Arterial Line Filter Research Articles

Intravenous Dabigatran Provides Adequate Anticoagulation for Cardiopulmonary Bypass Using a Rabbit Model.

Heparin anticoagulation has been used successfully for cardiopulmonary bypass (CPB). However, an alternative anticoagulant approach is desirable due to the cases of heparin-induced thrombocytopenia. Dabigatran provides anticoagulation for an in vitro model of simulated CPB. The current analysis tests the hypothesis that dabigatran provides sufficient anticoagulation for CPB in intact rabbits. Nonlinear mixed effects models were used to estimate dabigatran parameters for a two-compartment pharmacokinetic model in 10 New Zealand White rabbits. A dabigatran infusion designed to maintain a plasma concentration of 90 µg/ml was run throughout CPB based on the pharmacokinetics. Animals were subjected to sternotomy and anticoagulated with IV dabigatran (six animals) or heparin (four animals). Rabbits were cannulated centrally using the right atrium and ascending aorta and CPB was maintained for 120 min. Measurement of activated clotting time, thromboelastometric reaction time, and blood gases were performed during CPB. Then, the animals were euthanized, and the brain and one kidney were removed for histology. Sections of the arterial filters were inspected using electron microscopy. The observed dabigatran concentrations during CPB were greater than the target concentration, ranging from 137 ± 40 μg/ml at 5 min of CPB to 428 ± 150 μg/ml at 60 min, and 295 ± 35 μg/ml at 120 min. All rabbits completed 2 h of CPB without visible thrombosis. In the two groups, reaction time values were elevated, reaching 10,262 ± 4,198 s (dabigatran group) and 354 ± 141 s (heparin group) at 120 min of CPB. Brains and kidneys showed no evidence of thrombosis or ultrastructural damage. Sections of the arterial line filter showed minimal or no fibrin. There was no significant difference in outcomes between dabigatran- and heparin-treated animals. In this first-use, proof-of-concept study, the authors have shown that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis using a rabbit CPB model.

International Survey of Perfusion Practice for Pediatric and Congenital Heart Surgery: 2021 Results

The conduct of cardiopulmonary bypass in neonatal, infant, and pediatric patients continuously evolves as new devices and innovative techniques are introduced. Since 1989, periodic pediatric perfusion surveys have been conducted to ascertain practice patterns involving demographics, equipment, and perfusion techniques. The goal of this current project is to provide an updated perspective on international pediatric and congenital perfusion practice since the last survey conducted in 2016. In July 2021, a 100-question perfusion survey was distributed to 284 pediatric cardiac surgery centers using a secure web browser-based data application. Each center was given a unique survey hyperlink to ensure one response per institution and to monitor the response rate. Centers were given 1 month to complete the survey and electronic reminders were sent weekly to nonrespondents. After the survey was closed, information from completed surveys was exported to a software program for analysis. Responses were received from 153 of 284 pediatric centers for a response rate of 54%. Sixty respondents (39%) were from North American (NA) centers while 93 respondents (61%) were from non-North American (NNA) centers. The vast majority of centers use a roller head arterial pump (93%), hollow fiber oxygenators with open reservoirs (86%), and integrated arterial line filters (73%). The use of modified ultrafiltration was reported by 76% of centers. Ninety-two percent of centers reported the use of selective antegrade cerebral perfusion for aortic arch repairs. The N + 1 staffing model was most prevalent (52%), followed by two perfusionists per case (33%). Periodic surveys continue to be a useful modality in assessing regional variation in pediatric perfusion practice. This survey marked the first time the majority of responses came from non-North American institutions. Identifying these practice patterns may aid in the development of, and adherence to, regional standards and guidelines. This would foster the reduction of variation in practice and potentially improve patient safety.

International Survey of Perfusion Practice for Pediatric and Congenital Heart Surgery: 2021 Results.

