Eur J Cardiothorac Surg 2008;34:570-575. doi:10.1016/j.ejcts.2008.04.053
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Does the off-pump Fontan procedure ameliorate the volume and duration of pleural and peritoneal effusions?
Fumiaki Shikata,
Toshikatsu Yagihara*,
Koji Kagisaki,
Ikuo Hagino,
Shuichi Shiraishi,
Junjiro Kobayashi,
Soichiro Kitamura
Department of Cardiovascular Surgery, National Cardiovascular Center, Suita, Japan
Received 4 October 2007;
received in revised form 24 March 2008;
accepted 28 April 2008.
* Corresponding author. Address: Department of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. Tel.: +81 6 6833 5012; fax: +81 6 6872-7486. (Email: yagihara{at}hsp.ncvc.go.jp).
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Abstract
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Objective: We initiated an off-pump Fontan procedure by using temporary bypass from the inferior vena cava to the atrium and advanced the procedure in selected patients by simply cross-clamping the inferior vena cava. We aimed to investigate whether the off-pump Fontan procedure could ameliorate the volume and duration of pleural and peritoneal effusion. Methods: We retrospectively reviewed 74 patients (aged <4 years) who underwent Fontan completion between January 2001 and December 2006. The patients were classified into the following two groups: a cardiopulmonary bypass group in which cardiopulmonary bypass was required (n
= 27) and an off-pump group in which the procedure was completed without the use of cardiopulmonary bypass (n
= 47). A propensity score was used to control the treatment selection bias for the use of cardiopulmonary bypass. Fourteen patients from each group were successfully matched. Both bilateral pleural and peritoneal drainage tubes were placed in all the patients. The total volume of the effusion was measured at 6, 12, 24, 48, and 72 h postoperatively and was corrected for body weight (kg) and intervals (h). Results: Significantly reduced effusion (ml/kg/h) was noted in the off-pump group compared to the cardiopulmonary bypass group at 12 h (cardiopulmonary bypass group, 8.6 [4.8–11.5]; off-pump group, 2.5 [1.2–5.4]; p
= 0.006) and at 48 h (cardiopulmonary bypass group, 6.1 [2.6–9.9]; off-pump group, 1.4 [0.9–3.1]; p
= 0.008). Conclusions: The off-pump Fontan procedure may reduce the volume of postoperative pleural and peritoneal effusion.
Key Words: Off-pump Fontan • Pleural effusion • Morbidity • Extracardiac total cavopulmonary connection (TCPC) • Staged Fontan
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1. Introduction
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Fontan operation was first described by Fontan and Baudet; since then, this procedure and its modifications have been used for the physiological correction of complex congenital defects of the heart with a single functional ventricle [1]. Some of these procedural modifications have resulted in improvements in postoperative mortality and some causes of morbidity. However, pleural effusion developing after the Fontan procedure still contributes to morbidity and prolonged hospitalization [2]. Some authors have reported mechanisms that contribute to the development of persistent pleural effusion after the Fontan procedure; these include inflammatory, hydrostatic, and hormonal mechanisms [3,4]. It is known that cardiopulmonary bypass (CPB) causes inflammatory changes, resulting in capillary leakage and subsequent fluid retention [5,6].
To reduce the influences of CPB on pulmonary circulation, we initiated an off-pump Fontan procedure by using temporary bypass from the inferior vena cava (IVC) to the atrium in 1996 [7]. Since 2001, we have advanced the procedure by simply cross-clamping the IVC in selected patients having developed collateral veins [8].
Our objective was to investigate whether the off-pump Fontan procedure could ameliorate the volume and duration of pleural and peritoneal effusion.
