Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

Venovenous extracorporeal membrane oxygenation for COVID-19 associated severe respiratory failure: Case series from a Hungarian tertiary centre.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (V-V ECMO) is recommended for the support of patients with severe COVID-19 associated severe respiratory failure (SRF). We report the characteristics and outcome of COVID-19 patients supported with V-V ECMO in a Hungarian centre. METHODS: We retrospectively collected data on all patients admitted with proven SARS CoV-2 infection who received V-V ECMO support between March 2021 and May 2022. RESULTS: Eighteen patients were placed on ECMO during this period, (5 women, age (mean ± SD) 44 ± 10 years, APACHE II score (median (interquartile range)) 12 (10-14.5)). Before ECMO support, they had been hospitalised for 6 (4-11) days. Fifteen patients received noninvasive ventilation for 4 (2-8) days, two patients had high flow nasal oxygen therapy, for one day each. They had already been intubated for 2.5 (1-6) days. Prone position was applied in 15 cases. On the day before ECMO initiation the Lung Injury Score was 3.25 (3-3.26), the PaO2/FiO2 ratio was 71 ± 19 mmHg. The duration of V-V ECMO support was 26 ± 20 days, and the longest run lasted 70 days. Patients were mechanically ventilated for 34 ± 23 days. The intensive care unit (ICU) and the hospital length of stay were 40 ± 28 days and 45 ± 31 days, respectively. Eleven patients were successfully weaned from ECMO. The ICU survival rate was 56%, the in-hospital survival was 50%. All patients who were discharged from hospital reported a good health-related quality of life Rankin score (0-2) at the 5-16 months follow-up. CONCLUSIONS: During the last three waves of the COVID-19 pandemic, we achieved a 56% ICU and a 50% hospital survival rate at our low volume centre.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Background: Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. Methods: In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. Results: The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Conclusion: Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. Trial registration: NCT05812196.

Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics.

Objective: Veno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI). Methods: Anesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow (RAF) was measured in the post-ECMO period with an ultrasonic flowmeter. At the end of the experiments, renal tissue samples were taken for histology to measure myeloperoxidase (MPO) and xanthine oxidoreductase (XOR) activity and to examine mitochondrial function with high-resolution respirometry (HRR, Oroboros, Austria). Plasma and urine samples were collected every 6 hrs to determine neutrophil gelatinase-associated lipocalin (NGAL) concentrations. Results: During the post-ECMO period, RAF dropped (96.3 ± 21 vs. 223.6 ± 32 ml/min) and, similarly, hour diuresis was significantly lower as compared to the control group (3.25 ± 0.4 ml/h/kg vs. 4.83 ± 0.6 ml/h/kg). Renal histology demonstrated significant structural damage characteristic of ischemic injury in the tubular system. In the vv-ECMO group NGAL levels, rose significantly in both urine (4.24 ± 0.25 vs. 2.57 ± 0.26 ng/ml) and plasma samples (4.67 ± 0.1 vs. 3.22 ± 0.2 ng/ml), while tissue XOR (5.88 ± 0.8 vs. 2.57 ± 0.2 pmol/min/mg protein) and MPO (11.93 ± 2.5 vs. 4.34 ± 0.6 mU/mg protein) activity was elevated. HRR showed renal mitochondrial dysfunction, including a significant drop in complex-I-dependent oxidative capacity (174.93 ± 12.7 vs. 249 ± 30.07 pmol/s/ml). Conclusion: Significantly decreased renal function with signs of structural damage and impaired mitochondrial function developed in the vv-ECMO group. The vv-ECMO-induced acute renal impairment in this 30-hr research protocol provides a good basis to study the pathomechanism, biomarker combinations or possible therapeutic possibilities for AKI.

Extracorporeal membrane oxygenation in intensive care unit / Extracorporalis membránoxigenizáció intenzív osztályon.

