Erich Gygax

Preservation of Amputated Extremities by Extracorporeal Blood Perfusion; a Feasibility Study in a Porcine Model

BACKGROUND Successful extremity transplantations and replantations have to be performed within 6 h of amputation to avoid irreversible tissue loss. This study investigates ex vivo the technical feasibility and the limb preservation potential of extracorporeal whole blood perfusion in a porcine model. METHODS Forelimbs of eight large white pigs were divided into paired groups: I perfusion group, II contralateral cold ischemia controls. In group I axillary arteries and veins were cannulated and perfusion with anticoagulated autologous blood was performed for 12 h; O(2), CO(2), Hb, lactate, potassium, pH, and muscle contractility were monitored. Tissue biopsies were examined by histology and immunofluorescence. Group II was stored at 4°C. RESULTS Continuous limb perfusion could be performed in all extremities of group I for 12 h. pH was maintained normal and potassium controlled with insulin and glucose. Lactate levels increased initially during perfusion due to the lack of a metabolizing liver. Muscle stimulation was possible throughout the entire perfusion, whereas a complete loss of response was noted in cold ischemia controls. Minor tissue damage was observed histologically and by immunofluorescence in group I, whereas the samples of group II were apparently preserved with the exception of a loss of endothelial heparan sulfate. CONCLUSIONS The tissue preserving potential and the feasibility of extremity perfusion using common extracorporeal blood circulation techniques was demonstrated in this ex vivo study. The results encourage further investigations in prolonged perfusion followed by limb replantation. This approach harbors promising clinical potential for extremity preservation in extremity transplantation and replantation.

Minimized cardiopulmonary bypass combined with a smart suction device: the future of cardiopulmonary bypass?

OBJECTIVE The standard heart-lung machine is a major trigger of systemic inflammatory response and the morbidity attributed to conventional extracorporeal circulation (CECC) is still significant. Reduction of blood-artificial surface contact and reduction of priming volume are principal aims in minimized extracorporeal circulation (MECC) cardiopulmonary bypass systems. The aim of this paper is to give an overview of the literature and to present our experience with the MECC-smart suction system. METHODS AND RESULTS At our institution, 1799 patients underwent isolated coronary artery bypass grafting (CABG) surgery, 1372 with a MECC-smart suction system and 427 with CECC. All in-hospital data were assessed and the results were compared between the 2 groups. Patient characteristics and the distribution of EuroSCORE risk profile in our collective were similar between both groups. Average age in the MECC collective was 67.5 +/- 11.4 years and average EuroSCORE was 5.0 +/- 1.5. Average number of distal anastomoses was similar to the average number encountered in patients undergoing CABG surgery with CECC (3.3 +/- 1.0 for MECC versus 3.2 +/- 1.1 for CECC; P = ns). Myocardial protection is superior in MECC patients with lower postoperative maximal cTnI values (11.0 +/- 10.8 micromol/L for MECC versus 24.7 +/- 25.3 micromol/L for CECC; P < .05). Postoperative recovery was faster in patients operated on with the MECC-smart suction system and discharge from the hospital was earlier than for CECC patients (7.4 +/- 1.9 days for MECC versus 8.8 +/- 3.8 days for CECC; P < .05). CONCLUSIONS The MECC-smart suction system is a safe perfusion technique for CABG surgery. In patients operated on with this system, the clinical outcome seems to be better than in patients operated on with CECC. This promising and less damaging perfusion technology has the potential to replace CECC systems in CABG surgery.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS)

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Minimal invasive Extra-Corporeal Circulation (MiECC): a revolutionary evolution in perfusion

