Mehmet MUTLU, Yakup ASLAN, Şebnem KADER, Filiz Aktürk ACAR, Embiya DİLBER

Clinical signs and symptoms of toxic serum digoxin levels in neonates

Digoxin is widely used in the treatment of congestive heart failure andsome arrhythmias. Digoxin toxicity may occur easily because digoxin has anarrow therapeutic index. This retrospective study was conducted to evaluatethe clinical signs and symptoms of toxic serum digoxin levels in neonates.Medical reports of the neonates who had serum digoxin concentrations >2nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics,serum digoxin concentrations, signs and symptoms of digoxin toxicity, serumdigoxin and electrolyte levels, renal function tests, electrocardiograms,echocardiography, and treatments applied. Digoxin toxic levels were identifiedin the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%)were term and 8 (62%) were female. Twenty-three percent (3/13) ofnewborn infants were symptomatic. Symptomatic patients had statisticallysignificantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml,than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptomsrelated to toxic digoxin levels were observed in the three neonates withplasma digoxin levels >5 ng/ml. Gastrointestinal and central nervous systemsymptoms were the major clinic findings. Despite high digoxin levels, nodigoxin-related arrhythmia was observed on electrocardiography, other thansinus bradycardia. Two premature neonates were treated with digoxin-specificantibody Fab fragments (DigiFab®) and hypokalemia developed in both ofthem. Our data suggests that symptoms related with digoxin toxic levels wereobserved in neonates with plasma digoxin levels >5 ng/ml. Serum digoxinlevels should be measured in case of signs and symptoms of digoxin toxicityor risk factors for such toxicity.

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1. Park M. Congestive heart failure. In: Park MK, (ed) Pediatric Cardiology for Practitioners, (4th ed) St Louis: Mosby; 2002: 403-406.

2. Efstratiadis G, Sarigianni M, Gougourelas I. Hypomagnesemia and cardiovascular system. Hippokratia 2006; 10: 147-152

3. Cambonie G, an Haack K, Guyon G, et al. Digitalis intoxication during the neonatal period: role of dehydration. Arch Pediatr 2000; 7: 633-636.

4. Berkovitch M, Akilesh MR, Gerace R, et al. Acute digoxin overdose in a newborn with renal failure: use of digoxin immune Fab and peritoneal dialysis. Ther Drug Monit 1994; 16: 531-533.

5. Laurent G, Poulet B, Falcon-Eicher S, et al. Anti-digoxin antibodies in severe digitalis poisoning in an 11-day old infant. Review of the literature. Ann Cardiol Angeiol (Paris) 2001; 50: 274-284.

6. Woolf AD, Wenger T, Smith TW, Lovejoy FH Jr. The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med. 1992; 326: 1739-1744.

7. Rodgers GC, Condurache T, Reed MD, Bestic M, Gal P. Poisonings. In: RM Kliegman, RE Behrman, HB Jenson, BF Stanton, (eds) Nelson Textbook of Pediatrics, (18th ed) Philadelphia: WB Saunders, 2007: 339-357.

8. Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila) 2014; 52: 824-836.

9. DİGİFAB® ® DIGOXIN IMMUNE FAB (OVINE). BTG International. Available at:http://vardgivarwebb. regionostergotland.se/pages/233476/DigiFab®%20 2014.pdf Accessed August 2014.

10. Rao PS, Harris AD. Recent advances in managing septal defects: ventricular septal defects and atrioventricular septal defects [version 1; referees: 3 approved] F1000Research 2018; 7(F1000 Faculty Rev): 498.

11. Thacker D, Sharma J. Digoxin toxicity. Clin Pediatr (Phila) 2007; 46: 276-279.

12. Lang D, Hofstetter R, von Bernuth G. Digoxin intoxication in newborns. Correlation with digoxin plasma concentration. Monatsschr Kinderheilkd 1978; 126: 148-152.

13. Moffett BS, Garner A, Zapata T, Orcutt J, Niu M, Lopez KN. Serum digoxin concentrations and clinical signs and symptoms of digoxin toxicity in the paediatric population. Cardiol Young 498-493 :26 ;2016.

14. Jain S, Vaidyanathan B. Digoxin in management of heart failure in children: Should it be continued or relegated to the history books? Ann Pediatr Cardiol 2009; 2: 149-152.

15. Nybo M, Damkier P. Gastrointestinal symptoms as an important sign in premature newborns with severely increased S-digoxin. Basic Clin Pharmacol Toxicol 2005: 96: 465-468.

16. Dasgupta A. Therapeutic drug monitoring of digoxin: impact of endogenous and exogenous digoxin-like immunoreactive substances. Toxicol Rev :25 ;2006 281-273.

17. Koobatian TJ, Roberts JR. Falsely elevated serum digoxin levels secondary to endogenous digoxin-like immunoreactive substances. Acad Emerg Med ;1995 326-322 :2.

18. Ebara H, Suzuki S, Nagashima K, Shimano S, Kuroume T. Digoxin-like immunoreactive substances in urine and serum from preterm and term infants: relationship to renal excretion of sodium. J Pediatr 762-760 :108 ;1986.

19. Antman EM, Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 150 cases of life threatening digitalis intoxication with digoxin specific Fab antibody fragments. Final report of a multicenter study. Circulation 1990; 81: 1744-1752.