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Ann Thorac Surg 1998;65:S35-S39
© 1998 The Society of Thoracic Surgeons

Effects of Cardiopulmonary Bypass and Use of Modified Ultrafiltration

^a Division of Thoracic Surgery and Pediatrics, Duke University Medical Center, Durham, North Carolina, USA

Address reprint requests to Dr Ungerleider, Duke University Medical Center, Box 3178, Durham, NC 27710

Presented at Risk Assessment of Major Perioperative Issues in Pediatric Cardiac Surgery, Washington, DC, May 7, 1997.

	Abstract

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Background. Hemodilution is a prominent problem in cardiopulmonary bypass in a pediatric population. Ultrafiltration is a method used to reduce fluid volume and tissue edema and to increase hematocrit without the need for blood products. Modified ultrafiltration may offer advantages in comparison with conventional ultrafiltration.

Methods. This article reviews the technique of modified ultrafiltration and its use, results, complications, and safety in pediatric cardiopulmonary bypass.

Results. Modified ultrafiltration in pediatric cardiopulmonary bypass reduces total body water and serum levels of inflammatory mediators. It results in an elevated hematocrit without the need for transfusion, improved pulmonary compliance in the immediate postbypass period, and probably improved cerebral metabolic recovery after deep hypothermic circulatory arrest.

Conclusions. Modified ultrafiltration can be performed safely in neonatal patients after cardiopulmonary bypass and offers advantages in comparison with conventional ultrafiltration.

	Introduction

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
The most important limitation affecting the morbidity and even mortality of infant patients undergoing cardiac operations is the effect of cardiopulmonary bypass (CPB) on the patient as an organism. What we learn over the next few years about how to reduce the effect of bypass on the inflammatory system, the coagulation system, and the patient as a whole will provide the next major improvement in outcome benefit for patients.

The effect of hemodilution is a problem that has long plagued us. When infants are operated on, considerable hemodilution occurs just as the result of the volume required to prime the pump. Even with the smaller priming volumes now being used, we still are diluting patients’ blood by at least their own blood volume. After CPB, and the resulting hemodilution, the neonatal heart demonstrates impaired compliance compared with the adult heart exposed to CPB (Fig 1) [1].

View larger version (22K): [in this window] [in a new window]   Fig 1. Duration of hemodilution related to left ventricular end-diastolic volume and end-diastolic pressure in neonates: comparison with effects in adults. (Reprinted with permission from Mavroudis C, Ebert PA. Hemodilution causes decreased compliance in puppies. Circulation 1978;58:155–9.)

In 1991, Greeley and associates [2] showed that infant patients who were placed on bypass and cooled, thereby reducing their cerebral metabolic activity, had their cerebral metabolic activity return to normal when they were warmed. However, patients exposed to a period of circulatory arrest during bypass, during which time the brain was made ischemic, showed impairment in the ability of the brain to recover normal cerebral metabolic activity [2]. In our laboratory [3], we established in a piglet model that there is a dose-related duration-related response to ischemia, with greater impairment of the ability to recover normal cerebral metabolic activity after arrest as the duration of brain ischemia was increased up to 60 minutes. Impairment was somewhat reduced if the patient’s head was packed in ice during the period of arrest, or if low-flow bypass was used (Fig 2). The latter finding is the reason many surgeons now elect to use low-flow bypass rather than circulatory arrest when possible.

View larger version (21K): [in this window] [in a new window]   Fig 2. Percent recovery of cerebral metabolic activity (CMRO2) related to duration of deep hypothermic circulatory arrest (DHCA) in a piglet model: comparison with effect when patient’s head is packed in ice and comparison with effect of low-flow bypass. (Data from reference 3.)

Tissue edema certainly is a problem with bypass, and many methods have been suggested to decrease it. One approach is to decrease the prime volume to decrease hemodilution. Another suggested method is to put steroids in the pump prime; this approach has never made sense to us, because by the time the patient gets on the pump and gets the steroids, it is too late to achieve the desired effect. But over the last 6 months at Duke, we have been giving steroids 12 hours before the operation and have noticed a marked decrease in tissue-fluid accumulation with bypass. We now are studying this effect both in the laboratory and clinically with respect to inflammatory mediators [6]. Other methods tried to decrease tissue edema include increasing the hematocrit in the pump prime or on bypass, especially at increasing temperatures; ultrafiltration during or after bypass; postoperative peritoneal dialysis or postoperative arteriovenous hemofiltration; and even the use of diuretics.

