Use of diuretics in the neonatal period

Abstract

The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is immature necessitates a thorough knowledge of renal developmental physiology and pathophysiology. This review presents the basic aspects of body fluid homeostasis in the neonate, discusses the development of kidney function, and describes the mechanisms involved in electrolyte and water reabsorption along the nephron. Diuretics are then classified according to the site of their action on sodium reabsorption. The use of diuretics in sodium-retaining states, in oliguric states, in electrolyte disorders, and in arterial hypertension, as well as in a few specific disorders, is presented. Common and specific adverse effects are discussed. Recommended dosages for the main diuretics used in the neonatal period are given. New developments in diuretic therapy are briefly mentioned.

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References

  1. 1.

    Gouyon B, Martin-Mons S, Iacobelli S, Razafimahefa H, Kermorvant-Duchemin E, Brat R, Caeymaex L, Couringa Y, Alexandre C, Lafon C, Ramful D, Bonsante F, Binson G, Flamein F, Moussy-Durandy A, Di Maio M, Mazeiras G, Girard O, Desbruyeres C, Mourdie J, Escourrou G, Flechelles O, Abasse S, Rosenthal JM, Pages AS, Dorsi M, Karaoui L, ElGellab A, Le Bail Dantec F, Yangui MA, Norbert K, Kugbe Y, Lorrain S, Pignolet A, Garnier EM, Lapillonne A, Mitanchez D, Jacqz-Aigrain E, Gouyon JB (2019) Characteristics of prescription in 29 Level 3 Neonatal Wards over a 2-year period (2017-2018). An inventory for future research. PLoS One 14:e0222667. https://doi.org/10.1371/journal.pone.0222667

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Hagadorn JI, Sanders MR, Staves C, Herson VC, Daigle K (2011) Diuretics for very low birth weight infants in the first 28 days: a survey of the U.S. neonatologists. J Perinatol 31:677–681. https://doi.org/10.1038/jp.2011.11

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Iacobelli S, Guignard JP (2020) Maturation of glomerular filtration rate in neonates and infants: an overview. Pediatr Nephrol. https://doi.org/10.1007/s00467-020-04632-1

  4. 4.

    Gattineni J, Baum M (2015) Developmental changes in renal tubular transport—an overview. Pediatr Nephrol 30:2085–2098. https://doi.org/10.1007/s00467-013-2666-6

    Article  PubMed  Google Scholar 

  5. 5.

    Segar JL (2017) Renal adaptive changes and sodium handling in the fetal-to-newborn transition. Semin Fetal Neonatal Med 22:76–82. https://doi.org/10.1016/j.siny.2016.11.002

    Article  PubMed  Google Scholar 

  6. 6.

    Iacobelli S, Gouyon JB, Bonsante F, Mastrofrancesco L, Svelto M, Valenti G (2010) Aquaporin-2 urinary excretion in preterm infants: relationship to diuresis and vasopressin. Acta Physiol (Oxf) 200:339–345. https://doi.org/10.1111/j.1748-1716.2010.02164.x

    CAS  Article  Google Scholar 

  7. 7.

    Adhikari M, Moodley M, Desai PK (1990) Mannitol in neonatal cerebral oedema. Brain Dev 12:349–351. https://doi.org/10.1016/s0387-7604(12)80320-2

  8. 8.

    Tam B, Chhay A, Yen L, Tesoriero L, Ramanathan R, Seri I, Friedlich PS (2014) Acetazolamide for the management of chronic metabolic alkalosis in neonates and infants. Am J Ther 21:477–481. https://doi.org/10.1097/MJT.0b013e31825e792c

    Article  PubMed  Google Scholar 

  9. 9.

    Andrews MG, Johnson PN, Lammers EM, Harrison DL, Miller JL (2015) Acetazolamide in critically ill neonates and children with metabolic alkalosis. Ann Pharmacother 47:1130–1135. https://doi.org/10.1177/1060028013500468

    CAS  Article  Google Scholar 

  10. 10.

    Seikaly MG, Baum M (2011) Thiazide diuretics arrest the progression of nephrocalcinosis in children with X-linked hypophosphatemia. Pediatrics 108:E6. https://doi.org/10.1542/peds.108.1.e6

    Article  Google Scholar 

  11. 11.

