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Ann Thorac Surg 1998;65:1310-1312
© 1998 The Society of Thoracic Surgeons

Heparin-Coated Equipment Reduces the Risk of Oxygenator Failure

^a Department of Cardiothoracic Surgery, University of Regensburg, Regensburg, Germany

Accepted for publication December 16, 1997.

Address reprint requests to Dr Wahba, Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
e-mail: (wahba{at}klinik.uni.regensburg.de)

	Abstract

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Background. The development of an abnormal pressure gradient (APG) across the oxygenator is the most common cause of oxygenator failure during cardiopulmonary bypass. This necessitated changing the oxygenator in 4 patients in this series. A retrospective analysis of conditions predisposing to APG was performed.

Methods. One thousand nine hundred fifty-nine operations with cardiopulmonary bypass were performed in adults. A range of membrane oxygenators was used subject to availability; 769 oxygenators were heparin-coated and 1,190 were uncoated. The pressure gradient across the oxygenator was measured under standardized conditions. An APG was defined as a gradient of greater than twice the mean.

Results. An APG occurred in 44 uncoated and 3 heparin-coated oxygenators (p < 0.001). The mean age was higher for the APG group (p < 0.001). Fibrin deposits in the arterial line filter were noted in 45 patients. Logistic regression revealed that only fibrin deposition in the arterial line filter and the use of uncoated oxygenators were significantly associated with APG.

Conclusions. We conclude that a heparin-coated oxygenator effectively prevents APG. This adds significantly to the safety of open heart operations.

	Introduction

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The failure of an oxygenator during cardiopulmonary bypass (CPB) for open heart operations is a serious complication. In a survey carried out by Kurusz and colleagues [1], 365 oxygenators had to be changed during CPB in 575,000 perfusions. Four patients suffered permanent injury and 23 died [1]. An abnormal pressure gradient across the oxygenator (APG) is the most common cause of oxygenator failure [2]. At our institution four oxygenators had to be replaced during CPB between 1995 and 1997 because of an APG. In a retrospective analysis all 1,959 patients subjected to CPB during this period were analyzed for risk factors predisposing to APG.

	Material and methods

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A total of 1,959 patients were subjected to CPB for open heart operation at our institution within a period of 2 years (1995 to 1997). Platelet-active medication was stopped 10 days before operation in all patients except in urgent or emergency cases. In elective and urgent cases a blood sample was taken for routine laboratory investigations on the day before operation. In emergencies this was done before induction of anesthesia. Laboratory investigations included a full blood count, urea and electrolytes, antithrombin III, and a cross-match including a search for irregular antibodies (cold agglutinins). Immediately after operation and 6 hours thereafter another sample was taken for a platelet count. Routinely, patients had anesthesia induced with fentanyl, etomidate, and pancuronium, maintained with oxygen, isoflurane, and fentanyl. Aprotinin (Trasylol; Bayer, Leverkusen, Germany) was given in reoperations and when platelet active medication was given less than 10 days before operation. No other antifibrinolytic medication or topical preparation, such as thrombin, was used. Heparin (375 IU/kg body weight; Liquemin N; Hoffman La Roche, Germany) was given for anticoagulation before cannulation. Heparinization was monitored by measurement of activated clotting time (Hemotec ACT; Medtronic, Düsseldorf, Germany), using kaolin as the activating agent. The activated clotting time was kept at a level of more than 500 seconds during CPB. Supplemental heparin was given as required. In the great majority of patients CPB was performed in mild hypothermia in all patients with a nonpulsatile flow of 2.6 L · min^-1 · m^-2 with a roller pump (Stöckert Instrumente, Munich, Germany). A 40-µm arterial line filter (Jostra, Hirrlingen, Germany) and a hard-shell reservoir (D774; Dideco, Sorin Biomedica, Puchheim, Germany) was used. A range of heparin-coated and uncoated membrane oxygenators with a polypropylene microporous capillary membrane was used, subject to availability. No unit policy was developed as to which oxygenator would be used under particular circumstances. One of the following membrane oxygenators was used: Quadrox, Quadrox Special, Quadrox Bioline (Jostra, Hirrlingen, Germany), SMO 440 (3M Medica, Borken, Germany), D 703 (Dideco, Sorin Biomedica, Puchheim, Germany), Maxima, Maxima Carmeda (Medtronic, Düsseldorf, Germany), Affinity (Omnis, Hamburg, Germany), Optima (Cobe, Heimstetten, Germany), and Univox Spiral Gold (Baxter Deutschland, Unterschleißheim, Germany).

