| [Objective]To explore the efficacy and safety of pulsatile perfusion with different frequencies in vitro model and assess in the pressure decay of different parts; To study the organ protections and clinical outcomes during pediatric cardiopulmonary bypass (CPB)with pulsatile perfusion; To contrast the clinical outcomes between pulsatile perfusion group and non-pulsatile perfusion group in pediatric cardiopulmonary bypass for exploring the clinical application.[Subjects and Methods]Section Ⅰ:pulsatile perfusion in vitro modelStockert S5 type cardiopulmonary bypass machine was used to make pulsatile perfusion. The CPB circuit of vitro model included bypass tubes, oxygenator, blood reservoir, ultrafiltration, etc. Pump flow were 1.5L/min with Capiox Baby RX05 oxygenator and 2.25L/min with Dideco Lilliput 902 oxygenator. Pulse width and base flow ratio were fixed. The pulsatile frequency was studied at three kinds of frequency (30,60,100 times per minutes). Cardiopulmonary bypass had been simulated for 1 hour and pressure on the CPB circuits was monitored.Section Ⅱ:Effects of frequency on pediatric CPB.Sixty cases of non-cyanotic congenital heart disease were randomly divided into group A (n=20, the frequency f=30), group B (n=20, f=60) and Group C (n =20, f=100). Three groups underwent pulsatile perfusion after the aortic cross-clamping until the aortic cross-clamping removing and heart beat. Pulsatile perfusion was made by a roller pump Stockert S5 cardiopulmonary bypass machine. Flow rate was 100-150ml/kg/min, activated clotting time maintained above 480s, rectal temperature 30～32℃. Blood gas management was a strategy. Hematocrit was maintained between 25 and 30%. Venous oxygen saturation was above 75%. The transfusion amount of red blood cells was 0.5～1u and plasma dosage was 50-100 ml. Pulse width and base flow ratio were fixed. Pulsatile frequency depended on each group design. Pulsatile perfusion began from aortic-clamping to aortic-clamping removing and heart beat. All patients underwent median thoracotomy and cannulation on the ascending aorta and vena cava. After cooling to 30～32℃ of rectal temperature, the ascending aorta was clamped and cold crystal cardioplegia with 20 ml/kg infusing to the heart. Aorta-clamping was removed after completion of intra-cardiac procedure. Pulsatile perfusion changed to constant perfusion when heart beat. Patients uneventfully weaned off cardiopulmonary bypass according to the weaning standards.The basic information of patients, such as age, gender, weight, were recorded. Intraoperative hemodynamic parameters, urine volume, the amount of diuretics were monitored. Serum lactic acid was assayed before skin incision, at aorta-clamping, weaning off bypass, postoperative 12 hours. Cardiac enzymes (CK-MB, LDH), hepatic functional enzymes (ALT, AST) and renal functional index (BUN, CR) were detected preoperatively (t1), firstly at ICU (t2), at the first postoperative day (t3) respectively. Blood samples were obtained to assay the plasma free hemoglobin (PFH), neuron specific enolization enzyme (NSE), S-100 beta protein, endothelin 1 (ET 1) and serum nitric oxide (NO) before skin incision (T1), at aorta-clamping (T2), heart beat after aorta-clamping removing (T3),2 hours after returning to the ICU (T4). Duration of bypass, aorta-clamping time, whether automatic heart beat, the amount of cardiovascular drugs in ICU, tracheal extubation time, ICU stay time, the amount of thoracic drainage within 12 hours postoperatively.SectionⅢ:Comparison of pulsatile perfusion and non-pulsatile perfusionForty cases of non-cyanotic congenital heart disease were randomly divided into group A (n=20, pulsatile perfusion group), group B (n=20, non-pulsatile perfusion group). Two groups underwent pulsatile perfusion after the aortic cross-clamping until the aortic cross-clamping removing and heart beat. Pulsatile perfusion was made by a roller pump Stockert S5 cardiopulmonary bypass machine. Flow rate was 100-150ml/kg/min, activated clotting time maintained above 480s, rectal temperature 30～32℃. Blood gas management was a strategy. Hematocrit was maintained between 25 and 30%. Venous oxygen saturation was above 75%. The transfusion amount of red blood cells was 0.5～1u and plasma dosage was 50～100 ml. Pulse width and base flow ratio were fixed. Pulsatile frequency depended on each group design. Pulsatile perfusion began from aortic-clamping to aortic-clamping removing and heart beat. All patients underwent median thoracotomy and cannulation on the ascending aorta and vena cava. After cooling to 30～32℃ of rectal temperature, the ascending aorta was clamped and cold crystal cardioplegia with 20 ml/kg infusing to the heart. Aorta-clamping was removed after completion of intra-cardiac procedure. Pulsatile perfusion changed to constant perfusion when heart beat. Patients uneventfully weaned off cardiopulmonary bypass according to the weaning standards.The basic information of patients, such as age, gender, weight, were recorded. Intraoperative hemodynamic parameters, urine volume, the amount of diuretics were monitored. Serum lactic acid was assayed before skin incision, at aorta-clamping, weaning off bypass, postoperative 12 hours. Cardiac enzymes (CK.-MB, LDH), hepatic functional enzymes (ALT, AST) and renal functional index (BUN, CR) were detected preoperatively (t1), firstly at ICU (t2), at the first postoperative day (t3) respectively. Duration of bypass, aorta-clamping time, whether automatic heart beat, the amount of cardiovascular drugs in ICU, tracheal extubation time, ICU stay time, the amount of thoracic drainage within 12 hours postoperatively.