Extracorporeal Life Support Therapy Research Articles

BIO31: Novel Size-Variable Dedicated Rodent Oxygenator for ECLS Animal Models – Introduction of the “Ratox” Oxygenator and Preliminary In-Vitro Results

Introduction: Extracorporeal life support (ECLS) grows in relevance. However, the survival rate of ECLS remains low, overall at around 60 %, mostly due to hemocompatibility issues. Research and development in the field is slow due to several factors, including the lack of sophisticated experimental platforms and models. This publication introduces a rodent–sized oxygenator module (“RatOx”) to enable early and large–scale in–vitro and in–vivo studies, followed by preliminary in–vitro classification tests on gas transfer performance. The oxygenator is designed to allow extensive in–vitro testing with donated human blood as well as economic and reproducible in–vivo testing for fundamental research. Materials and Methods: The novel RatOx’ main feature is the adaptable fiber module size suitable for various rodents like mice, rats, or hamsters. The effective membrane surface area is variable between approximately 10 cm2 and 600 cm2. The priming volume, and hence the hemodilution of the supported small animal, is kept at a minimum. Any type of semipermeable hollow fiber with any surface modification or coating can be mounted. The housing is transparent, hemocompatible, sterilizable and reusable. Oxygen transfer and carbon dioxide transfer over the oxygenator membrane were tested for different blood flows and fiber module sizes according to DIN EN ISO 7199. Similar experiments were conducted by an independent laboratory to test the transferability of the system to other institutions. Results: At the maximum possible amount of effective fiber surface and a blood flow of 100 ml/min, the oxygenator performance has been tested to a maximum of 5.5 ml O2/min and –5.5 ml CO2/min, respectively. For the same operating point, results from the independent laboratory showed transfer rates of 6.27 ml O2/min and –8.2 ml CO2/min, respectively. The priming volume for this the largest fiber module is 5.4 ml, while the smallest possible configuration with a single fiber mat layer has 1.1 ml of priming volume. Discussion, conclusion and outlook: The novel RatOx ECLS system has been evaluated in–vitro to comply to a high degree with all predefined functionality criteria for rodent–sized animal models. The maximum gas transfer efficacy for full-support-scenarios was measured to be approximately 70–80 % of the intended value pre–defined as the demand of a resting Sprague–Dawley rat. The priming volume translates into an oxygenator–caused hemodilution of approximately 25 %. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology. This presentation includes evidence that this system is variable, yet very robust, allowing cross–lab and cross–model testing.

Novel Size-Variable Dedicated Rodent Oxygenator for ECLS Animal Models—Introduction of the “RatOx” Oxygenator and Preliminary In Vitro Results

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator (“RatOx”) and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.

Quality of life after extra corporeal life support therapy.

Extra Corporeal Life Support (ECLS) may be a life-saving treatment for patients with reversible cardiac and/or respiratory failure. ECLS is associated with a high risk of complications and mortality. Because only a small number of studies have been conducted into the long-term effects of ECLS, we investigated the difference in quality of life, anxiety and depressive complaints and PTSD 3months after ICU discharge. It is a retrospective case-control study covering the period January 2012 to December 2017. The ECLS patient group was compared to a matched similar patient group in the Intensive Care (IC) that did not have ECLS therapy. Quality of life was measured with the Short-Form-36 (SF-36) questionnaire, anxiety and depression was measured with the Hospital Anxiety and Depression Scale (HADS) questionnaire and for PTSD the Impact of Events Scale (IES) questionnaire was used, comparing sum scores and cut-off points of scores from both groups. Included were 19 patients in the ECLS group and 38 in the control group. The mean sum scores on the sub scales of the SF36 questionnaire were the same for both groups. Only the mean score of 66.2 (scale 0-100) on the domain 'general health experience' was statistically significantly different in the ECLS group than in the control group (56.8, p = .02). There was no significant difference between the sum scores of both groups on anxiety and depressive complaints. In the ECLS group 32% of the patients may have a depressive disorder versus 18% from the control group (p = .32). And 26% of the patients from the ECLS group may have an anxiety disorder versus 7% from the control group (p = .51). The incidence of PTSD was 42% in the ECLS group and 24% in the control group (p = .22). We found no statistically significant difference in quality of life, anxiety and depressive symptoms and PTSD symptoms between ECLS patients and the matched control group - 3months after the ICU discharge. The incidence of anxiety and depressive symptoms and PTSD in the ECLS group is higher than in the control group, however, this difference is not significant.

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients.

BackgroundExtracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time.MethodsThis retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019.ResultsECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87–0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock.ConclusionsIn-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy.

