ATG-Fresenius inhibits blood circulating cell proliferation in a dose-dependent manner: an experimental study.

INTRODUCTION: Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. METHODS: PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [(3)H] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius in the absence/presence of 40 µg/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 µg/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37°C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. RESULTS: Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 µg/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 µg/mL was seen, and higher concentrations (>100 µg/mL) totally inhibited proliferation. CONCLUSIONS: Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell proliferation.

Pre-filling of the extracorporeal circuit with autologous blood is safe, but not effective in optimizing biocompatibility in high-risk patients.

OBJECTIVES: Haemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusions in high-risk cardiac surgery patients. We designed this study to evaluate the effects of antegrade autologous priming (AAP) on reducing perioperative blood transfusion and markers of the inflammatory response in older patients (>75 years). METHODS: Seventy-two patients undergoing first-time coronary bypass and/or aortic valve replacement were prospectively randomised to a cardiopulmonary bypass (CPB) with or without AAP. AAP was performed by adding the patient's own blood to the prime solution (mean 280 ml). Perfusion and anaesthetic techniques were as usual. The haematocrit was maintained at a minimum of 21% during CPB. Patients were well matched for all preoperative variables, including established transfusion risk factors. The primary endpoint was the requirement of red cell transfusion. The surrogate endpoints were renal function, inflammatory response and ischaemic parameters. Blood samples were drawn pre- and intraoperatively and at intervals of 6 hours till POD 6. RESULTS: Current analysis shows no differences in patients receiving homologous packed red cell transfusions. Also, markers of the inflammatory response (IL6, IL8), renal function (cystatin C, creatinine) and myocardial ischaemia (troponin T, CK-MB) were comparable in both groups (p>0.05). Clinical outcomes were similar with respect to pulmonary, renal and hepatic function, length of ICU stay and hospital stay. CONCLUSION: These data suggest that antegrade autologous priming is a safe procedure, but an ineffective way for improving biocompatibility and reducing the need for blood transfusion in older patients.

Levosimendan in patients with acute myocardial ischaemia undergoing emergency surgical revascularization.

BACKGROUND AND OBJECTIVE: Levosimendan is a calcium-sensitizing drug that enhances myocardial contractility without increasing intracellular calcium. By activating adenosine triphosphate-dependent potassium channels it exerts cardioprotective and vasodilatory effects. METHODS: A retrospective matched pair analysis was performed in 52 patients undergoing emergency coronary artery bypass grafting for acute myocardial ischaemia with or without cardiogenic shock. A total of 27 patients received levosimendan (bolus 6 microg kg(-1); continuous infusion 0.2 microg kg(-1) min(-1)) in addition to catecholamines, while 25 patients were treated with catecholamines only. RESULTS: Predicted mortality by logistic EuroSCORE was 42% (14-90%) in the levosimendan group and 38% (9-90%) in the control group (median, range). Cardiogenic shock was diagnosed in 52% of the patients in both groups. Compared to the control group, levosimendan-treated patients had fewer intra-aortic balloon pumps inserted (33% vs. 76%, P 0.05) and need for dialysis (11% levosimendan; 32% control, P > 0.05) did not reach statistical significance. Length of hospital stay did not differ (14 +/- 18 days, levosimendan; 13 +/- 19 days, control; P > 0.05) between the two groups. CONCLUSION: In this retrospective matched pair analysis of 52 patients undergoing emergency coronary artery bypass grafting for acute ischaemia, levosimendan reduced morbidity. The reduced morbidity did not translate into reductions in mortality or length of stay. A larger, prospective randomized trial is warranted to confirm the potentially beneficial effects of levosimendan in patients with acute ischaemia.

Prevention of atrial fibrillation after coronary artery bypass graft surgery using a potassium-magnesium-aspartate solution (Inzolen).

