Despite the mortality following Fontan operation has being reduced, morbidity remains considerable. Real cause of persistent effusions is obscure and likely multifactorial. We apply a medical treatment protocol that was reported to reduce amount of total pleural drainage and LOHS in the immediate postoperative period after Fontan procedure since 2018 (4). Nevertheless, still some patients have PPE, which was the source of inspiration for the current study to uncover the risk factors for PPE despite protocol. We defined pleural effusion "prolonged" >7 days oppose to many published series that defined PPE as >14 day (7, 8). Although this explains slightly elevated rate of our cohort group for PPE (%40), which is still consistent with the literature, we claim that “7 days” was a more appropriate cut-off interval for defining “prolonged” in order to detect and intervene problems in the Fontan circulation earlier, and to reduce length of hospitalization and susceptibility to infections (8-10).
Appropriate timing for Fontan completion is associated with postoperative outcomes and PPE. Iyengar et al from Anzac registry including 1071 Fontan patients claim that early Fontan operation does not bring superiority and later age at surgery seems to be associated with worse late functional outcomes but also worse early outcomes (2). Our cohort also showed that the incidence of PPE increased in patients who had Fontan operation at older age, though it did not reach a statistical significance due to limited number of patients. Surgical timing is also important at Glenn shunt stage. Although age at Glenn shunt did not differ in terms of PPE, we suggest that Glenn anastomosis plays a crucial role by partially unloading the systemic ventricle and should not be perfomed too late once pulmonary arterial development is considered sufficient (11).
As for morphology, the frequency of PPE has been reported to be higher in right ventricular dominant circulations or specifically in patients with hypoplastic left heart syndrome (HLHS) in the literature (2, 9, 12, 13). Even though we had only one patient with primary diagnosis of HLHS, tricuspid atresia is less likely to be a risk factor for PPE compared to other pathologies in the current study. From this point of view, it can be speculated that a ventricle with preserved systemic ventricular AV valve functions and congenitally programmed to support systemic circulation is a more suitable candidate for Fontan physiology. Another anatomical consideration is the competence of pulmonary vasculature to adopt total cavopulmonary anastomosis. Lo et al. claimed that pulmonary atresia was a predictor of PPE which we approve by having 35% of pulmonary atresia in the PPE group (8). The underlying pathology may be the incomplete adaptation process in the postnatal period of the vascular bed that was not sufficiently perfused in the intrauterine period even though PVR calculations and pulmonary artery Z-scores were proven to be within normal range.
Atrioventricular valvular regurgitation is another concern in patients undergoing Fontan operation with most patients having mild degree of regurgitation before surgery in both literature and in our cohort (7, 14). Moderate to severe regurgitation status is considered for concomitant AV valve repair at surgery in our institution to preserve diastolic functions of the "long-time sufferer" ventricle though concomittant AV valve repair and preoperative moderate/severe AVVR were not related to PPE in the present study. Tran et al published AVVR as a preoperative variable for PPE and Podzolkov et al suggested correction of moderate to severe AVVR not after Fontan completion despite the contradictory findings on the proper timing of AV valve repair in univentricular hearts (7, 14).
New "Fontan circulation" is an altered form of hemodynamics and strictly intolerant to stenosis at any site through the vascular tubing system including pulmonary arteries, systemic ventricular outflow tract, any of which needs to be corrected before or at Fontan stage. For this reason, we prefer to perform cardiac catheterization before Fontan operation for evaluation of aforementioned concepts. We also welcome new imaging techniques in this patient population allowing us to identify preoperative high‐grade abnormal thoracic lymphatic perfusion as a risk factor for the development of early post‐Fontan complications. Currently, we initiated to obtain cardiac magnetic resonance imaging (MRI) of these patients pre-Fontan routinely. Among variables extracted from catheterization data, preoperative mPAP, which was also the most common angiographically obtained "high risk" factor in patients with PPE, was found to be elevated in PPE group and intraoperative measurements were found mostly within normal limits even in patients with PPE and elevated mPAP at pre-Fontan catheterization maybe due to effect of general anesthesia on PVR. Lo rito et al with 324 patients claimed that a 5-mm Hg increment in pre-Fontan mPAP was associated with a 25% increase in the duration of chest tube requirement (8). Sasaki et al reported that increased mPAP was associated with prolonged length of stay among their 218 patients (15). Therefore, though there was no absolute cut-point, a preoperative mPAP ≥15 mm Hg is a reliable data for early outcomes and PPE as many publications support (3, 8). Another important finding of ours that patients with more than one catheterization "high risk" factor had PPE lasted more than 14 days. Interestingly, among all, 30% had PPE despite having no angiographic risk factor at all. Seven patients out of 11 (70%) with effusion lasted more than 14 days had no risk factors. To summarize, the absence of a risk factor does not exclude the possibility of early complications, whereas high mPAP in the pre-Fontan catheter can be considered as predictive of PPE. Another goal of our catheter examination is to close the defects that will create hemodynamic significance (any arterio-pulmonary collaterals that potentially increases Fontan pressure) in the post-Fontan period and the defects that will be unreachable in the surgical field as they were proven to increase postoperative chest drain volume, chest drain duration, and ICU stay after Fontan operation (16).
