Handling ability of gaseous microemboli of two pediatric arterial filters in a simulated CPB model.

OBJECTIVE: The purpose of this experiment was to compare the Sorin KIDS D131 and the Terumo Capiox AF02 pediatric arterial filters in a simulated CPB procedure to determine which filter is the better for clinical use. METHODS: The experimental circuit was primed with an 800 ml combination of lactated Ringer's solution and human blood (hematocrit (Hct) 30%). The two filters were tested under flow rates of 500, 1000, and 1500 ml/min at room temperature and their purge lines opened and closed as 5cc of air was injected into the circuit. RESULTS: As the flow rates increased, the number of gaseous microemboli (GME) being returned to the pseudo patient increased for both of the pediatric arterial filters. Having an open purge line increased the number of GME removed from the CPB circuit, caused less of a pressure drop than when closed and increased the total hemodynamic energy loss than when closed. Both of the filters performed and reacted similarly in decreasing GME, hemodynamic energy loss and pressure drop. The only minor difference was that the Capiox AF02 had slightly less stolen blood flow (109.5 ± 1.7 ml/min at 500 ml/min, 114.7 ± 1.1 ml/min at 1000 ml/min and 105.8 ± 4.2 ml/min at 1500ml/min) from the open purge line than the KIDS D131 (119.5 ± 2.5 ml/min at 500 ml/min, 128.3 ± 1.0 ml/min at 1000 ml/min and 126.3 ± 3.1 ml/min at 1500 ml/min). CONCLUSION: Our study confirmed that both the Sorin KIDS D131 and the Terumo Capiox AF02 were equivalent in their ability to remove significant numbers of GME, the amount of pressure drop and the total hemodynamic energy loss across the arterial filters at the various flow rates. An arterial filter is not an option, but a necessity for removing microemboli delivered to the patient.

Evaluation of four pediatric cardiopulmonary bypass circuits in terms of perfusion quality and capturing gaseous microemboli.

This study compared four pediatric cardiopulmonary bypass (CPB) circuits with four different hollow-fiber membrane oxygenators and their specific reservoirs, Capiox RX15, Quadrox-i pediatric, Quadrox-i pediatric with integrated arterial filter (IAF) and KIDS D101, in a simulated CPB circuit identical to that used in the clinical setting at our institution to test their ability to maintain hemodynamic properties, remove gaseous microemboli (GME), and to test the amount of blood "stolen" by the arterial filter purge line. The circuit was first primed with Ringer's Lactate solution, then red blood cells were added and the hematocrit was maintained at 30%. A 5-cc bolus of air was injected just proximal to the venous reservoir over a thirty-second interval and GME were monitored using an Emboli Detection and Classification quantifier. Transducers were placed at pre-oxygenator, post-oxygenator and distal arterial line (post-filter) positions. Flow probes were also placed both pre and post filter. The injections were made at three flow rates, hypothermic and normothermic temperatures, and with the purge line in both the opened and closed positions. Six injections were done at each of the 12 experimental conditions. Results demonstrated that GME in the arterial line increased with increasing temperature and flow rate. The Capiox RX15 had the least GME in the arterial line at all experimental conditions. The KIDS D101 had the largest pressure drop and the lowest retention of hemodynamic energy, while the Capiox had the lowest pressure drop. All of the oxygenators had a similar amount of "stolen" blood flow and it was consistently under 10% of the total flow reaching the patient.

Current ultrafiltration techniques before, during and after pediatric cardiopulmonary bypass procedures.

Ultrafiltration, which is currently considered as a standard method to remove excess water administered during pediatric cardiopulmonary bypass (CPB), aims to minimize the adverse effects of hemodilution, such as tissue edema and blood transfusion. Three ultrafiltration techniques can be used before, during and after CPB procedures, including conventional ultrafiltration (CUF), modified ultrafiltration (MUF) and zero-balance ultrafiltration (Z-BUF). These methods are widely different, but they have common benefits on hemoconcentration, less requirement for blood products, and reduction of the systemic inflammatory responses (SIRS). The present review attempts to restate these ultrafiltration circuitries, application methods, end-points, and clinical impacts.

Evaluation of Quadrox-i and Capiox FX neonatal oxygenators with integrated arterial filters in eliminating gaseous microemboli and retaining hemodynamic properties during simulated cardiopulmonary bypass.

