Call me Ish-chyle. Indeed, managing refractory chylothorax can sometimes feel like plodding through a summer reading assignment of Herman Melville’s 200,000-word classic, Moby Dick, while your friends spend their days at the beach. This well described leakage of lymphatic fluid occurring after 3–4% of all pediatric cardiac surgery is associated with malnutrition, prolonged mechanical ventilation, poor wound healing, infection, longer hospital and ICU length of stay (LOS), and increased risk of hospital mortality (1–5). Much has been written about and recommended regarding the treatment of postoperative chylothorax, but less is known about preventing this dangerous complication.

Although not always clear for an individual patient, the mechanistic etiologies of postoperative chylothorax include direct intraoperative injury to lymphatic structures, elevated central venous pressures, or localized lymphatic obstruction from venous thrombosis or stenosis (4–6). Younger age (specifically neonates), single ventricle physiology, genetic syndromes, extracardiac anomalies, surgical complexity, longer duration of cardiopulmonary bypass (CPB), higher postoperative vasoactive infusion scores, and thromboses associated with upper extremity central venous catheters are a few important risk factors that have been associated with chylothorax (1–4). Two large multicenter studies demonstrated a five- to seven-fold increased risk of chylothorax in neonates compared with adolescents (1,3). Neonates tend to undergo more complex surgical procedures, but increased friability of lymphatic vessels may also be implicated. Neonates are also most vulnerable to the deleterious effects of chylothorax, with higher risk for morbidity and mortality (1,3).

In this issue of Pediatric Critical Care Medicine, Brandewie et al (7) sought to explore the impact of postoperative fluid balance on the occurrence of chylothorax in neonates who underwent cardiac surgery. To conduct the study by Brandewie et al (7), a retrospective, secondary analysis of multicenter data from the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry was performed. Patients included in this dataset were neonates (< 30 d old) who underwent cardiac surgery at 22 participating Pediatric Cardiac Critical Care Consortium (PC4) centers between 2015 and 2018. Patients who developed chylothorax requiring treatment during the postoperative day (POD) 2–21 were compared with those who did not, and the authors hypothesized that a more positive fluid balance following cardiac surgery would be associated with the development of chylothorax.

The analysis benefited from a large cohort of 2240 neonates who underwent cardiac surgery during the study period, with chylothorax occurring in 4% of patients during the postoperative window of interest. This rate is likely an underestimate due to the exclusion criteria of the NEPHRON collaborative (excluded early postoperative ECMO and reoperations) and the chylothorax data definition used by PC4 (“chylothorax requiring intervention”), which may not capture some low-output, self-limited effusions. Approximately one third of the chylothorax patients had single ventricle physiology, 91% underwent surgery utilizing CPB, and 76% had complex index operations classified as Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 or 5.

The key finding reported by the authors is that higher (more positive) fluid balance that occurs early in the postoperative course increases the risk for development of postoperative chylothorax. In the multivariable analysis, a higher fluid balance on POD 2 was independently associated with chylothorax. Interestingly, chylothorax patients had higher fluid balance on POD 1–2 but lower fluid balance on POD 4–6 (compared with nonchylothorax patients), highlighting the notion that the timing of fluid overload in relation to surgery is important. The authors hypothesize that the lower fluid balance on POD 4–6 observed in chylothorax patients may be due to more complicated early postoperative courses resulting in continued aggressive diuresis and delayed enteral feeding. Perhaps, it is this proximity to surgery and its associated deleterious effects of CPB (inflammation, ischemia/reperfusion, endothelial injury, etc.), when early fluid overload acts as a “second hit” that confers the greatest risk for stressing the lymphatic system. As such, by the time these patients start achieving more negative fluid balance (POD 4–6), the damage has already been done.

Once again, chylothorax was demonstrated to be a dangerous complication resulting in longer durations of mechanical ventilation, inotropic support, and hospital LOS in this neonatal study population. Importantly, the rate of postoperative acute kidney injury was not different between chylothorax and nonchylothorax patients, suggesting that renal dysfunction is not solely to blame for the relationship found between fluid overload and chylothorax. A deeper investigation of our postoperative fluid management practices in the ICU is warranted. In congruence with a previous report from PC4 (3), significant center variation in chylothorax rates was observed (ranging from 0% to 13%), supporting the idea that some chylothoraces may be preventable.

Fluid status and the timing of achieving a negative fluid balance have been shown to be important clinical indicators of neonatal recovery following congenital cardiac surgery (2,8,9). While previous single center reports about the impact of fluid overload on chylothorax have been mixed (2,4), the associations reported in the current analysis are strengthened by the clever study design that leverages the robust, multicenter PC4 database, and granular fluid balance data from the NEPRHON registry. Although registry studies permit rapid investigation of large patient populations and shine light on important associations, the strict and limited variables collected often leave us wanting more. Intraoperative and postoperative fluid management practices such ultrafiltration, fluid restriction, diuretic strategies, passive peritoneal drainage, and peritoneal dialysis were not described in detail in the current study by Brandewie et al (7). Additional investigation is needed to determine whether optimization of these practices to avoid early fluid overload can impact the incidence of postoperative chylothorax.

Last, patient age is not typically a highly modifiable risk factor when it comes to neonatal cardiac surgery. Although pediatric cardiac surgery outcomes continue to improve, neonates, particularly those with single ventricle physiology, remain vulnerable (10,11). Wernovsky et al (12) suggested that placement of rapid bilateral pulmonary artery bands within 48 hours of life for hypoplastic left heart syndrome may allow for stabilization of neonatal circulation and improved end organ maturity (including increased renal blood flow) before the more definitive Norwood operation. Recent reports describing the percutaneous placement of pulmonary artery flow restrictors have shown promising results as an alternative, nonsurgical approach to limit pulmonary blood flow before patients undergo more definitive surgical palliation (13,14). As innovation expands, we should maintain the mental flexibility to challenge dogma and continue to shift the landscape from not only preventing mortality but also improving morbidity.

The work performed by Brandewie et al (7) helps to broaden our understanding of the factors and physiologic states that may contribute to the development of chylothorax after neonatal cardiac surgery. Differences in fluid management practices after neonatal cardiac surgery may explain some of the variation observed in postoperative chylothorax rates across centers. Similar to the recent work describing a collaborative learning network to prevent cardiac arrest, it may be time to study the high performers and create a “chylothorax prevention bundle” to reduce the burden of this dangerous complication for our patients (15). While the management of chylothorax remains a hot topic of conversation and percutaneous lymphatic interventions may represent the next frontier, an ounce of prevention is worth a pound of cure.

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