	Conventional ultrafiltration

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Conventional ultrafiltration is on-bypass ultrafiltration. It filters the blood during rewarming on bypass to remove some of the extra fluid. The way it works is that blood is taken from the patient through the venous line and after it is pumped through the oxygenator/heat exchanger it is passed through an ultrafilter, where some of the fluid is removed. The hemoconcentrated blood is returned to the arterial line. Obviously, taking fluid out of the reservoir can cause pump balance problems, and something has to be added. In some cases blood is added, which increases blood-product use. Conventional ultrafiltration has uncertain effects on edema and hemoconcentration; many studies have shown it to be extremely ineffective at increasing the hematocrit or removing fluid [7].

Two new forms of conventional or on-bypass ultrafiltration have been introduced in recent years. One is zero-balance ultrafiltration, in which the fluid that is removed during bypass is replaced with crystalloid. The objective is to remove inflammatory mediators but avoid pump-balance problems. Of course, with this procedure, no overall volume is removed during bypass. A second new form of conventional ultrafiltration is dilutional ultrafiltration. In this procedure, a small amount of fluid is removed during the bypass, equivalent to the cardioplegia dose plus another 20 to 30 mL/kg. This method may be reasonably effective but has not been studied as a stand-alone modality for removing fluid and mediators. Generally, on-bypass filtration has not proved very useful.

	Modified ultrafiltration

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Modified ultrafiltration [8, 9] involves filtering the patient’s blood after removal from bypass. In our technique, we leave the aortic cannula in situ. Some practitioners have encountered difficulties doing this, but we believe these difficulties may be related to the type of cannula used. Others use venovenous ultrafiltration, which also works. In some cases, we remove the venous cannula and replace it with a 10F vent; in others, we just use the venous cannula. Then we run the ultrafilter pump at 10 to 30 mL · kg^-1 · min^-1, with a vacuum on the ultrafilter. We infuse volume from the reservoir as necessary. There are different ways of deciding when to stop filtering; some just use a cutoff time of 15 to 20 minutes and others stop when the circuit volume has become diluted or when the desired hematocrit is reached. Filtering also will be stopped if the patient becomes unstable.

It should be noted that in this technique the blood is removed from the aorta; the patient is no longer on the normal bypass circuit with blood coming from the right atrium. After the blood passes through the ultrafiltration filter, it is passed through the cardioplegia warmer, which very effectively keeps the patient from cooling. The blood then is returned to the right atrium for reentry into the circulation.

Characteristically, about 600 to 750 mL of clear fluid is removed from the patient over 15 to 20 minutes. This amazes me; I have no idea where this amount of fluid comes from. Nevertheless, before we started giving steroids well before the operation, patients still appeared quite edematous even after removal of this volume of fluid. Edema is no longer seen as much with steroids [6].

We use the COBE filter, which we judge to be the most effective filter available. If you are not getting at least 600 mL of fluid from your patients, consider using this particular filter.

A survey by our group in 1996 of 50 North American pediatric open heart centers found that 22 (44%) were using modified ultrafiltration; a similar survey done today probably would show a higher percentage. Reasons given for not using modified ultrafiltration included surgeon impatience, some bad experience, increased complexity, and doubts about cost-effectiveness. Some thought of modified ultrafiltration as just a fad; others were content with the results they were obtaining without its use and took the position that "if it ain’t broke, don’t fix it."

	Results with modified ultrafiltration

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Modified ultrafiltration offers two major advantages. The removal of so much fluid increases the patient’s hematocrit after bypass, thereby decreasing the need for donor blood. All studies consistently show reduced requirement for blood transfusion. And the removed fluid contains low-molecular-weight inflammatory mediators and other deleterious factors including C3a, C5a, interleukin-6a, interleukin-8, tumor necrosis factor, myocardial depressant factor, various other cytokines, and the possible lung vasoconstrictor endothelin-1.

Studies [8, 10] have shown that compared with control patients, patients who have modified ultrafiltration after bypass have substantially less increase in total body water (Fig 3), have less interleukin-8 and complement in their bloodstream [11, 12], require less blood transfusion [7, 13], and show faster recovery of systolic blood pressure (Fig 4) [13, 14], pulmonary compliance (Fig 5) [15], and cerebral metabolic activity (Fig 6) [16].

View larger version (10K): [in this window] [in a new window]   Fig 3. Percentage rise in total body weight (TBW) with conventional ultrafiltration (UF), modified ultrafiltration (MUF), and no filtration. (Reprinted with permission from Naik SK, Knight A, Elliott MJ. A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. Circulation 1991;84(Suppl 3):422–31.)

View larger version (14K): [in this window] [in a new window]   Fig 4. Systolic blood pressure (BP) at weaning from cardiopulmonary bypass (CPB) and 15 minutes after weaning with and without modified ultrafiltration (MUF). (Data from reference 13.)

View larger version (17K): [in this window] [in a new window]   Fig 5. Dynamic pulmonary compliance (Cdyn) immediately after cardiopulmonary bypass (CPB) and 20 minutes later with and without modified ultrafiltration (MUF). (Data from reference 15.)

