Extracorporeal Membrane Oxygenation Settings Research Articles

Antifungal Prophylaxis for Adult Recipients of Veno-Venous Extracorporeal Membrane Oxygenation: A Cautionary Stance During the COVID-19 Pandemic.

Antifungal Prophylaxis for Adult Recipients of Veno-Venous Extracorporeal Membrane Oxygenation: A Cautionary Stance During the COVID-19 Pandemic.

P0221 / #500: THE MOST AFFORDABLE CENTRIFUGAL PUMP ACHIEVES THE BEST HEMODYNAMIC PERFORMANCE IN NEONATAL AND PEDIATRIC ECMO CIRCUITS

Aims & Objectives: The objective of this translational study was to evaluate the PediMag, CentriMag, and RotaFlow centrifugal blood pumps in terms of hemodynamic performance using simulated neonatal and pediatric extracorporeal membrane oxygenation (ECMO) circuits with different sizes of arterial and venous cannulae. Cost of disposable pump heads was another important variable for this particular study. Methods: The experimental circuit was composed of one of the centrifugal pump heads, a polymethylpentene membrane oxygenator, neonatal and pediatric arterial/venous cannulae, and 1/4-inch ID tubing. Circuits were primed with lactated Ringer’s solution and packed human red blood cells (hematocrit 35%). Trials were conducted at 36°C using the three pump heads and different cannulae (arterial/venous cannulae: 8 Fr/18 Fr, 10 Fr/20 Fr, and 12 Fr/22 Fr) at various flow rates and rotational-speeds. Pseudo patient pressure was 60 mm Hg. Results: The RotaFlow pump had a higher pressure head and flow range compared with the PediMag and CentriMag pumps at the same rotational speed and identical experimental settings (P < 0.001). The PediMag pump had lower flow output than others (P < 0.001). Small-caliber arterial cannulae and higher flow-rates predictably created higher circuit-pressures and pressure-drops.Conclusions: The RotaFlow centrifugal pump had a significantly better hemodynamic performance when compared to the PediMag and CentriMag blood pumps at identical experimental conditions in simulated neonatal and pediatric ECMO settings. In addition, the cost of the RotaFlow pump head ($400) is 20 to 30-fold less than the other centrifugal pumps that were evaluated in this translational study.

Utilization of the Cabrol shunt in aortic surgery-from the ‘wrap technique’ to veno-arterial extracorporeal membrane oxygenation setting : A narrative review

The Cabrol shunt has been broadly used to control postoperative heamorrhage in aortic surgery since its first description in 1981. The initial description and its modifications aim to divert the blood from within the aneurysm wrap and/or the periaortic space to the venous system. We describe a modification in the context of central veno-arterial extracorporeal membrane oxygenation (VA-ECMO) after complex aortic surgery. A query on the PubMed was carried out using such keywords as ‘Cabrol shunt’, ‘Cabrol fistula’, ‘Aorta-atrial shunt’, ‘Perigraft shunt’, ‘Periaortic baffle’, and ‘Left-to-right shunts’. Original articles and case reports in which patients had undergone a Cabrol shunt or a modification to divert aortic bleeding to the venous circulation in the context of aortic surgery were included in the study. All publications were limited to the English language. On the other hand, abstracts and conference presentations, editorials, and correspondence comments were excluded. Finally, 18 articles and case reports were retrieved. A total of 392 cases of Cabrol shunt or a modification have been reported since 1987 with successful control of postoperative bleeding. Long-term results, when available, prove that the addition of a Cabrol shunt does not negatively affect mortality or postoperative complications, rather it decreases re-operation rates, blood transfusion, and hospital stay. Furthermore, the patency of the shunts beyond the immediate postoperative period has been described. The use of a modified Cabrol shunt in the setting of complex aortic surgery can effectively control peri-operative bleeding. Moreover, its application in other complex settings, such as central VA-ECMO, seems satisfactory.

