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Ann Thorac Surg 2003;76:136-140
© 2003 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, Shanghai Childrens Medical Center, Xinhua Hospital, Shanghai Second Medical University, Shanghai, China
Accepted for publication February 4, 2003.
* Address reprint requests to Dr Huang, Department of Cardiothoracic Surgery, Childrens Medical Center, Xinhua Hospital, Shanghai Second Medical University, 1678, Dongfang Rd, Shanghai 200127, China.
e-mail: wenfeik{at}online.sh.cn
| Abstract |
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METHODS: Thirty patients with congenital heart defects were divided into two groups. In the control group conventional cardiopulmonary bypass was used without ultrafiltration. In the treated group, in addition to the same cardiopulmonary bypass procedure, balanced ultrafiltration plus modified ultrafiltration was used throughout cardiopulmonary bypass. Pulmonary function, hematocrit, serum albumin, and some inflammatory mediators were measured.
RESULTS: Compared with measurements before anesthesia the pulmonary static compliance at 15 minutes and 6 hours post bypass had decreased by 27.8% and 34.0% in the control group versus 12.6% and 15.4% in the treated group, the airway resistance had increased by 38.0% and 45.2% in the control group versus 9.5% and 4.7% in the treated group, and the alveolar-arterial oxygen difference increased by 73.4% and 62.0% in the control group versus 52.1% and 35.9% in the treated group. Hemodilution from cardiopulmonary bypass caused the hematocrit and serum albumin to decrease by 35.8% and 32.8% in the control group versus 36.1% and 34.5% in the treated group at the termination of CPB. After 10 to 15 minutes modified ultrafiltration the hematocrit and serum albumin increased by 40.0% and 47.6%. At the termination of CPB the serum concentrations of interleukin-6, thromboxane B2, and endothelin-1 were increased by 160%, 265%, and 890% in the control group versus 103%, 208%, and 838% in the treated group compared with those before anesthesia.
CONCLUSIONS: The combined use of balanced ultrafiltration and modified ultrafiltration can effectively concentrate the blood, modify the increase of some harmful inflammatory mediators, attenuate the lung edema and inflammatory pulmonary injury, and mitigate the impairment of pulmonary function.
| Introduction |
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We report the effect of continuous ultrafiltration in moderating pulmonary injury during cardiopulmonary bypass.
| Material and methods |
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Cardiopulmonary bypass
A membrane oxygenator (Minimax plus; Medtronic, Minneapolis, MN) and a roller pump (Sarns 8000; Sarns, 3M Health Care, Ann Arbor, MI) were used in the extracorporeal circuit for both groups, and a blood hemoconcentrator (Hemocor HPH 400; Minntech, Minneapolis, MN) was placed with the inlet connected to the arterial line and outlet to the venous line for the treated group. Perfusion flow was maintained at 100 to 120 mL/kg. Cold crystalloid cardioplegic solution was used for myocardial preservation. Systemic hypothermia (25°C to 28°C) was maintained during aortic crossclamping. After discontinuation of CPB in the control group or after modified ultrafiltration in the treated group, heparin was neutralized with protamine sulfate. Cardiopulmonary bypass lasted 45.3 ± 10.5 minutes in the control group and 48.7 ± 11.5 minutes in the treated group; aortic crossclamping duration was 34.3 minutes in the control group and 37.2 minutes in the treated group. No significant differences were found between the two groups for either bypass duration or crossclamping duration.
Continuous ultrafiltration was used in the treated group. At the beginning of CPB the hemoconcentrator was kept isolated by clamping the inlet line. After 3 to 5 minutes of bypass to reach perfusion stability the clamp was released and conventional ultrafiltration was begun. The blood flowed from the arterial line through the hemoconcentrator and the venous line into the venous reservoir. The flow rate of 5 to 10 mL · kg-1 · min-1 was controlled by an additional roller pump throughout the CPB. After weaning from bypass, ultrafiltration was switched to the modified method. The inlet of the venous reservoir was clamped and blood flowed from the aorta through the arterial line, the hemoconcentrator, and the venous line into the right atrium. The flow rate was kept at 15 to 20 mL · kg-1 · min-1 by the roller pump. During the modified ultrafiltration period blood from the venous reservoir was transfused to compensate for the lost water, keeping the arterial blood pressure above 60 mm Hg. The venous reservoir was kept primed by adding the crystalloid solution. The time of modified ultrafiltration was 10 to 15 minutes.
Blood samples and measurements
Blood samples were taken before induction of anesthesia (T1), before CPB (T2), 5 minutes after the start of CPB (T3), at the termination of CPB (T4), 15 minutes after CPB (just after the termination of modified ultrafiltration in the treated group, T5), and 6 hours after operation (T6). Interleukin-6 (IL-6), endothelin-1 (ET-1), thromboxane B2 (TXB2), hematocrit, serum albumin, and blood gases were measured.
Pulmonary variables
At the same times that blood was sampled (except for the T3 sample) pulmonary variables including peak pressure (Ppeak), pause pressure (Ppause), tidal volume (TV), respiratory frequency (F), and inspired oxygen fraction (Fio2) were recorded. Based on these and the blood gas analysis, pulmonary static compliance (Cstat), airway resistance (Raw), and alveolar-arterial oxygen difference (A-a DO2) were calculated.
