Despite chronic dialysis treatment, patients with end stage renal disease undergoing maintenance haemodialysis (HD) remain at a substantially increased risk of morbidity. Previous reports using Doppler ultrasound (DU) during HD have revealed microembolic signals (ME) in the venous circulation. In vitro studies confirm the emergence of microbubbles of air that may pass the security system of the HD circuit without triggering the alarm. The aim of this thesis was to elucidate the presence of ME during HD and examine methods that might reduce exposure to ME in vivo. The first study utilized DU to verify the presence of ME in 40 patients during standard HD. Investigation within 30 minutes after the start of HD and just before the end of session revealed the presence of ME in the venous blood line during both phases. The air trap did not alert for the presence of ME. This indicated that ME may pass into the patient during the entire HD run. Study 2 analyzed the presence of ME prior to start and during HD when measured at the AV-access and also carotid artery. A total of 54 patients were examined using DU as the investigative technique. ME increased significantly after start of HD in the AV-access, but also at the carotid artery site. These data indicated that ME can enter the body and even pass the lung barrier. The question arose if microbubbles of air are resorbed or may cause ischemic lesions in organs such as the brain. Study 3 examined whether the amount of ME detected in the AV-access would change by using either a high or a low blood level in the venous air trap/chamber. This was a prospective, randomized and double-blind study of 20 HD patients who were their own controls. After 30 min of standard HD, measurement of ME with DU was performed for two minutes. The chamber setting was changed and after another 30 minutes a new recording was carried out for two minutes. Data showed that setting a high blood level significantly reduced the extent of ME that entered the patient. The results also indicated that ME consisted mainly of microbubbles. In study 4, twenty patients were randomized in a cross-over setting of HD. Three options were used: a wet-stored dialyzer with high blood level (WH) and a dry-stored dialyzer using either a high (DH) or a low (DL) blood level in the venous chamber. The exposure of ME, detected by DU, was least when using mode WF, more with mode DH, and most with mode DL. There was a correlation between higher blood flow and more extensive exposure to ME. Study 5 was an autopsy study of a chronic HD patient with the aim of searching for microbubbles deposited in organs. Microbubbles of gas were verified in the vessels of the lungs, brain and heart. By using a fluorescent stain of anti-fibrinogen it was verified that the microbubbles were covered by clots that had to be preformed before death occurred. This indicated that air microbubbles are not completely absorbed and could result in embolic deposition in the organs of HD patients. In conclusion, these in vivo studies showed that ME pass the air trap without inducing an alarm and enter the venous blood line of the patient. The data confirmed the presence of ME in the AV-access and also in the carotid artery. Autopsy data of a deceased HD patient demonstrated the presence of microbubbles in the capillaries of the lungs, but also in the systemic circulation such as in the brain and the heart. A high blood level in the venous chamber and wet-stored dialyzer can reduce, but not eliminate the exposure to microbubbles for patients undergoing HD.

Introduction: Haemodialysis (HD) is a treatment in which blood from the patient is lead through a tubing system into a dialysis device in a extracorporeal circuit. This circuit contains semipermeable membranes (dialyzer). Blood with uraemic toxins flows on one side, and a salt solution flows on the other side. The salt solution flushes away waste products that have passed the membrane by diffusion or convection through small pores. From there the blood returns to the patient through a tubing system that contains an air-trap and a sensor to avoid air contamination in the blood. Besides air contamination, this treatment is burdened with safety problems such as biocompatibility, electrical safety and mechanical safety. The aim of this thesis was to investigate the safety issues in haemodialysis devices regarding leakage current and air contamination during standard procedures and simulated fault conditions. Does the dialysis device constitute a risk for the patient? Methods: To determine the extent of leakage current in HD machines, measurements at the filter-coupling site were performed in vitro according to the safety standard, IEC 601-1, in 5 types of dialysis machines. To determine, in vitro, to what extent blood and priming fluid allowed leakage current to pass to the patient, leakage current were also measured in the blood lines. The blood line was filled with blood from donors or priming fluid in eight different runs. To determine if leakage current could influence biocompatibility, a Fresenius 2008C dialysis machine and 8 hemophan dialyzers were used. Blood lines contained about 400 ml heparinized blood from each of 8 different donors (in vitro). C3d was measured, in vitro, before start of a simulated dialysis and at 15, 30, 45 and 60 min. during standard dialysis procedure. Then 1.5 mA current was switched on and additional samples were drawn at 75 and 90 min. Some patients need a central dialysis catheter (CDC) for access, placed close to or within the heart. To analyze