Early rehabilitation during extracorporeal membrane oxygenation has minimal impact on physiological parameters: A pilot randomised controlled trial

BackgroundPatients on extracorporeal membrane oxygenation (ECMO) often require prolonged periods of bed rest owing to their severity of illness along with the care required to maintain the position and integrity of the ECMO cannula. Many patients on ECMO receive passive exercises, and rehabilitation is often delayed owing to medical instability, with a high proportion of patients demonstrating severe muscle weakness. The physiological effects of an intensive rehabilitation program started early after ECMO commencement remain unknown. ObjectivesThe primary objective of this study was to describe the respiratory and haemodynamic effects of early intensive rehabilitation compared with standard care physiotherapy over a 7-d period in patients requiring ECMO. MethodsThis was a physiological substudy of a multicentre randomised controlled trial conducted in one tertiary referral hospital. Consecutive adult patients undergoing ECMO were recruited. Respiratory and haemodynamic parameters, along with ECMO settings, were recorded 30 min before and after each session and continuously during the session. In addition, the minimum and maximum values for these parameters were recorded outside of the rehabilitation or standard care sessions for each 24-h period over the 7 d. The number of minutes of exercise per session was recorded. ResultsFifteen patients (mean age = 51.5 ± standard deviation of 14.3 y, 80% men) received ECMO. There was no difference between the groups for any of the respiratory, haemodynamic, or ECMO parameters. The minimum and maximum values for each parameter were recorded outside of the rehabilitation or standard care sessions. The intensive rehabilitation group (n = 7) spent more time exercising per session than the standard care group (n = 8) (mean = 28.7 versus 4.2 min, p < 0.0001). Three patients (43%) in the intensive rehabilitation group versus none in the standard care group mobilised out of bed during ECMO. ConclusionsIn summary, early intensive rehabilitation of patients on ECMO had minimal effect on physiological parameters.

EXTRACORPOREAL MEMBRANE OXYGENATION AS RESCUE THERAPY FOR COVID-19 INDUCED HYPOXIA: SINGLE-CENTER STUDY

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: To examine COVID-19 patients requiring invasive mechanical ventilation (MV) and/or Extracorporeal Membrane Oxygenation (ECMO) to better understand patient selection for ECMO, clinical management, and short-term outcomes. METHODS: Retrospective study of patients >18-years-old admitted to the hospital with COVID-19 requiring MV. Lung-protective ventilation was used in all patients with initial set PEEP of 8-10 cm H20 for plateau pressure <30 cm H20. ECMO was considered per pre-specified institutional criteria for refractory hypoxemia despite maximum-medical therapy, in qualifying patients. Exclusion criteria for ECMO included age >65 years, multi-system organ failure, and MV >10 d. Data captured included baseline patient characteristics, co-morbidities, pre-ECMO respiratory support, ECMO settings, laboratory results, and COVID-19 therapeutic interventions. RESULTS: We analyzed 59 patients who required invasive MV, including 13 who met criteria for ECMO. There were no between-group differences in gender, BMI, or co-morbidities. More ECMO patients received Tocilizumab (p=.003), but steroid use was similar (p=.44). Nine ECMO (69.2%) patients were decannulated. Crude ICU mortality was comparable between the ECMO and MV groups (6/13 [46.15%] vs. 22/46 patients [47.82%]; p=0.92). Higher pre-ECMO D-dimer (9.740 [4.84-20.00] mcg/mL vs. 3.800 [2.19-9.11] mcg/mL; p=0.05), LDH (1158 ±344.5 units/L vs. 575.9 ±124.0 units/L; p=0.001), and troponin (0.4315 ±0.465 ng/mL vs. 0.034 ±0.043 ng/mL; p=0.04) were associated with mortality. Time on MV was significantly longer in the ECMO group (563.3 [422.1-613.9] h vs. 247.9 [101.8-479] h in MV; p<.001) as well as ICU length of stay (LOS) (576.2 [457.5-652.8] h in ECMO vs. 322.2 [120.6-569.3] h in MV; p=0.01). CONCLUSIONS: ECMO was associated with prolonged MV and extended ICU LOS. Markers of coagulation, inflammation and cardiac injury were elevated in ECMO patients who did not survive. CLINICAL IMPLICATIONS: ECMO is a potentially effective rescue therapy for COVID-19 associated pneumonia. DISCLOSURES: No relevant relationships by Muhtadi Alnababteh, source=Web Response No relevant relationships by Rajus Chopra, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 07/01/2020 by Gail Drescher, source=Web Response, value=Consulting fee Technical Editor Resp Care Journal relationship with American Association for Respiratory Care Please note: $1001 - $5000 Added 07/01/2020 by Gail Drescher, source=Web Response, value=Salary No relevant relationships by Muhammad Hashmi, source=Web Response No relevant relationships by Fatima Hayat, source=Web Response No relevant relationships by Akshay Kohli, source=Web Response No relevant relationships by Emil Oweis, source=Web Response No relevant relationships by Karthik Vedantam, source=Web Response No relevant relationships by Akram Zaaqoq, source=Web Response

Low Spontaneous Breathing Effort during Extracorporeal Membrane Oxygenation in a Porcine Model of Severe Acute Respiratory Distress Syndrome.