Extubation and Noninvasive Ventilation of Patients Supported by Extracorporeal Life Support for Cardiogenic Shock: A Single-Center Retrospective Observational Cohort Study.

Background:Temporary extracorporeal life support (ECLS) by venoarterial extracorporeal membrane oxygenation is an emerging therapy for patients with severe, ongoing cardiogenic shock. After stabilization of the hemodynamic status and end-organ function, sedation weaning, extubation, and noninvasive ventilation (NIV) can be attempted. The goal of this study was to analyze the feasibility of extubation and NIV during versus after ECLS for cardiogenic shock.Methods:Single-center retrospective observational study of 132 patients undergoing ECLS due to severe cardiogenic shock between January 2015 and December 2016 at a tertiary care university hospital.Results:Patients received ECLS due to acute myocardial infarction (20.6%), ongoing cardiogenic shock (15.2%), postoperative low-cardiac-output syndrome (24.2%), and extracorporeal cardiopulmonary resuscitation (40.2%). Overall, intensive care unit survival was 44.7%. Sixty-nine (52.3%) patients could never be extubated. Forty-three (32.6%) were extubated while on ECLS support (group 1) and 20 (15.1%) were extubated after weaning from ECLS (group 2). Patients extubated during ECLS had a significantly shorter total time on ventilator (P = .003, mean difference: −284 hours [95% confidence limits: −83 to −484]) and more invasive ventilation free days (P = .0018; mean difference 8 days [95%CL: 2-14]). Mortality and NIV failure rates were similar between groups.Conclusions:Extubation and NIV are feasible in patients who stabilize during ECLS therapy. Further studies need to address whether extubation has the potential to improve patients outcome or if the feasibility to extubate is a surrogate for disease severeness.

Insight into ECMO, Mortality and ARDS: A Nationwide Analysis of 45,647 ECMO Runs

Background: Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. Methods: Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The ICD and OPS codes for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used. Findings: A total of 45,647 hospitalized patients treated with ECLS were analysed. Overall hospital mortality remains higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% percent from 825 in 2005 to 2,768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. Interpretation: ARDS is a severe disease with a high mortality rate despite ECLS therapy. The mortality rate differs widely in studies such as the CESAR trial and the EOLIA trial and the ELSO Registry in Germany. Funding Statement: This study was supported by internal institutional research funds from the Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt Germany. Declaration of Interests: Dr. Mutlak received lecture fees from GETINGE and conducted workshops for GETINGE. Dr. Friedrichson, Dr. Piekarski and Prof. Zacharowski have no conflicts of interest regarding the article.

Hemoadsorption treatment with CytoSorb® in patients with extracorporeal life support therapy: A case series.

Extracorporeal life support is an increasingly used technique for respiratory and cardiocirculatory support. Besides primary organ dysfunction, an excessive systemic hyperinflammatory response can be the underlying cause for acute organ failure necessitating extracorporeal life support therapy, or it may be associated with the extracorporeal life support itself. Controlling this overwhelming inflammatory response using CytoSorb® hemoadsorption has been shown to be associated with improved hemodynamics and restored metabolic balance resulting in preserved organ functions. In this retrospective case series, we describe 23 patients undergoing extracorporeal life support therapy and CytoSorb hemoadsorption. Cytokine levels were monitored, hemodynamic and metabolic variables were recorded, and outcome measures such as duration of organ support, intensive care unit mortality, and hospital mortality were noted. CytoSorb treatment was associated with a trend toward a reduction in plasma cytokine levels (first treatment median interleukin-6 pre 595 vs post 350 pg/mL (n.s.); second treatment median interleukin-6 317 vs 108 pg/mL, p < 0.05), a reduced vasoplegic response resulting in a reduction in vasopressor requirements (first treatment median norepinephrine pre 0.15 vs post 0.02 µg/kg/min (n.s.); second treatment median norepinephrine 0.1 vs 0.02 µg/kg/min, p < 0.05) as well as rebalancing of deranged metabolic parameters (first treatment median lactate pre-treatment 6 vs post-treatment median lactate 2 mmol/L, p < 0.05). The hemoperfusion treatment was well tolerated and safe, without the occurrence of any CytoSorb device-related adverse events. Hemoadsorption may offer a potentially promising therapeutic option for critically ill patients undergoing extracorporeal life support therapy, with cytokine reduction and a consecutively mitigated inflammatory response, decreased vasoplegia, and improved organ function as seen in our patients.

Impact of preoperative extracorporeal life support on left ventricular assist device outcomes: A comparative study.