BACKGROUND: Atrial fibrillation (AFIB) following cardiac surgery is a frequent complication. The purpose of this study was to evaluate the efficacy of a potassium-magnesium-aspartate solution (Inzolen) for the prevention of AFIB. METHODS: In a randomised, prospective, double-blinded study, we studied 88 patients undergoing elective coronary artery bypass graft surgery (CABG). After surgery, patients were allocated randomly to one of two groups. Group A (n = 43) received a potassium-magnesium-aspartate solution (Inzolen), group B (n = 45) received potassium chloride; both solutions were administered continuously for 48 hours to keep the potassium serum levels between 4.5 and 5.5 mmol/l. Patients were observed for 5 days postoperatively and the incidence of atrial fibrillation was noted. At the end of surgery (T0), 4 h (T1), 24 h (T2), 48 h (T3), and 120 h (T4) postoperatively, magnesium and potassium serum levels were measured. RESULTS: The two groups did not differ significantly with regard to demographics and perioperative data. No significant difference in the incidence of postoperative atrial fibrillation was seen (group A: 41.9 % vs. group B 31.1 %; P = 0.53). In group A, the magnesium serum levels were significantly higher at T1 (1.15 +/- 0.18 vs. 0.87 +/- 0.11 mmol/l), T2 (1.24 +/- 0.22 vs. 0.82 +/- 0.10 mmol/l) and T3 (1.15 +/- 0.18 vs. 0.81 +/- 0.20 mmol/l) compared to group B, whereas potassium levels were similar in the two groups throughout the study period. CONCLUSIONS: The use of a potassium-magnesium-aspartate solution (Inzolen) showed no significant difference in potassium chloride for the prophylaxis of postoperative atrial fibrillation secondary to CABG.

Bispectral index and electroencephalographic entropy in patients undergoing aortocoronary bypass grafting.

BACKGROUND AND OBJECTIVE: This study was conducted to compare bispectral index, state entropy and response entropy in patients undergoing coronary artery bypass grafting. METHODS: In 66 patients, anaesthesia was maintained at two different levels using bispectral index. Doses of sufentanil and midazolam were adjusted to achieve a bispectral index in the range of 45-55 in 33 patients (BIS 50 group) and 35-44 in another 33 patients (BIS 40 group). Simultaneously, state entropy and response entropy were recorded. RESULTS: The targeted values of bispectral index were achieved in both groups and the bispectral index values differed significantly during whole anaesthesia. Median response entropy and state entropy fell to 19-26 during anaesthesia in both groups. Response entropy and state entropy values in the two groups differed significantly only after induction of anaesthesia and did not differ during further anaesthesia. There was no explicit intraoperative recall in both groups. Patients in Group BIS 40 received significantly (P<0.05) more sufentanil than the BIS 50 group (704+/-181 microg vs. 490+/-107 microg, respectively) and midazolam (18.5+/-6.1 mg vs. 15.6+/-3.8 mg, respectively). After cardiopulmonary bypass, significantly (P<0.05) more patients in Group BIS40 needed inotropic support with dobutamine (79%) than in the BIS50 group (52%). Time to extubation did not differ between the two groups. CONCLUSION: In patients undergoing coronary artery bypass grafting, no relationship was found between bispectral index levels and state entropy and response entropy at two different stages of a sufentanil-midazolam anaesthesia. A bispectral index level of 45-55 reduced anaesthetic medications used and the need for inotropic support.

[A comparison of the Arndt endobronchial blocker with a double lumen tube in robotic cardiac surgery]. / Ein Vergleich des Arndt-Bronchusblockers mit einem Doppellumentubus im Rahmen robotergestützter Eingriffe in der Herzchirurgie.