A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.

C-reactive protein-induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII.

Activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) activity are used to monitor unfractionated heparin therapy in children on extracorporeal membrane oxygenation (ECMO). Elevated C-reactive protein (CRP) can prolong aPTT and cause discrepancy between these two assays. We aimed to evaluate CRP effect on aPTT and anti-Xa assays in the presence of heparin and to determine whether elevated CRP affects laboratory monitoring in pediatric ECMO patients. Citrated normal specimens were spiked with CRP, heparin, and recombinant factor VIII (FVIII) and followed by measurement of aPTT and anti-Xa activity. Additionally, aPTT, anti-Xa activity, FVIII, fibrinogen, and CRP were measured in 18 ECMO specimens. Elevated CRP prolonged aPTT in normal specimens with or without heparin, but did not affect anti-Xa assay. In contrast, ECMO specimens showed similar aPTT and anti-Xa values regardless of CRP level. Elevated CRP in specimens was accompanied by increased fibrinogen and FVIII activity. Additional in vitro experiments confirmed that FVIII spiked simultaneously with CRP attenuated CRP-induced aPTT prolongation in heparinized specimens. In vitro CRP-induced aPTT prolongation is not observed in pediatric ECMO samples due to concomitant FVIII increase. Discordant changes of CRP and FVIII in plasma could contribute to aPTT/anti-Xa discrepancies observed during heparin therapy in the pediatric population. The anti-Xa assay is preferable for heparin monitoring in pediatric ECMO settings.

Concerns About the Timing and Settings of Initiating Extracorporeal Membrane Oxygenation in Patients With Severe Coronavirus Disease 2019 Pneumonia

To the Editor: We read with great interest the clinical investigation reported by Yang et al (1) published in a recent issue of Critical Care Medicine. The authors describe the characteristics of patients with acute respiratory distress syndrome (ARDS) induced by the novel coronavirus disease 2019 (COVID-19) requiring extracorporeal membrane oxygenation (ECMO). They reported the mortality rate of COVID-19-induced ARDS requiring ECMO as 57.1%, which is similar to the 58.3% reported for outcomes (death or coma) in another case series (2). They also described the timing of initiation and the initial settings of ECMO in patients with severe ARDS induced by COVID-19. We would like to discuss whether the strategy they reported can be considered as standard for ECMO treatment for severe COVID-19 pneumonia. First, regarding the timing of initiating ECMO, the authors state that earlier initiation after mechanical ventilation may be associated with improved outcomes. Although early initiation is reported to be associated with good prognosis in adult ARDS patients (3), COVID-19 pneumonia is reported to present with features different from typical ARDS (4). Would different phenotypes of respiratory failure require different ECMO treatment strategies? We are still doubtful whether early initiation of ECMO can be considered similarly for typical ARDS and COVID-19 pneumonia. Addressing this will require comparisons between early initiation and late initiation groups. Second, the initial setting of ECMO in the study by Yang et al (1) seems to be unique. The authors report that many patients developed bradycardia while the centrifugal pump was on. This raises the question of whether this phenomenon is unique to COVID-19 pneumonia. Looking at the many COVID-19 case series reported to date, we find no descriptions of bradycardia elsewhere. To avoid bradycardia, the authors suggest increasing ECMO pump rotation slowly from 1,500 revolutions per minute (rpm) to the target rotation at increments of 500 rpm every 10 minutes. We speculate venovenous ECMO does not, in fact, have a significant effect on hemodynamics when initiating ECMO as long as a sufficient intravascular volume is maintained. Another report of patients with COVID-19 pneumonia requiring ECMO also described gradually increasing the rotation speed of the centrifugal pump when starting ECMO (5), but at a seemingly faster rate than Yang et al (1) reported. We question then whether it is actually possible to prevent bradycardia using the authors’ method. Finally, have the laboratory test values presented for survivors and nonsurvivors in Table 2 in (1) mistakenly been switched, given that the authors state that “survivors had a significant lower creatinine than nonsurvivors prior to ECMO”; the numbers in Table 2 in (1) are reversed. We are still in the pandemic phase of COVID-19, and thus, appropriate indications and methods for initiating ECMO support in critically ill patients with COVID-19 pneumonia are important to establish.

