The Jena Method: Perfusionist Independent, Standby Wet-Primed Extracorporeal Membrane Oxygenation (ECMO) Circuit for Immediate Catheterization Laboratory and/or Hybrid Operating Room Deployment.

Background: The timely initiation of extracorporeal membrane oxygenation (ECMO) is crucial for providing life support. However, delays can occur when perfusionists are not readily available. The Jena Method aims to address this issue by offering a wet-primed ECMO system that can be rapidly established without the perfusionist's presence. Methods: The goal was to ensure prompt ECMO initiation while maintaining patient safety. The method focuses on meeting hygienic standards, safe primed storage of the circuit, staff training, and providing clear step-by-step instructions for the ECMO unit. Results: Since implementing the Jena Method in 2015, 306 patients received VA-ECMO treatment. Bacterial tests confirmed the sterility of the primed ECMO circuits during a 14-day period. The functionality of all the components of the primed ECMO circuit after 14 days, especially the pump and oxygenator, were thoroughly checked and no malfunction was found to this day. To train staff for independent ECMO initiation, a step-by-step system involves safely bringing the ECMO unit to the intervention site and establishing all connections. This includes powering up, managing recirculation, de-airing the system, and preparing it for cannula connection. A self-developed picture-based guide assists in this process. New staff members learn from colleagues and receive quarterly training sessions by perfusionists. After ECMO deployment, the perfusionist provides a new primed system for a potential next patient. Conclusions: Establishing a permanently wet-primed on-demand extracorporeal life support circuit without direct perfusionist support is feasible and safe. The Jena Method enables rapid ECMO deployment and has the potential to be adopted in emergency departments as well.

Impact of a VA-ECMO in Combination with an Extracorporeal Cytokine Hemadsorption System in Critically Ill Patients with Cardiogenic Shock-Design and Rationale of the ECMOsorb Trial.

BACKGROUND: Cardiogenic shock and arrest present as critical, life-threatening emergencies characterized by severely compromised tissue perfusion and inadequate oxygen supply. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) serves as a mechanical support system for patients suffering shock refractory to conventional resuscitation. Despite the utilization of VA-ECMO, clinical deterioration due to systemic inflammatory response syndrome (SIRS) resulting from the underlying shock and exposure of blood cells to the artificial surfaces of the ECMO circuit may occur. To address this issue, cytokine adsorbers offer a valuable solution by eliminating blood proteins, thereby controlling SIRS and potentially improving hemodynamics. Consequently, a prospective, randomized, blinded clinical trial will be carried out with ECMOsorb. METHODS AND STUDY DESIGN: ECMOsorb is a single-center, controlled, randomized, triple-blinded trial that will compare the hemodynamic effects of treatment with a VA-ECMO in combination with a cytokine adsorber (CytoSorb®, intervention) to treatment with VA-ECMO only (control) in patients with cardiogenic shock (with or without prior cardiopulmonary resuscitation (CPR)) requiring extracorporeal, hemodynamic support. Fifty-four patients will be randomized in a 1:1 fashion to the intervention or control group over a 36-month period. The primary endpoint of ECMOsorb is the improvement of the Inotropic Score (IS) 72 h after the intervention. Prognostic indicators, including mortality rates, hemodynamic parameters, laboratory findings, echocardiographic assessments, quality of life measurements, and clinical parameters, will serve as secondary outcome measures. The safety evaluation encompasses endpoints such as air embolisms, allergic reactions, peripheral ischemic complications, vascular complications, bleeding incidents, and stroke occurrences. CONCLUSIONS: The ECMOsorb trial seeks to assess the efficacy of a cytokine adsorber (CytoSorb®; CytoSorbents Europe GmbH, Berlin, Germany) in reducing SIRS and improving hemodynamics in patients with cardiogenic shock who are receiving VA-ECMO. We hypothesize that a reduction in cytokine levels can lead to faster weaning from inotropic and mechanical circulatory support, and ultimately to improved recovery.

Using a roller pump for establishing extra-corporal membrane oxygenation (ECMO) - technical considerations for times of crisis.