Összefoglaló. Az extracorporalis membránoxigenizációt egyre gyakrabban alkalmazzák világszerte refrakter légzési és/vagy keringési elégtelenség kezelésében. Intézetünkben 2015-ben kezdtük meg a program elokészítését és felépítését. Célunk az extracorporalis membránoxigenizációs kezelés élettani alapjainak rövid ismertetése, különös tekintettel a venovenosus konfigurációra, és az eddig kezelt eseteink eredményeinek összefoglalása. Az irodalom szisztematikus áttekintése és a kezelt esetek adatainak retrospektív értékelése voltak a módszereink. 2016 óta összesen 14 beteg esetében használtunk extracorporalis membránoxigenizációt (8 férfi, 6 no, életkor 51 ± 15 év, APACHE II. score 24 ± 7). Az indikáció 9 esetben súlyos refrakter hypoxaemiás légzési elégtelenség, 1 esetben tracheooesophagealis fistula és légzési elégtelenség, 1 esetben mutét alatti támogatás tervezett trachearekonstrukció során és 3 beteg esetében refrakter cardiogen shock volt. Az extracorporalis membránoxigenizáció 11 betegben a légzés, 3 betegben a keringés támogatását szolgálta, 13 venovenosus, 1 venoarteriosus konfigurációban. Az extracorporalis támogatás ideje légzéstámogatás esetében 14 ± 6 nap, a cardialis támogatások esetében 5 ± 4 nap volt. Az intenzív osztályos ápolási ido 27 ± 13, illetve 21 ± 17 nap volt a két betegcsoportban. 9 beteget jó funkcionális állapotban bocsátottunk el, 5 beteg halt meg osztályunkon, további 3 késobb a kórházi bennfekvés során. Az extracorporalis membránoxigenizációs program regionális centrumokban Magyarországon is megvalósítható. A nemzetközi ajánlások, oktatási módszerek alkalmazásával a nemzetközi irodalomban közölt túlélési eredményekhez hasonló eredmények érhetok el hazánkban is. Orv Hetil. 2021; 162(11): 425-431. Summary. Extracorporeal membrane oxygenisation is commonly used worldwide for refractory respiratory and circulatory failure. We started to organise the introduction of this therapeutic modality in 2015. Our aim is to give a short review about extracorporeal life support, especially veno-venous extracorporeal membrane oxygenation, and to present our first results. We provide a systematic review of the currently available literature and a summary of our first treatments. As of 2016, we supported 14 patients with extracorporeal membrane oxygenisation (8 men, age 51 ± 15 years, APACHE II score 24 ± 7). The indications were refractory hypoxaemic respiratory failure in 9, tracheo-oesophageal fistula and respiratory failure in 1, support during surgery for planned tracheal reconstruction in 1, and refractory cardiogenic shock in 3 patients. We provided respiratory support in 11, circulatory support in 3 cases, with 13 veno-venous and 1 veno-arterial configuration. The support lasted for 14 ± 6 days in respiratory, and for 5 ± 4 days in cardiac cases. Intensive care length of stay was 27 ± 13 and 21 ± 17 days in the two patient groups. We discharged 9 patients in good functional state, 5 patients died during intensive care and further 3 later, during the hospital stay. Our results show that the implementation of an extracoporeal membrane oxygenation program is feasible in Hungarian tertiary centers. In line with international recommendations and adapting international training courses, the survival is very similar to that reported in the literature. Orv Hetil. 2021; 162(11): 425-431.

Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane Analysis in Rat and Pig Models of Mesenteric Circulatory Distress.

OBJECTIVES: Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. DESIGN: Randomized, controlled in vivo animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). INTERVENTIONS: In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). CONCLUSIONS: we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.

Methane inhalation reduces the systemic inflammatory response in a large animal model of extracorporeal circulation.