Since the beginning of extracorporeal circulation (ECC) in cardiac surgery, a multitude of changes and improvements were aimed to reduce the adverse systemic effects caused by the artificial surfaces of the perfusion circuit. The clinical picture is similar to a systemic inflammatory response syndrome [1]. The magnitude of the inflammatory response adversely influences clinical outcomes [2]. Hence, the overall morbidity associated with cardiac surgery is substantial [3]. The off-pump coronary artery bypass (OPCAB) technique was introduced as a strategy to decrease the side effects of cardiopulmonary bypass (CPB). But the real advantages of OPCAB have been questioned in recent years [4]. In the early 2000s, a simplified perfusion system comprising all technological advancements was designed [5]. The modifications of the new system were much more revolutionary than the individual improvements to the existing conventional CPB circuits. The idea was to create a system including all established benefits in one CPB set-up. The Minimal Extra-Corporeal Circulation (MiECC) technology was born. Since then, MiECC systems have been developed to increase the technical ease of on-pump surgery while tempering its disadvantages. For many years, cardiac surgeons, anaesthesiologists and perfusionists considered MiECC systems as a miniaturization or simplification of traditional CPB only. MiECC significantly attenuated morbidity attributed to conventional ECC, as for beatingheart procedures, while permitting optimal technical surgical conditions [6]. ‘The authors believe that MiECC technology represents more than a miniaturization process: it is a major step forward and a totally new philosophy to be integrated in contemporary cardiac surgery’. The idea of MiECC systems has initiated new efforts to improve the biocompatibility of CPB systems and minimize their side effects, offering finally better postoperative end-organ function. Characteristics of MiECC include the following: (1) a blood pump with optimal biocompatibility, low thrombogenicity, minimal haemolysis and activation of leucocytes as well as proinflammtory mediators; (2) a minimal tubing length to reduce the priming volume required and thus minimize haemodilution, decreasing the need for foreign blood transfusions; (3) coated surfaces to reduce protein adsorption and platelet activation; (4) separation of shed blood and exclusion of activated blood components via cell salvage; (5) closed system to avoid blood–air contact; (6) temperature management depending on the need and magnitude of surgery should be possible; (7) use of modern concepts of myocardial protection, like blood cardioplegia, must be easy to integrate; (8) safe de-airing must be possible following open heart procedures; (9) finally, it should help modern concepts of fast-track anaesthesia [7, 8]. These characteristics will help to make MiECC an element of a minimal invasive procedure rather than simply a miniaturized CPB system. Numerous randomized clinical studies have proved that MiECC exerts significant beneficial effects on postoperative morbidity, by reducing haemodilution, mediastinal bleeding, need for blood transfusion and inflammatory response. Clinical benefits are: improved end-organ (myocardial, renal and cerebral) protection and reduction of the length of intensive care unit stay [5–8]. Moreover, it is associated with a significant survival benefit in coronary procedures compared with conventional ECC as shown in a recent meta-analysis. This analysis reported randomized trials including 24 studies with a total of 2770 patients [9] and provided a Scientific Class I, Level of evidence A for implementation of MiECC, at least for coronary revascularization. Despite these clear clinical advantages, penetration of the MiECC technology into clinical practice remains significantly low. Thus, the authors took the initiative to organize the ‘1st International Symposium on Minimal invasive Extracorporeal Circulation Technologies (1st MiECT)’ in Thessaloniki, Greece during June 13–14 to create a dedicated international forum to stimulate the exchange of ideas in clinical application and research in the field of Minimal invasive Extracorporeal Circulation Technology without geographical bias (www.miect.org). More than 400 participants from all continents registered. Beside scientific sessions, wet-labs with two simulators for ‘hands-on training’ allowed participants to practice on all commercially available MiECC systems. Twenty abstracts were selected for publication and are part of this Interactive Cardiovascular and Thoracic Surgery issue. During the congress, the ‘Minimal invasive Feedback from the 1st International Symposium on Minimal invasive Extracorporeal Circulation Technologies, Thessaloniki, Greece, 13–14 June 2014.

Continuous flow left ventricular assist devices: a valid option for heart failure patients

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group 0 or B, with a body weight over 90 kg and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent peri-operative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of a LVAD represents a surgical challenge. This review summarises the current knowledge about LVAD and continuous flow devices especially since the latter have been increasingly used worldwide in the most recent years. The review is also based on the institutional experience at Berne University Hospital between 2000 and 2012. Apart from short-term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non-pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an initial learning curve, one-year mortality dropped to 10.4% in the last 58 patients.

Is reduced systemic heparinization justified with heparin-bonded bypass circuits in cardiac surgery?––Experience with and without aprotinin

The effects of aprotinin combined with heparin-bonded bypass circuits and reduced systemic heparinization on haemostasis and inflammatory reactions were measured in patients with elective CABG operation. Patients were randomized to be operated on either without aprotinin (NOAPRO, n=15) or with aprotinin (APRO, n=15) at a low dose of 2 Mio KIU in the priming volume. Activated clotting time was adjusted to 400 +/- 50 s during cardiopulmonary bypass (CPB). Haemostasis (fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), D-Dimer, plasmin-antiplasmin (PAP), plasminogen-activator inhibitor (PAI)), inflammatory reaction (lactoferrin, IL-6, sTNF-IIR, SC5b-9) and clinical data were evaluated perioperatively. Perioperative clinical and laboratory data including mediastinal drainage volume, postoperative morbidity and mortality were comparable for patients in both groups. FPA was elevated in the APRO group during CPB (P=0.001), D-Dimer in the NOAPRO group after CPB (P=0.002). No differences were seen for TAT, PAP or PAI between the groups. Lactoferrin was elevated in NOAPRO at the end of CPB (P=0.01) and after heparin reversal with protamine sulphate (P=0.02). No intergroup differences were seen for IL-6, sTNF-IIR or SC5b-9 between the groups. In association with reduced heparinization, pump prime aprotinin retains its antifibrinolytic effect in modified bypass equipment with a heparin surface besides an anti-inflammatory effect in terms of inhibition of leukocyte activation. However, thrombin activation may be increased with aprotinin. We therefore recommend sufficient systemic heparinization despite heparin surface modification of bypass equipment.