OBJECTIVE: The COVID-19 pandemic requires thinking about alternatives to establish ECMO when often-limited hardware resources are exhausted. Heart-lung-machines may potentially be used for ECMO but contain roller pumps as compared to centrifugal pumps in ECMO-circuits. We here tested roller pumps as rescue pump for ECMO-establishment. METHODS: We set up in vitro circuits on roller pumps from C5 heart-lung-machine with 5 l/minutes flow. In two series, we placed either PVC or silicon tubing for an ECMO circuit into the roller pump. We assessed the mechanical stress on the tubing (aiming to run the pump for at least 1 week), measured the temperature increase generated by the friction and assessed flow characteristics and its measurement in simulated situations resembling tube kinking and suction. RESULTS: The roller pumps led to expected and unexpected adverse events. PVC tubing burst between 36 and 78 hours, while silicon tubing lasted for at least 7 days. At 7 days, the silicone tubing showed significant signs of roller pump wear visible on the outside. The inside, however, was free of surface irregularities. Using these tubings in a roller pump led to a remarkable increase in circuit temperature (PVC: +12.0°C, silicone +2.9°C). Kinking or suction on the device caused the expected dramatic flow reduction (as assessed by direct measurement) while the roller pump display continued to show the preset flow. The roller pump is therefore not able to reliably determine the true flow rate. CONCLUSION: Roller pumps with silicone tubing but not PVC tubing may be used for running ECMO circuits. Silicone tubing may endure the roller pump shear forces for up to 1 week. Thus, repeated tubing repositioning may be a solution. Circuit heating and substantial limitations in flow detection should increase attention if clinical use in situations of crisis is considered.

Heater-Cooler Devices and Risk of Contamination during Cardiac Surgery.

BACKGROUND: Heater-cooler devices (HCD) have been implicated in a cardiosurgical contamination scenario causing prosthetic valve endocarditis. AIM: We characterized contamination of new HCDs and assessed the risk of intraoperative microorganism transmission from the HCD to the operating field. METHODS: We initially acquired four new FlexTherm and then four new Maquet HCU40 HCDs and assessed occurrence and speed of microbial contamination (including mycobacteria) assessing swab and water samples from the device. In parallel, we collected repeated samples from different sites in the operating room either by swab sticks or by exposing different sample plates to room air. We also reviewed microbiological results from the hospital and compared them to cardiosurgical wound infections and endocarditis cases. Finally, we simulated cardiosurgical conditions and assessed the devices' ability to expel air to the operative field. RESULTS: All new HCDs were clean before first use. Despite authority-mandated decontamination procedures, microbial growth (Fusarium solani, Sphingomonas paucimobilis, Pseudomonas aeruginosa, Mycobacterium chelonae, and gordonae) was identified in all HCDs over time and could not be permanently eliminated. Four of these mircoorganisms were also found in tap water. However, none of the HCD-organisms were found inside the laminar airflow operating area. Importantly, except for P. aeruginosa, none of the HCD organisms were found in patients with surgical wound infections or endocarditis. HCD-expelled air did not rise more than 40 cm above ground. CONCLUSION: HCDs cannot be expected to remain sterile despite extensive decontamination procedures. However, airborne transmission of microorganisms directly from the HCD to the operating field appears unlikely.

Monitoring of the Progression of the Perioperative Serum Lactate Concentration Improves the Accuracy of the Prediction of Acute Mesenteric Ischemia Development After Cardiovascular Surgery.

OBJECTIVES: To examine the sensitivity and specificity of perioperative lactate gradients for the prediction of subsequent acute mesenteric ischemia development in patients undergoing cardiovascular surgery. DESIGN: Retrospective, single-center, case-control study. SETTING: University hospital. PARTICIPANTS: The study comprised 108 (1.15%) patients with acute mesenteric ischemia who were selected from 9,385 patients who underwent cardiovascular surgery and were matched to 324 control patients by age and surgery type. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Univariate and logistic regression analyses were used to examine intraoperative and early postoperative lactate levels in patients with and without mesenteric ischemia after cardiac surgery. Late intraoperative lactate concentrations were significantly greater in patients who subsequently developed mesenteric ischemia (p < 0.001). Patients with lactate levels >3 mmol/L had a four-fold increased risk of mesenteric ischemia development (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.4-7.5; area under the curve [AUC] 0.597; p < 0.002). Patients whose lactate levels remained >3 mmol/L on the first postoperative day had a nearly eight-fold increased risk (OR 7.8, 95% CI 4.6-13.3; AUC 0.68; p < 0.001), indicating that mesenteric ischemia developed at an early stage in almost every second patient (p < 0.001). For patients with normal or less elevated lactate levels, similar results were obtained for a >200% increase between the intraoperative and early postoperative periods (OR 4.1, 95% CI 2.4-6.8; AUC 0.62; p < 0.001). CONCLUSION: Late intraoperative and early postoperative lactate levels >3 mmol/L and increases >200%, even when remaining within the normal range, should raise the suspicion of subsequent mesenteric ischemia development.