OBJECTIVES: Extracorporeal circulation induces cellular and humoral inflammatory reactions, thus possibly leading to detrimental secondary inflammatory responses. Previous data have demonstrated the bioactive potential of methane and confirmed its anti-inflammatory effects in model experiments. Our goal was to investigate the in vivo consequences of exogenous methane administration on extracorporeal circulation-induced inflammation. METHODS: Two groups of anaesthetized Vietnamese minipigs (non-treated and methane treated, n = 5 each) were included. Standard central cannulation was performed, and extracorporeal circulation was maintained for 120 min without cardiac arrest or ischaemia, followed by an additional 120-min observation period with haemodynamic monitoring. In the methane-treated group, 2.5% v/v methane-normoxic air mixture was added to the oxygenator sweep gas. Blood samples through the central venous line and tissue biopsies from the heart, ileum and kidney were taken at the end point to determine the whole blood superoxide production (chemiluminometry) and the activity of xanthine-oxidoreductase and myeloperoxidase, with substrate-specific reactions. RESULTS: Methane treatment resulted in significantly higher renal blood flow during the extracorporeal circulation period compared to the non-treated group (63.9 ± 16.4 vs 29.0 ± 9.3 ml/min). Whole blood superoxide production (548 ± 179 vs 1283 ± 193 Relative Light Unit (RLU)), ileal myeloperoxidase (2.23 ± 0.2 vs 3.26 ± 0.6 mU/(mg protein)) and cardiac (1.5 ± 0.6 vs 4.7 ± 2.5 pmol/min/mg), ileal (2.2 ± 0.6 vs 7.0 ± 3.4 pmol/min/mg) and renal (1.2 ± 0.8 vs 13.3 ± 8.0 pmol/min/mg) xanthine-oxidoreductase activity were significantly lower in the treated group. CONCLUSIONS: The addition of bioactive gases, such as methane, through the oxygenator of the extracorporeal circuit represents a novel strategy to influence the inflammatory effects of extracorporeal perfusion in cardiac surgical procedures.

Experimental pericardial tamponade-translation of a clinical problem to its large animal model.

OBJECTIVES: Pericardial tamponade is a life-threatening medical emergency, when the hemodynamic consequences of low cardiac output severely disturb the perfusion of the peripheral tissues. Our aim was to design a reliable large animal model to reproduce the clinical scenario with the relevant pathophysiological consequences of pericardial tamponade -induced cardiogenic shock. MATERIAL AND METHODS: Anesthetized Vietnamese mini pigs were used (n=12). Following laparotomy, a cannula was fixed into the pericardium through the diaphragm without thoracotomy. A sham-operated group (n=6) served as control, while in the second group (n=6) pericardial tamponade was induced by intra-pericardial injection of heparinized own blood. Throughout the 60-min pericardial tamponade and the 180-min reperfusion, macro hemodynamics, renal circulation and the mesenteric macro- and micro-circulatory parameters were monitored. Myeloperoxidase activity was measured to detect neutrophil leukocyte accumulation and in vivo histology was performed by confocal laser scanning endomicroscopy to observe the structural changes of the intestinal mucosa. RESULTS: PT increased the central venous pressure, heart rate, and decreased mean arterial pressure. The mesenteric artery flow (from 355.5±112.4 vs 182.0±59.1 mL/min) and renal arterial flow (from 159.63±50.7 vs 35.902±27.9 mL//min) and the micro-circulation of the ileum was reduced. The myeloperoxidase activity was elevated (from 3.66±1.6 to 7.01±1.44 mU/mg protein) and manifest injury of the ileal mucosa was present. CONCLUSION: This experimental model suitably mimics the hemodynamics and the pathology of clinical pericardial tamponade situations, and on this basis, it provides an opportunity to study the adverse macro- and micro-circulatory effects and biochemical consequences of human cardiogenic shock.

[Pathophysiology, clinical and experimental possibilities of pericardial tamponade]. / A pericardialis tamponád kórélettana, klinikuma és állatkísérletes vizsgálati lehetoségei.