if leakage current during standard HD would influence the ECG, patients with CDC or with AV-fistula as access were investigated. To analyse if air contamination could occur without activating security alarms in the dialysis device, various modes of in vitro dialysis settings were studied, some using a dextran solution to mimic blood viscosity. Besides visual inspection an ultrasound detector for microemboli and microbubbles was also used. Results: The data showed leakage current at the filter coupling site that was significantly higher for some devices than for others. The leakage current could pass through blood and priming fluid. It exceeded the cardiac floating (CF)-safety limit (<50μA) at the top of the CDC using the test mains on applied part for saline (median 1008μA), for blood (median 610μA) and for a single fault condition using saline (median 68 μA) or blood (47 μA). The leakage current experiments showed that complement activation worsened as the leakage current increased. During standard dialysis arrhythmia could occur. Microbubbles were visible at the bottom of the air-trap and bubbles could pass the air-trap towards the venous line without triggering the alarm. During recirculation, several ml of air could be collected in an intermediate bag after the venous line. Ultrasound showed the presence of bubbles of sizes 2.5-50 μm as well as more than 50 μm silently passing to the venous line in all runs performed. In conclusion, the data showed that a leakage current in HD devices can be high enough to be a safety risk for the patient. This risk is greater if a single fault arises in the dialysis machine or another device connected to the same patient, or during mains contact to the patient. Then the current flow may be high enough to cause arrhythmia for the patient, especially when using a CDC. There is also reason for concern that micro bubble transmission may occur without inducing an alarm. These factors need to be looked over to improve safety regulations and optimize HD treatment and service schedules.

Introduction: During cardiac surgery aided by cardiopulmonary bypass (CPB) the autotransfusion of pericardial suction blood (PSB) is regarded mandatory to limit allogeneic blood exposure. PSB is however proposed as a source of lipid microemboli and to contribute to brain damage. This thesis addresses the logistics of allogeneic blood transfusion during coronary artery bypass grafting (CABG), the embolic potential of reinfused PSB, and means to reduce PSB fat contamination, investigated both clinically and experimentally. Methods: Study I) Patients undergoing CABG surgery (n=2469) were included in a database study. The magnitude of surgical bleeding versus blood transfusion was analyzed to extract a subgroup of patients (n=982) in whom transfusions were independent from bleeding. Study II) PSB and venous-blood samples were collected from patients undergoing routine CABG (n=20). The in vitro capillary-flow properties of blood subcomponents and the effects of routine screen filtration were tested. PSB fat contamination was evaluated by imprint microscopy. Study III) Heat extracted liquid human fat or soya oil were mixed with mediastinal drain blood (n=20) and incubated in a temperature controlled column, to evaluate spontaneous density separation of fat. Study IV) The findings from study-III were applied to develop a fat-reducing system (FRS) using two stacked compartments. The FRS was experimentally tested (n=12), with similar methods as in study-III, and clinically evaluated (n=10). A single-chamber blood bag (n=10) served as reference. Results: Study I) A surgical bleeding of less than 400 mL showed no correlation to blood transfusion, although 64 of 982 patients still received allogeneic blood. The strongest predictors for this kind of transfusion were; female gender, weight ≤70 kg, CPB time ≥90 minutes, CPB temperature ≤32 ºC, and advanced age (P<.001 - .038). Study II) The capillary-flow profile of PSB plasma was highly impaired compared to venous plasma (P<.001). Conversely, blood-cell components showed no difference between PSB and venous blood. Routine screen filtration showed no ameliorating effect on capillary-flow resistance. Fat debris was detected on imprints in all PSB samples in contrast to venous plasma (P<.05). Study III) After 10-min of incubation had 77% of added soya oil separated and found contained in the top 20% fraction of blood (P<.001), aimed to be discarded. The density separation of human fat was less efficient compared to soya oil (P=.011). Fat also adsorbed to surface which was more pronounced at low temperature (P<.001). The overall reduction of human fat was 70%. Study IV) PSB contained 1.5 mL fat suspended in 418 mL PSB. Of this fat was 24% surface-bound. Experimental analysis of the proposed FRS revealed an 83% fat-reduction which was clinically confirmed, suggesting 80% reduction (P=.001). The FRS also gave a small but significant erythrocyte-concentrating effect. Conclusions: Transfusion of allogeneic blood during CABG surgery appeared associated with an institutional, individual, and technical bias of an anticipated need and not only used to compensation for surgical bleeding. In part may this reflect a non-compliant CPB methodology and hemodilution. It was confirmed that PSB plasma contained fat, with a suggested embolic potential. Human fat was significantly reduced from mediastinal drain blood by spontaneous density separation and surface adsorption. The prototype FRS used for PSB incubation during CPB allowed an efficient fat reduction.