Outcome predictors in cardiopulmonary resuscitation facilitated by extracorporeal membrane oxygenation.

INTRODUCTION: Cardiac arrest is the major cause of sudden death in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) employs extracorporeal membrane oxygenation (ECMO) in patients without return of spontaneous circulation (ROSC) by conventional cardiopulmonary resuscitation (CPR). Aim of the current study was to assess short- and long-term outcome in patients treated with ECPR in our tertiary center and to identify predictors of outcome. METHODS: We retrospectively collected data of all patients treated with ECPR at our institution from 2002 to 2013. Outcome was assessed according to patient records; good neurological outcome was defined as cerebral performance category 1 or 2. Quality of life data was collected using EQ-5 questionnaire. Uni- and multivariate analysis was applied to identify predictors of outcome. RESULTS: One-hundred and seventeen patients were included into the study. Weaning from ECMO was successful in 61 (52 %) patients. Thirty-day survival endpoint was achieved by 27 (23 %) patients. Good neurological outcome was present in 17 (15 %) patients. Multivariate analysis revealed baseline serum lactate as the strongest predictor of outcome, whereas age and out-of-hospital CPR did not predict outcome. The optimal lactate cut-off to discriminate outcome was determined at 4.6 mmol/l [HR 3.55 (2.29-5.49), p < 0.001, log-rank test]. CONCLUSION: ECPR represents a treatment option in patients without ROSC after conventional CPR rescuing 15 % of patients with good neurological outcome. Serum lactate may play a crucial role in patient selection for ECPR.

Application of ECMO in multitrauma patients with ARDS as rescue therapy.

BACKGROUND: Despite recent advances in critical care management, the mortality of acute respiratory distress syndrome (ARDS) remains high. The final rescue therapy for patients with severe hypoxia refractory to conventional therapy modalities is the extracorporeal gas exchange. METHODS: We report the management of three polytraumatized patients with life-threatening injuries, severe blunt thoracic trauma, and consecutive ARDS treating by extracorporeal membrane oxygenation (ECMO). Two patients suffered a car accident with severe lung contusion and parenychmal bleeding. Bronchial rupture and mediastinal emphysema was found in one of them. Another patient developed ARDS after attempted suicide with multiple fractures together with blunt abdominal and thoracic trauma. RESULTS: All patients were placed on ECMO and could be rapidly stabilized. They were weaned from ECMO after a mean of 114 +/- 27 hours of support without complications, respectively. Mean duration of ICU stay was 37 +/- 23 days. CONCLUSIONS: Quick encouragement of ECMO for the temporary management of gas exchange may increase survival rates in trauma patients with ARDS.

Simple on-site assembled blower-mister device provides sufficient humidification and visualization in off-pump surgery.

To effectively perform an anastomosis on a coronary artery under beating heart conditions, the anastomotic site must be cleared of blood to allow visualization for accurate suturing. We describe a simple, cost effective, on-site assembled blower-mister system.

Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: selected parameters of coagulation and inflammatory system.

