Venovenous Extracorporeal Membrane Oxygenation Research Articles

Systemic Coagulation Derangement as an Early Sign of Oxygenator Failure in Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) Without Anticoagulation

Background and Clinical Significance: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a widely accepted supportive treatment for severe acute respiratory distress syndrome (ARDS) in intensive care units (ICUs). Although it has gained popularity, some of its aspects, including optimal anticoagulation management and the best means of monitoring hemostasis, remain unresolved. Thrombosis and bleeding are still important complications of ECMO. Case Presentation: A 44-year-old male patient, with no underlying conditions, was diagnosed with severe acute respiratory distress syndrome (ARDS) due to AH1N1 influenza. He presented severe hypoxemia despite the use of mechanical ventilation, neuromuscular blocking agent infusion and prone position. VV ECMO was used, and coagulation was stopped on ECLS day 6 due to severe pulmonary hemorrhage. The systemic hemostatic disorders found in this patient were difficult to differentiate from disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), improved transiently after circuit exchange, and resolved only after discontinuation of ECMO. The patient was discharged fully conscious and cooperative, with no apparent neurological deficit. Conclusions: Systemic hemostatic abnormalities may precede oxygenator failure and mimic DIC or SIC. Timely oxygenator exchange may therefore be considered. However, it is a high-risk procedure, especially in fully ECLS-dependent patients.

Nutritional Intake in Venovenous ECMO Patients: A Single-Center Study in a North American PICU

Nutritional Intake in Venovenous ECMO Patients: A Single-Center Study in a North American PICU

An investigation into the contributing factors to survival of ARDS patients supported by veno-venous ECMO.

This study aimed to identify characteristics associated with survival during and post Extra Corporeal Membrane Oxygenation (ECMO) therapy, in patients with acute respiratory distress syndrome (ARDS) during the COVID-19 pandemic. A retrospective observational study on 94 consecutive patients with confirmed COVID-19 induced ARDS supported by ECMO was carried out 49/94 (52.7%) patients survived to hospital discharge. Non-survivors were found to have significantly (p < .05) higher: Pre-ECMO International normalized ratios (INR), carbon dioxide partial pressure (pCO2), Acute Kidney Injury (AKI) scores and blood urea levels. Also, lower pre-ECMO peak inspiratory pressures (PIP), mean arterial pressure, saturation of arterial oxygen (SaO2), blood bicarbonate levels (HCO3), blood Ph and fewer trials off ECMO with shorter combined trial off times. Patients that did not survive were more likely to have renal impairment and have received peri-ECMO haemofiltration. Poor prognosis was significantly associated with: receiving pre-ECMO nitric oxide (HR = 3.047, CI = 1.247-7.447, p = .015), renal impairment (HR = 3.023, CI = 1.586-5.763, p < .001), AKI of 2 (HR = 3.611, CI = 1.382-9.441, p = .009) or 3 (HR = 3.275, CI = 1.235-8.685, p = .017), peri-ECMO haemofiltration (HR = 2.412, CI = 1.310-4.442, p = .005) and the ABO blood group B (HR = 3.103, CI = 1.335-7.212, p = .008). pre-ECMO high CO2 (HR = 1.134, CI = 1.031-1.248, p = .010), blood lactate (HR = 1.350, CI = 1.156-1.576, p < .001), INR (HR = 2.571, CI = 1.438-4.598, p=<0.001) and lower blood Ph (HR = 0.023, CI = 0.002-0.210, p < .001). Commonly used mortality scores may not be of use in a COVID-19 cohort of ECMO patients. The initiation of ECMO needs to be implemented prior to metabolic derangements, renal and fulminant respiratory failure.