Perfusion quality during cardiopulmonary bypass (CPB) procedures can contribute to postoperative neurological complications and influence patient recovery and outcome. Gaseous microemboli generated in the circuit and hemodynamic properties of blood reaching the patient can be monitored during CPB to optimize perfusion. Oxygenators that oxygenate the blood during CPB can significantly influence the quality of blood reaching the patient by their manufacturing designs. New hollow-fiber membrane oxygenators are developed with integrated arterial filters to reduce priming volume and eliminate a separate arterial filter in the circuit. To evaluate the performance of these new oxygenators, we used a simulated model to compare the Quadrox-i Neonatal and the Capiox Baby FX05 neonatal oxygenators and to provide a review of these oxygenators with their respective counterparts which have separate arterial filters. We found that microemboli counts for the new Quadrox-i and Capiox FX05 oxygenators are similar in the arterial line, but different across the oxygenator for all experimental conditions. The arterial purge line diverting blood from the patient reduces microemboli count for the Capiox FX05, but is inconsistent for the Quadrox-i Neonatal. While hemodynamic energy delivered to the patient is similar for both oxygenators, shunted blood flow for the Quadrox-i Neonatal oxygenator is three times higher than the Capiox FX05 (103.6 mL/min vs 33.0 mL/min at 400 mL/min and 35°C) (p<0.001).

Evaluation of three hollow-fiber membrane oxygenators without integrated arterial filters for neonatal cardiopulmonary bypass.

The cardiopulmonary bypass (CPB) procedure has been shown to be a possible cause of postoperative neurological morbidity for various reasons, including: large amounts of gaseous microemboli (GME) reaching the patient and hypoperfusion of the patient due to "stolen" blood flow. This study used a simulated CPB circuit identical to that in a clinical setting to examine three different hollow-fiber membrane oxygenators without intergrated arterial filters - the Capiox RX05, the Quadrox-i neonatal, and the KIDS D100 - to determine their ability to reduce the number of GME delivered to the neonatal patient and their hemodynamic properties in response to varying flow rates, normothermic vs hypothermic conditions, and open vs closed purge line. The circuit was primed with Ringer's Lactate and then human blood with a hematocrit of 30%. Injections of 5cc bolusses of air were injected into the venous line proximal to the venous reservoir over a thirty-second interval. Six injections were done for each oxygenator at each of the eight different experimental conditions for a total of 64 experiments per oxygenator (192 total injections). A flow probe, pressure transducer, and Emboli Detection and Classification (EDAC) quantifier transducer were positioned both upstream and downstream of the oxygenator to measure differences in each parameter. Results demonstrated that the Capiox RX05 is the most effective oxygenator at reducing the number of microemboli that potentially can be delivered to the neonatal patient. In regards to the hemodynamic properties, the Quadrox-i has the most favorable results, with the lowest mean pressure drop and the best energy retention across the oxygenator.

Benefits of pulsatile flow in pediatric cardiopulmonary bypass procedures: from conception to conduction.

This review on the benefits of pulsatile flow includes not only experimental and clinical data, but also attempts to further illuminate the major factors as to why this debate has continued during the past 55 years. Every single component of the cardiopulmonary bypass (CPB) circuitry is equally important for generating adequate quality of pulsatility, not only the pump. Therefore, translational research is a necessity to select the best components for the circuit. Generation of pulsatile flow depends on an energy gradient; precise quantification in terms of hemodynamic energy levels is, therefore, a necessity, not an option. Comparisons between perfusion modes should be done after these basic steps have been taken. We have also included experimental and clinical data for direct comparisons between the perfusion modes. In addition, we included several suggestions for future clinical trials for other interested investigators.

Hemodynamic evaluation of arterial and venous cannulae performance in a simulated neonatal extracorporeal life support circuit.