Pharmacokinetic Assessment of Pre- and Post-Oxygenator Vancomycin Concentrations in Extracorporeal Membrane Oxygenation: A Prospective Observational Study.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life support frequently utilized in catastrophic lung and or cardiac failure. Patients on ECMO often receive vancomycin therapy for treatment or prophylaxis against Gram-positive organisms. It is unclear if ECMO affects vancomycin pharmacokinetics, thus we modeled the pharmacokinetic behavior of vancomycin according to ECMO-specific variables. Adult patients receiving vancomycin and Veno-Arterial-ECMO between 12/1/2016 and 10/1/2017 were prospectively enrolled. Extracorporeal membrane oxygenation settings and four sets of pre- and post-oxygenator vancomycin concentrations were collected for each patient. Compartmental models were built and assessed ECMO flow rates on vancomycin clearance and potential circuit sequestration. Bayesian posterior concentrations of the pre- and post-oxygenator concentrations were obtained for each patient, and summary pharmacokinetic parameters were calculated. Simulations were performed from the final model for efficacy and toxicity predictions. Eight patients contributed 64 serum concentrations. Patients were a median (interquartile range) age of 58.5years (50.8-62.3) with a calculated creatinine clearance of 39mL/min (29.5-62.5) and ECMO flow rates of 3980mL/min (interquartile range = 3493.75-4132.5). A three-compartment model best fit the data (Bayesian: plasma pre-oxygenation R2 = 0.99, post-oxygenation R2 = 0.99). Vancomycin clearance was not impacted by ECMO flow rate (p = 0.7). Simulations demonstrated that vancomycin 1g twice daily was rarely sufficient for minimum inhibitory concentrations > 0.5mg/L. Doses ≥ 1.5g twice daily often exceeded toxicity thresholds for exposure. Extracorporeal membrane oxygenation flow rates did not influence vancomycin clearance between flow rates of 3500 and 5000mL/min and vancomycin was not sequestered in ECMO. Common vancomycin regimens resulted in suboptimal efficacy and/or excessive toxicity. Individual therapeutic drug monitoring is recommended for patients on ECMO.

New noninvasive methodology to measure cardiac output in veno-venous extracorporeal membrane oxygenation patients.

Cardiac output (CO) measurement is vital in veno-venous extracorporeal membrane oxygenation patient population to evaluate oxygen delivery and to early identify right heart failure. Standard clinical methods like pulmonary artery thermodilution and transpulmonary thermodilution are known to be inaccurate in the veno-venous extracorporeal membrane oxygenation setting, especially at high levels of recirculation. The aim of the study was to develop a simple noninvasive method to measure CO in patients during veno-venous extracorporeal membrane oxygenation. A mathematical model was developed where CO was analyzed as a combination of two flows: oxygenated blood from extracorporeal membrane oxygenation and less oxygenated mixed venous blood. The system of two mass balance equations for oxygen saturations was introduced to calculate CO. The procedure included measurement of recirculation (ELSA Monitor Transonic Systems Inc. Ithaca, USA) and arterial saturation at two extracorporeal membrane oxygenation flows after temporary pump flow decrease. Mathematic modeling that utilized a crude Monte Carlo method was used to analyze theoretical errors in CO calculations from unknown behavior of venous saturation. The developed concept was retrospectively applied to clinical data archive of 17 adult patients on veno-venous extracorporeal membrane oxygenation that included 52 measurement sessions. Mathematical modeling suggests that proportion of results with error ⩽10% was between 86% and 100% if pre-oxygenated saturation was available and it was between 78% and 86% if pre-oxygenated saturation was not available. Application of two mass balance equation concept to clinical data suggests that as the decrease of the arterial saturation reaches 6% due to flow decrease, then CO calculations becomes highly reliable as 96% (2 standard deviations) of the results has a reproducibility within 6.4%. The mathematical model and clinical retrospective analysis demonstrates that the new methodology has the potential to accurately measure CO in veno-venous extracorporeal membrane oxygenation patients. The next step is validation in animal and clinical settings.

Characteristics and outcomes of extracorporeal life support in pediatric trauma patients.