The extracorporeal circuit was primed with 1,300 mL of Ringer’s solution and 200 ml of mannitol 20%. Heparin (100 IU/kg body weight) were added to the pump prime. The temperature of the prime was kept at 25°C. During the first phase of CPB the patient was cooled with the temperature of the heat exchanger set at 25°C until completion of cold crystalloid cardioplegia. Thereafter, the patient was actively warmed to 34°C. After removal of the cross-clamp the body temperature was raised up to 37°C until termination of CPB. Heparin was completely neutralized after discontinuation of CPB with protamine sulfate (Protamin, Hoffman La Roche, Germany) according to the manufacturer’s recommendation (1 mL of protamine sulfate solution for each 1,000 IU of heparin given).

During CPB the line pressure was monitored continuously before the oxygenator, between oxygenator and arterial line filter, and after the arterial line filter using a Computer Aided Perfusion System (CAPS, Stöckert Instrumente, München, Germany). The pressure gradient across the oxygenator was recorded during every perfusion at a flow of 5 L/min and a temperature of 34°C (during reperfusion) to determine the mean pressure gradient of each type of oxygenator. If the pressure gradient across the oxygenator was significantly higher than expected at any time during the perfusion, the maximum value was recorded in the perfusion protocol. If the maximum pressure was more than twice the mean for the respective oxygenator type, the diagnosis of APG was made for the purpose of this study. The arterial line filter was carefully inspected for fibrin deposits after each perfusion. The findings were recorded in the perfusion protocol. This protocol was prospectively entered into an Oracle database.

Statistical analysis was performed using SPSS 6.0 software. ² Analysis was used for data arranged in contingency tables. The Mann-Whitney-Wilcoxon test for nonparametric data was used for comparison of groups including the complete set of data. Logistic regression analysis was used to investigate determinants of the development of abnormal pressure gradients.

	Results

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The data of 1,959 patients was included into this analysis (1,382 men and 577 women). The mean age was 63.6 ± 10.1 years (range, 5 to 90 years). One thousand five hundred eleven patients (77%) were operated on for coronary artery disease. The remainder underwent open heart operations for valvular heart disease, congenital heart disease, heart transplantation, and other diseases. Aprotinin was used in 595 patients. The numbers, brand names, and the mean pressure gradients of the oxygenators used are summarized in Table 1.

Two patients with APG died postoperatively; however, their death seemed unrelated to the development of an APG. One 22-year-old man who suffered from massive pulmonary embolism due to deep venous thrombosis died of multiorgan failure 2 days after pulmonary embolectomy. A 68-year-old woman died 12 days after successful coronary artery bypass grafting of extensive small and large bowel gangrene of unknown cause.

Statistical analysis revealed that APG was significantly more common in patients with uncoated oxygenators (44 versus 3; p < 0.001 by ²). Abnormal pressure gradients occurred in all uncoated oxygenators except in Affinity and D 703, which were used infrequently. A comparison of the same oxygenator in a coated and an uncoated version (Quadrox and Quadrox Special) again showed a highly significant difference (p < 0.001 by ²). The age of patients in whom APG developed was significantly higher (67 ± 9 years versus 64 ± 10 years; p < 0.001 by Mann-Whitney-Wilcoxon). The type of operation performed influenced the occurrence of abnormal pressure gradients as well. Abnormal pressure gradient was noted in 42 patients undergoing operation for coronary artery disease but only in 5 others; however, the difference was not statistically significant (p = 0.071 by ²). There was no significant association between the occurrence of APG and the preoperative or postoperative platelet count, activated clotting time at the start of and during CPB, preoperative hemoglobin, gender of the patient, duration of CPB, and the use of aprotinin. Antithrombin III levels were slightly lower for APG patients (94% ± 16% versus 90% ± 14%; p = 0.07 by Mann-Whitney-Wilcoxon). Their was no difference in antithrombin III levels between coated and uncoated oxygenators. Aprotinin was used more often in patients with coated oxygenators (32% versus 25%, p = 0.01, Mann-Whitney-Wilcoxon). The platelet count after operation was significantly higher when heparin-coated oxygenators were used (p = 0.006 by Mann-Whitney-Wilcoxon). These data are presented in Table 2.