OBJECTIVE: To construct an ideal extracorporeal life support (ECLS) circuit in terms of hemodynamic performance, each component of the circuit should be evaluated. Most cannulae manufacturers evaluate their products using water as the priming solution. We conducted this study to evaluate the different sizes of arterial and venous cannulae in a simulated neonatal ECLS circuit primed with human blood. METHODS: The simulated neonatal ECLS circuit was composed of a Capiox Baby RX05 oxygenator, a Rotaflow centrifugal pump and a heater & cooler unit. Three Medtronic Bio-Medicus arterial cannulae (8Fr, 10Fr, 12Fr) and three venous cannulae (10Fr, 12Fr, 14Fr) were tested in seven combinations (8A-10V, 8A-12V, 10A-10V, 10A-12V, 10A-14V, 12A-12V, 12A-14V). All the experiments were conducted using human blood at a hematocrit of 40% and at a constant temperature of 37°C. The "tip to tip" priming volume of the entire circuit was 135ml. The blood volume of the pseudo patient was 500ml. RESULTS: Flow rates increased linearly with increasing size in both venous and arterial cannulae at the same pump speeds. The increase in flow rate was greater when changing the arterial cannulae (next size larger) compared to changing the venous cannulae (next size larger). The pressure drops of the arterial cannula were correlated with the flow rates, regardless of the pseudo patient pressure and the venous cannula used simultaneously. CONCLUSIONS: The results show the difference in flow ranges and pressure drops of seven combinations of arterial and venous cannulae. It also suggests that the arterial cannula, not the venous cannula, has greater impact on the flow rate when a centrifugal pump is used in a neonatal ECLS circuit. The results of this study have been translated to further advancing the clinical practice in our institution.

Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C.

To investigate the influence of hypothermic cardiopulmonary bypass (HCPB) at 25 degrees C and circulatory arrest at 18 degrees C on the global and regional cerebral blood flow (CBF) during pulsatile perfusion, we performed the following studies in a neonatal piglet model. Using a pediatric physiologic pulsatile pump, we subjected six piglets to deep hypothermic circulatory arrest (DHCA) and six other piglets to HCPB. The DHCA group underwent hypothermia for 25 min, DHCA for 60min, cold reperfusion for 10 min, and rewarming for 40 min. The HCPB group underwent 15 min of cooling, followed by 60 min of HCPB, 10min of cold reperfusion, and 30 min of rewarming. The following variables remained constant in both groups: pump flow (150 ml/kg/min), pump rate (150 bpm), and stroke volume (1 ml/kg). During the 60-min aortic crossclamp period, the temperature was kept at 18 degrees C for DHCA and at 25 degrees C for HCPB. The global and regional CBF (ml/100g/min) was assessed with radiolabeled microspheres. The CBF was 48% lower during deep hypothermia at 18degrees C (before DHCA) than during hypothermia at 25 degrees C (55.2 +/- 14.3ml/100g/min vs 106.4 +/- 19.7 ml/100 g/min; p < 0.05). After rewarming, the global CBF was 45% lower in the DHCA group than in the HCPB group 48.3 +/- 18.1 ml/100g/min vs (87 +/- 35.9ml/100g/min; p < 0.05). Fifteen minutes after the termination of CPB, the global CBF was only 25% lower in the DHCA group than in the HCPB group (42.2 +/- 20.7 ml/100 g/min vs 56.4 +/- 25.8ml/100g/min; p = NS). In the right and left hemispheres, cerebellum, basal ganglia, and brain stem, blood flow resembled the global CBF. In conclusion, both HCPB and DHCA significantly decrease the regional and global CBF during CPB. Unlike HCPB, DHCA has a continued negative impact on the CBF after rewarming. However, 15 min after the end of CPB, there are no significant intergroup differences in the CBF.

Impact of membrane oxygenators on pulsatile versus nonpulsatile perfusion in a neonatal model.

We investigated the effects of two new hollow-fiber membrane oxygenators, the Capiox SX10 and the Lilliput 901, on pulsatile versus nonpulsatile perfusion in an in vitro model designed to simulate a 3 kg infant. The experiments were divided into eight groups (six pulsatile and two nonpulsatile), according to the equipment and settings used. Each group included six tests. In all experiments, the pseudo-patient's mean arterial pressure was 40 mmHg, and the pump flow rate was 550 ml/min. During pulsatile cardiopulmonary bypass, the pump's base flow was set at 30%, and the pump rate was set at 80, 100, 120, 140, or 150 beats/min. The PUMP START and PUMP STOP timing points were adjusted to produce different pulse-width settings. We were especially interested in evaluating the pre- and postoxygenator extracorporeal circuit pressure (ECP), the oxygenator pressure drop, and the precannula ECP. When used with a pulsatile roller pump, the Capiox produced a significantly lower preoxygenator ECP than the Lilliput (p < 0.001); moreover, the Capiox yielded a significantly lower oxygenator pressure drop (p < 0.001). During nonpulsatile perfusion, the Capiox again produced a lower preoxygenator ECP than the Lilliput (p < 0.001). These results suggest that the Capiox may be more suitable than the Lilliput when the pulsatile flow is employed, and pulsatile flow does not increase the ECP with either oxygenator.