Vaptans for edematous and hyponatremic disorders in childhood: a systematic literature review

Aims: To systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children. Methods: Through a database search (Web of Science, the National Library of Medicine, Excerpta Medica), we identified case series and case reports and extracted clinical and laboratory data. Results: Twenty-six articles, published since 2008, reported on 226 patients. Among 115 children with hyponatremic (n=63) and edematous disorders (n=52), a 48h course of tolvaptan with an initial dose of 0.38±0.27 mg/kg was administerd in 106, while intravenous conivaptan was reported in 9 cases. An increase (p<0.02) in urine output was shown in both edematous (from 3.2±2.0 to 5.3±6.7 mL/kg/day) and hyponatraemic (from 3.0±1.5 to 4.4±2.3 mL/kg/day) patients. In these latter, sodium increased from 125±6 to 133±6 mmol/L (p<0.0001). The increase in sodium level correlated with its basal value, but not with the administered vaptan dose. Among 111 children undergoing cardiac surgery, after tolvaptan 0.21±0.01 mg/kg/day, mostly combined with conventional diuretics, an increase in diuresis by 41±4% was seen within 24h (p<0.0001). Similarly, a single add-on dose of tolvaptan 0.45 mg/kg allowed a reduced additional intravenous furosemide administration (0.26±0.23 versus 0.62±0.48 mg/kg, p<0.005). Side effects were rarely reported, and included excessive thirst and xerostomia in seven, skin rash in one and elevated aminotransferases in one patient(s). Conclusion: Vaptans appear to be safe for edematous and hyponatremic disorders also in children. Although they increase diuresis and natremia, no superiority to traditional diuretics and sodium supplements has been demonstrated. Reported side effects are rare and non-serious.