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2. Materials and methods
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2.1 Patient population and data
Between January 2001 and December 2006, 74 patients (aged <4 years) underwent staged Fontan completion following the bidirectional Glenn (BDG) procedure at the National Cardiovascular Center in Japan. The off-pump extracardiac Fontan procedure was performed in 47 patients (off-pump group), and the extracardiac Fontan procedure with CPB in the remaining 27 patients (CPB group). The median age at Fontan procedure was 17.5 months (range, 11–46 months) and the median body weight, 8.8 kg (range, 6.2–14.2 kg) (Table 1
). The median interval between the abovementioned BDG procedure and Fontan completion was 11.3 months (range, 2–37 months). Each patient underwent preoperative evaluation, including cardiac catheterization, at our institution to assess the indication for Fontan completion. To compare these groups, a propensity score was used to control the treatment selection bias for the use of CPB [9].
The total volume of effusion was measured at 6, 12, 24, 48, and 72 h postoperatively and was corrected for body weight (kg) and intervals (h). The duration of pleural and peritoneal drainage was expressed as the number of days. The required reinsertion duration of the pleural and peritoneal drains was also calculated and added to the drainage duration. Patients with postoperative chylothorax were excluded from this study (eight patients: CPB group, three and off-pump group, five). We used the diagnostic criteria for chylothorax as described by Buttiker and colleagues [10].
2.2 Postoperative care
In all the patients, bilateral pleural and peritoneal drainage tubes were placed at the time of operation. Diuretics were intravenously administered to all the patients. Heparin infusion was started on the day after the operation and was replaced with that of warfarin and dipyridamole after the initiation of oral intake. The drainage tubes were removed when the drainage reduced to <1 ml/kg/d for each tube.
2.3 Off-pump Fontan procedure
To assess the effect of temporary bypass in the off-pump group, we compared the patients with temporary bypass (group T, n
= 15) and those in whom the IVC was cross-clamped (group S, n
= 32). Table 3 lists the demographic and clinical characteristics of each group. There was no significant difference with respect to preoperative characteristics between the two groups. The volume and duration of pleural effusion were calculated by the same method as described in Section 2.1.
2.4 Operative technique
The operative technique has been reported previously [7,8]. At the time of the BDG procedure, we augmented the central part of the pulmonary artery at its inferior aspect similar to a pouch as a preparation for the off-pump Fontan procedure involving cross-clamping of the IVC. This was followed by the construction of a central shunt from the ascending aorta or the brachiocephalic artery in order to avoid thrombosis within the blind-ended pouch. The azygos vein was intentionally left open in order to allow probable venovenous communication between the superior vena cava (SVC) and the IVC at the time of future Fontan completion with cross-clamping of the IVC.
During Fontan completion, the systemic-to-pulmonary shunt was divided first. Next, the augmented part of the central pulmonary artery was clamped and incised open, and a new extended polytetrafluoroethylene tube was anastomosed to that orifice. We performed the off-pump Fontan completion with temporary bypass in cases where the femoral venous pressure exceeded 20 mmHg at the time of a test cross-clamping maneuver or in the absence of collateral veins between the IVC and SVC. After this maneuver, the inferior vena caval cuff was anastomosed to the extracardiac graft. CPB was used for intracardiac maneuvers or independent hepatic venous connection. A fenestration is not routinely placed. In our study, a fenestration was placed in cases where the calculated preoperative pulmonary resistance was >3.0 Wood U m2 or the transpulmonary gradient was >15 mmHg immediately after coming off bypass or 10 mmHg immediately after the commencement of the off-pump Fontan circulation.
2.5 Statistical analysis
All data sets were reviewed retrospectively. The patient profiles were summarized using median with 25th and 75th percentiles for continuous variables and counts for categorical variables. Univariate comparisons were made with Mann–Whitney U-test for continuous variables and 
2-tests for categorical variables.
To compare the CPB and off-pump groups, a propensity score was used to control the treatment selection bias for the use of CPB. The propensity score that was used to determine the requirement for CPB was determined without considering the outcomes, using multivariable logistic regression analysis. Variables considered for this model included mean pulmonary pressure, pulmonary vascular resistance, pulmonary artery (PA) index [11], the viral respiratory season of Fontan operation [12], preoperative systemic oxygen saturation, ventricular end-diastolic pressure, ventricular end-diastolic volume, ejection fraction, cardiac index, and degree of atrioventricular valve regurgitation. The viral respiratory season was defined as the time period between November 1 and March 31. The patients in the CPB group were matched with those in the off-pump group who had an identical 5-digit propensity score. If this could not be done, we proceeded to a 4-, 3-, 2-, or 1-digit match.