Giant lung abscess complicating pneumonia managed with veno venous extracorporeal membrane oxygenation

Giant lung abscess complicating pneumonia managed with veno venous extracorporeal membrane oxygenation

Pulmonary Hemorrhage During Pulmonary Artery Stenting Necessitating Venovenous Extracorporeal Membrane Oxygenation

Pulmonary Hemorrhage During Pulmonary Artery Stenting Necessitating Venovenous Extracorporeal Membrane Oxygenation

Developing a veno-venous extracorporeal membrane oxygenation program during the COVID-19 pandemic: don’t forget to notify the blood bank

ObjectivesDuring the SARS-CoV-2 pandemic, there has been significant increased use of vvECMO as rescue therapy. Patients with COVID-19 as anticoagulation is needed for vvECMO support, may develop bleeding complications requiring an increased number of RBC transfusions. We would like to report the RBC transfusion needs following the implementation of an ECMO program. Data on blood usage in this population is important in view of the decline in donations due to the pandemic.Study Design and Methods: We analyzed data on RBC transfusions in patients who required vvECMO for COVID-19 related ARDS in a Belgian ICU from March 2020 to March 2022. The primary end point was RBC transfusion requirements. and the relationship to outcome. We also analyzed the evolution of this requirement during the four waves. ResultsWe admitted 538 patients for hypoxemic ARDS due to COVID-19. Sixty patients (11%) required vvECMO, of whom 27 (45%) died. Forty-seven (78 %) of the vvECMO patients were transfused a total of 403 packed RBC units.. Sites of hemorrhagic complications were ECMO cannulation sites and lungs. RBC transfusion per patient per day on vvECMO was 0.50 [0.30-0.67] units. There were no differences in hemorrhagic complications in vvECMO survivors and non-survivors.The percentage of vvECMO patients receiving a RBC transfusion increased slightly during the last COVID-19 wave, with 92 % of patients transfused. ConclusionsvvECMO program is associated with a major need for RBC transfusions. These data are important when blood availability is decreased due to a pandemic and illustrates the need for studies on optimizing blood management including therapeutic anticoagulation target, threshold for RBC transfusion or alternatives to RBC transfusion.

Impact of Extracorporeal Membrane Oxygenation (ECMO) on Serum Concentrations of Cefepime

ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to determine the impact of ECMO circuitry and to guide therapeutic dosing. Methods: Patients 19 years or older admitted to the ICU, treated with ECMO and beta-lactam antibiotics for presumed or documented infection, were enrolled. Three blood samples (peak, midpoint, trough) were obtained before ECMO (pre-ECMO) and during ECMO (intra-ECMO) at a steady state. Results: Eight patients met inclusion criteria; six received cefepime. All patients were male. Average ± SD age was 45.8 ± 14.7. Four patients received ECMO for severe SARS-CoV-2 infection, and one each for Pneumocystis pneumonia and influenza A infection. Mean ± SD APACHE II and SOFA scores prior to ECMO were 24.6 ± 7.1 and 11.0 ± 3.9, respectively. All but one of the patients received venovenous (VV) ECMO. Cefepime 1 g every 6 h intravenously over 2 min was administered to all patients before and during ECMO. Cefepime concentrations were fit to non-compartment analysis (NCA) and area under the serum concentration–time curve averaged ± SE 211.9 ± 29.6 pre-ECMO and 329.6 ± 32.3 mg*h/L intra-ECMO, p = 0.023. No patients displayed signs of cefepime neurotoxicity. Patients received ECMO for 43.1± 30 days. All patients expired. Cefepime dosed at 1 g every 6 h intravenously appears to achieve therapeutic levels for critically ill patients on ECMO.

Reply to Jha: Cardiopulmonary Effects of Increased Mixed Venous Saturation During Veno-Venous ECMO.

Reply to Jha: Cardiopulmonary Effects of Increased Mixed Venous Saturation During Veno-Venous ECMO.

Cardiopulmonary Effects of Increased Mixed Venous Saturation During Veno-Venous ECMO.

Cardiopulmonary Effects of Increased Mixed Venous Saturation During Veno-Venous ECMO.

VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION IMPROVES OUTCOMES IN TRAUMA PATIENTS SUFFERING RESPIRATORY FAILURE.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) improves hypoxemia and carbon dioxide clearance in patients with severe respiratory derangements. A greater understanding of the potential benefits of VV ECMO in trauma patients could lead to broader adoption. We hypothesize that trauma patients who receive VV ECMO have improved mortality outcomes when compared to those receiving conventional ventilator management given the rapid stabilization VV ECMO promotes. We performed a single center, propensity score matched cohort study. All trauma patients from January 1, 2014, to October 30, 2023, who were placed on VV ECMO or who would have met institutional guidelines for VV ECMO but were managed with conventional ventilator strategies were matched 1:1. The primary outcome analysis was survival at hospital discharge. Significance was defined as p < 0.05. Eighty-one trauma VV ECMO patients and 128 patients who received conventional management met criteria for inclusion. After matching, VV ECMO and conventional treatment cohort characteristics were similar in age and MOI. Matched ISS, SI, lactate levels, and frequency of TBI were also similar. Finally, respiratory parameters including pre-intervention, pH, partial pressure of carbon dioxide (PaCO2), lactate levels, and oxygen saturation were similar between matched groups. VV ECMO patients had higher survival rates at discharge when compared to the matched conventional treatment group (70% v 41%, p < 0.001). Corresponding hazard ratio for VV ECMO use was 0.31 (95%CI 0.18-0.52; p < 0.001). The odds ratio of mortality in matched trauma patients who receive VV ECMO versus conventional treatment was 0.29 (95%CI 0.14-0.58; p < 0.001). VV ECMO may represent a safe, alternative treatment approach for appropriately screened trauma patients with acute respiratory failure, however further studies are warranted.

Identification of novel sub-phenotypes of severe ARDS requiring ECMO using latent class analysis

BackgroundSub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO).MethodsWe conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes.ResultsWe identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036).ConclusionsThe three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.

Extracorporeal Membrane Oxygenation for COVID-19 During the Delta and Omicron Waves in North America.

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave.

Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study

Introduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear which covariates influence Ang-II concentration in the early phase of sepsis, especially if extracorporeal therapies also do. Methods: Ang-II concentrations were measured in 171 patients with sepsis after the first day of antibiotic treatment between 03/2013 and 01/2015. Ang-II was correlated with potential influencing factors (Spearman correlation). A multivariate model was established including the significant correlating parameters. The Mann–Whitney U test and the Kruskal–Wallis test were used to detect significant differences in Ang-II concentration. Results: The median Ang-II concentration was 8015 pg/mL (interquartile range (IQR): 5024–14,185). A total of forty patients were treated with kidney replacement therapy (KRT) and 20 were supported by venovenous extracorporeal membrane oxygenation (vv-ECMO). Sequential organ failure assessment (SOFA) score (r = 0.541), creatinine clearance (r = −0.467), urinary output (r = −0.289), interleukin (IL)-6 (r = 0.529), C-reactive protein (CRP) (r = 0.241), platelet count (r = −0.419), bilirubin (r = 0.565), lactate (r = 0.322), KRT (r = 0.451), and fluid balance (r = 0.373) significantly correlated with Ang-II concentration and were included in the multivariate model. There, creatinine clearance (p &lt; 0.01, b = −26.3, 95% confidence interval (CI) −41.8–−10.8), fluid balance (p = 0.002, b = 0.92, 95% CI 0.33–1.51), and CRP (p = 0.004, b = 127.6, 95% CI 41.6–213.7) were associated with Ang-II concentration. Furthermore, patients with KRT (median: 15,219 pg/mL, IQR: 10,548–20,270) had significantly (p &lt; 0.01) higher Ang-II concentrations than those with vv-ECMO support (median: 6412 pg/mL, IQR: 5246–10,257) or those without extracorporeal therapy (median: 7156 pg/mL, IQR: 4409–12,741). Conclusion: Increased CRP, positive fluid balance, and impaired kidney function were associated with higher Ang-II concentrations in critically ill patients in the early stage of sepsis in this post hoc analysis. In particular, patients with KRT had very high Ang-II concentrations, whereas the use of vv-ECMO was not related to higher Ang-II concentrations. The significance for clinical practice should be clarified by a prospective study with standardized measurements.

Veno-venous extracorporeal membrane oxygenation for severe COVID-19 associated acute respiratory distress syndrome: A retrospective, nationwide, Danish cohort study.