Currently, extracardiac conduit use is becoming the preference of anastomosis in patients undergoing Fontan surgery. However, which patient should be fenestrated is still in need for consensus. Fenestration rates were similar between PPE and non-PPE groups in our study. Given the relatively small number of patients and the fact that this study is from a single institution, the immediate utility of this finding is limited. In many previous reports, fenestration has been associated with better outcomes, including a decreased risk of death, PPE, and longer hospitalization. Lemler et al performed the prospective randomized trial to evaluate the clinical utility of fenestration in patients with standard preoperative risk profiles for 49 consecutive Fontan operations. They concluded that baffle fenestration improves short-term outcome in standard-risk patients by decreasing pleural drainage, LOHS, and need for additional postoperative procedures (17). In our unit, we suggest that opening fenestration in risky patients would be appropriate bearing the decrease in saturation and the risk of embolic phenomena in mind.
The relationship between the course of laboratory parameters and PPE in the postoperative period raised curiosity, since there are not many publications on this subject. At the same time, the opening of the pleural cavities during the operation, the subsequent inflammatory process and the increase in vascular permeability as a result of possible pressure changes in the lymphatic system contribute to the formation and prolongation of pleural effusion. Harmoniously, it was demonstrated that in postoperative Fontan patients, the inflammation within the pleural space, which is significantly greater when compared to controls undergoing CPB, is out of proportion to the systemic inflammation (18). Our findings indicate that postoperative albumin levels (late) were lower, whereas both early and late CRP levels were elevated in PPE group. Although high CRP levels in the late period indicates ongoing inflammation and low albumin levels indicates protein wasting due to capillary leakage secondary to inflammation, considering the contribution of variables such as infection, fluid balance, blood transfusions, diuretic therapy in the postoperative period, it is debatable how much these findings can be adapted to daily practice. However, early CRP levels which defines the average of CRP levels postoperative 0-3 days may be a good predictor for PPE. In this context, we postulate that inflammation and vascular permeability within the pleura and factors affecting this permeability such as CPB and infections are effective in prolonging the effusion. Moreover, providing an infection-free postoperative follow-up and to strengthen the medical treatment with corticosteroids and anti-inflammatory agents in cases without active infection are becoming prevalent in our unit for PPE. In spite of application to a small number of cases yet, the decrease in effusion duration and LOHS appears encouraging.
Through this study, we tried to predict prolonged effusion after Fontan surgery over conventional variables due to the retrospective design. Nevertheless, we are well aware of that in order to approach perfection in Fontan physiology innovative variables need to be involved. Methods such as computational fluid dynamics initiating the evaluation from Glenn shunt stage even possibly from the palliation period to reveal the hemodynamics in the pulmonary arteries, MRI before Fontan to evaluate lymphatic system which is of great importance and maybe utilization of “flow study” to evaluate the pulmonary arterial vasculature readiness by simulating a Qp/Qs of 1 in the intraoperative period would be our future interests.
Limitations: This study was limited by its retrospective and single-center design. Due to limited number of patients multivariate model could not be constructed despite many variables available. Although we had patients with infections or complicated with acute kidney failure during long stays in the ward, statistical significance of infection and kidney injury could not be performed due to the limited number of patients complicated with those entities.