Discussion

The prevalence of capillary leak syndrome after cardiac surgery with cardiopulmonary bypass in paediatric patients varies across studies. Seghaye et al. ^{Reference Seghaye, Grabitz and Duchateau3} , Stiller et al. ^{Reference Stiller, Sonntag and Dähnert5} , and Zhang et al. ^{Reference Zhang, Wang and Li18} reported a capillary leak syndrome prevalence of 54.2% (13 of 24 patients), 5.2% (3 of 58 patients), and 37.0% (10 of 27 patients), respectively. However, it is important to note that these studies were conducted on relatively small cohorts. In our cohort of 164 neonates and infants, 7.3% (12 patients) met the capillary leak syndrome criteria. This comparatively lower prevalence could be due to advances in surgical techniques, perioperative care, and specific criteria for the diagnosis of capillary leak syndrome. The large proportion of patients in our cohort with high STAT scores and in higher Bethesda risk categories suggests that the lower capillary leak syndrome prevalence does not necessarily reflect fewer complex cases.

It has been concluded from previous studies that severe protein extravasation is likely to occur at first within hours postoperatively, coinciding with the peak of the inflammatory response. ^{Reference Seghaye, Grabitz and Duchateau3,Reference Levy and Kelly19} In addition to cardiopulmonary bypass, anaesthetics, reperfusion injury to the myocardium and lungs, and surgical trauma have been recognised as significant triggers of inflammation. ^{Reference Suleiman, Zacharowski and Angelini20–Reference Prondzinsky, Knüpfer and Loppnow23} We propose that mechanical factors, including SL/kg, may also play a role in exacerbating postoperative capillary leak syndrome by affecting systemic venous return. This, in turn, could contribute to increased egress of interstitial fluid and influence the patient’s postoperative course. This hypothesis draws upon the insights of Corno et al. ^{Reference Corno24} who, while not directly investigating the effect of stent length during open chest management on systemic venous return, emphasised the importance of surgical techniques and decisions and their mechanical effects on the venous circulation. In addition, a study by Haddad et al. ^{Reference Haddad, Lange and Raisky25} investigated the impact of delayed sternal closure on postoperative outcomes and associated mortality and found it to be a significant risk factor for mortality after postoperative cardiac catheterisation in children. In our study, a significant difference was found, suggesting a higher SL/kg in patients who developed capillary leak syndrome. Notably, there was also a significant difference in SL/kg between patients who succumbed postoperatively and those who survived, with the former group having a higher SL/kg. Surgical stress, which has been identified as a risk factor for the development of an inflammatory response and postoperative complications, ^{Reference Wan, Arifi and Wan21–Reference Prondzinsky, Knüpfer and Loppnow23} is thought to play a role in this context.

While we initially hypothesised that longer stents might impair venous return, this relationship appears complex and multifactorial. Theoretically, increased sternal opening could reduce intrathoracic pressure and thereby facilitate venous return. However, our data suggest that the adverse effects associated with higher SL/kg outweigh these potential benefits. One possible explanation is that longer stents may induce anatomical distortion and increase tension on the great veins and right atrium, leading to elevated central venous pressure and impaired preload augmentation. Moreover, prolonged open chest management with excessive sternal separation may further compromise cardiopulmonary interactions, exacerbating right ventricular dysfunction, venous congestion, and interstitial fluid accumulation.

It is also possible that longer stents are not causative per se, but rather reflect the underlying severity of the patient’s condition. Patients requiring wider sternal separation often present with greater haemodynamic instability and require more extensive postoperative support and prolonged intensive care. Thus, SL/kg may serve as an accompanying factor or a surrogate marker of overall illness severity, rather than an independent risk factor for capillary leak syndrome or mortality. Future studies incorporating detailed haemodynamic assessments could help clarify the interplay between stent length, venous return, and postoperative outcomes.

Importantly, SL/kg emerges as a predictive parameter for postoperative mortality in neonates and infants undergoing open-heart surgery with cardiopulmonary bypass and delayed sternal closure. The length of the stent is determined by the surgeon based on intraoperative conditions, including thoracic compliance, haemodynamic stability, and overall patient status. Therefore, the association between higher SL/kg and worse outcomes may, at least in part, reflect the underlying severity of illness rather than a modifiable surgical factor. Previous studies have reported a higher incidence of capillary leak syndrome and multiorgan failure in neonates and infants than in older children, ^{Reference Seghaye, Grabitz and Duchateau3,Reference Stiller, Sonntag and Dähnert5,Reference Seghaye, Duchateau and Grabitz6} suggesting that immaturity of the membrane response and development of the serological system contribute to this trend. ^{Reference Stiller, Sonntag and Dähnert5} Younger age has also been recognised as a risk factor for increased total body water retention after cardiac procedures. ^{Reference Maehara, Novak, Wyse and Elliot26,Reference Elliott27}

Extended cardiopulmonary bypass times have been associated with greater endothelial injury and postoperative capillary leak syndrome, likely due to more pronounced host dysregulation. ^{Reference Kubicki, Grohmann and Siepe4,Reference Allan, Newburger and McGrath28–Reference Wollborn, Zhang and Gaa30} Both Stiller et al. ^{Reference Stiller, Sonntag and Dähnert5} and Meri et al. ^{Reference Meri, Aronen and Leijala29} have found correlations between cardiopulmonary bypass time and capillary leak syndrome, with the latter noting a linear increase in complement activation that correlated with perfusion time and postoperative complications. Given the relatively low operative mortality rate observed in our study, we did not find a significant association between cardiopulmonary bypass time and all-cause mortality in the multivariate analysis.

Our findings suggest several hypotheses for the association between higher SL/kg and capillary leak syndrome or mortality. One potential mechanism is that longer stent lengths could exacerbate capillary leak syndrome by further impeding systemic venous return and increasing interstitial fluid leakage in this group of critically ill patients. Alternatively, the inflammatory response triggered by surgical stress and prolonged cardiopulmonary bypass time could be more pronounced in patients requiring longer stents.

In addition, we retrieved data on left and right ventricular function in patients with capillary leak syndrome and found that only 2 out of 12 cases had more than mild reductions in left ventricular and/or right ventricular systolic function at the time of surgery. This finding suggests that the association between stent length and outcomes such as capillary leak syndrome or mortality is unlikely to be attributable to significant pre-existing systolic dysfunction in most patients. However, it is important to acknowledge that impaired diastolic function, rather than systolic dysfunction, may be a key contributor to capillary leak syndrome, as it can lead to impaired venous filling. Unfortunately, diastolic function is challenging to assess in this setting. Thus, while our data suggest that systolic dysfunction is unlikely to be a major factor in the observed associations, the potential role of diastolic dysfunction remains an important, yet difficult-to-measure, consideration in this patient population.