View larger version (14K): [in this window] [in a new window]   Fig 6. Cerebral metabolism (CMRO2) immediately and 30 minutes after cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest with or without modified ultrafiltration (MUF).

	Modified ultrafiltration end point

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Our 1996 survey showed that most centers using modified ultrafiltration as the end point to stop filtration either used the complete salvage of circuit contents or a time cutoff (Table 1). Our practice is to stop filtration after about 15 to 20 minutes; however, if our perfusionists tell us after 10 minutes that the circuit contents are completely salvaged, we stop filtration at that point. We no longer use the hematocrit as an end point. A review of 23 patients showed that our average duration of filtration was about 16 minutes.

	Complications of modified ultrafiltration

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

Although most groups in our survey reported some technical complications, these probably are attributable to the learning curve. Complications are minimal once a center gains experience with the technique.

	Conclusions

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
Modified ultrafiltration can be performed safely in neonatal patients after CPB. During the modified filtration period (15 to 20 minutes), patients often have improved hemodynamics. In neonates, modified ultrafiltration usually removes 500 to 750 mL of fluid from the patient and the circuit and results in an elevated hematocrit without the need for transfusion. It probably results in improved cerebral metabolic recovery after deep hypothermic circulatory arrest, although the long-term benefit on neurobehavioral outcome is unknown. It results in improved pulmonary compliance in the immediate postbypass period, but again, the benefit on outcome is unclear.

Further randomized, prospective studies are in progress to further elucidate the benefits of modified ultrafiltration.

	Discussion

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 
QUESTION FROM THE AUDIENCE: We have chosen to combine conventional with modified ultrafiltration, very simply because it is sitting in the circuit. Have you had any experience with such a combination?

DR UNGERLEIDER: We have done some clinical studies comparing conventional with modified ultrafiltration, but we have not combined them. When we looked at pulmonary compliance, it was apparent that just as in the laboratory, conventional ultrafiltration showed no real effectiveness in the clinical setting.

The technique of dilutional ultrafiltration described elsewhere by the group from Indiana may have some benefit. But it poses a quandary for the perfusionists in that if you take fluid out of the circuit while warming, you have to put something back in. If you put back crystalloid, you have not reduced volume. Although you may have removed mediators, that could be done just as well after bypass. If you put back blood you have the advantage of elevating the hematocrit as you warm but the disadvantage of exposing patients to blood products they may not need.

DR PHILLIPPE POUARD (Paris, France): We use conventional ultrafiltration, primarily because we believe that it is very difficult to have surgical inpatients spend the additional 20 minutes in the operating room required for modified ultrafiltration. Also, we find that conventional ultrafiltration goes very smoothly, with no instability during rewarming.

We have shown in our Journsis study that conventional ultrafiltration is effective in complement activation. The problem when comparing both techniques is that when doing conventional ultrafiltration you have to ultrafiltrate more than with modified ultrafiltration to show the same effect. But I do think that, when it is possible, modified ultrafiltration probably is more effective than conventional ultrafiltration.

DR UNGERLEIDER: When you remove fluid during rewarming with conventional ultrafiltration, what do you replace it with?

DR POUARD: In most cases we use cells from the cell-saving device, even in small babies. But sometimes we have to add some red cells. That is why I think the technique is less efficient than modified ultrafiltration. But it is faster.

DR WULF DIETRICH (Munich, Germany): I have a number of technical questions. What do you do with the content of the oxygenator? Is it within your system, or do you retransfuse it to the patient? Also, what is the flow, or pressure gradient, over your filter? And finally, all drugs with molecular weights of, let us say, less than 20,000 daltons that are not bound to others will be removed during modified ultrafiltration. Is this a matter of concern? For example, is it necessary to increase the dosage of anesthetic drugs or to give more heparin during this period?

DR UNGERLEIDER: To answer your last question first, it has been fairly well demonstrated that the filters will take out low-molecular-weight proteins up to about 50 kilodaltons or so. Fentanyl has been demonstrated not to come out in the filter. So you do not have to give more anesthesia. This also means that the improvement in pressures and hemodynamics seen with modified ultrafiltration are not related to less anesthesia. An interesting question was raised about whether or not aprotinin comes out in the filter, but I just do not know the answer to that. This has proved not to be a factor for most drugs.

With respect to the blood in the reservoir, what we basically are doing is taking blood from the patient’s aorta, passing it through the filter to remove fluid, and then returning the hemoconcentrated blood back into the aorta. Patients seem to improve during the 15 minutes or so that they are on this filtration, apparently doing better at lower volumes. But occasionally patients need to have some volume added, and then we infuse blood from the reservoir that again goes through the filter and becomes hemoconcentrated. So in these cases we do scavenge some of the blood in the reservoir and reinfuse it into the patient.