To investigate whether preoperative short-term extracorporeal life support therapy in patients undergoing continuous-flow left ventricular assist device implantation has an impact on the outcome regarding survival and adverse events. Between January 2011 and May 2018, 100 consecutive patients received HeartMate II, HeartWare, or HeartMate III for end-stage heart failure. Mean age was 64.2 ± 10.3 years. Three patient groups were identified: without preoperative extracorporeal life support (non-extracorporeal life support group, n = 80), with preoperative extracorporeal life support due to postcardiotomy shock after conventional cardiac surgery (postcardiotomy shock group, n = 9), and with preoperative extracorporeal life support without previous surgery (non-postcardiotomy shock group, n = 11). The primary endpoint was overall survival after device implantation. Secondary endpoints were adverse events during the follow-up period. Survival was significantly different between the groups (p < 0.05): 30-day, 6-month, and 1-year survival rates were 85%, 68%, and 61% for non-extracorporeal life support group; 44%, 22%, and 22% for postcardiotomy shock group; and 45%, 27%, and 24% for non-postcardiotomy shock group, respectively. Furthermore, in both extracorporeal life support groups (postcardiotomy shock and non-postcardiotomy shock), there were a higher incidence (p < 0.05) of postoperative right heart failure (30% vs 66.7% vs 54.5%), acute renal failure requiring dialysis (20% vs 77.8% vs 54.5%), and respiratory failure (31.3% vs 88.9% vs 81.8%). Continuous-flow left ventricular assist device implantation with prior extracorporeal life support appears to have a worse outcome regarding survival, right heart failure, renal and respiratory dysfunction (p < 0.05). Future studies have to be done to evaluate the outcome after extracorporeal life support bridge pre-left ventricular assist device, especially as ultima ratio in postcardiotomy shock patients.

Extracorporeal Life Support as a Bridge to Lung Transplantation: A Single-Center Experience With an Emphasis on Health-Related Quality of Life.

Extracorporeal life support (ECLS) as a bridge to lung transplantation is increasingly used, but information on long-term outcome is scarce. We aim to summarize our experience with an emphasis on health-related quality of life. Secondary outcomes include ICU and hospital stay and pre- and post-transplant mortality. A retrospective cohort study of all adult subjects receiving ECLS as a bridge to lung transplantation from 2010 to 2014 was reviewed and compared with all adult subjects who underwent bilateral lung transplantation in the same period. For the ECLS group, the general health status was assessed with the use of the EuroQol Group 5-Dimension Self-Report Questionnaire. A total of 130 bilateral transplants were performed, 9 transplants were performed after ECLS therapy. Another 11 subjects died on the waiting list while receiving ECLS. Quality of life, at 12 months after surgery, from a subject's perspective was comparable in both groups with a median score of 80 on the visual analog scale. The median (interquartile range [IQR]) EuroQol Group 5-Dimension Self-Report Questionnaire 3L score from the societal perspective in the ECLS group was 0.73 (0.5-0.9). Median (IQR) ICU stay was 25 d (9-68 d) for the ECLS group versus 7 d (4-18 d) for the control group (P = .001), and in-hospital stay was 66 d (40-114 d) versus 42 d (29-62 d) (P = .004). ECLS can be used as a bridge to lung transplantation. A significant number of subjects were not bridged successfully due to different reasons. Outcomes after successful transplantation after ECLS might be comparable with the general population undergoing lung transplantation in terms of quality of life, lung function, performance tests, and mortality, although ICU and hospital stay are longer.

Hospital Costs Of Extracorporeal Life Support Therapy.

To conduct an exploration of the hospital costs of extracorporeal life support therapy. Extracorporeal life support seems an efficient therapy for acute, potentially reversible cardiac or respiratory failure, when conventional therapy has been inadequate, or as bridge to transplant, but unfortunately, no evidence in randomized controlled trials is delivered yet. Single-center retrospective exploratory cohort cost study. The study is performed from a hospital perspective with a time horizon of patients' complete hospital admission in which they received extracorporeal life support. ICU of a university teaching hospital in The Netherlands. All 67 consecutive adult patients who were admitted to the ICU of the University Medical Center Groningen in the period 2010-2013 and received extracorporeal life support treatment. None. The bottom-up microcosting method was used except when stated otherwise. Medical costs were estimated by multiplying every registered healthcare consumption with unit prices. Unit prices were largely based on Dutch reference prices. For each patient, the personnel costs and material costs were assessed in detail. The costs of extracorporeal life support were differentiated in costs of procedures and costs of daily surcharge of therapy. Procedure-related costs were subdivided in costs of devices and disposables, costs of additional human resources, and surgery hours. The mean total hospital costs were € 106.263 (€ 83.841 to € 126.266) per patient ($145,580). On average, 52% of the total costs arose from hospital nursing days and 11% of direct procedure-related extracorporeal life support costs. Surgery and diagnostics represented a vast amount of the remaining costs. This large and detailed economic evaluation of hospital costs of extracorporeal life support therapy in the Netherlands showed that mean total hospital cost of extracorporeal life support treatment is € 106.263 per patient. The majority of the costs are composed of nursing days.