Extracorporeal life support utilizing extracorporeal membrane oxygenation (ECMO) techniques has been used in the pediatric population for numerous indications, but its use in trauma has been understudied. We sought to examine the indications, characteristics, and outcomes of children placed on ECMO for trauma and hypothesized that outcomes would be equivalent to those of patients placed on ECMO for other indications. We performed a retrospective review of all pediatric trauma patients in the Extracorporeal Life Support Organization registry from 1989 to 2018. Patient characteristics, indications for ECMO, pre- and post-ECMO ventilator settings and blood chemistry, complications, and survival rates were examined. Categories were stratified by mode: venovenous (VV), veno-arterial (VA), or conversion. Data were analyzed using SPSS software, with significance considered at p value less than 0.05. We identified 573 patients with a median age of 4.82 years. The majority of patients (62.3%) were male and on VA support (54.5%). Drowning (38.7%) was the most common mechanism, followed by burns (21.1%) and thoracic trauma (17.8%). Complication rates were high (81.9%), with the most frequent types being cardiovascular, mechanical, and hemorrhagic. Incidences of complications (overall and by type) were similar to those reported in other Extracorporeal Life Support Organization cohorts. Overall survival was 55.3% and was significantly higher (p = 0.00) for patients on VV (74.3%) compared with those on VA (41.7%), even when controlling for mechanism. Survival and complication rates of pediatric trauma patients on ECMO are comparable to those reported for other indications. Trauma should not be considered a contraindication for ECMO. Therapeutic, level V.

Fluid Overload and Mortality in Patients with Severe Acute Kidney Injury and Extracorporeal Membrane Oxygenation.

Volume overload is increasingly being understood as an independent risk factor for increased mortality in the setting of AKI and critical illness, but little is known about its effect in the setting of extracorporeal membrane oxygenation (ECMO). We sought to evaluate the incidence of AKI and volume overload and their effect on all-cause mortality in adults after ECMO cannulation. We identified all adult patients who underwent ECMO cannulation at the University of Chicago between January 2015 and March 2017. We evaluated the incidence of KDIGO-defined AKI, RRT, and volume overload. Volume overload was defined as achieving a positive fluid balance of 10% above admission weight over the first 72 hours after ECMO cannulation. The primary outcome collected was 90 day all-cause mortality. Secondary outcomes included 30-day mortality, duration of ECMO and RRT therapy, length of stay, and dialysis independence at 90 days. There were 98 eligible patients, 83 of whom developed AKI (85%); 48 (49%) required RRT and 19 (19%) developed volume overload at 72 hours. Patients with volume overload had increased risk of death at 90 days compared with those without volume overload (HR, 2.3; 95% CI, 1.3 to 4.2; P=0.004). Patients with AKI-D had increased risk of death at 90 days compared with those without AKI-D (HR, 2.2; 95% CI, 1.3 to 3.8; P=0.004). Volume overload remained an independent predictor of 90-day mortality when adjusting for RRT, APACHE score, weight (kg), diabetes, and heart failure (HR, 2.9; 95% CI, 1.4 to 6.0; P=0.003). Volume overload and AKI are common and have significant prognostic value in patients treated with ECMO. Initiating RRT may help to control the deleterious effects of volume overload and improve mortality.

Viability of Mesenchymal Stem Cells in an Ex Vivo Circulation System.

Extracorporeal membrane oxygenation (ECMO) is a well-known therapy for refractory cardiac and respiratory failure. Stem cell therapy has been investigated as an adjunctive treatment for use during ECMO, but little is known about the viability of stem cells during ECMO support. We evaluated the viability and activity of mesenchymal stem cells (MSCs) in ex vivo circulation (EVC) conditions. The experimental groups were divided into two subgroups: EVC with oxygenator (OXY group) and EVC without oxygenator (Non-OXY group). Mesenchymal stem cells (1.0 × 10) were injected into the EVC system. Cell counting, a lactate dehydrogenase (LDH) cytotoxicity assay, and the mitochondrial functions of viable MSCs were analyzed. The post-EVC oxygen consumption rate (OCR) was significantly lower than the pre-EVC OCR, regardless of whether the oxygenator was used. The LDH levels were significantly higher in the OXY group than in the Non-OXY group. The cellular loss was mainly due to lysis of the cells whereas the loss of cellular activity was attributed to the nonphysiologic condition itself, as well as the oxygenator. We concluded that direct infusion of MSCs during ECMO support did not serve as adjunctive therapy. Further studies are needed to improve the viability in an ECMO setting.