OBJECTIVE: Closed circuit extracorporeal circulation (CCECC) has been developed to reduce deleterious effects of standard cardiopulmonary bypass (CPB). This study compares the effects of CCECC (CORx system), CPB, and off-pump coronary artery bypass grafting (OPCAB) on red blood cell damage, coagulation activation, fibrinolysis and cytokine expression. METHODS: Thirty patients underwent coronary artery bypass grafting (CABG). Twenty of them were randomized into two groups: CCECC (n = 10), CPB (n = 10). While not randomized, OPCAB (n = 10) served as a separate reference group. CCECC and CPB patients received cardioplegic arrest. Interleukin 6 (IL-6), free hemoglobin (fHb), von Willebrand factor activity (vWf), thrombin-antithrombin-III-complex (TATc), prothrombin fragment 1.2 (F 1+2) and plasmin-antiplasmin complex (PAPc) were assessed preoperatively, perioperatively and 24 h postoperatively. RESULTS: CCECC showed significantly lower red blood cell damage than CPB (fHb: CCECC, 7.1+/- 5.7 micromol/l; CPB, 16.8+/-11.4 micromol/l; P = 0.025; OPCAB, 3.4+/-1.1 micromol/l). Perioperatively, CCECC exhibited significantly lower activation of coagulation and fibrinolysis than CPB, but did not differ from OPCAB (vWf: CCECC, 133+/-52%; CPB, 241+/-128%; P = 0.052; OPCAB, 153+/-58%; TATc: CCECC, 4.7+/-0.9 ng/ml; CPB, 31.1+/-15.8 ng/ml; P < 0.001; OPCAB, 2.4+/-0.6 ng/ml; PAPc: CCECC, 214+/-30 ng/ml; CPB, 897+/-367 ng/ml; P < 0.001; OPCAB, 253+/-98 ng/ml). In contrast, fibrinolysis markers and IL-6 were markedly increased in CCECC postoperatively (PAPc: CCECC, 458+/-98 ng/ml; CPB, 159+/-128 ng/ml; P < 0.001; OPCAB, 262+/-174 ng/ml; IL-6: CCECC, 123.4+/-49.8 pg/dl; CPB, 18.8+/-13.1 pg/dl; P < 0.001; OPCAB, 31.6+/-26.2 pg/dl). CONCLUSIONS: CCECC for CABG is associated with a significant reduction of red blood cell damage and activation of coagulation cascades similar to OPCAB when compared with conventional CPB while a delayed fibrinolytic and inflammatory activity was observed. These findings require further investigation to verify the promising concept of CCECC.

Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the native lung tissue.

OBJECTIVE: Efficacy of in vivo isolated lung perfusion (ILP) with cisplatin could be shown in different rodent tumor models. Despite the use of this alternative therapeutical strategy in very few patients with lung metastases, there are no systematic studies regarding the tolerance of the native lung tissue in large animal models or humans. METHODS: In a novel ILP pig model, groups with two different concentrations of cisplatin (group CP150: 150 mg/m(2) cisplatin, n=5; group CP300: 300 mg/m(2) cisplatin, n=5) were compared with a control group (n=5) and a Sham group (n=5) concerning the influence on hemodynamic, ventilatory and gas exchange parameters as well as on structural integrity of the lung. In the additional CP300-HT group the potentially cumulative effect of hyperthermia and high-dose cisplatin perfusion was evaluated (300 mg/m(2) cisplatin, 41.5 degrees C, n=5). Following the ILP of the left lung for 40 min, right main bronchus and right pulmonary arteries were clamped and survival as well as lung function parameters were dependent on the previously perfused lung for the 6-h-reperfusion period. Quantification of histological acute lung injury was performed using the score of Chiang. ANOVA, ANOVA with repeated measures and Pearson's correlation estimation were applied for statistical evaluation. RESULTS: All animals survived ILP and the entire reperfusion period. Platinum levels of the perfusate and lung tissue showed a significant correlation with the dose given (P<0.001) but no correlation with the very low plasma levels in all groups (P=0.825). ILP resulted in a slight deterioration of most functional parameters compared to the Sham group. Although there were no differences between the perfusion groups regarding hemodynamic and ventilatory parameters, gas exchange parameters (pO(2)/FiO(2)-index, pCO(2), AADO(2)) demonstrated a trend toward dose-related functional impairment. Histological evaluation confirmed a dose-depending damage of lung tissue (P<0.001, correlation coefficient 0.670). The hyperthermic ILP with high-dose cisplatin led to improved gas exchange parameters and a reduction of morphological lung damage. CONCLUSIONS: In vivo ILP with high-dose cisplatin represents a safe procedure in this pig model. Hyperthermic perfusion up to 41.5 degrees C was beneficial to reduce the acute lung injury. The promising results of this study might be used for initiation of clinical trials as an alternative treatment in patients with a very poor prognosis.