The conduct of cardiopulmonary bypass in neonatal, infant, and pediatric patients continuously evolves as new devices and innovative techniques are introduced. Since 1989, periodic pediatric perfusion surveys have been conducted to ascertain practice patterns involving demographics, equipment, and perfusion techniques. The goal of this current project is to provide an updated perspective on international pediatric and congenital perfusion practice since the last survey conducted in 2016. In July 2021, a 100-question perfusion survey was distributed to 284 pediatric cardiac surgery centers using a secure web browser-based data application. Each center was given a unique survey hyperlink to ensure one response per institution and to monitor the response rate. Centers were given 1 month to complete the survey and electronic reminders were sent weekly to nonrespondents. After the survey was closed, information from completed surveys was exported to a software program for analysis. Responses were received from 153 of 284 pediatric centers for a response rate of 54%. Sixty respondents (39%) were from North American (NA) centers while 93 respondents (61%) were from non-North American (NNA) centers. The vast majority of centers use a roller head arterial pump (93%), hollow fiber oxygenators with open reservoirs (86%), and integrated arterial line filters (73%). The use of modified ultrafiltration was reported by 76% of centers. Ninety-two percent of centers reported the use of selective antegrade cerebral perfusion for aortic arch repairs. The N + 1 staffing model was most prevalent (52%), followed by two perfusionists per case (33%). Periodic surveys continue to be a useful modality in assessing regional variation in pediatric perfusion practice. This survey marked the first time the majority of responses came from non-North American institutions. Identifying these practice patterns may aid in the development of, and adherence to, regional standards and guidelines. This would foster the reduction of variation in practice and potentially improve patient safety.

Rivaroxaban Reduces the Dabigatran Dose Required for Anticoagulation During Simulated Cardiopulmonary Bypass.

Heparin is the standard anticoagulant for cardiopulmonary bypass (CPB); however, there are problems with its use that make the development of suitable alternatives desirable. Currently, no ideal alternative exists. We have previously reported that the direct thrombin inhibitor dabigatran can prevent coagulation in simulated CPB at high concentrations. These high concentrations may cause difficulties in achieving the reversal of dabigatran with idarucizumab, given the markedly different pharmacokinetics of the 2 drugs. Herein, we test the hypothesis that the addition of the anti-Xa drug rivaroxaban would provide suitable anticoagulation at a lower concentration of dabigatran given likely synergy between the 2 classes of drugs. The primary goal of the study was to investigate whether the addition of rivaroxaban reduces the concentration of dabigatran necessary to allow 2 hours of simulated CPB. The study was performed in sequential steps. Blood collected from consenting healthy donors was used throughout. First, we added graded concentrations of dabigatran and rivaroxaban alone and in combination and assessed inhibition of anticoagulation using thromboelastometry. Using results from this step, combinations of dabigatran and rivaroxaban were tested in both Chandler loop and simulated CPB circuits. Dabigatran and rivaroxaban were added before recalcification, and the circuits were run for 120 minutes. In both models of CPB, 120 minutes of circulation without visible thrombus was considered successful. In the Chandler loop system, idarucizumab was added to reverse anticoagulant effects. In the CPB circuits, the arterial line filters were examined using scanning electron microscope (SEM) to qualitatively assess for fibrin deposition. In vitro analysis of blood samples treated with dabigatran and rivaroxaban showed that dabigatran and rivaroxaban individually prolonged clotting time (CT) in a dose-dependent manner. However, when combined, the drugs behaved synergistically. In the Chandler loop system, dabigatran 2400 and 4800 ng/mL plus rivaroxaban (150 ng/mL) effectively prevented clot formation and reduced the dynamics of clot propagation for 120 minutes. Idarucizumab (250-1000 µg/mL) effectively reversed anticoagulation. In the CPB circuits, dabigatran (2500 ng/mL) and rivaroxaban (200 ng/mL) were successful in allowing 120 minutes of simulated CPB and prevented fibrin deposition. Biomarkers of coagulation activation did not increase during simulated CPB. Heparin controls performed similarly to dabigatran and rivaroxaban. The dual administration of oral anticoagulant drugs (dabigatran and Rivaroxaban) with different pharmacologic mechanisms of action produced synergistic inhibition of coagulation in vitro and successfully prevented clotting during simulated CPB.