The use of extracorporeal membrane oxygenation in human immunodeficiency virus-positive patients: a review of a multicenter database.

We chose to evaluate the survival of extracorporeal membrane oxygenation among patients with human immunodeficiency virus in a multicenter registry. Retrospective case review of the Extracorporeal Life Support Organization Registry respiratory failure of all patients with human immunodeficiency virus supported with extracorporeal membrane oxygenation. A total of 126 patients were included. Survival to discharge was 36%. Eight infants were supported with extracorporeal membrane oxygenation and three (37.5%) survived to discharge. Respiratory extracorporeal membrane oxygenation was the primary indication (78%) with a 39% survival, while cardiac and extracorporeal cardiopulmonary resuscitation indications accounted for 16% and 6% of patients with survivals of 30% and 12.5%, respectively. These differences did not reach significance. There were no significant differences between survivors and non-survivors in demographic data, but non-survivors had significantly more non-human immunodeficiency virus pre-extracorporeal membrane oxygenation infections than survivors. There were no differences in other pre-extracorporeal membrane oxygenation supportive therapies, mechanical ventilator settings, or arterial blood gas results between survivors and non-survivors. The median duration of mechanical ventilation prior to cannulation was 52 (interquartile range: 13-140) hours, while the median duration of the extracorporeal membrane oxygenation exposure was 237 (interquartile range: 125-622) hours. Ventilator settings were significantly lower after 24 hours compared to pre-extracorporeal membrane oxygenation settings. Complications during extracorporeal membrane oxygenation exposure including receipt of renal replacement therapy, inotropic infusions, and cardiopulmonary resuscitation were more common among non-survivors compared to survivors. Central nervous system complications were rare. Survival among patients with human immunodeficiency virus infection who receive extracorporeal membrane oxygenation was less than 40%. Infections before extracorporeal membrane oxygenation cannulation occurred more often in non-survivors. The receipt of renal replacement therapy, inotropic infusions, or cardiopulmonary resuscitation during extracorporeal membrane oxygenation was associated with worse outcome.

Exposure of patients to di(2-ethylhexy)phthalate (DEHP) and its metabolite MEHP during extracorporeal membrane oxygenation (ECMO) therapy.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) is often used for PVC medical devices, that are also largely used for intensive care medical treatments, like extracorporeal membrane oxygenation (ECMO) therapy. Due to the toxicological potential of DEHP, the inner exposure of patients with this plasticizer is a strong matter of concern as many studies have shown a high leaching potential of DEHP into blood. In this study, the inner DEHP exposure of patients undergoing ECMO treatment was investigated. The determined DEHP blood levels of ECMO patients and the patients of the control group ranged from 31.5 to 1009 μg/L (median 156.0 μg/L) and from 19.4 to 75.3 μg/L (median 36.4 μg/L), respectively. MEHP blood levels were determined to range from < LOD to 475 μg/L (median 15.9 μg/L) in ECMO patients and from < LOD to 9.9 μg/L (median 3.7 μg/L) in the control group patients, respectively. Increased DEHP exposure was associated with the number of cannulas and membranes of the ECMO setting, whereas residual diuresis decreased the exposure. Due to the suspected toxicological potential of DEHP, its use in medical devices should be further investigated, in particular for ICU patients with long-term exposure to PVC, like in ECMO therapy.

IP153. Patients Undergoing Fasciotomy in the Setting of Extracorporeal Membrane Oxygenation Have a High Rate of Amputation With Poor Overall Survival and Functional Status