OBJECTIVE: In this prospective, randomised study a double lumen tube (DLT) or an Arndt bronchial blocker (BB) was used for one lung ventilation (OLV). Intraoperative oxygenation, ventilation, haemodynamics, and ease of placement were compared. METHODS: In 32 patients undergoing robotic harvesting of the left internal thoracic artery (ITA) a left-sided DLT or a BB controlled by bronchoscopy was used for OLV of the right lung. In 2 patients randomised for DLT, a single lumen tube and BB was used for difficult visualisation of the larynx. These 2 patients were excluded from the study. RESULTS: Correct placement of DLT (8.8 +/- 5.4 min, 87.5 % of the patients) as well as BB (6.5 +/- 4.0 min; n. s.; 100 % of the patients) was achieved rapidly. The Cormack-Lehane score for visualisation of the larynx was 2, 1 - 3 (median, range) in group DLT and 3, 1 - 4 (median, range) in group BB (p < 0.05). OLV lasted for 93 +/- 29 min in group DLT and 88 +/- 34 min in group BB (n. s.). Satisfactory conditions for harvesting ITA were achieved in all patients of both groups. There was no difference in any haemodynamic parameter at any time between the two groups. Mean pulmonary arterial pressure and pulmonary vascular resistance were increased without significant differences between the two groups during thoracoscopy for robotic preparation of left ITA. During OLV, index of paO (2)/FiO (2) was significantly (p < 0.05) lower in DLT patients compared to BB patients. Time to extubation did not differ between the two groups (DLT 14.3 +/- 4.6 h; BB 11.8 +/- 3.8 h). CONCLUSION: OLV in patients undergoing robotic cardiac surgery was safely achieved either by BB or by left-sided DLT. Positioning of the BB was easier than that of a DLT when intubation was difficult and tube exchange at the end of surgery is avoided. Therefore, we prefer a BB in patients undergoing robotic harvesting of left ITA.

Biventricular pacing in patients with ICD: how many patients are possible candidates?

BACKGROUND: About 80 % of patients receiving an implantable cardioverter-defibrillator (ICD) due to life-threatening episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) have structural heart disease. ICD implantation reduces the risk of sudden cardiac death to less than 2 %. However, the major obstacle in these patients is chronic heart failure (CHF). Biventricular stimulation (BIV) has shown its efficiency as an alternative therapy in drug refractory CHF. METHODS: According to the InSync registry, we predefined possible indications for BIV as follows: complete branch bundle block (> 120 ms), left-ventricular ejection fraction (EF) < 35 % and NYHA class > II. We evaluated the number of patients presenting this indication at time of implant and during follow-up (FU) at our ICD clinic. RESULTS: Between 1992 and 1998, 360 patients were provided with an ICD (mean age 64.6 +/- 5.4 yrs, mean EF 37 +/- 14 % at implant, 82 % of patients with organic heart disease). Mean FU was 34 +/- 21 months. During FU 46 patients (13 %) died, 15 of these (33 %) presenting criteria for BIV. 33 patients died of heart failure, there was 1 sudden death and 12 patients died for non-cardiac reasons. 35 % of the patients who died of heart failure had an indication for BIV. CONCLUSIONS: About 10 % of ICD patients had an indication for BIV at time of implant. Over a mean FU period of 34 months, 16% of all patients presented an indication for BIV. Patients with an indication for BIV had a higher mortality rate and more frequent atrial fibrillation compared to patients without. With this data and the good clinical results after BIV-ICD implantation, we consider the implantation of a BIV-ICD system in every patient with appropriate indications.

VAMOS--ventilator assisted model for off-pump surgery.

BACKGROUND: Introduction of innovative cardiac procedures mostly depends on extensive evaluation using laboratory animal models. Avoiding living creatures in the experimental setup where possible without loss of reliability would be progressive from a logistical as wells as an ethical perspective. METHODS: Hearts of meat-production animals (pigs) were removed without structural damage. Two tracheotomy tubes (length 35 mm, diameter 10 mm) were inserted into aortic and pulmonal positions. The atrial inflow had to be ligated. The ventilation tubes were joined to a respirator. The "ventilation" frequency was limited to a maximum of 100/min, "inspiration" volume at 100 ml and ventilation pressure at up to 60 mbar. RESULTS: "Air beats" triggered by the frequency of the respirator occurred in the ventilated heart. Insufflation and deflation generated movement that was almost the same as physiological action. CONCLUSIONS: Air-animation of the heart using a standard respirator is an easily conducted alternative to extensive and expensive laboratory experiments for development and quality control of new devices or techniques without compromising the scientific value of results and without using living animals.