Blockage of extracorporeal circulation during emergency surgery for fulminant infective endocarditis.

A 37-years-old man with a history of alcohol abuse and pancreatitis, presented to the emergency department with a 1-week history of progressively worsening dyspnoea with a fever up to 39°C. Echocardiography revealed bicuspid aortic valve with additional mobile structure and perforation of leaflet with acute aortic regurgitation. Due to rapidly deteriorating condition of the patient, a decision about immediate surgery was made. In the operating room, cardiac arrest in the asystole mechanism occurred. Extracorporeal circulation was turned on during direct heart massage. After opening of the aorta, the circulation was blocked by total clogging of the arterial line filter by fibrine deposits. The oxygenator was replaced which resulted a break in extracorporeal circulation lasting about 10 min. Patients survived surgery and was discharged after 6 week antibiotic therapy.

The effect of SANGUINATE® (PEGylated carboxyhemoglobin bovine) on cardiopulmonary bypass functionality using a bovine whole blood model of normovolemic hemodilution.

Cardiac surgery using cardiopulmonary bypass carries a high risk of bleeding and need for blood transfusion. Blood administration is associated with increased rates of morbidity and mortality. Perioperatively, strategies are often employed to reduce blood transfusions in high-risk patients or in situations where blood transfusion is contraindicated. Normovolemic hemodilution is a blood conservation technique used during cardiac surgery that involves replacement of blood with fluids. SANGUINATE® (PEGylated carboxyhemoglobin bovine) is a novel hemoglobin-based oxygen carrier that can deliver oxygen effectively to tissues in the presence of severe hypoxia. The use of a hemoglobin-based oxygen carrier during hemodilution may augment tissue oxygen delivery and reduce blood transfusion. Six standardized cardiopulmonary bypass runs simulating normovolemic hemodilution using varying proportions of bovine whole blood and SANGUINATE were performed. Pump speed, flow rate, line pressures, hemoglobin concentration, oxygenation, and degree of anticoagulation were assessed at regular intervals. Membrane oxygenators and arterial line filters were inspected for evidence of clotting following each run. Increases in the pressure drop across the membrane oxygenator were detected during runs 5 and 6. Median activated clotting time values were able to be maintained at goal during the runs, and SANGUINATE did not appear to be thrombogenic. Hemoglobin concentration decreased following the addition of SANGUINATE. Oxygenation was maintained during all runs that included SANGUINATE. SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass.

Effects of bubble size differences on the bubble-trapping performance of arterial line filters

Effects of bubble size differences on the bubble-trapping performance of arterial line filters

Effects of bubble size differences on the bubble-trapping performance of arterial line filters

Effects of bubble size differences on the bubble-trapping performance of arterial line filters

Assessment of three methods for removing massive air in a cardiopulmonary bypass circuit: simulation-based multi-discipline training in West China Hospital.

A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.

Goal-Directed Perfusion Methodology for Determining Oxygenator Performance during Clinical Cardiopulmonary Bypass