[Results]Section Ⅰ:Bypass time of the vitro model was 120 min. Switching between pulsatile perfusion and constant perfusion is convenient. The pressure attenuation of the arterial line filter is greater than that of oxygenator under the different pulsatile frequency conditions. Tans-oxygenator pressure difference and trans-arterial line filter pressure difference were significantly highest in the pulsatile frequency of 30 times per minute than that of 60 times per minute and 100 times per minute.Section Ⅱ:There were no statistical difference in age, weight, sex, bypass time, aorta-clamping time among three groups. During the pulsatile perfusion, arterial systolic and diastolic pressure difference in group A was 21.0±7.9 mmHg, group B 12.4±6.5 mmHg, group C 7.5±4.4 mmHg (p<0.01). The blood pressure increased gradually after pulsatile perfusion. There were 40% children in group A with normal systolic blood pressure after pulsatile perfusion. However,15% in group B and 5% in group C showed normal systolic blood pressure during pulsatile perfusion. The difference among three groups was significant (p<0.01). There was no statistical difference among three groups in creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspertate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CR) and blood urea nitrogen (BUN). Although urine output had no statistical differences among three groups, the ratio of diuretics usage within postoperative 12 h was the lowest in group A (25%) compared with group B (40%) and group C (70%). The amount of thoracic drainage within postoperative 12 h, tracheal extubation time and ICU stay time had no significant difference among three groups. The serum level of lactic acid increased gradually and reached maximum at the end of cardiopulmonary bypass and then decreased postoperatively in three groups, however there was no significant difference among three groups. Plasma free hemoglobin (PFH) levels rose gradually during cardiopulmonary bypass with the peak at T3. The PFH level in group A at T3 was higher than that of group B (p<0.01). There was no statistical difference in PFH level among three groups postoperatively. Serum neuron specific enolization enzyme (NSE) had some changes during cardiopulmonary bypass, but had no remarkable difference among three groups. The changes of serum S-100 beta protein were similar to that of serum NSE. But there was a significant difference between group B and group C at T3. Serum S-100 beta protein in group B was 969.87±345.13 ng/L and that in group C was 1363.92±539.68 ng/L (p<0.01). Serum NO levels rose gradually and reached the peak when heart beat after aorta-clamping removing (p< 0.01). Comparison between groups A and group C showed the significant difference. The serum NO level in groups A at T3 was 391.17±225.41 umol/L and that of groups C was 219.37±117.07 umol/L (p<0.01). The change trend of serum ET-1 levels was similar to that of serum NO levels. There was a significant difference among three groups in serum ET-1 levels (p<0.01). The serum ET-1 level in groups A at T3 was 67.89±62.59 ng/ml, which was the lowest than that of groups B 157.93±141.4 ng/ml and group C 137.60 C ±125.15 ng/ml. There were no death, no nerve complications and no other systemic complications in three groups in the hospital.Section Ⅲ:There were no statistical difference in age, weight, sex, bypass time, aorta-clamping time between two groups. Arterial systolic and diastolic pressure difference in group A was 21.0+7.9 mmHg, group B 2.6+2.9 mmHg(p<0.01). The blood pressure increased gradually after pulsatile perfusion. There were 40% children in group A and 5% children in group B with normal systolic blood pressure after pulsatile perfusion. The difference between two groups was significant (p<0.01). There was no statistical difference among three groups in creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspertate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CR) and blood urea nitrogen (BUN). Although urine output had no statistical differences between two groups, the ratio of diuretics usage within postoperative 12 h was the lowest in group A (25%) compared with group B (80%). The amount of thoracic drainage within postoperative 12 h, tracheal extubation time and ICU stay time had no significant difference between two groups. The serum level of lactic acid increased gradually and reached maximum at the end of cardiopulmonary bypass and then decreased postoperatively in two groups, however there was no significant difference between two groups. There were no death, no nerve complications and no other systemic complications in two groups in the hospital.[Conclusions]Section Ⅰ:The pressure attenuation of arterial line filter was greater than that of oxygenator. Low pulsatile frequency made the higher perfusion pressure in the circuits and the more significant pressure attenuation trans-oxygenator and trans-arterial line filter.Section Ⅱ:Low pulsatile frequency can produce the more significant pulsatile effects than that of high pulsatile frequency in pediatric cardiopulmonary bypass.Section Ⅲ:Pulsatile perfusion with low pulsatile frequency can improve renal function compared with non-pulsatile perfusion in pediatric cardiopulmonary bypass. However, there was no significant difference in clinical outcomes between the two groups. |
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