Diuretics in infants with chronic lung disease

DIURETICS IN INFANTS WITH CHRONIC LUNG DISEASE
Background
The association between CL, high fluid intakes and PDA has led to thebelief that pulmonary oedema may play an important role in the pathogenesisof CLD. Pulmonary interstitial oedema is one of the characteristic pathologicalchanges seeen in infants with CLD and may rsult in reduced lung complianceand increased airway resistance.
Loop diuretics (eg Frusemide) and thiazide diuretics (eg Chlorothiazide andhydrochlorothiazide) act by reducing the reabsorption of sodium and chlorideions in the ascending limb of the loop of Henle or in the distal tubule,respectively. Reabsorption of water from the renal tubule is impaired, with anoverall reduction in extracellular fluid volume. Hyponatraemia and/orhypokalaemia are common side effects of diuretic therapy. Potassium sparingdiuretics such as Amiloride or Spironolactone act at the distal tubule affectingNa-K exchange and have a mild diuretic effect only.Some reports suggest thatFrusemide may also have some bronchodilator effects in infants with CLD.
Clinical Trials
1 Efficacy
Several randomised controlled trials in preterm infants with CLD havedemonstrated short to medium term improvements in pulmonary function witha reduction in airway resistance lung compliance with both frusemide andthiazide diuretics. These changes were associated with a reduction in oxygenand ventilator requirements after one week of treatment. Systematic reviewsof these studies have been published (1,2).
Two RCTs (2,4) have investigated the effects of long ter oral therapy withthiazide diuretics in infants with developing or established CLD. One study ofventilator-dependent infants with severe CLD demonstrated a significant (andclinically important, NNT = 3) reduction in mortality prior to discharge fromhospital in infants treated with an 8 week course of hydrochlorothiazide andspironolactone (3). The other study showed a reduction in supplementaloxygen requirements in non-ventilated infants treated with four weeks ofchlorothiazide and spironolactone (4).However there was no evidence of abenefit in total duration of respiratory support or hospital stay with diuretictherapy in either study although a large proportion of control infants in bothstudies received extra doses of frusemide.Babies treated with long termthiazide therapy received less extra doses of frusemide(3,4). There isvirtuallyno information from RCTs about the longterm safety and efficacy offrusemide therapy in infants with CLD(2).
Adverse effects
Uncontrolled series have suggested a number of potential complicationswith diuretic therapy including electrolyte disturbance, deranged phosphateand calcium metabolism, nephrotoxicity, and ototoxicity. In particulartreatment with frusemide is associated with hypercalcuria andnephrocalcinosis. However there is no evidence from individual RCTs of anexcess of significant adverse effects (eg nephrocalcinosis, hearing loss,growth) with diuretic therapy although this may reflect the small number ofinfants studied. One small RCT evaluating the efficacy of addingspironolactone to a thiazude diuretic did not demonstrate any benefit in termsof efficacy or electrolyte balance (5).
Recommendations
1 Ventilator dependent pre-term infants with developing or established CLDmay benefit from long term diuretic therapy. Treatment with regular oralhydrochlorothiazide and spironolactone should be considered in such infants.
2 Diuretics should not be used routinely in non-ventilated pre-term infants withCLD. However, it would be resonable to consider treatment with eitherhydrochlorothiazide and spironolactone (if tolerating enteral feeds) or IVfrusemide in non-ventilated infants requiring high fractional oxygenconcentrations.
3. All babies recieving diuretics should be monitored for electrolytedisturbance (including Na K Ca and phosphate levels) and renal dysfunction.
References
1 Brion LP, Primhak RA, Ambrosio-Perez I. Diuretics acting on the distalrenal tubule for preterm infants with (or developing) chronic lung disease(Cocjrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: UpdateSoftware.
2 Brion LP, Primhak RA. Intravenous or enteral loop diuretics for preterminfants with (or developing) chronic lung disease (Cochrane Review). In: TheCochrane Library, Issue 2, 2003. Oxford: Update Software.
3 Kao, L.C., Durand, D.J., McCrea, R.C., et al. Randomized trial of long termdiuretic therapy for infants with oxygen-dependent bronchopulmonarydysplasia. J Pediatr 124:772-781, 1994.
4 Albersheim, S.G., Solimano, A.J., Sharma, A.K., and et al Randomized,double blind controlled trial of long term diuretic therapy for bronchopulmonarydysplasia. J Pediatr 115:615-620, 1989.
5 Hoffmann DJ Gerdes JS Abbasi S Pulmonary function and electrolytebalabnce following spironolactone treatment in preterm infants with CLD. Adouble blind placebo controlled randomised trial. J Perinatol 2000;20:41-5.
October 11th 2007 (version 4-NICU7)

Source: http://www.thewomens.org.uk/Library/health_professionals/Neonatal_policy_library/DIURETICS%20IN%20INFANTS%20WITH%20CHRONIC%20LUNG%20DISEASE.pdf