The rate of extracorporeal membrane oxygenation (ECMO) placement is increasing. The large cannulas needed for ECMO can result in significant peripheral vascular complications. Lower extremity fasciotomy is performed relatively frequently in the setting ECMO and compartment syndrome. The outcomes of lower extremity fasciotomy in the setting of ECMO are not well-described in the literature. The purpose of our study was to evaluate survival, limb salvage rate and functional status at 6 months of patients undergoing lower extremity fasciotomy in the setting of ECMO. A single institution, a retrospective review of a prospectively maintained database identifying all patients placed on ECMO at our institution from 2015 through 2018 was performed. All patients who underwent fasciotomy were evaluated. The primary end point was amputation-free survival at time of discharge. Five hundred two patients were placed on ECMO from 2015 to 2018 (Fig). Twenty-three patients (4.5%) required one or more fasciotomies for compartment syndrome. Twenty-two of 23 patients were placed on VA ECMO for cardiogenic shock, with one patient on veno-venous (VV) ECMO for acute respiratory distress syndrome. The mean age of patients receiving fasciotomy was 54.6 ± 14.9 years. Sixteen patients had reperfusion catheters in place at the time of diagnosis of compartment hypertension. No patients had reperfusion catheters placed after the time of diagnosis. Of the 23 who received fasciotomies, 16 patients died during their index hospitalization. Seven patients survived to discharge. Five of the surviving seven (71%) required major amputation. The two patients whose limbs were salvaged continued to have limited mobility at the 6-month follow-up. The only patient with no functional deficits, received an above the knee amputation while hospitalized (Fig). This is the first study to specifically evaluate the morbidity and mortality of ECMO patients who require fasciotomy. These data demonstrate that the majority of individuals requiring fasciotomy die during their hospitalization and of those who survive, most require amputation. Overall amputation-free survival is less than 9% in this patient population, with those surviving having poor functional status at the 6-month follow-up. The high mortality rates and poor long-term functional status question efficacy of fasciotomy in ECMO patients.

Two-stage weaning strategy using veno-veno-arterial perfusion for patients on extracorporeal membrane oxygenation following cardiogenic shock.

Veno-arterial extracorporeal membrane oxygenation represents the last therapy option in refractory cardiogenic shock. Successful weaning becomes difficult if the myocardial function recovers but pulmonary impairment persists. We present our experience with a new weaning strategy, using a stepwise mode-switch from veno-arterial to veno-veno-arterial and veno-venous extracorporeal membrane oxygenation setting for patients with primary cardiogenic shock and subsequent respiratory failure. From 81 patients treated with veno-arterial extracorporeal membrane oxygenation following acute cardiogenic shock between January 2014 and April 2018, eight patients with cardiac and pulmonary failure were identified to be treated using the following protocol: patients were put on veno-arterial extracorporeal membrane oxygenation, a second inflow cannula was inserted via the right jugular vein and cardiac weaning was performed via veno-veno-arterial support. Finally, patients were pulmonary weaned via veno-venous extracorporeal membrane oxygenation mode. In the mode-switch group, etiologies of cardiogenic shock were cardiac arrest (12.5%), myocardial infarction (12.5%) and post-cardiotomic heart failure (75%). Mean time between onset of cardiogenic shock and start of veno-arterial extracorporeal membrane oxygenation was 76 ± 117 min. At implantation, lactate and pH values were 9.5 ± 5.0 mmol/L and 7.2 ± 0.2. Total extracorporeal membrane oxygenation-time was 9.3 ± 4.7 days, with a mode-switch from veno-arterial to veno-veno-arterial after 3.9 ± 2.7 days. The weaning rate in the mode-switch group was 75% (vs. 41% in the entire cohort) and the 30-day survival was 50% (vs 32% in the cohort). 38% of the patients presented a favorable neurological outcome. Mode-switch from veno-arterial to veno-veno-arterial and weaning via veno-venous extracorporeal membrane oxygenation mode is feasible for combined cardiac and pulmonary failure, with promising results due to an optimized pre-pulmonary oxygenation.

Mesenchymal stem cells may ameliorate inflammation in an ex vivo model of extracorporeal membrane oxygenation.

Mesenchymal stem cells exhibit immunomodulatory properties which are currently being investigated as a novel treatment option for Acute Respiratory Distress Syndrome. However, the feasibility and efficacy of mesenchymal stem cell therapy in the setting of extracorporeal membrane oxygenation is poorly understood. This study aimed to characterise markers of innate immune activation in response to mesenchymal stem cells during an ex vivo simulation of extracorporeal membrane oxygenation. Ex vivo extracorporeal membrane oxygenation simulations (n = 10) were conducted using a commercial extracorporeal circuit with a CO2-enhanced fresh gas supply and donor human whole blood. Heparinised circuits (n = 4) were injected with 40 × 106-induced pluripotent stem cell-derived human mesenchymal stem cells, while the remainder (n = 6) acted as controls. Simulations were maintained, under physiological conditions, for 240 minutes. Circuits were sampled at 15, 30, 60, 120 and 240 minutes and assessed for levels of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumour necrosis factor-α, transforming growth factor-β1, myeloperoxidase and α-Defensin-1. In addition, haemoglobin, platelet and leukocyte counts were performed. There was a trend towards reduced levels of pro-inflammatory cytokines in mesenchymal stem cell-treated circuits and a significant increase in transforming growth factor-β1. Blood cells and markers of neutrophil activation were reduced in mesenchymal stem cell circuits during the length of the simulation. As previously reported, the addition of mesenchymal stem cells resulted in a reduction of flow and increased trans-oxygenator pressures in comparison to controls. The addition of mesenchymal stem cells during extracorporeal membrane oxygenation may cause an increase in transforming growth factor-β1. This is despite their ability to adhere to the membrane oxygenator. Further studies are required to confirm these findings.