For the comparison of the volumes of pleural and peritoneal effusion in each group at the five postoperative time points, the Bonferroni correction test was applied where a p value of <0.05/5 (i.e., <0.01) was considered statistically significant. The duration of pleural and peritoneal drainage in each group was compared by the log-rank test, and the ratio of the removal of drainage tubes from each group was described using Kaplan–Meier survival curves. Analogous methods were used for comparison of temporary bypass and simple cross-clamping.
The data were analyzed using the SPSS version 11.0 (SPSS, Inc., Chicago, Illinois). For all statistical tests, the alpha-level was 0.05 (2-sided), unless otherwise indicated.
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3. Results
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3.1 Propensity score matched patients: off-pump Fontan versus on-pump Fontan
Fourteen patients from each group were successfully matched. Patient characteristics were well matched, as shown in Table 2
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Table 2 Propensity score matched patients: preoperative demographic data, catheterization data, and concomitant procedures in the CPB and off-pump groups
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A significant reduction in the volume of effusion (ml/kg/h) was observed in the off-pump group as compared to that in the CPB group at 12 h (CPB group, 8.6 [4.8–11.5]; off-pump group, 2.5 [1.2–5.4]; p
= 0.006) and at 48 h (CPB group, 6.1 [2.6–9.9]; off-pump group, 1.4 [0.9–3.1]; p
= 0.008) (Fig. 1(a)). There was no difference between these groups with respect to time to removal of drainage tubes (Fig. 1(b)). In the CPB group, all patients needed blood transfusion during the procedure. The postoperative PF ratio (PaO2/FiO2 [fraction of inspired oxygen]) was significantly higher in the off-pump group (CPB group, 209 [148–236]; off-pump group, 246 [219–278]; p
= 0.02). Duration of mechanical ventilatory support (h) in the intensive care unit (ICU) was 22 (11–38) and 6 (4–11) in the CPB and off-pump groups, respectively (p
= 0.019). Postoperative maximum serum concentration of hepatic enzymes did not differ between the two groups, i.e., alanine transaminase (U/ml) (CPB group, 294 [52–1229]; off-pump group, 82 [18–388]; p
= 0.37) and total bilirubin (mg/dl) (CPB group, 2.8 [1.9–3.9]; off-pump group, 2.4 [1.0–2.9]; p
= 0.054). Postoperative maximum serum concentration of renal enzymes also did not differ between the two groups, i.e., blood urea nitrogen (mg/dl) (CPB group, 19 [13–35]; off-pump group, 27 [16–42]; p
= 0.55) and creatinine (mg/dl) (CPB group, 0.4 [0.3–0.6]; off-pump group, 0.4 [0.3–0.5]; p
= 0.43). These promptly returned to their standard values in the ICU for all the patients. No significant difference was observed between the groups with regard to the median duration of ICU stay (d) (CPB group, 11 [7–13]; off-pump group, 6 [4–11]; p
= 0.11) and postoperative hospital stay (d) (CPB group, 57 [42–76]; off-pump group, 46 [37–56]; p
= 0.16).
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Fig. 1. (a) Propensity score matched patients: total volume of pleural and peritoneal drainage in the CPB and off-pump groups. There were significant differences between the groups at 12 and 48 h postoperatively. *
p
= 0.006, 
p
= 0.008. Data are expressed as the median with 25th and 75th percentiles (solid line: CPB group; dashed line: off-pump group). (b) Propensity score matched patients: Duration of pleural and peritoneal drainage in the CPB and off-pump groups. The Kaplan–Meier survival curve demonstrates that there was no significant difference between the CPB and off-pump groups with respect to the duration of pleural and peritoneal drainage (solid line: CPB group; dashed line: off-pump group).
