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Background. When blood passes the extracorporeal circuit, air microbubbles (MBs) contaminate the blood. Some MBs will end up as microemboli in the lung, heart, and brain. MB exposure has no medical purpose and is considered to be bio-incompatible. Selecting venous chambers with a high removal rate of MBs is warranted to reduce the risks of air bio-incompatibility. The primary aim was to compare the Fresenius 5008 (F5008-VC) and the Emboless® (Emboless-VC) venous chambers regarding the elimination of MBs in the return bloodline during hemodialysis (HD).

Methods. Twenty patients underwent 80 sessions of cross-over HD using both the F5008-VC and the Emboless-VC randomized such that half started with the F5008-VC and half with the Emboless-VC. For 32 of the 80 sessions, measurements were also performed during hemodiafiltrations (HDF) after the initial HD. MBs were measured with an ultrasound device (within the size range of 20–500 μm) at the “inlet” and “outlet” bloodline of the venous chambers. The Wilcoxon pairwise test compared the percentage of MB elimination between venous chambers.

Results. During HD, the median reduction of MBs for the outlet was 39% with the F5008-VC and 76% with the Emboless-VC (P < .001). During HDF, the reduction was 28% with the F5008-VC and 70% with the Emboless-VC (P < .001).

Conclusion. Fewer MBs and subsequently fewer microemboli entered the bloodline of the patient using the Emboless-VC compared to the F5008-VC venous chamber during HD and during HDF. Venous chambers with a high removal rate of MBs will reduce the extent of air emboli.

Background: Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. The aim of this autopsy study was to investigate if microbubbles of air accidently entering the bloodline may be detected as microemboli (ME) in tissue such as lungs, brain and heart. If so, do differences in prevalence exist between haemodialysis (HD) and amyotrophic lateral sclerosis (ALS) patients.

Methods: Included were data from 44 patients treated by medical healthcare before death. Twenty-five cases had been treated with chronic HD and 19 cases died from ALS. Since air in the bloodline activates coagulation, ME could appear. To discriminate between microbubbles caused by artificial contamination during autopsy versus microbubbles deposited in vivo, tissues were stained with a polyclonal fluorescent antibody against fibrinogen, fibrin and fragments E and D. Fluorescence staining was used to visualize ME counted within 25 microscopic fields (600x) of a tissue preparation. One tissue preparation was used if available from the lung, heart and frontal lobe of the brain and in five cases also the cerebellum.

Results: Microbubbles can be verified at autopsy as ME in the lung, heart and brain in tissue from patients exposed to more extensive medical care. There were significantly more ME in the lungs versus the heart or brain. Women had fewer ME than men. The HD group had a higher median of ME per section than the ALS group (lung: 6 versus 3, P = .007; heart: 2.5 versus 1, P = .013; brain: 7.5 versus 2, P = .001) and had more sections with ME findings than the ALS group (P = .002). A correlation existed between the time on HD (months) and ME in the lungs.

Conclusions: More ME were present in HD patients compared with those who suffered from ALS. Minimizing air contamination from syringes, infusions and bloodlines will decrease ME and subsequent tissue injury. Lay Summary Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. Microbubbles can be verified at autopsy as microemboli (ME) by air in lung, heart and brain in tissue from patients exposed to dialysis and more cannulation and infusions. Minimizing air exposure from syringes, infusions and bloodlines may decrease the risk of ME by air and subsequent tissue injury.

Background: During hemodialysis (HD), blood passes through an extracorporeal circuit (ECC). To prevent air administration to the patient, a venous chamber (chamber) is located before the blood return. Microbubbles (MBs) may pass through the chamber and end up as microemboli in organs such as the brain and heart. This in vitro study investigated the efficacy of various chambers in MB removal.

Materials and Methods: The in vitro recirculated setting of an ECC included an FX10 dialyzer, a dextran-albumin solution to mimic blood viscosity and chambers with different flow characteristics in clinical use (Baxter: AK98 and Artis, Fresenius: 5008 and 6008) and preclinical test (Embody: Emboless®). A Gampt BCC200 device measured the presence and size of MBs (20–500 μm). Percentage change of MBs was calculated: ΔMB% = 100*(outlet–inlet)/inlet for each size of MB. Blood pump speed (Qb) was 200 (Qb200) or 300 (Qb300) ml/minute. Wilcoxon paired test determined differences.

Results: With Qb200 median ΔMB% reduction was: Emboless −58%, AK98 −24%, Fresenius 5008 −23%, Artis −8%, and Fresenius 6008 ± 0%. With Qb300 ΔMB% was: Emboless −36%, AK98 ± 0%, Fresenius 5008 ± 0%, Artis +25%, and Fresenius 6008 + 21%. The Emboless was superior to all other chambers with Qb200 and Qb300 (p < 0.001). Further, the Emboless with Qb300 still eliminated more MBs than all other chambers with Qb200 (p ≤ 0.003).

Conclusion: The results from the present study indicate that flow characteristics of the chamber and the Qb are important factors to limiting exposure of MB to the return bloodline. The Emboless chamber reduced MBs more effective than those chambers in clinical use investigated.

Aims: To investigate if a single low-flux HD induces a rise in cardiac biomarkers and if a change in clinical approach may limit such mechanism.

Material and methods: A total of 20 chronic HD patients each underwent three different study-dialyses. Dialyzers (low-flux polysulfone, 1.8 sqm) had been stored either dry or wet (Wet) and the blood level in the venous chamber kept low or high. Laboratory results were measured at baseline, 30 and 180 min, adjusted for the effect of fluid shift. Ultrasound measured microemboli signals (MES) within the return line.