	Comment

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Failure of the oxygenator during CPB is a serious hazard to the patient [1]. For the oxygenator to be changed, the patient must be weaned from bypass, if possible, or a short period of circulatory arrest has to be accepted. Although a number of mechanisms may lead to oxygenator failure [1], an abnormal inlet pressure before the oxygenator due to a pathologic fibrin formation is probably the most common cause [2]. This parallels our experience, where an APG across the oxygenator caused four of five failures. Consequently, we analyzed factors predisposing to APG using the perfusion protocol that was entered prospectively into an electronic database. The data included a careful evaluation of abnormal pressure gradients within the perfusion circuit and the occurrence of visible fibrin deposits in the arterial line filter.

The main finding of our analysis is that heparin coating of oxygenators significantly decreases the incidence of abnormal pressure gradients. A similar observation has not been reported previously.

In this study the increase in pressure across the oxygenator usually took place during the initial phase of the perfusion. It was suggested previously that cooling of the blood at the beginning of the perfusion with a high temperature gradient between heat exchanger and blood initiates the development of an APG [2]. In this study the temperature of the heat exchanger was set at 25°C before CPB. By the time CPB is begun the temperature of the blood draining from the patient has dropped down to about 33° to 34°C at the inlet of the heat exchanger. Hence the temperature gradient at the heat exchanger was below 10°C. Apparently the phenomenon of APG occurs nevertheless. Therefore, other causative factors need to be considered. Blombäck and colleagues [2] showed that APG was associated with an increased tendency to form tighter fibrin gel networks. Also protein S and antithrombin III were significantly lower in patients developing APG [2]. In our study preoperative antithrombin III was lower when APG developed during CPB; however, the difference was not significant. It appears that patients generating an APG during CPB have a procoagulatory activity with a tendency to form tighter fibrin gels. Heparin-coated oxygenators seem to effectively counteract this tendency. This may be attributable to the improved biocompatibility ascribed to heparin-coated equipment [3–5]. Heparin-coated oxygenators in uncoated circuits and completely heparin-coated circuits were shown to reduce cell activation and thrombus formation during clinical and simulated CPB [6–8].

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
We thank Mrs Rita Spatz, Department of Statistics of the University of Regensburg, for her invaluable help.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Kurusz M., Conti V.R., Arens J.F. Oxygenator failure. Ann Thorac Surg 1990;49:511-513.[Medline]
2. Blombäck M., Kronlung P., berg B., et al. Pathologic fibrin formation and cold-induced clotting of membrane oxygenators during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1995;9:34-43.
3. Von Segesser L.K., Weiss B.M., Pasic M., Garcia E., Turina M.I. Risk and benefit of low systemic heparinization during open heart operations. Ann Thorac Surg 1994;58:285-286.[Medline]
4. Moen O., Høgsen K., Fosse E., et al. Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1997;63:105-111.[Abstract/Free Full Text]
5. Wendel H.P., Heller W., Gallimore M.J., Hoffmeister H.E. Heparin-coated oxygenators significantly reduce contact system activation in an in vitro cardiopulmonary bypass model. Blood Coagul Fibrinolysis 1994;5:673-678.[Medline]
6. Bannan S., Danby A., Cowan D., Ashraf S., Martin P.G. Low heparinization with heparin-bonded bypass circuits: is it a safe strategy?. Ann Thorac Surg 1997;63:663-668.[Abstract/Free Full Text]
7. Øvrum E., Fosse E., Mollnes T.E., et al. Complete heparin-coated cardiopulmonary bypass and low heparin dose reduce complement and granulocyte activation. Eur J Cardio-thorac Surg 1996;10:54-60.[Abstract]
8. Fukutomi M., Kobayashi S., Niwaya K., Hamada Y., Kitamura S. Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment. Artif Organs 1996;20:767-776.[Medline]

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