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3.2 Temporary bypass versus simple cross-clamping
A significant reduction in the volume of effusion (ml/kg/h) was observed in group T as compared to that in group S at 6 h (group T, 3.2 [1.9–7.0]; group S, 10.1 [5.9–13.7]; p
= 0.001). There was no significant difference between the groups at 12, 24, 48, and 72 h with regard to the volume of effusion (Fig. 2(a)). There was a tendency of longer operative time (min) in group T than in group S (group T, 300 [260–542]; group S, 265 [230–360]; p
= 0.36). No difference was observed between the groups with respect to the drainage on postoperative day 30 (Fig. 2(b)). Postoperative maximum serum concentration of hepatic and renal enzymes did not differ statistically between the two groups, i.e., alanine transaminase (U/ml) (group T, 37 [30–88]; group S, 81 [18–144]; p
= 0.87), total bilirubin (mg/dl) (group T, 2.9 [1.9–3.5]; group S, 2.0 [1.2–2.9]; p
= 0.71), blood urea nitrogen (mg/dl) (group T, 9 [6–24]; group S, 11 [6–22]; p
= 0.79), and creatinine (mg/dl) (group T, 0.4 [0.3–0.5]; group S, 0.3 [0.3–0.4]; p
= 0.98). The median duration of ICU stay (d) (group T, 9.5 [5–15]; group S, 6.5 [4–10]; p
= 0.14) and postoperative hospital stay (d) (group T, 54 [42–64]; group S, 49 [43–70]; p
= 0.65) did not differ significantly between the two groups.
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Fig. 2. (a) Total volume of pleural and peritoneal drainage in group S and group T. There were significant differences between the groups at 6 h postoperatively. *
p
= 0.001. Data are expressed as the median with 25th and 75th percentiles (black line: group S; grey line: group T) (group S: simple cross-clamping method; group T: temporary bypass method). (b) Duration of pleural and peritoneal drainage in group S and group T. The Kaplan–Meier survival curve demonstrates that there was no significant difference between group S and group T with respect to the duration of pleural and peritoneal drainage (black line: group S; grey line: group T).
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4. Discussion
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Fontan operation has undergone various innovative modifications, and its postoperative complications and survival rate have improved [2,7,8,13]. However, pleural and peritoneal effusion, arrhythmias, thromboembolic complications, and exercise intolerance continue to remain the major complications occurring after the Fontan operation [2,13]. Many intraoperative factors, i.e., factors influential during the procedure, and postoperative medical therapies have been considered to be responsible for pleural effusion by some authors [14–17]. As described in various reports, many factors such as age, CPB time, dominant right ventricular morphology, fenestration, aortopulmonary collateral vessels, the season in which the Fontan operation is performed, and the use of angiotensin-converting enzyme (ACE) inhibitors have been reported to affect the volume and duration of pleural and peritoneal drainage after the Fontan operation [14,16,17]. We, in this study, investigated the effect of the use of CPB that was considered as one of the factors having deleterious effects on postoperative effusion. The CPB generates a systemic inflammatory response by complement activation and cytokine generation and causes an elevation in the vascular resistance and fever postoperatively [3,6] along with reperfusion of the lungs and development of the capillary leak syndrome [5]. In our results, a significant difference was observed between the CPB and off-pump groups with respect to the volume of pleural and peritoneal effusion; however, the two groups did not differ significantly with respect to the duration of drainage. One of the reasons for this might be the timing of the removal of the drainage tubes. Our regimen for the removal of the drains was stricter as compared to those reported in other papers [2,4,15]. However, we think that our study indicates that the off-pump Fontan procedure is useful, considering the advantages such as higher PF ratio and reduction in the volume of drainage when initiating Fontan circulation in the early postoperative phase.