HOSPITAL COSTS OF EXTRACORPOREAL LIFE SUPPORT THERAPY

Extracorporeal life support (ECLS) seems an efficient therapy for acute, potentially reversible cardiac or respiratory failure, when conventional therapy has been inadequate, or as bridge to transplant, but there is no evidence for cost-effectiveness. Our aim was to conduct an exploration of the hospital costs of ECLS therapy.

Abstract 21: Mobile Extracorporeal Life Support for Patients With Refractory Cardiogenic Shock or Reanimation - The Concept of a Regional Supply Network

Objectives: To prove the concept of a regional supply network for mobile extracorporeal life support (ECLS), provided by an university heart centre, specialised on mechanical support. Methods: We established a mobile ECLS service for regional catheter laboratories (cath-lab). We included patients with severe refractory cardiogenic shock and/or resuscitation if locally available therapies failed and a safe transport to a heart centre was not possible. Without immediate mechanical support the patients are considered to die. Logistic optimization was achieved by 1) use of a miniaturized ECLS device (Life Box, Sorin), which is 24-hours instantly ready for use, 2) provision of a passenger car with flash lights for going, 3) placement of stickers with the 24 hours emergency numbers on prominent places, 4) training of cardiologists in insertion of femoral ECLS cannulae. Results: Seven cath-labs joined the supply network. From 08/2011 until 05/2012 mobile ECLS was used in 39 cases (age: 3 to 86 years; mean 58). Distance: 0.5 to 224 km. Resuscitation time: 5 -240 min. All patients received on-site femoral veno-arterial ECLS. Duration of support: 1 to 28 days (mean:8.3). Further treatment include: implantation of a ventricular assist device, cardiac transplantation, coronary artery bypass grafting, left ventricular thrombectomie, PTCA, mitral- and aortic valve replacement. 30-day survival without significant neurological deficits was 44% for men, 50% for women. Conclusion: Mobile ECLS therapy, using recent technology, offers new options for patients, who are otherwise likely to die. The concept of a regional ECLS supply network ensures an optimized logistic and minimization of loss of time

Nosocomial catheter-related bloodstream infections in a pediatric intensive care unit: Risk and rates associated with various intravascular technologies*

Nosocomial bloodstream infections are associated with increased patient morbidity, mortality, and hospital costs. More than 90% of these infections are related to the use of intravascular catheter devices. This study was done to assess the risk and rates of catheter related-bloodstream infections (CR-BSI) associated with different intravascular technologies in a pediatric intensive care unit population. Retrospective cohort study. A 16-bed pediatric intensive care unit in a tertiary children's hospital. All admissions between July 1997 and December 1999 requiring placement of an intravascular access device for care were examined. Patients with CR-BSI were identified through ongoing surveillance using Centers for Disease Control/National Nosocomial Infections Surveillance System definitions for bloodstream infection. None. Of the 2,728 admissions during the review period, 1,043 (38.3%) required placement of an intravascular access device. Bivariate analysis revealed that patients who required intravascular cannulae for extracorporeal life support had a 10-fold increased risk of developing a CR-BSI, and patients requiring vascular access for renal replacement therapy demonstrated a 4-fold increase in the risk of developing CR-BSI compared with the referent group. There was a significant increase in the CR-BSI rate associated with the use of more intravascular access devices per patient admission. Multivariate logistic regression identified the use of extracorporeal life support therapy and the total duration of use of intravascular access devices as significant independent predictors of CR-BSI when controlling for other predictors. The use of extracorporeal life support therapy, the presence of multiple intravascular access devices, and the total duration of intravascular access device use were associated with an increase in the rate and risk of developing CR-BSI in our pediatric intensive care unit population. Larger, prospective studies may help elucidate additional factors responsible for these observations.

Management of profound hypothermia in children without the use of extracorporeal life support therapy

Profound hypothermia is managed more and more with extracorporeal life support technology, especially when a patient's circulation is compromised. Many centres do not have rapid access to this service, however, and are still dependent on active internal rewarming techniques--eg, peritoneal and pleural lavage. Such interventions are invasive, and associated with inherent risk. Here, we report our successful experience with an active external rewarming technique in children with profound hypothermia (core temperature <20 degrees C).