Acute pericardial tamponade is one of the most emergent clinical scenarios in cardiac surgery. With numerous causes in the background, pericardial tamponade can lead to cardiogenic shock and death. In modern diagnostic era, the recognition of pericardial tamponade is simple, but its management and the long-term effects can still be challenging. Without the detailed understanding of the pathophysiological pathways diagnostic and therapeutic management plans of pericardial tamponade is very difficult. The aim of this review was to give a complex picture of pericardial tamponade, from its role in medical history to pathophysiology and its significance in surgical experimental models. Orv Hetil. 2018; 159(5): 163-167.

[Experimental model for cardiogenic shock with pericardial tamponade]. / A cardiogen sokk modellezése pericardialis tamponáddal.

INTRODUCTION: Pericardial tamponade (PT) is a life-threatening condition, with low cardiac output. The hemodynamic consequences of PT can severely affect the circulation of all tissues, including the microcirculation of the kidneys and the intestinal mucosa. Our aim was to develop a hemodynamically stable and controllable large animal model of PT to study the consequences of cardiogenic shock. METHODS: Two groups of anesthetized vietnamese minipigs (n = 6, both groups) were used. Following laparotomy, a cannula was fixed into the pericardium through the diaphragm without thoracotomy. A sham-operated group served as control, in the second group 60-min PT was induced by intrapericardial injection of heparinised own blood. Throughout PT and 180-min reperfusion, macrohemodynamics, renal circulation and mesenteric macro- and microcirculation were monitored. Myeloperoxidase (MPO) activity was measured and in vivo histology was performed by confocal laser scanning endomicroscopy. RESULTS: The PT increased central venous pressure, heart rate and decreased mean arterial pressure, mesenteric flow (from 355.5 ± 112.4 vs 182.0 ± 59.1 ml/min) and renal arterial flow (from 159.63 ± 50.7 vs 35.902 ± 27.9 ml/min) and the microcirculation of the ileum. Elevated MPO activity (3.66 ± 1.6 vs 7.01 ± 1.44 mU/mg protein) and injury of the ileal mucosa were present also. SUMMARY: The reproducible large animal model is suitable for clinically relevant investigations of the hemodynamic and biochemical consequences of PT.

[Early experiences with the Sorin Perceval S arteficial biological valve]. / Kezdeti tapasztalatok a Sorin Perceval S aorta biológiai billentyu beültetésével.

OBJECTIVES: We examined the Sorin Perceval S artificial biological valve implantation techniques, and present the initial experiences in our unit. METHODS: In the last 1.5 years, 27 patients had been implanted with Sorin Perceval S biological arteficial valve due to aortic valve disease. The device was mainly used in high-risk patients, in reoperative circumstances, in cases of calcified aortic root, and in elderly patients. RESULTS: The valve implantation time, aortic cross clamp time is shorter, but the risk of the operation cannot be eliminated entirely, because of the high risk patients' severe comorbidities. Furthermore, we performed echocardiography in the postoperative period, which demonstrated that the valve function is excellent, the valve fitted tightly in the anulus, and there was no paravalvular leakage. CONCLUSIONS: The Sorin Perceval S biological arteficial aortic valve is safe to use in high risk patients, and the surgical procedure is easier in case of partial sternotomy, too.

[The role of mini-sternotomy in aortic valve surgery]. / A ministernotomia szerepe az aortabillentyu-sebészetben.

INTRODUCTION: Minimal access aortic valve replacement plays a significant role in modern cardiac surgery. The technical evolution of aortic bioprostheses, particularly sutureless valves, leads to simplify minimal access aortic valve surgery and it allows easier implantation in a narrow work field with the need of less manipulation. AIM: The aim of this study is to summarize the historical and technical aspects of minimal access aortic valve replacement, especially concentrating on sutureless valves, and to present data of own patients of the authors. METHOD: Pre- and post-operative data of 13 minimal access aortic replacement cases who were operated at the Deparment of Cardiac Sugery at the University of Szeged are summarized. RESULTS AND CONCLUSIONS: As compared to full sternotomy, minimal access aortic surgery is safe, and it does not require special instrumentation. It is technically more demanding but it can be learned quickly, and the overall pre- and post-operative results are not worse with the benefit of less pain and superior cosmetics.