    Krzyżaniak N, Pawłowska I, Bajorek B (2016) Review of drug utilization patterns in NICUs worldwide. J Clin Pharm Ther 41:612–620. https://doi.org/10.1111/jcpt.12440

    Article  PubMed  Google Scholar 

  12. 12.

    Manfredini VA, Cerini C, Clavenna A, Dotta A, Caccamo ML, Staffler A, Massenzi L, Rezzonico RM, Study Group of Neonatal Pharmacotherapy of the Italian Society of Neonatology (2020) Furosemide use in Italian neonatal intensive care units: a national survey. Ital J Pediatr 46:86. https://doi.org/10.1186/s13052-020-00851-2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    van der Vorst MM, Ruys-Dudok van Heel I, Kist-van Holthe JE, den Hartigh J, Schoemaker RC, Cohen AF, Burggraaf J (2001) Continuous intravenous furosemide in haemodynamically unstable children after cardiac surgery. Intensive Care Med 27:711–715. https://doi.org/10.1007/s001340000819

    Article  PubMed  Google Scholar 

  14. 14.

    van der Vorst MMG, Kist-van Holthe JE, den Hartigh J, van der Heijden AJ, Cohen AF, Burggraaf J (2007) Absence of tolerance and toxicity to high-dose continuous intravenous furosemide in haemodynamically unstable infants after cardiac surgery. Br J Clin Pharmacol 64:796–803. https://doi.org/10.1111/j.1365-2125.2007.02913.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Klinge JM, Scharf J, Hofbeck M, Gerling S, Bonakdar S, Singer H (1997) Intermittent administration of furosemide versus continuous infusion in the postoperative management of children following open heart surgery. Intensive Care Med 23:693–697. https://doi.org/10.1007/s001340050395

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Baylen BG, Johnson G, Tsang R, Srivastava L, Kaplan S (1980) The occurrence of hyperaldosteronism in infants with congestive heart failure. Am J Cardiol 45:305–310. https://doi.org/10.1016/0002-9149(80)90650-5

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Pacifici G (2012) Clinical pharmacology of the loop diuretics furosemide and bumetanide in neonates and infants. Pediatr Drugs 14:233–246. https://doi.org/10.2165/11596620-000000000-00000

    Article  Google Scholar 

  18. 18.

    Sutiman N, Koh JC, Watt K, Hornik C, Murphy B, Chan YH, Lee JH (2020) Pharmacokinetics alterations in critically ill pediatric patients on extracorporeal membrane oxygenation: a systematic review. Front Pediatr 8:260. https://doi.org/10.3389/fped.2020.00260

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Jalanko H (2009) Congenital nephrotic syndrome. Pediatr Nephrol 24:2121–2128. https://doi.org/10.1007/s00467-007-0633-9

    Article  PubMed  Google Scholar 

  20. 20.

    Hölttä T, Jalanko H (2020) Congenital nephrotic syndrome: is early aggressive treatment needed? Yes. Pediatr Nephrol. https://doi.org/10.1007/s00467-020-04578-4

  21. 21.

    Reynolds BC, Oswald RJA (2019) Diagnostic and management challenges in congenital nephrotic syndrome. Pediatric Health Med Ther 10:157–167. https://doi.org/10.2147/PHMT.S193684

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Bagshaw SM, Delaney A, Haase M, Ghali WA, Bellomo R (2007) Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resusc 9:60–68

    PubMed  Google Scholar 

  23. 23.

    Dubourg L, Drukker A, Guignard JP (2000) Failure of torasemide to improve renal function of hypoxemic vasomotor nephropathy in the newborn rabbit. Pediatr Res 47:504–508. https://doi.org/10.1203/00006450-200004000-00015

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Gouyon JB, Guignard JP (2000) Management of acute renal failure in newborns. Pediatr Nephrol 14:1037–1044. https://doi.org/10.1007/s004670050068

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Guignard JP, Ali US (2016) Acute renal failure in the neonate. J Pediatr Intensive Care 5:42–49. https://doi.org/10.1055/s-0035-1564735

    Article  PubMed  Google Scholar 

  26. 26.