New generation oxygenators incorporate arterial line filtration either sequential to, or directly in, the gas exchange module. This unique design may affect gas exchange performance by altering the operational characteristics of the device. The present study was designed to evaluate three oxygenators in a clinical setting using a goal-directed perfusion algorithm during cardiopulmonary bypass (CPB). After institutional review board approval, 60 adult patients undergoing cardiac surgery for acquired heart disease were matched for disease state and body size into three groups based on oxygenator type: Terumo SX18™(n= 20), Terumo FX15™(n= 20), and LivaNova Inspire6F™6 Dual (n= 20). An external arterial line filter was used with the FX15, whereas the SX18 and Inspire6F had integrated arterial filters. All perfusion, anesthetic and postoperative care management was standardized using institutional goal-directed patient management processes. Data were collected and stored according to quality improvement guidelines. There were no differences in demographics or type of surgical procedure performed among groups. The Inspire6F patients required lower fraction of inspired oxygen values as compared to the SX18 (67.9% ± 6.2% vs. 75.4% ± 6.5%,p&lt; .005) and FX15 (79.1% ± 8.4%,p&lt; .0001) groups. Arterial oxygen content and oxygen delivery were slightly higher in the FX15 group as compared to SX18 (13.1 ± 1.4 mL O2/dL vs. 12.4 ± 1.1 mL O2/dL, 611.1 ± 150.4 mL O2vs. 528.2 ± 102.3 mL O2,p&lt; .05). The FX15 patients had significantly higher CPB hematocrits compared to SX18 patients (30.3% ± 3.9% vs. 27.7% ± 2.6%,p&lt; .05), but were not different when compared to the Inspire6F group (28.8% ± 3.5%,p&lt; .50). There were no differences in intraoperative transfusion rates, but a higher percent of patients received postoperative transfusions in the SX18 group as compared to either FX15 or Inspire6F groups (p&lt; .039). There were no differences in postoperative morbidity or complications in any group. In conclusion, the use of the SX18 was comparable to newer generation oxygenators in regard to gas exchange performance and the degree of hemodilution.

The scientific evidence of arterial line filtration in cardiopulmonary bypass.

The indication for arterial line filtration (ALF) is to inhibit embolisation during cardiopulmonary bypass. Filtration methods have developed from depth filters to screen filters and from a stand-alone component to an integral part of the oxygenator. For many years, ALF has been a standard adopted by a majority of cardiac centres worldwide. The following review aims to summarize the available evidence in support for ALF and report on its current practice in Europe. The principles and application of ALF in Europe was investigated using a survey conducted in 2014. The scientific evidence for ALF was examined by performing a systematic literature search in six different databases, using the following search terms: "Cardiopulmonary bypass AND filters AND arterial". The primary endpoint was protection against cerebral injury verified by the degree of cerebral embolisation or cognitive tests. The secondary endpoint was improvement of the clinical outcome verified elsewise. Only randomised clinical trials were considered. The response rate was 31% (n=112). The great majority (88.5%) of respondents were using ALF, following more than 10 years of experience. Integrated arterial filtration was used by 55%. Of respondents not using ALF, fifty-four percent considered starting using integrated arterial filtration. The systematic literature database search returned 180 unique publications where 82 were specifically addressing ALF in cardiopulmonary bypass. Only four out of the 82 identified publications fulfilled our inclusion criteria. Of these, three were more than 20 years old and based on the use of bubble oxygenation. ALF is a standard implemented in a majority of cardiopulmonary bypass procedures in Europe. The level of scientific evidence available in support of current arterial line filtration methods in cardiopulmonary bypass is, however, poor. Large, well-designed, randomised trials are warranted.

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.

Removal of Gross Air Embolization from Cardiopulmonary Bypass Circuits with Integrated Arterial Line Filters: A Comparison of Circuit Designs

Advances in technology, the desire to minimize blood product transfusions, and concerns relating to inflammatory mediators have lead many practitioners and manufacturers to minimize cardiopulmonary bypass (CBP) circuit designs. The oxygenator and arterial line filter (ALF) have been integrated into one device as a method of attaining a reduction in prime volume and surface area. The instructions for use of a currently available oxygenator with integrated ALF recommends incorporating a recirculation line distal to the oxygenator. However, according to an unscientific survey, 70% of respondents utilize CPB circuits incorporating integrated ALFs without a path of recirculation distal to the oxygenator outlet. Considering this circuit design, the ability to quickly remove a gross air bolus in the blood path distal to the oxygenator may be compromised. This in vitro study was designed to determine if the time required to remove a gross air bolus from a CPB circuit without a path of recirculation distal to the oxygenator will be significantly longer than that of a circuit with a path of recirculation distal to the oxygenator. A significant difference was found in the mean time required to remove a gross air bolus between the circuit designs (p = .0003). Additionally, There was found to be a statistically significant difference in the mean time required to remove a gross air bolus between Trial 1 and Trials 4 (p = .015) and 5 (p =.014) irrespective of the circuit design. Under the parameters of this study, a recirculation line distal to an oxygenator with an integrated ALF significantly decreases the time it takes to remove an air bolus from the CPB circuit and may be safer for clinical use than the same circuit without a recirculation line.