Severe acute respiratory syndrome (ARDS) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to provide data on patient selection and outcome in a nationwide cohort study of patients with COVID-19 associated ARDS supported with V-V ECMO. We identified all patients with COVID-19, who were supported with V-V ECMO in Denmark from March 10, 2020, to December 31, 2021, and retrieved data on patients who were referred to- and accepted for ECMO, demographics, outcome data, and complications. Risk factors for mortality were analysed using multivariate Cox regression analysis. During the study period, 1836 patients were admitted to Danish intensive care units (ICUs). In the same period, there were 197 enquiries for ECMO of whom 118 patients were considered eligible. Overall, 71 patients were cannulated for ECMO; three patients were cannulated for veno-arterial extracorporeal membrane oxygenation (V-A ECMO) due to right sided heart failure and 68 patients were cannulated for V-V ECMO. Two patients accepted for V-V ECMO died during cannulation. The median age was 55 years (IQR 45-60) and 66% were males. The median duration of ECMO support was 13 days (IQR 7-21), mechanical ventilation median 26 days (IQR 14-42), ICU stay median 34 days (IQR 17-46), and length of hospital stay median 41 days (IQR 25-56). Ninety-day mortality was 43%. Age of 60 years or more was associated with an increased risk of mortality. Pre-existing hypertension was associated with a decreased risk of mortality. A nationwide, Danish cohort study of 68 COVID-19 patients supported with V-V ECMO, showed a 90-day survival of 43%, which is in accordance with reports from comparable cohorts. Age of 60 years or more was associated with an increased risk of mortality. Pre-existing hypertension was associated with a decreased risk of mortality.

Neurosurgical Procedures in Patients Requiring Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is often withheld in patients with significant neurologic injury or recent neurosurgical intervention due to perceived futility. Studies of neurosurgical interventions before or during ECMO are limited to case reports or single-center series, limiting generalizability, and outcomes in this population are unknown. We therefore sought to report the outcomes of ECMO patients with acute neurosurgical interventions at four high-volume ECMO and comprehensive stroke centers. Retrospective case series. Four academic tertiary referral hospitals in the United States. Adults (n = 24) having undergone neurosurgical procedures before or during ECMO. None. We retrospectively reviewed adults at four institutions who had undergone neurosurgical procedures immediately before or during ECMO from 2015 to 2023. The primary outcome was survival to hospital discharge. Secondary outcomes included favorable neurologic outcome (Cerebral Performance Category 1 or 2) and neurosurgical complications. Twenty-four of 2957 ECMO patients (0.8%) were included. Primary indications for neurosurgical intervention included traumatic brain (n = 8) or spinal (n = 3) injury, spontaneous intracranial hemorrhage (n = 6), and acute ischemic stroke (n = 5). Procedures included extraventricular drain (EVD) and/or intracranial pressure monitor placement (n = 10), craniectomy/craniotomy (n = 5), endovascular thrombectomy (n = 4), and spinal surgery (n = 3). Fifteen patients (63%) survived to hospital discharge, of whom 12 (80%) were discharged with favorable neurologic outcomes. Survival to discharge was similar for venoarterial and venovenous ECMO patients (8/12 vs. 7/12; p = 0.67) and those who had neurosurgery before vs. during ECMO (8/13 vs. 7/11; p = 0.92). One patient (4%) experienced a neurosurgical complication, a nonlethal tract hemorrhage from EVD placement. Survival to discharge was similar for neurosurgical and nonneurosurgical ECMO patients at participating institutions (63% vs. 57%; p = 0.58). Patients with acute neurologic injury can feasibly undergo neurosurgery during ECMO or can undergo ECMO after recent neurosurgery. Larger studies are needed to fully understand risks for bleeding and other procedure-related complications.