    Nada A, Bonachea EM, Askenazi DJ (2017) Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med 22:90–97. https://doi.org/10.1016/j.siny.2016.12.001

    Article  PubMed  Google Scholar 

  27. 27.

    Pandey V, Kumar D, Vijayaraghavan P, Chaturvedi T, Raina R (2016) Non-dialytic management of acute kidney injury in newborns. J Renal Inj Prev 6:1–11. https://doi.org/10.15171/jrip.2017.01

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Borasino S, Wall KM, Crawford JH, Hock KM, Cleveland DC, Rahman F, Martin KD, Alten JA (2018) Furosemide response predicts acute kidney injury after cardiac surgery in infants and neonates. Pediatr Crit Care Med 19:310–317. https://doi.org/10.1097/PCC.0000000000001478

    Article  PubMed  Google Scholar 

  29. 29.

    Oliveros M, Pham JT, John E, Resheidat A, Bhat R (2011) The use of bumetanide for oliguric acute renal failure in preterm infants. Pediatr Crit Care Med 12:210–214. https://doi.org/10.1097/PCC.0b013e3181e912a7

    Article  PubMed  Google Scholar 

  30. 30.

    Merheb RC, Kruzer KA, Mhanna MJ (2014) The effect of bumetanide in extremely low birth weight infants with acute kidney injury during their first weeks of life. J Clin Pediatr Nephrol 2:53–63. https://doi.org/10.15401/jcpn/2014/v2i1/50526

    Article  Google Scholar 

  31. 31.

    Pandey V, Dummula K, Go M, Parimi P (2015) Bumetanide use in the management of oliguric preterm infants with acute kidney injury–a single center experience. J Clin Pediatr Nephrol 2:33–38. https://doi.org/10.15401/jcpn/2014/v2i2/66346

    Article  Google Scholar 

  32. 32.

    Gouyon JB, Guignard JP (1988) Functional renal insufficiency: role of adenosine. Biol Neonate 53:237–242. https://doi.org/10.1159/000242796

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Gouyon JB, Guignard JP (1989) Adenosine in the immature kidney. Dev Pharmacol Ther 13:113–119. https://doi.org/10.1159/000457592

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Gouyon JB, Guignard JP (1988) Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits. Kidney Int 33:1078–1083. https://doi.org/10.1038/ki.1988.114

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Bhatt GC, Gogia P, Bitzan M, Das RR (2019) Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review. Arch Dis Child 104:670–679. https://doi.org/10.1136/archdischild-2018-315805

    Article  PubMed  Google Scholar 

  36. 36.

    Bellos I, Pandita A, Yachha M (2019) Effectiveness of theophylline administration in neonates with perinatal asphyxia: a meta-analysis. J Matern Fetal Neonatal Med. https://doi.org/10.1080/14767058.2019.1673722

  37. 37.

    Chock VY, Cho SH, Frymoyer A (2020) Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia. Pediatr Res. https://doi.org/10.1038/s41390-020-0999-y

  38. 38.

    Sharma D (2019) Hypertension in neonates: need for future research. J Neonatal Biol 06:3. https://doi.org/10.4172/2167-0897.1000261

    Article  Google Scholar 

  39. 39.

    Alon U, Hellerstein S, Warady BA (1991) Oral acetazolamide in the assessment of (urine-blood) PCO2. Pediatr Nephrol 5:307–311. https://doi.org/10.1007/BF00867488

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Plumb LA, Van't Hoff W, Kleta R, Reid C, Ashton E, Samuels M, Bockenhauer D (2016) Renal apnoea: extreme disturbance of homoeostasis in a child with Bartter syndrome type IV. Lancet 388:631–632. https://doi.org/10.1016/S0140-6736(16)00087-8

    Article  PubMed  Google Scholar 

  41. 41.

    Kirchlechner V, Koller D, Seidl, Waldhauser F (1999) Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride. Arch Dis Child 80:548–552. https://doi.org/10.1136/ade.80.6.548

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Pacifici GM (2013) Clinical pharmacology of furosemide in neonates: a review. Pharmaceuticals (Basel) 6:1094–1129. https://doi.org/10.3390/ph6091094

    CAS  Article  Google Scholar 

  43. 43.