Statistical analysis
Statistical analysis was performed with Students t test in all matched groups. All the results were expressed as mean ± standard error. A p value of less than 0.05 was considered significant.
| Results |
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A-aDO2
Before bypass no significant difference in A-a DO2 existed between the two groups. Fifteen minutes and 6 hours after bypass the A-aDO2 increased by 73.4% and 62.0% in the control group versus 52.1% and 35.9% in the treated group. The differences are statistically significant (Table 1).
Effects of continuous ultrafiltration on blood concentration
Hemodilution used in cardiopulmonary bypass caused the hematocrit and serum albumin to decrease by 35.8% and 32.8% in the control group and 36.1% and 34.5% in the treated group by the termination of CPB. After 10 to 15 minutes modified ultrafiltration the hematocrit and serum albumin increased by 40.0% and 47.6%, significantly higher than that of the control group (Table 2).
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ET-1
The serum concentrations of ET-1 increased significantly after anesthesia and during CPB. No significant difference could be found between groups at any of the sample selection times (Table 3). In the filtrates the ET-1 could hardly be measured.
Clinical results
All the patients survived. The duration of postoperative mechanical ventilation was 9.3 hours in the control group and 8.7 hours in the treated group (p > 0.05). But the intensive care unit stay was 59.9 ± 18.6 hours in the control group versus 47.6 ± 13.2 hours in the treated group; the difference is statistically significant (p < 0.05).
| Comment |
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Since the 1970s conventional ultrafiltration has been suggested as a means of reducing the fluid accumulation but it has not proved satisfactory in pediatric practice because of a relatively lower volume in the venous reservoir. A modified method was reported by Naik in 1991 [10]. The apparent advantages of modified ultrafiltration are that it is less limited by the level of fluid in the venous reservoir and more suitable for younger pediatric patients. Recently it has been found that, in addition to the effect of blood concentration, the ultrafiltration will remove some harmful medium-size inflammatory mediators and relieve the inflammatory response. Hence balanced ultrafiltration has been reported. By this method ultrafiltration is kept throughout CPB and harmful medium-size solutes are removed constantly. The crystalloid solution is added to maintain a safe volume level in the reservoir [59]. Evidently relieving fluid accumulation in the interstitial space of the lung and decreasing the systemic inflammatory response are valuable for the preservation of postoperative pulmonary function.
The effects of blood concentration and inflammatory mediator removal led us to consider the combined use of balanced ultrafiltration and modified ultrafiltration during pediatric cardiopulmonary bypass. We term it continuous ultrafiltration. By this method the ultrafiltration proceeded throughout almost all the CPB period, mainly removing the harmful inflammatory mediators produced during CPB. After weaning from CPB the patient was switched from balanced to modified ultrafiltration to further remove the harmful inflammatory mediators and also concentrate the blood.
The results of our research have demonstrated the preserving effect of continuous ultrafiltration on pulmonary function. First, pulmonary ventilation function was improved as shown by the increased pulmonary compliance and decreased airway resistance compared with those in the control group. Second, pulmonary air exchange was also improved after CPB as demonstrated by decreased A-aDO2 compared with that of the control group.
The preserving effects of continuous ultrafiltration on postoperative pulmonary function were attributed to its effects on concentration of blood and removal of inflammatory mediators. In this report hematocrit and serum albumin concentration in the treated group were 25.5% and 44.1% higher than those of control group after 10 to 15 minutes modified ultrafiltration, almost back to preoperative levels. Having a higher hematocrit and serum albumin maintained the oxygen supply and prevented interstitial edema of the lung. To determine the ability of ultrafiltration to remove harmful medium-size solutes produced in CPB we selectively measured IL-6, TXB2, and ET-1 at various points. Interleukin-6 is an important inflammatory factor and is closely associated with the systemic inflammatory response. Ultrafiltration clearly affected IL-6. After bypass the serum IL-6 concentration was much lower than that in control group and concentration in blood and filtrates were similar, showing that IL-6 can move through the hemoconcentrator membrane freely. During bypass platelets were activated and secreted TXA2, which has been proved harmful to lung function by increasing pulmonary blood vessel permeability. Because TXA2 is unstable in circulating blood we measured its metabolic product, TXB2. The TXB2 in the ultrafiltrate was much less than that in serum, showing that the removal rate of ultrafiltration was restricted. Of interest we also found that the serum TXB2 concentration in the treated group was much lower than that in the control group after bypass. That may be the result of less platelet activation and secretion owing to the removal of other inflammatory mediators. Endothelin-1 is another important factor and it increased significantly during CPB. It too may impair pulmonary function. Our results show that continuous ultrafiltration did not affect the ET-1 increase and concluded that ultrafiltration may not prevent pulmonary injury caused by ET-1.
In conclusion the combined use of balanced ultrafiltration and modified ultrafiltration can effectively concentrate the hemodiluted blood and remove some harmful inflammatory mediators. That in turn can reduce pulmonary edema and inflammatory pulmonary injury. The technique should beconsidered for pulmonary protection during CPB.
| Acknowledgments |
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| References |
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