Results: Hemodialysis raised cardiac biomarkers (p < 0.001): Pentraxin 3 (PTX) at 30 min (by 22%) and at 180 min PTX (53%), Pro-BNP (15%), and TnT (5%), similarly for all three HD modes. Baseline values of Pro-BNP correlated with TnT (rho = 0.38, p = 0.004) and PTX (rho = 0.52, p < 0.001). The changes from pre- to 180 min of HD (delta-) were related to baseline values (Pro-BNP: rho = 0.91, p < 0.001; TnT: rho = 0.41, p = 0.001; PTX: rho = 0.29, p = 0.027). Delta Pro-BNP (rho = 0.67, p < 0.001) and TnT (rho = 0.38, p = 0.004) correlated with inter-dialytic-weight-gain (IDWG). Biomarkers behaved similarly between the HD modes. The least negative impact was with an IDWG <= 2.5%. Multiple regression analyses of the Wet-High mode does not exclude a relation between increased exposure of MES and factors such as release of Pro-BNP.

Conclusion: Hemodialysis, independent of type of dialyzer storage, was associated with raised cardiac biomarkers, more profoundly in patients with higher pre-dialysis values and IDWG. A limitation in IDWG to <2.5% and prolonged ultrafiltration time may limit cardiac strain during HD, especially in patients with cardiovascular risk.

Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage. Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. The lung tissue was investigated by microscopy after autopsy using a fluorescein-marked polyclonal antibody against fibrinogen as a marker for clots preformed before death. Results: All five hemodialysis patients had microbubbles of air in the lung tissue, whereas two of seven amyotrophic lateral sclerosis patients had such findings (Fisher's test p = 0.0278, relative risk = 3.5, confidence interval: 1.08-11.3). There were more microbubbles of air/10 randomly investigated microscopic fields of tissue in the hemodialysis patients than the amyotrophic lateral sclerosis patients (Student's test, p < 0.05). All hemodialysis patients had a medium graded extent of pulmonary fibrosis that was not found in any of the ALS patients. The microbubbles of air were surrounded by fibrin as a sign of development of clots around the air bubbles while the patients were still alive. Conclusion: Exposure to microbubbles of air during various treatments such as hemodialysis may result in microemboli. Future studies should clarify whether microbubbles of air contribute to tissue scarring. We suggest preventive measures against the exposure to microbubbles of air during especially repeated exposures such as hemodialysis.

During hemodialysis (HD), microemboli develop in the blood circuit of the apparatus. These microemboli can pass through the venous chamber and enter into the patient's circulation. The aim of this study was to investigate whether it is possible to reduce the risk for exposure of microemboli by altering of the treatment mode. Twenty patients on chronic HD were randomized to a prospective cross-over study of three modes of HD: (a) a dry-stored dialyzer (F8HPS, Fresenius, steam sterilized) with a low blood level in the venous chamber (DL), (b) the same dialyzer as above, but with a high level in the venous chamber (DH), and (c) a wet-stored dialyzer (Rexeed, Asahi Kasei Medical, gamma sterilized) with a high blood level (WH). Microemboli measurements were obtained in a continuous fashion during 180 minutes of HD for all settings. A greater number of microemboli were detected during dialysis with the setting DL vs. WH (odds ratio [OR] 4.07, 95% confidence interval [CI] 4.03–4.11, P < 0.0001) and DH vs. WH (OR 1.18, 95% CI 1.17–1.19, P < 0.0001) and less for DH vs. DL (OR 0.290, 95% CI 0.288–0.293, P < 0.0001). These data indicate that emboli exposure was least when using WH, greater with DH, and most with DL. This study shows that using a high blood level in the venous chamber and wet-stored dialyzers may reduce the number of microemboli.

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.

Previous studies have demonstrated the presence of air microemboli in the dialysis circuit and in the venous circulation of the patients during hemodialysis. In vitro studies indicate that a high blood level in the venous air trap reduces the extent of microbubble formation. The purpose of this study was to examine whether air microbubbles can be detected in the patient's access and if so, whether the degree of microbubble formation can be altered by changing the blood level in the venous air trap. This was a randomized, double-blinded, interventional study of 20 chronic hemodialysis patients. The patients were assigned to hemodialysis with either an elevated or a low blood level in the air trap. The investigator and the patient were blinded to the settings. The numbers of microbubbles were measured at the site of the arteriovenous (AV) access for 2 min with the aid of an ultrasonic Doppler device. The blood level in the air trap was then altered to the opposite setting and a new measurement was carried out after an equilibration period of 30 min. Median (range) for the number of microbubbles measured with the high air trap level and the low air trap level in AV access was 2.5 (0-80) compared with 17.5 (0-77), respectively (P = 0.044). The degree of microbubble formation in hemodialysis patients with AV access was reduced significantly if the blood level in the air trap was kept high. The exposure of potentially harmful air microbubbles was thereby significantly reduced. This measure can be performed with no additional healthcare cost.

During hemodialysis (HD), blood that passes the dialysis device gets loaded with microbubbles (MB) of air that are returned to the patient without inducing an alarm. The aim with this study was to clarify if these signals are due to microembolies of air, clots, or artifacts, by histopathology of autopsy material of HD patients. These first results are from a patient on chronic HD. Due to pulmonary edema he was ultrafiltered. Within 30 minutes after the start, he suffered from a cardiac arrest and died. Autopsy verified the clinical findings. Microscopic investigation verified microembolies of air that were surrounded by fibrin in the lungs, brain, and heart. The study verified that MBs can enter the blood during HD and are trapped in the lungs. In addition, MBs pass the pulmonary capillaries and enter the arterial part of the body and are dispersed throughout the body. This can contribute to organ damage and be part of the poor prognoses seen in HD patients. Data support the importance to reduce MBs in the dialysis circuit.