    Suyagh M, Hawwa AF, Collier PS, Millership JS, Kole P, Millar M, Shields MD, Halliday HL, McElnay JC (2012) Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients. Br J Clin Pharmacol 74:864–872. https://doi.org/10.1111/j.1365-2125.2012.04257.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Bestic M, Reed MD (2012) Common diuretics used in the preterm and term infant. NeoReviews 13:e410–e419. https://doi.org/10.1542/neo.13-7-e410

    Article  Google Scholar 

  45. 45.

    Segar JL (2012) Neonatal diuretic therapy: furosemide, thiazides, and spironolactone. Clin Perinatol 39:209–220. https://doi.org/10.1016/j.clp.2011.12.007

    Article  PubMed  Google Scholar 

  46. 46.

    Stewart A, Brion LP, Soll RF (2011) Diuretics for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev 1:CD001454. https://doi.org/10.1002/14651858.CD001454.pub3

    Article  Google Scholar 

  47. 47.

    Blaisdell CJ, Troendle J, Zajicek A (2018) Prematurity and respiratory outcomes program. Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study. J Pediatr 197:42–47. https://doi.org/10.1016/j.jpeds.2018.01.066

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Kassab M, Khriesat WM, Anabrees J (2015) Diuretics for transient tachypnoea of the newborn. Cochrane Database Syst Rev 11:CD003064. https://doi.org/10.1002/14651858.CD003064.pub3

    Article  Google Scholar 

  49. 49.

    Michael Z, Spyropoulos F, Ghanta S, Christou H (2018) Bronchopulmonary dysplasia: an update of current pharmacologic therapies and new approaches. Clin Med Insights Pediatr 12:1179556518817322. https://doi.org/10.1177/1179556518817322

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Stewart A, Brion LP (2011) Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev 9:CD001453

    Google Scholar 

  51. 51.

    Brion LP, Primhak RA, Yong W (2006) Aerosolized diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev 2:CD001694

    Google Scholar 

  52. 52.

    Greenberg RG, Gayam S, Savage D, Tong A, Gorham D, Sholomon A, Clark RH, Benjamin DK, Laughon M, Smith PB, Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee (2019) Furosemide exposure and prevention of bronchopulmonary dysplasia in premature infants. J Pediatr 208:134–140.e2. https://doi.org/10.1016/j.jpeds.2018.11.043

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Stewart A, Brion LP, Ambrosio-Perez I (2011) Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev 9:CD001817

    Google Scholar 

  54. 54.

    Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W, Caffeine for Apnea of Prematurity Trial Group (2006) Caffeine therapy for apnea of prematurity. N Engl J Med 354:2112–2121. https://doi.org/10.1056/NEJMoa054065

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Lee BS, Byun SY, Chung ML, Chang JY, Kim HY, Kim EA, Kim KS, Pi SY (2010) Effect of furosemide on ductal closure and renal function in indomethacin-treated preterm infants during the early neonatal period. Neonatology 98:191–199. https://doi.org/10.1159/000289206

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Thompson EJ, Greenberg RG, Kumar K (2018) Association between furosemide exposure and patent ductus arteriosus in hospitalized infants of very low birth weight. J Pediatr 199:231–236. https://doi.org/10.1016/j.jpeds.2018.03.067

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Iacobelli S, Lorrain S, Gouyon B, Gambacorta S, Laforgia N, Gouyon JB, Bonsante F (2020) Drug exposure for PDA closure in France: a prospective, cohort-based, analysis. Eur J Clin Pharmacol. https://doi.org/10.1007/s00228-020-02974-1

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Correspondence to Silvia Iacobelli.

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Guignard, JP., Iacobelli, S. Use of diuretics in the neonatal period. Pediatr Nephrol (2021). https://doi.org/10.1007/s00467-021-04921-3

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Keywords

  • Neonates
  • Diuretics
  • Furosemide
  • NICU
  • VLBW
  • AKI
  • Bronchopulmonary dysplasia