Survival and quality of life after a long-term intensive care stay.

OBJECTIVE: The growing number of high-risk patients in cardiac surgery unavoidably leads to more complications, and therefore to a prolonged stay in an intensive care unit (ICU). The aim of our investigation was to elaborate on the fate of patents after long-term ICU treatment. METHODS: Out of 5055 patients, 232 had to be treated for longer than 5 days in ICU. These 232 patients were analyzed for in-hospital mortality and followed up for quality of life. The Barthel mobility index and geriatric depression scale by Sheikh and Yesavage were used to evaluate physical ability and mood disturbances. Follow-up time was 82 months, and could be completed for 99 % of the patents. RESULTS: In-hospital mortality was 34.6 %, with the majority of cases being coronary artery bypass grafting procedures (59.9 %). Average stay in ICU was 12.0 days for the survivors and 17 days for non-survivors. During follow-up time (6 - 82 months), another 56 patients (23 %) died. Survivors (n = 98) were predominantly in NYHA classes l-ll (83 %) with a Barthel index of more than 80, representing adequate mobilization during daily life in 78 % of the patients. Results according to the geriatric depression scale were normal in the vast majority of patients (91 %) with severe or life threatening depressions in only 6 patients (8 %). CONCLUSION: Long-term treatment of critically ill patients is admittedly burdened with high in-hospital and follow-up mortality. However, the excellent physical and psychological recovery of survivors unequivocally supports the employment of all technical and personnel resources within modern intensive care medicine.

Effects of solvent/detergent-treated plasma and fresh-frozen plasma on haemostasis and fibrinolysis in complex coagulopathy following open-heart surgery.

BACKGROUND AND OBJECTIVES: Solvent/detergent-treated plasma (SDP) contains markedly lower protein S (PS) and plasmin inhibitor (PI) activity than standard fresh-frozen plasma (FFP). It has also been reported that SDP contains no alpha(1)-antitrypsin. Despite the lack of clinical data, it is suspected that SDP may be less effective than FFP in the treatment of complex coagulopathies. We therefore conducted a prospective trial to study the impact of SDP and FFP on haemostasis and fibrinolysis in complex coagulopathy after open-heart surgery. MATERIALS AND METHODS: Patients received either 600 ml of SDP (n = 36) or 600 ml of FFP (n = 31) at an infusion rate of 30 ml/min. The following parameters were measured before treatment and 60 min after termination of plasma infusion: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIII, antithrombin, protein C (PC), free PS and PS activity, prothrombin fragments F1+2 (F1+2), D-dimers (DD), fibrinogen degradation products (FDP), plasmin-plasmin inhibitor complexes (PPI), plasminogen, PI and alpha(1)-antitrypsin. RESULTS: The rise in fibrinogen, factor VIII, antithrombin, PC, free PS, alpha(1)-antitrypsin and plasminogen, and the decrease in PT and APTT, did not significantly differ between the two study arms. However, PS activity did not increase after SDP infusion but did show a significant elevation after infusion with FFP. PI declined significantly after SDP and remained uninfluenced by FFP. Neither SDP nor FFP had any significant influence on F1+2, DD or FDP. However, a significant decrease in PPI levels caused by both types of plasma indicated a reduction in hyperfibrinolysis. Clinical haemostasis evaluation revealed no significant difference between the two treatment regimens. No adverse reactions were observed. CONCLUSION: With the exception of PS and PI, SDP and FFP improved haemostasis and fibrinolysis to a similar degree. The clinical significance of these findings has to be determined in patients with severe acquired PS and PI deficiency requiring plasma transfusions.