DR DIETRICH: And the remaining portion of the blood in the reservoir?

DR UNGERLEIDER: There usually is not much left when we finish. We use very small oxygenators when working on infants, with very low prime volumes and reservoir volumes of only about 50 to 100 mL. We usually end up giving that back to the patient during the course of the modified ultrafiltration.

Perhaps Dr Hill can provide information about the pressure drop across the filter.

DR AARON HILL: The drop across the filter is about 75 mm Hg.

With respect to heparin, we have found it being concentrated during modified ultrafiltration. In 1 case, the child’s heparin level rose from 3.5 mg/kg when measured off bypass to 5 mg/kg when concentrated. We are going to collect more data, but you do have to take into consideration that you will concentrate heparin with modified ultrafiltration.

DR GLYN D. WILLIAMS (Seattle, Washington): To support that point, we have done a study that shows that heparin levels are increased with modified venovenous ultrafiltration.

DR POUARD: We measured midazolam and alfentanil plasma levels during conventional hemofiltration in the two studies that we conducted. Levels of both are decreased a bit, but they remain high enough to provide stable anesthesia. Aprotinin is removed by ultrafiltration, so this is another consideration that must be taken into account during modified ultrafiltration, which takes place after bypass. Many heparin solutions are a mixture of different kinds of molecules, and only the smaller molecules are ultrafiltered. The major portion of heparin is not ultrafiltered, and so its concentration may be increased by the end of the filtration.

	References

Top Abstract Introduction Conventional ultrafiltration Modified ultrafiltration Results with modified... Modified ultrafiltration end... Complications of modified... Conclusions Discussion References

 

1. Mavroudis C., Ebert P.A. Hemodilution causes decreased compliance in puppies. Circulation 1978;58:155-159.
2. Greeley W.J., Kern F.H., Ungerleider R.M., et al. The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children. J Thorac Cardiovasc Surg 1991;101:783-794.[Abstract]
3. Mault J.R., Ohtake S., Klingensmith M.E., Heinle J.S., Greeley W.J., Ungerleider R.M. Cerebral metabolism and circulatory arrest: effects of duration and strategies for protection. Ann Thorac Surg 1993;55:57-64.[Abstract]
4. Wernovsky G., Wypij D., Jonas R.A., et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants: A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1992;8:2226-2235.
5. Skaryak L.A., Lodge A.J., Kirshbom P.M., et al. Low-flow cardiopulmonary bypass produces greater pulmonary dysfunction than circulatory arrest. Ann Thorac Surg 1996;62:1284-1288.[Abstract/Free Full Text]
6. Lodge AJ, Chai PJ, Williamson A, Scarborough J, Ungerleider RM, Jaggers J. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonates: timing of dose is important. J Thorac Cardiovasc Surg (in press).
7. Daggett C.W., Lodge A.J., Scarborough J.E., Chai P.J., Jaggers J., Ungerleider R.M. Modified ultrafiltration versus conventional ultrafiltration: a randomized perspective study in neonatal piglets. J Thorac Cardiovasc Surg 1998;115:336-342.[Abstract/Free Full Text]
8. Elliott M.J. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 1993;56:1518-1522.[Abstract]
9. Naik S.K., Elliott M.J. Ultrafiltration and paediatric cardiopulmonary bypass. Perfusion 1993;8:101-112.[Free Full Text]
10. Naik S.K., Knight A., Elliott M.J. A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. Circulation 1991;84(Suppl 3):422-431.
11. Journois D., Poupard P., Greeley W.J., Mauriat P., Vouhé P., Safran D. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology 1994;81:1181-1189.[Medline]
12. Wang M.J., Chiu I.S., Hsu C.M., et al. Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations. Ann Thorac Surg 1996;61:651-656.[Abstract/Free Full Text]
13. Naik S., Balaji S., Elliott M. Modified ultrafiltration improves hemodynamics after cardiopulmonary bypass in children [Abstract]. J Am Coll Cardiol 1992;19:37A.
14. Davies M.J., Nguyen K., Gaynor J.W., Elliott M.J. Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1998;115:361-370.[Abstract/Free Full Text]
15. Meliones J.N., Gaynor J.W., Wilson B.G., et al. Modified ultrafiltration reduces airway pressures and improves lung compliance after congenital heart surgery [Abstract]. J Am Coll Cardiol 1995;25:271A.
16. Skaryak L.A., Kirshbom P., DiBernardo L., et al. Modified ultrafiltration improves cerebral metabolic recovery after circulatory arrest. J Thorac Cardiovasc Surg 1995;109:744-752.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ungerleider, R. M. Search for Related Content PubMed PubMed Citation Articles by Ungerleider, R. M.