) cm H2O for pediatric subjects. By multivariable analysis, higher PEEP on ECMO day 1 in neonates was associated with lower odds of in-hospital mortality (odds ratio 0.77, 95% CI 0.62-0.92; P = .01), with a further amplified effect in neonates with congenital diaphragmatic hernia (odds ratio 0.59, 95% CI 0.41-0.86; P = .005). No ventilator type or parameter was associated with mortality in pediatric subjects. CONCLUSIONS: Avoiding low PEEP on ECMO day 1 for neonates on ECMO may be beneficial, particularly those with a congenital diaphragmatic hernia. No additional ventilator parameters were associated with mortality in either neonatal or pediatric subjects. PEEP is a modifiable parameter that may improve neonatal survival during ECMO and requires further investigation.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Extracorporeal Membrane Oxygenation in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research. DATA SOURCES: Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement. CONCLUSIONS: Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS.

Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.

BACKGROUND: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence. METHODS: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI. RESULTS: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89). CONCLUSIONS: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (<19 years), between January 2012 and September 2014. The primary outcome was bleeding or thrombotic events. Bleeding events included a blood product transfusion >80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p <0.001). Thrombosis odds decreased with increased day prior heparin dose (OR 0.88, 95% CI 0.81, 0.97, p=0.006). Lower ACT values and increased fibrinogen levels may be considered to decrease the odds of bleeding. Use of this single measure, however, may not be sufficient alone to guide optimal anticoagulation practice during ECMO.

The interplay of inflammation and coagulation in COVID-19 Patients receiving extracorporeal membrane oxygenation support.

OBJECTIVE: Bleeding and thrombosis are common complications during Extracorporeal Membrane Oxygenation (ECMO) support for COVID-19 patients. We sought to examine the relationship between inflammatory status, coagulation effects, and observed bleeding and thrombosis in patients receiving venovenous (VV) ECMO for COVID-19 respiratory failure. STUDY DESIGN: Cross-sectional cohort study. SETTINGS: Quaternary care institution. PATIENTS: The study period from April 1, 2020, to January 1, 2021, we included all patients with confirmed COVID-19 who received VV ECMO support. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were supported with VV ECMO during the study period, and 17 patients (53%) survived to hospital discharge. The ECMO nonsurvivors mean lactate dehydrogenase (LDH) levels were markedly elevated in comparison to survivors (1046 u/L [IQR = 509, 1305] vs 489 u/L [385 658], p = 0.003). Platelet/fibrinogen dysfunction, as reflected by the low Maximum Amplitude (MA) on viscoelastic testing, was worse in nonsurvivors (65.25 mm [60.68, 67.67] vs 74.80 mm [73.10, 78.40], p = 0.01). Time-group interaction for the first seven days of ECMO support, showed significantly lower platelet count in the nonsurvivors (140 k/ul [103, 170] vs 189.5 k/ul [ 146, 315], p < 0.001) and higher D-dimer in (21 µg/mL [13, 21] vs 14 µg/mL [3, 21], p < 0.001) in comparison to the survivors. Finally, we found profound statistically significant correlations between the clinical markers of inflammation and markers of coagulation in the nonsurvivors group. The ECMO nonsurvivors experienced higher rate of bleeding (73.3% vs 35.3%, p = 0.03), digital ischemia (46.7% vs 11.8%, p = 0.02), acute renal failure (60% vs 11.8%, p = 0.01) and bloodstream infection (60% vs 23.5%, p = 0.03). CONCLUSION: The correlation between inflammation and coagulation in the nonsurvivors supported with VV ECMO could indicate dysregulated inflammatory response and worse clinical outcomes.

Extracorporeal carbon dioxide removal for acute respiratory failure: a review of potential indications, clinical practice and open research questions.

Extracorporeal carbon dioxide removal (ECCO2R) is a form of extracorporeal life support (ECLS) largely aimed at removing carbon dioxide in patients with acute hypoxemic or acute hypercapnic respiratory failure, so as to minimize respiratory acidosis, allowing more lung protective ventilatory settings which should decrease ventilator-induced lung injury. ECCO2R is increasingly being used despite the lack of high-quality evidence, while complications associated with the technique remain an issue of concern. This review explains the physiological basis underlying the use of ECCO2R, reviews the evidence regarding indications and contraindications, patient management and complications, and addresses organizational and ethical considerations. The indications and the risk-to-benefit ratio of this technique should now be carefully evaluated using structured national or international registries and large randomized trials.

Activated clotting time in inpatient diagnostic and interventional settings.

Monitoring for the anticoagulant effect of unfractionated (UFH) at the point of care using activated clotting time in real time is vital where risk of thrombosis is high. Although monitoring UFH effect is a routine and important task, changing from one ACT instrument type or technology to another must be preceded by a clinical and statistical evaluation to determine the suitability and repeatability and establish normal and treatable ranges of this newer instrument. In this multi-center prospective evaluation we tested 1236 paired ACT+ samples, and 463 paired ACT-LR samples (1699 total) from enrolled study subjects. Clinical settings included CVOR cardiopulmonary bypass, at the beside in extracorporeal life support (ELS), the Cardiac Catheterization Lab (CCL) during diagnostic studies and percutaneous coronary interventions (PCI), interventional radiology procedures and EP interventions. This study found more consistent clinical performance from the GEM Hemochron 100 as compared to the current clinical model, the Hemochron Signature Elite. The bias of GEM Hemochron 100 for ACT+ and ACT-LR was greatest in the setting of the CVOR where ACT levels were high. ACT-LR measurements by the GEM Hemochron 100 were comparable to the SE when performed in settings of CCL, ECM, EP and ICU. Results obtained for both ACT-LR and ACT+ in all clinical settings in this study using the GEM Hemochron 100 are as accurate and more repeatable as those with the current clinically available Signature Elite.

Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study.

OBJECTIVE: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN: Observational study. SETTING: 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS: ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS: 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO2/FiO2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO2/FiO2 <80 mm Hg or with driving pressures >15 cmH2O during the first 10 days of mechanical ventilation. CONCLUSIONS: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting.

Objectives: Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. Data sources: Embase, Medline, Web of Science, Cochrane Library and Google Scholar. Study selection: English original studies of pediatric ECMO patients describing hemostatic tests or outcome. Data extraction: Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. Data synthesis: A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. Conclusions: This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.

Impact of Noninvasive Respiratory Support in Patients With COVID-19 Requiring V-V ECMO.

The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83), IMV (HR: 0.42; 95% CI: 0.20-0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.

Candidacy for Extracorporeal Life Support in Children After Hematopoietic Cell Transplantation: A Position Paper From the Pediatric Acute Lung Injury and Sepsis Investigators Network's Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup.

OBJECTIVES: The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients. DATA SOURCES: All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation. STUDY SELECTION: All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems). DATA EXTRACTION: All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions. DATA SYNTHESIS: Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process. CONCLUSIONS: Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.