The Influence of Prone Positioning on Energy and Protein Delivery in COVID-19 Patients Requiring ECMO Support

Background: Gastrointestinal dysfunction is a common complication of medical nutrition therapy in critically ill patients. Whether prone positioning leads to a deterioration in gastrointestinal function has not been fully clarified. Thus, we aimed to analyze the influence of prone positioning on the tolerance of medical nutrition therapy. Methods: We conducted a retrospective analysis of 102 SARS-CoV-2 infected patients with venovenous extracorporeal membrane oxygenation support (VV ECMO). Gastric residual volume (GRV) was used to assess the tolerance of enteral nutrition. Results: Nutritional data were collected for 2344 days. Undernutrition was observed in 40.8%, with a significantly higher incidence on days in prone position (48.4% versus 38.6%, p &lt; 0.001). On days in supine position, significantly more calories were administered enterally than on days in prone position (p &lt; 0.001). The mean GRV/24 h was 111.1 mL on days in supine position and 187.3 mL on days in prone position (p &lt; 0.001). Prone positioning was associated with higher rates of GRV of ≥500 mL/24 h independent of age, disease severity at ECMO start, ECMO runtime and ICU length of stay (adjusted hazard ratio: 4.06; 95%CI: 3.0–5.5; p &lt; 0.001). Conclusions: Prone position was associated with lower tolerance of enteral nutrition, as indicated by an increased GRV. As a result, reduced enteral nutritional support was administered.

Functional and Social Recovery and Outcomes After Extracorporeal Membrane Oxygenation Support in COVID-19 Patients.

With the COVID pandemic, veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was implanted in many patients around the world. Data regarding follow-up and recovery of patients who are placed on ECMO support after COVID-related acute respiratory distress syndrome (ARDS) or ARDS for any other reason are limited. In our study, we share the 1 year follow-up results and cardiopulmonary exercise test results of the discharged patients. Between April 2020 and February 2022, a total of 29 patients who were supported with VV ECMO due to coronavirus disease 2019 (COVID-19)-related ARDS, weaned successfully and discharged to home, and who came for regular follow-up after discharge from the hospital and underwent examinations were included in the study. A total of 35 patients weaned successfully. Thirty patients were discharged to home. Mean age of the patients was 37.1 (±10.3) and 16 (55%) patients were male. Mean ECMO support time was 49.1 (±22.3) days. One year of survival after discharge was 100%. None of the patients had mobilization problems at the end of 12 month follow-up. Mean VO2 max was 18.9 at the end of 12 months. Return to work rate was 90%. We think that starting rehabilitation in the early period, and including patients in post-ECMO follow-up programs by ECMO centers will contribute significantly not only to the functional recovery of patients but also to their integration into social life.

Association Between Cerebral Microbleeds and Neurological Outcomes in Patients Who Underwent Extracorporeal Membrane Oxygenation.

Cerebral microbleeds (CMBs) are common and varied in patients receiving extracorporeal membrane oxygenation (ECMO). Here, the authors describe CMB findings in patients receiving ECMO and their association with clinical factors. A total of 138 patients receiving ECMO were enrolled and categorized as venovenous and venoarterial. Blood coagulation profiles during ECMO support and Glasgow Coma Scale (GCS) scores within 7 days were recorded. Patients with CMBs exhibited prolonged activated clotting time (P<0.001), decreased fibrinogen levels (P<0.001), reduced platelet counts (P<0.001), and extended prothrombin time (P<0.001). A significant correlation (P<0.05) was observed between the presence of CMBs and most coagulation parameters among all patients. Patients with venoarterial ECMO had significantly higher activated partial thromboplastin time, activated clotting time, and prothrombin time compared with those with venovenous ECMO (all P<0.05). Patients with a less severe CMB burden exhibited higher GCS scores and better neurological injury outcomes at both 7 and 90 days. CMB burden in all patients with ECMO was significantly correlated (P<0.05) with most blood coagulation profiles and neurological injury. CMB burdens after ECMO are common, varied, and associated with a variety of clinical conditions. These findings may guide ECMO management.

Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation.

Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients. Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (Pocc), and airway occlusion pressure during the first 0.1 seconds (P0.1) for respiratory effort. Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ2) of 0.78. There was a significant increase in propofol (p=0.01) and fentanyl (p=0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance. ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

Blood trauma in veno-venous extracorporeal membrane oxygenation: low pump pressures and low circuit resistance matter

BackgroundVeno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis.MethodsWe combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis.ResultsMinimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman’s r = 0.8) between simulated and observed hemolysis, irrespective of the pump type.ConclusionsIntegrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.