Physiological coagulation can be maintained in extracorporeal circulation by means of shed blood separation and coating.

OBJECTIVE: Conventional extracorporeal circulation results in an activation of coagulation cascades. Coating of extracorporeal circulation tubes as well as avoidance of shed blood recirculation have been shown to reduce these phenomena. We evaluated a new shed blood separation system (AVANT D 970) utilizing a coated cardiopulmonary bypass tube system (PHISIO). METHODS: Forty patients (62 +/- 10 years) underwent isolated coronary revascularization. Four groups (n = 10/group) were defined: no extracorporeal circulation, conventional uncoated extracorporeal circulation, uncoated extracorporeal circulation with shed blood separation, and coated extracorporeal circulation with shed blood separation. Thrombin-antithrombin complex and free Hb were analyzed and statistically compared. RESULTS: Conventional extracorporeal circulation exhibited the highest intraoperative activation of coagulation (thrombin-antithrombin complex: extracorporeal circulation, 31.1 +/- 15.8 microg/L; uncoated extracorporeal circulation with shed blood separation, 15.3 +/- 7.8 microg/L; coated extracorporeal circulation with shed blood separation, 8.1 +/- 4.8 microg/L; no extracorporeal circulation, 2.4 +/- 0.6 microg/L; P <.05 extracorporeal circulation vs all others) and red blood cell damage (free Hb: extracorporeal circulation, 16.8 +/- 11.4 micromol/L; uncoated extracorporeal circulation with shed blood separation, 10.3 +/- 3.5 micromol/L; coated extracorporeal circulation with shed blood separation, 6.8 +/- 2.9 micromol/L; no extracorporeal circulation, 3.4 +/- 1.1 micromol/L; P <.05 extracorporeal circulation vs no extracorporeal circulation, coated extracorporeal circulation with shed blood separation). Coated extracorporeal circulation with shed blood separation showed only slight activation and cell trauma, which did not differ significantly from no extracorporeal circulation. CONCLUSIONS: Combination of coating and avoidance of shed blood recirculation maintained physiological coagulation levels and markedly reduced red blood cell trauma in extracorporeal circulation procedures. These combined modalities may therefore offer an alternative for off-pump procedures in patients with contraindications for conventional extracorporeal circulation.

Intermittent antegrade warm myocardial protection compared to intermittent cold blood cardioplegia in elective coronary surgery--do we have to change?

OBJECTIVE: Intermittent antegrade warm blood cardioplegia (IAWBC) is a simple and cost-effective method of myocardial preservation. However, there are only few prospective trials comparing this type of cardioplegia to established cardioplegic strategies in elective on-pump coronary surgery with respect to myocardial protection and outcome. METHODS: In a prospective, randomized trial IAWBC (33 degrees C) (n=100) was compared to intermittent antegrade cold (4 degrees C) blood cardioplegia (n=100), regarding clinical outcome and myocardial protection using cardiac troponin-I (cTNI) and creatine kinase MB isoenzyme (CK-MB) measurements to assess ischemia. RESULTS: Preoperative parameters were comparable in both groups. Results demonstrated no differences in-between the groups regarding mortality (2.0% both), incidence of perioperative myocardial infarction (2 versus 3%), need for intra-aortic balloon pump (3 versus 4%), length of ICU stay (2.0+/-2.5 versus 2.1+/-3.0 days) and incidence of postoperative atrial fibrillation (41 versus 34%). However, the necessity of defibrillation after cardiac arrest (18 versus 43%, P<0.001) was significantly less frequent and of lower intensity (3.4+/-10.8 versus 10.8+/-20.6 J, P<0.001) in the IAWBC-group. Postoperatively the ischemia markers were significantly lower in the IAWBC-group, cTNI within the first 72 h (from P<0.001 to P=0.013) and even CK-MB within the first 24 h (from P=0.004 to P<0.011). CONCLUSION: IAWBC is a safe and simple method in elective on-pump coronary artery bypass surgery. Significantly lower ischemic markers suggest an improved myocardial protection compared to cold blood cardioplegia in these patients.