Embolic Activity During In Vivo Cardiopulmonary Bypass

Neurologic injury after cardiac surgery is principally associated with emboli. Although much work has focused on surgical sources of emboli, less attention has been focused on emboli associated with the heart–lung machine. We tested whether emboli are associated with discrete processes during cardiopulmonary bypass (CPB). One hundred patients undergoing cardiothoracic surgery were enrolled between April 2008 and May 2011 at a single medical center. During each surgical procedure, emboli were counted in three CPB locations: the venous side (Channel 1), before the arterial line filter (Channel 2), and after the arterial line filter (Channel 3). We used prespecified event markers to identify perfusionist interventions. Identical circuits were used on all patients. Of the 100 patients enrolled, 62 underwent isolated coronary artery bypass grafting (CABG), 17 underwent isolated valve operations, and 21 underwent CABG plus valve. Median counts across Channels 1, 2, and 3 were 69,853, 3,017, and 1,251, respectively. The greatest contributor to emboli in Channels 1, 2, and 3, respectively, were achieving the calculated CPB flow, opening of the electronic arterial line clamp, and introducing a hemofilter. The circuit technology was efficient in reducing total emboli counts from Channels 1–2 irrespective of the size of the emboli. Nearly 71% of all emboli 30–100 mm in size were removed from the circuit between Channels 2 and 3. No significant association was found between emboli counts and S100B release. Emboli occur frequently during CPB and are predominantly associated with the initiation of bypass, operation of the electronic arterial line clamp, and the initiation of a hemofilter. Continued work to reduce the occurrence of emboli is warranted.

Can the Oxygenator Screen Filter Reduce Gaseous Microemboli?

Gaseous microemboli (GME) define small bubbles as &lt;200 μm in size. GME are reported to increase morbidity after cardiopulmonary bypass (CPB) and cardiac surgery. To prevent intrusion of GME into the systemic circulation during CPB, arterial line filtration is generally recommended. New trends in oxygenator design promote location of arterial filtration as an integral part of the oxygenator housing. The present experimental study aimed to evaluate the GME removal properties of an integrated arterial screen filter in a standard microporous oxygenator. The GME properties of Terumo Capiox® FX25 with an integrated arterial screen filter was assessed in an experimental setup and compared with Capiox® RX25, in which no arterial screen filter is present. A blood analog prime solution was recirculated using a roller pump at 4 and 6 L per minute flow rate, respectively, through a customized CPB circuit comprising oxygenator, reservoir, and connecting tubing. A controlled volume of air was introduced into the circuit. The GME activity was measured and computed using a Gampt BCC200® ultrasonic device placing one probe at the venous inlet and one other at the arterial outlet of the oxygenator. Transmembrane delta values of GME activity were used to calculate the removal efficacy based on counts and volume of GME. Use of screen filtration reduced the GME volume by 99.1% ± .1% compared with 98.0% ± .1% for controls at 4 L/min flow rate (p&lt; .001). At 6 L/min, the reduction was 97.9% ± .1% compared with 97.0% ± .1% (p&lt; .001). In contrast, the reduction of GME counts was less effective after screen filtration compared with controls: 89.6 ± .6% versus 91.4 ± .4% at 4 L/min and 55.6% ± 1.6% versus 76.0% ± 1.4% at 6 L/min, respectively (p&lt; .001). The tested oxygenator with incorporated arterial screen filter reduced GME activity based on the calculated volume at the same time as counts of GME increased.