The mechanism underlying a larger volume of drainage in the acute phase in the patients in whom cross-clamping was performed was the difference in the transition to Fontan circulation. In the temporary bypass method, venous blood flows from the IVC to the atrium through the temporary bypass, and BDG physiology is maintained before the initiation of Fontan circulation. As a result, the systemic venous pressure might be low during the procedure. On the other hand, the venous blood from the IVC to the SVC passes through narrow collateral vessels in the simple cross-clamping method. As a result, the systemic venous pressure might be high during the procedure. We think that these points contribute to the differences between the groups with regard to pleural and peritoneal effusion in the acute phase.
We opted for the cross-clamping method after test clamping of the IVC because in patients who do not have well-developed collateral veins, the transition to Fontan circulation would not have been feasible. This strategy may contribute to result in a slight elevation of maximum level of alanine transaminase in simple cross-clamping of the IVC [8]. We, therefore, believe that simple cross-clamping has advantages such as a simple surgical procedure and a good surgical view, which contribute to easy construction of the IVC channel and shorter operative time.
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5. Limitations
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It is thought that many factors are associated with pleural and peritoneal effusion. The changes in brain natriuretic peptide (BNP), other hormones, and cytokines may have an influence on the Fontan circulation and on the volume and duration of pleural and peritoneal drainage; therefore, further studies involving these are desired [3,4,6]. Additionally, this is a retrospective study; although we performed propensity score matched analysis to control the treatment selection bias for the use of CPB. It is desirable to conduct a randomized study on the same.
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6. Conclusion
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The off-pump Fontan procedure may reduce postoperative pleural and peritoneal effusion. In the off-pump Fontan procedure, the difference in the transition to the Fontan circulation with the use of temporary bypass appears to affect the reduction in effusion immediately after the procedure.
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Appendix A
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Conference discussion
Dr V. Tsang (London, United Kingdom): Just to help me clarify one thing in my mind, you said the off-pump Fontan procedure with a temporary bypass decreases effusion. In that particular group, were there any patients with a high EDP?
Dr Shikata: No, no high EDP in the off-pump.
Dr Tsang: So there is a selection of patients for the off-pump?
Dr Shikata: For the off-pump, VEDP is not contained as an indication for the off-pump Fontan procedure.
Dr Tsang: In your conclusion you said a higher preoperative EDP is a strong predictor for long-term drainage.
Dr Shikata: Yes.
Dr Tsang: So it would be ideal to test your hypothesis using off-pump in the group with a high EDP to see whether it would help.
Dr Shikata: We think the higher VEDP contributes to the resulting high pulmonary artery pressure, so high pulmonary pressure results in prolonged drainage. We can’t find the higher VEDP in the off-pump group. So we think the off-pump procedure is not a risk factor for prolonged drainage.
Dr G. Ziemer (Tuebingen, Germany): Well, I’m a little bit confused. There must be a difference between the groups preoperatively by means of clinical signs, like status of cyanosis, because if you say that you can do a simple clamping of the inferior vena cava when there are collaterals, I mean the liver blood has to go somewhere, then you must have your huge collaterals which before surgery were run from the superior vena cava to the inferior vena cava and making a significant amount of cyanosis. What I know for sure is to clamp the inferior vena cava if you really want to have your liver enzymes explode. So, as you say correctly in your presentation that the inferior vena cava pressure needs to be very high in the off-pump procedure, I would like to know how high, and I really would love to see your postoperative liver enzymes, the numbers, whether there were three digits or four digits.
Dr Tsang: Can you repeat the questions? Make it shorter.
Dr Ziemer: What was the preoperative difference in these two patient groups as far as cyanosis is concerned, and, second, what were the values for the liver enzymes in these two groups postoperatively?
Dr Tsang: Are there any differences in terms of the degree of cyanosis in your different groups?
Dr Shikata: No.
Dr Tsang: Do you have preop or postop hepatic function data?
Dr Shikata: It is the same in the off-pump group.
Dr Tsang: He answered your questions.
Dr Ziemer: Okay. I accept it.
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Acknowledgments
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We wish to express our appreciation for the statistical advice from Dr Yoichi Ii (Statistics and clinical programming, Pfizer Global Research and Development, Pfizer Japan, Inc., Japan).
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Footnotes
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Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.
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References
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Abstract
1. Introduction