Autotransfusion system or integrated automatic suction device in minimized extracorporeal circulation: influence on coagulation and inflammatory response

OBJECTIVE To measure surrogate markers of coagulation activation as well as of the systemic inflammatory response in patients undergoing primary elective coronary artery bypass grafting (CABG) using either the so-called Smart suction device or a continuous autotransfusion system (C.A.T.S.®). METHODS Fifty-eight patients being operated with a miniaturized circuit (minimal extracorporeal circuit, MECC) were prospectively randomized to using a so-called Smart suction device or a routine continuous autotransfusion system (C.A.T.S.®) for collection of mediastinal shed blood. The coagulation response was measured by thrombin-antithrombin complex (TAT) and D-dimer. The inflammatory response was measured by Interleukin 6 (IL-6) and complement factor 3a (C3a) at three different time points, before surgery, 2h after surgery, as well as 18 h after surgery. RESULTS No serious adverse cardiovascular event was observed. Serum levels of TAT significantly differed between both groups 2h after surgery (Smart suction 16.12 ± 13.51 μg l⁻¹ vs C.A.T.S® 9.83 ± 7.81 μg l⁻¹, p = 0.040) and returned to baseline values after 18 h in both groups. Serum levels of D-dimer showed a corresponding pattern with a peak 2h after surgery (Smart suction 1115 ± 1231 ng ml⁻¹ vs C.A.T.S.® 507 ± 604 ng ml⁻¹, p = 0.025). IL-6 levels also significantly differed between both groups 2h after surgery (Smart suction 186 ± 306 pg ml⁻¹ vs C.A.T.S.® 82 ± 71 pg ml⁻¹, p = 0.072). No significant changes in serum levels of C3a over time could be observed. CONCLUSIONS Despite no differences in the clinical course of patients with either Smart suction or C.A.T.S.® being observed, surrogate markers of coagulation and inflammation seem to be less pronounced in patients where cardiotomy blood is not being directly reinfused. As such, C.A.T.S.® should be preferred in routine CABG, as long as no extensive volume substitution is anticipated.

Point-of-care testing in the cardiovascular operating theatre

Abstract Point-of-care testing (POCT) remains under scrutiny by healthcare professionals because of its ill-tried, young history. POCT methods are being developed by a few major equipment companies based on rapid progress in informatics and nanotechnology. Issues as POCT quality control, comparability with standard laboratory procedures, standardisation, traceability and round robin testing are being left to hospitals. As a result, the clinical and operational benefits of POCT were first evident for patients on the operating table. For the management of cardiovascular surgery patients, POCT technology is an indispensable aid. Improvement of the technology has meant that clinical laboratory pathologists now recognise the need for POCT beyond their high-throughput areas. Clin Chem Lab Med 2006;44:1060–5.

Cerebral Microembolization During Aortic Valve Replacement Using Minimally Invasive or Conventional Extracorporeal Circulation: A Randomized Trial

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.

Aprotinin in cardiac surgery: a different point of view.

Aprotinin is widely used in cardiac surgery to reduce postoperative bleeding and the need for blood transfusion. Controversy exists regarding the influence of aprotinin on renal function and its effect on the incidence of perioperative myocardial infarction (MI) and cerebrovascular incidents (CVI). In the present study, we analyzed the incidence of these adverse events in patients who underwent coronary artery bypass grafting (CABG) surgery under full-dose aprotinin and compared the data with those recently reported by Mangano et al [2006]. For 751 consecutive patients undergoing CABG surgery under full-dose aprotinin (>4 million kalikrein-inhibitor units) we analyzed in-hospital data on renal dysfunction or failure, MI (defined as creatine kinase-myocardial band > 60 iU/L), and CVI (defined as persistent or transient neurological symptoms and/or positive computed tomographic scan). Average age was 67.0 +/- 9.9 years, and patient pre- and perioperative characteristics were similar to those in the Society of Thoracic Surgeons database. The mortality (2.8%) and incidence of renal failure (5.2%) ranged within the reported results. The incidence rates of MI (8% versus 16%; P < .01) and CVI (2% versus 6%; P < .01) however, were significantly lower than those reported by Mangano et al. Thus the data of our single center experience do not confirm the recently reported negative effect of full-dose aprotinin on the incidence of MI and CVI. Therefore, aprotinin may still remain a valid option to reduce postoperative bleeding, especially because of the increased use of aggressive fibrinolytic therapy following percutaneous transluminal coronary angioplasty.