Reduced embolic load during clinical cardiopulmonary bypass using a 20 micron arterial filter

To compare the efficiency of 20 and 40 µm arterial line filters during cardiopulmonary bypass for the removal of emboli from the extracorporeal circuit. Twenty-four adult patients undergoing surgery were perfused using a cardiopulmonary bypass circuit containing either a 20 µm or 40 µm arterial filter (n = 12 in both groups). The Emboli Detection and Classification system was used to count emboli upstream and downstream of the filter throughout cardiopulmonary bypass. The mean proportion of emboli removed by the filter was compared between the groups. The 20 µm filter removed a significantly greater proportion of incoming emboli (0.621) than the 40 µm filter (0.334) (p=0.029). The superiority of the 20 µm filter persisted across all size groups of emboli larger than the pore size of the 40 µm filter. The 20 µm filter removed substantially more emboli than the 40 µm filter during cardiopulmonary bypass in this comparison.

Leukodepletion for patients undergoing heart valve surgery

There is some evidence for the benefits of leukodepletion in patients undergoing coronary artery surgery. Its effectiveness in higher risk patients, such as those undergoing heart valve surgery, particularly in terms of overall clinical outcomes, is currently unclear. To assess the beneficial and harmful effects of leukodepletion on clinical, patient-reported and economic outcomes in patients undergoing heart valve surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 3 of 12) in The Cochrane Library, the NHS Economic Evaluations Database (1960 to April 2013), MEDLINE Ovid (1946 to April week 2 2013), EMBASE Ovid (1947 to Week 15 2013), CINAHL (1982 to April 2013) and Web of Science (1970 to 17 April 2013) on 19 April 2013. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), the US National Institutes of Health (NIH) clinical trials database and the International Standard Randomised Controlled Trial Number Register (ISRCTN) in April 2013 for ongoing studies. No language or time period restrictions were applied. We examined the reference lists of all included randomised controlled trials and contacted authors of identified trials. We searched the 'grey' literature at OpenGrey and handsearched relevant conference proceedings. Randomised controlled trials comparing a leukocyte-depleting arterial line filter with a standard arterial line filter, on the arterial outflow of the heart-lung bypass circuit, in elective patients undergoing heart valve surgery. Data were collected on the study characteristics, three primary outcomes (1. post-operative in-hospital all-cause mortality within three months, 2. post-operative all-cause mortality excluding inpatient mortality < 30 days, 3. length of stay in hospital, 4. adverse events and serious adverse events) and seven secondary outcomes (1. tubular or glomerular kidney injury, 2. validated health-related quality of life scales, 3. validated renal injury scales, 4. use of continuous veno-venous haemo-filtration, 5. length of stay in intensive care, 6. costs of care). Data were extracted by one author and verified by a second author. Insufficient data were available to perform a meta-analysis or sensitivity analysis. Eight studies were eligible for inclusion in the review but data on prespecified review outcomes were available from only one, modestly powered (24 participants) study (Hurst 1997). There were no differences between a leuko-depleting versus standard filter in length of stay in the intensive care unit (ICU) (mean difference (MD) 0.80 days; 95% confidence interval (CI) -0.24 to 1.84) or length of hospital stay (MD 0.20 days; 95% CI -1.78 to 2.18). There are currently insufficient good quality trials with valve surgery patients to inform recommendations for changes in clinical practice. A future National Institute for Health Research (NIHR)-funded feasibility study (recruiting mid-year 2013) comparing leukodepletion with a standard arterial line filter in patients undergoing elective heart valve surgery (the ROLO trial) will be the largest study to date and will make a significant contribution to future updates of this review.

