Microemboli induced by air bubbles may be deposited in organs as a consequence of contamination during medical care.

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 (600×) 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.

Venous chambers in clinical use for hemodialysis have limited capacity to eliminate microbubbles from entering the return bloodline: An in vitro study.

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.

Interdialytic weight gain of less than 2.5% seems to limit cardiac damage during hemodialysis.

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.

Air contamination during medical treatment results in deposits of microemboli in the lungs: An autopsy study.

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.

A high blood level in the venous chamber and a wet-stored dialyzer help to reduce exposure for microemboli during 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.

A high blood level in the air trap reduces microemboli during hemodialysis.

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.

Microbubbles of air may occur in the organs of hemodialysis patients.

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.

Microemboli, developed during haemodialysis, pass the lung barrier and may cause ischaemic lesions in organs such as the brain.

BACKGROUND: Chronic haemodialysis (HD) may relieve some medical problems of terminal uraemia, but the life expectancy of patients is still significantly shortened, and there is a greatly increased morbidity. This includes pulmonary morbidity and chronic central nervous system (CNS) abnormalities. Previous studies have shown that a considerable amount of air microbubbles emanate within the blood lines of the dialysis device and pass the air detector without sounding an alarm. The aim of this study was to investigate whether microemboli can pass to the patient and whether they could be detected in the carotid artery. METHODS: A total of 54 patients on chronic HD (16 with central dialysis catheter) were investigated with an ultrasound detector (Hatteland, Røyken, Norway) for the presence of microemboli at the arteriovenous (AV) fistula/graft and at the common carotid artery before and during HD. Measurements were taken for 2 and 5 min, respectively. Non-parametric paired statistics were used (Wilcoxon). RESULTS: The median number (range) and mean +/- SD of microembolic signals detected at the AV access site before commencing dialysis and during HD were 0 (0-3) and 0.2+/- 0.5 versus 4 (0-85) and 13.5 +/- 20 (P = 0.000); at the carotid artery, 1 (0-14) and 1.7 +/- 2.9 versus 2 (0-36) and 3.5 +/- 5.8 (P = 0.008). CONCLUSIONS: The infused and returning fluid from HD devices contains air microbubbles that enter the patient without triggering any alarms. These small emboli pass the lung and may cause ischaemic lesions in organs supported by the arterial circuit, such as the brain.

Development of air micro bubbles in the venous outlet line: an in vitro analysis of various air traps used for hemodialysis.

Venous air traps were tested in vitro with respect to presence of micro bubbles. Three types of venous air traps were measured (Bioline, Bioline GmbH, Luckenwalde, Germany; Gambro, Gambro AB, Lund, Sweden; Fresenius M.C., Fresenius Medical Care AG & Co. KGaA, Bad Homburg, Germany). Measurements (n = 10) were taken for each air trap, fluid flow (50-600 mL/min), and fluid level (high/low). A 1.5-MHz ultrasound probe was used with an analysis device. The probe was mounted on the outlet line downstream of the venous air trap. A semisynthetic fluid was used to resemble blood viscosity. Occurrences of micro bubbles, without inducing an alarm of the dialysis device, were detected in almost all measurements. The amount of bubbles increased with increasing flow. There were more bubbles with low fluid level compared with high level. The Bioline tubing released the least bubbles in high fluid level. At low level, the Gambro tubing showed the least bubbles at flows 50-400 mL/min, and the Fresenius M.C. tubing showed the least bubbles at flows 400-600 mL/min. High fluid level in the air trap reduced generation of micro bubbles compared to low level, as did lower fluid flow versus high flow. The design of the air trap was also of importance.

Air bubbles pass the security system of the dialysis device without alarming.

During hemodialysis microembolic findings have been noted after the venous chamber (subclavian vein). The aim of this study was to evaluate if air could pass the venous chamber and, if so, if it passes the safety-system detector for air-infusion without triggering an alarm. Various in vitro dialysis settings were performed using regular dialysis devices. A dextran fluid was used instead of blood to avoid the risk of development of emboli. Optical visualization as well as recirculation and collection of eventual air into an intermediate bag were investigated. In addition, a specifically designed ultrasound monitor was placed after the venous air trap to measure the presence of eventual microbubbles. Speed of dialysis fluid was changed, as was the level of the fluid in the air trap. Thereby a fluid level was considered "high" if it was close to the top of the air trap and "low" if it was around the mid part of the air trap. By optical vision microbubbles were seen at the bottom of the air trap and could pass the air trap towards the venous line without alarming. During recirculation several mL of air were collected in an intermediate bag after the venous line. Ultrasound monitoring exhibited the presence of microbubbles of the size of approximately 5 microm upwards passing to the venous line in all runs performed. Amount of bubbles differed between devices and in general an increased fluid speed correlated significantly with the increased counts of microbubbles/min. No alarming of the detector occurred. A more concentrated fluid allowed higher counts/min when flow was increased to 600 mL/min. Data revealed that air passes the safety-sensor in the air trap without alarming. The presence of air increased in general with fluid speed and a lower fluid level in the air trap. Differences were present between devices. If this affects the patients has to be elucidated.

The sensor in the venous chamber does not prevent passage of air bubbles during hemodialysis.

We previously showed, in vitro, that micro bubbles pass the air trap without inducing an alarm. The aim was to investigate if micro bubbles bypass the detector during hemodialysis (HD). During HD (40 patients, 47 HD sessions, 231 measurements), an ultrasound detector was fixed just after the venous air trap. Micro bubble size was measured in the range from 5 microm up to >42.5 microm. Blood flow was at a mean 346 mL/min (SD +/- 57). The mean of all micro bubbles per minute, without inducing an alarm, was at start 128 (range 0-769). Measurements revealed the presence of micro bubbles in all of the series and in 90% of the measurements. There was no difference between start and end of the same dialyses. There was a correlation between blood flow and extent of micro bubbles for the smaller sizes and the sum of all bubbles (r > or = 0.29, P < or = 0.026). Micro bubbles passed the air trap without alarming. Most bubbles were approximately 5 microm.