Quantitative assessment of peripheral limb perfusion using a modified distal arterial cannula in venoarterial ECMO settings.

In cases of severe cardiopulmonary deterioration, quick establishment of venoarterial extracorporeal membrane oxygenation (ECMO) represents a support modality. After successful arterial peripheral cannulation, a certain grade of peripheral limb malperfusion is a fairly common phenomenon. Detection of peripheral malperfusion is vital, since it can result in compartment syndrome or even loss of the affected limb. To prevent or resolve emerging lower limb ischaemia, a newly designed perfusion catheter is placed into the superficial femoral artery, distal to the arterial cannula via ECMO. The aim of our study was to evaluate flow and haemodynamic characteristics of this novel distal limb perfusion cannula for ECMO therapy and present these important findings for the first time. The distal perfusion cannula blood flow increases in linear correlation with ECMO blood flow The variability of distal perfusion cannula blood flow with a 15 Fr cannula ranges between 160 ± 0.40 mL min-1 at 1.5 L min-1 ECMO flow rate and 480 ± 80 mL min-1 at 5.0 L min-1 ECMO blood flow, respectively. Comparatively, the 17-Fr-sized cannula performs on a scale of 140 ± 20 to 390 ± 60 mL distal perfusion cannula blood flow at 1.5-5.0 L min-1 ECMO blood flow, respectively. The quantitative assessment of the distal perfusion cannula blood flow has revealed that distal perfusion cannula blood flow can measure up to 10% of the ECMO blood flow. Furthermore, it has been also well demonstrated that the novel distal perfusion cannula is sufficient to compensate peripheral limb ischaemia.

Evaluation of centrifugal blood pumps in term of hemodynamic performance using simulated neonatal and pediatric ECMO circuits

The objective of this translational study was to evaluate the FDA-approved PediMag, CentriMag, and RotaFlow centrifugal blood pumps in terms of hemodynamic performance using simulated neonatal and pediatric extracorporeal membrane oxygenation (ECMO) circuits with different sizes of arterial and venous cannulae. Cost of disposable pump heads was another important variable for this particular study. The experimental circuit was composed of one of the centrifugal pump heads, a polymethylpentene membrane oxygenator, neonatal and pediatric arterial/venous cannulae, and 1/4-inch ID tubing. Circuits were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 35%). Trials were conducted at 36°C using the three pump heads and different cannulae (arterial/venous cannulae: 8Fr/18Fr, 10Fr/20Fr, and 12Fr/22Fr) at various flow rates (200-2400 mL/min, 200 mL/min increments) and rotational speeds. Pseudo patient pressure was 60 mmHg. Real-time pressure and flow data were recorded for analysis. The RotaFlow pump had a higher pressure head and flow range compared with the PediMag and CentriMag pumps at the same rotational speed and identical experimental settings (P<0.001). The PediMag pump had lower flow output than others (P<0.001). Small-caliber arterial cannulae and higher flow rates predictably created higher circuit pressures and pressure drops. There was no significant difference in hemodynamic energy delivered to the pseudo patient with each of the three pumps. The arterial cannula had the highest pressure drop and hemodynamic energy loss in the circuit when compared to the oxygenator and arterial tubing. The RotaFlow centrifugal pump had a significantly better hemodynamic performance when compared to the PediMag and CentriMag blood pumps at identical experimental conditions in simulated neonatal and pediatric ECMO settings. In addition, the cost of the RotaFlow pump head ($400) is 20 to 30-fold less than the other centrifugal pumps [CentriMag ($12000) or PediMag ($8000)] that were evaluated in this translational study.