The Dynamic Observation of Plasma Concentration of Antimicrobial Agents During Balanced Ultrafiltration In Vitro

Routine perioperative intravenous antimicrobial agents are administered as surgical prophylaxis. However, whether balanced ultrafiltration during extracorporeal circulation has substantial effect on the concentration of antimicrobial agents remains unclear. The concentrations of antimicrobial agents in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model. Extracorporeal circulation consisted of cardiotomy reservoir, membrane oxygenator, and pediatric arterial line filter. A hemoconcentrator was placed between the arterial purge line and oxygenator venous reservoir. Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24-28%. Two kinds of antimicrobial agents, cefotiam (320 mg) and cefmetazole (160 mg), were bolus added into the circuit. After 30 min of extracorporeal circulation, zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg with a Hoffman clamp. The rate of ultrafiltration (12 mL/min) was controlled by ultrafiltrate outlet pressure. An identical volume of Plasmalyte A was dripped into the circuit to maintain stable hematocrit during 45 min of experiment. Plasma and ultrafiltrate samples were drawn every 5 min, and concentrations of antimicrobial agents (including cefotiam and cefmetazole) were measured with high performance liquid chromatography. Both antimicrobial agents were detected in ultrafiltrate, demonstrating hemoconcentration may remove antimicrobial agents. The concentrations of plasma antimicrobial agents decreased linearly with the increase of ultrafiltrate volume. At end of balanced ultrafiltration, the concentration of plasma cefotiam was 104.96 ± 44.36 mg/L, which is about 44.38% ± 7.42% of the initial concentration (238.95 ± 101.12 mg/L) (P < 0.001); the concentration of plasma cefmetazole decreased linearly to 25.76 ± 14.78 mg/L, which is about 49.69% ± 10.49% of the initial concentration (51.49 ± 28.03 mg/L) (P < 0.001). The total amount of cefotiam in ultrafiltrate is 27.16% ± 12.17% of the total dose administered, whereas cefmetazole in ultrafiltrate is 7.74% ± 4.17%. Balanced ultrafiltration may remove antimicrobial agents from plasma and has a prominent influence on plasma concentration of antimicrobial agent. The strategy of surgical prophylaxis should consider this unique technique during extracorporeal circulation.

The Effects of Pressure on Gases in Solution: Possible Insights to Improve Microbubble Filtration for Extracorporeal Circulation

Improvements in micropore arterial line filter designs used for extracorporeal circulation are still needed because microbubbles larger than the rated pore sizes are being detected beyond the filter outlet. Linked to principles governing the function of micropore filters, fluid pressures contained in extracorporeal circuits also influence the behavior of gas bubbles and the extent to which they are carried in a fluid flow. To better understand the relationship between pressure and microbubble behavior, two ex vivo test circuits with and without inline resistance were designed to assess changes in microbubble load with changes in pressure. Ultrasound Doppler probes were used to measure and compare the quality and quantity of microbubbles generated in each test circuit. Analysis of microbubble load was separated into two distinct phases, the time periods during and immediately after bubble generation. Although microbubble number decreased similarly in both test circuits, changes in microbubble volume were significant only in the test circuit with inline resistance. The test circuit with inline resistance also showed a decrease in the rate of volume transferred across each ultrasound Doppler probe and the microbubble number and size range measured in the postbubble generation period. The present research proposes that fluid pressures contained in extracorporeal circuits may be used to affect gases in solution as a possible method to improve microbubble filtration during extracorporeal circulation.

Anesthetic management for transfusion-free Rastelli's procedure in a pediatric Jehovah's Witness patient

