Tolvaptan as an Additive Diuretic in Infants with Capillary Leak after Cardiac Surgery

Objectives: Capillary leak syndrome (CLS), refractory to conventional diuretic therapy represents a rare but severe problem after open heart surgery on cardiopulmonary bypass. CLS is associated with increased mortality due to hemodynamic problems, longer stay on ICU and time of mechanical ventilation. Tolvaptan (vasopressin receptor 2 antagonist) is an oral drug: used to treat hyponatremia associated with congestive heart failure, cirrhosis, and SIADH. We investigated if Tolvaptan is able to mobilize fluid from the third space in patients with postoperative, diuretic refractory CLS and improves clinical course.

Methods: We performed a retrospective analysis in 26 patients who underwent cardiac surgery and developed severe third space volume retention. All individuals received additive Tolvaptan after insufficient response to furosemide and hydrochlorothiazide. We distinguished between patients who developed CLS versus other reason for volume retention. CLS was determined as non-cardiac edema/ascites/pleural effusions and increased subcutaneous-thoracic ratio (S/T) >12.5% according to literature. S/T ratio was calculated by chest X-ray. In 18/26 patients the S/T ratio confirmed CLS whereas 8/26 patients did not qualify for CLS.

Results: S/T Ratio was higher in CLS group (19.8 vs. 9.3%; p < 0.01). CLS patients were significantly younger (90 ± 137 vs. 564 ± 818; p < 0.01) and average application time of Tolvaptan was shorter than in Non-CLS group (9.6 ± 10 vs. 15.8 ± 13 days). Mean Tolvaptan dose administrated was lower in CLS than in Non-CLS group (0.51 ± 0.27 vs. 0.65 ± 0.28 mg/kg/d). CLS group showed a significant reduction of body weight after 4 days (p < 0.01), increase of Serum sodium after 7 days (p < 0.05) and serum osmolality (p < 0.05). 4 of CLS patients were extubated during and 8 after Tolvaptan therapy. No significant effect on body weight, electrolytes or clinical course was observed in the Non-CLS group. Clinical or laboratory side effects did not occur.

Conclusion: In a setting of diuretic refractory volume overload after cardiac surgery, the use of Tolvaptan enabled a significant reduction of body weight in infants with CLS, which supported or even enabled weaning from the ventilator. Tolvaptan was not effective in patients with cardiac edema, even if higher dosages were administrated for a longer time. Our retrospective analyses indicate an effect of Tolvaptan as an additive diuretic in infants who develop significant CLS after cardiac surgery.