Cell saver, ultrafiltration and direct transfusion: comparative study of three blood processing techniques.

BACKGROUND: Intraoperative blood salvage is an important part of blood conservation efforts in cardiac surgery. The purpose of this study is to examine the effects of three different circuit blood-salvaging techniques: centrifugation, ultrafiltration and direct infusion. METHODS: Sixty patients undergoing elective coronary bypass graft procedures were randomly assigned in a prospective manner to one of the three blood-salvaging methods. RESULTS: Intra- and postoperative blood samples demonstrated increased hemoglobin values in the direct infusion group and higher platelet count in the ultrafiltration group. There were no significant differences in these results. The analysis of coagulation parameters revealed a similar prolongation of partial thromboplastin time and activated clotting time in all groups. The amount of blood loss was not significantly different between the three blood conservation methods. The effect of direct infusion method does not result in either major disturbance of coagulation parameters or in increased blood loss. CONCLUSION: In a sample of adult patients undergoing coronary artery bypass grafting, direct transfusion is, in consideration of the cost-effective factor, an appropriate approach for returning cardiopulmonary bypass circuit blood.

Surface modification of extracorporeal circuits: is there really an impact on cerebral performance after cardiopulmonary bypass?

BACKGROUND: Pathophysiology of extracorporeal circulation is multifactorial, and the link between newly developed "biomaterials" and clinical outcome is not easy to illustrate. MATERIAL AND METHODS: We designed a randomized, double-blinded, prospective study in order to verify the impact of a new surface modification [SMAR(X)T] in combination with an optimized blood air interface, on the cerebral performance after cardiopulmonary bypass. 80 patients were randomly divided into two subgroups (SMAR(X)T vs. standard PVC control) and analyzed for the kinetic of cerebral ischemia markers neuronspecific enolase, protein S100 and neuropsychologically tested with the Mini-Mental-Status Test (MMST) before and after the operation. RESULTS: We could not show significant differences of protein S100 and neuron-specific enolase (NSE) levels between SMAR(X)T patients and the controls, but the incidence of neurological complications was exceptionally low. Although no statistically significant differences could be obtained for the MMST, the different pointloss between both groups trends toward a better cerebral performance in SMAR(X)T patients. CONCLUSION: The use of a biologically inert circuit in combination with an optimized perfusion management seems to be worthy of recommendation.

Minimally invasive saphenous vein harvesting: is there an improvement of the results with the endoscopic approach?

OBJECTIVES: In the postoperative course after conventional open removal of the greater saphenous vein, wound healing disturbances are common and often painful. Therefore the primary goal of this investigation was to prove the safety and practicability of this new less invasive technique for saphenous vein harvesting and the effect on complications and morbidity. METHODS: The study comprised 103 coronary artery bypass grafting (CABG) patients with an endoscopic approach to harvest the saphenous vein (MIVH). We used the VasoView II system developed by Origin, and compared the intraoperative procedure time and the clinical results with 105 equivalent patients in which a conventional open technique was used. RESULTS: In 101 patients endoscopic vein harvesting was successful; a conversion into open technique was necessary in two patients. On average 2.6 vein segments could be harvested in the endogroup versus 2.9 segments in the opengroup. The mean procedure time was 13.2 min per segment in the endogroup compared to 12.2 min per segment in the opengroup. Relevant hematoma were found in 29 patients (27.6%) of the opengroup, whereas only nine patients (8.7%) of the endogroup revealed severe hematoma. Infection was apparent in nine patients (8.5%) after conventional vein harvesting. Two infections were found after endoscopic intervention. CONCLUSIONS: Endoscopic saphenous vein harvesting as part of a less invasive concept in cardiac surgery is a safe and after the learning curve, fast alternative to harvest the saphenous graft. The cosmetic result is excellent and the complication rate seems to be lower. It must be noted however, that the cost effectiveness of the method has to be proved and that further histological and functional studies are needed in order to check the intimal structure of the vein.