Transfusion-free cardiac surgery in small cyanotic children is challenging to anesthesiologists because of cardiopulmonary bypass (CPB)-induced hemodilution and coagulopathy. Redo-complex cardiac procedures increase the incidence and volume of the transfusion [1]. Rastelli's procedure is a high risk procedure (RACHS; risk adjustment in congenital heart surgery category 4) and usually requires a blood transfusion. We present a 27 month-old girl (78.5 cm height and 7.7 kg weight) who was admitted for Rastelli's operation. The patient underwent the modified Blalock-Taussig shunt and patent ductus arteriosus closure 1 year ago without a transfusion. Her parents were Jehovah's Witnesses. They refused a perioperative blood transfusion, which included packed red blood cells, fresh frozen plasma, platelets, and albumin. They also refused usage of a cell saver. The anesthesiologist explained acute normovolemic hemodilution (ANH) and the parents agreed to ANH with the understanding that the collected autologous blood was not separated from the patient. One week before the surgery, recombinant human erythropoietin (2000 IU) was administered three times per week and iron sucrose was administered every day to stimulate the patient's blood cell production. After treatment, the hematocrit (Hct) increased from 47.2 to 49.1%. Platelet count and coagulation factors were within the normal range. After induction of anesthesia, 10 mg/kg tranexamic acid was infused for 30 minutes, then a continuous infusion was started at a rate of 5 mg/kg/hr. Cerebral oximetry (INVOS 5100, Somanetics, NY, USA) monitoring was started and the initial regional cerebral oxygen saturation (rSO2) values were 48/47% on the right/left sides. For ANH, 190 ml of whole blood was withdrawn from the patient's central line to the blood bag (single-320 ml blood bag, Greencross, Seoul, Korea), which contained 44.8 ml of citrate phosphate dextrose adenine. The same volume of hydroxyethyl starch (Voluven®, Fresenius Kabi, Bad Homburg, Germany) was infused while collecting the blood. The Hct decreased from 45 to 35% after ANH. The changes in rSO2 were < 10% from baseline, and blood lactate was within the normal range during ANH. A high-performance, low prime volume oxygenator (RX-05™, Terumo, Tokyo, Japan) was used and the arterial line filter was excluded to minimize the priming volume for CPB. During CPB, the Hct and pH ranged from 24 to 28%, and from 7.23 to 7.33 respectively. Intraoperative changes in blood lactate during surgery were within the normal range. After weaning from CPB, the collected autologous blood was transfused after protamine administration. Total operation time was 7 h and 20 minutes. The estimated blood loss and urine output was 130 and 720 ml. The patient received 190 ml of autologous blood and 215 ml of other fluids. The hematologic data are shown in Table 1. Table 1 Changes in Hematological Data Erythropoietin and iron sucrose were re-started. The lowest hemoglobin concentration in the ward was 7.6 g/dl, which increased to 9.4 g/dl on day 13 after surgery. The patient was discharged on postoperative day 19 with oral iron therapy and no complications. Three important issues must be considered for transfusion-free surgery. First, the volume of red blood cells should be increased before surgery. Second, the volume of blood loss should be minimized during surgery. Third, bleeding should be prevented after surgery. The patient received erythropoietin and simultaneous oral iron supplementation preoperatively. These have been shown to promote red blood cell production and reduce allogenic blood transfusion in children undergoing open heart surgery [2]. ANH is a blood conservation method to collect a patient's red blood cells before or just after induction of anesthesia. In a previous report, the non-transfusion rate of Rastelli's procedure was only 17%, but it increased to 75% following autologous blood donation [3]. The ANH-induced decrease in Hct may have impaired tissue oxygenation. Therefore, target Hct was determined to be 35%, and 190 ml of blood was collected as calculated. During ANH, safety was assessed using vital signs, lactate values, and rSO2, which is a useful indicator of trends in cerebral oxygenation [4]. Complex transfusion-free procedures can be accomplished safely in pediatric patients with a miniaturized CPB system for low priming volume [5]. In our case, we used a neonatal CPB system (Heart-Lung machine HL 30™, Maquet, Hirrlingen, Germany) to reduce hemodilution and maintain adequate oxygen supply. Additionally, tranexamic acid was continuously infused during the operation to reduced intra- and post-operative blood loss. In summary, we performed a transfusion-free Rastelli's procedure in a child weighing 7.7 kg. We conclude that multidisciplinary approaches, including perioperative erythropoietin, ANH, a low-prime CPB circuit, and tranexamic acid, enable high risk transfusion-free cardiac surgery in children.