Effects of ACE Gene Insertion/Deletion Polymorphism on Response to Spironolactone in Patients with Chronic Heart Failure Mariantonietta Cicoira, MD, Andrea Rossi, MD, Stefano Bonapace, MD, Luisa Zanolla, MD,Andreas Perrot, MSc, Darrel P. Francis, MRCP, Giorgio Golia, MD, Lorenzo Franceschini, MD, BACKGROUND: Angiotensin-converting enzyme (ACE) is tients were assigned to spironolactone
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Postnatal steroidsSteroid use in chronic neonatal respiratory disease
Postnatal corticosteroids lead to earlier extubation and are associated with a
reduction in the combined incidence of chronic lung disease or death, irrespective of
when steroids are given postnatally [1-3]. However, the systematic reviews
highlighted concerns regarding long term side effects (neurodevelopmental
impairment and impaired growth) of systemic steroid use in the neonate .
Clinical experience and post hoc review of RCTs suggest that among infants with
established chronic lung disease, postnatal corticosteroids reduce the risk of death
and neurodevelopmental impairment. In other words, infants at high risk of
neurodevelopmental impairment because of postnatal corticosteroids are the ones
who have mild or no chronic lung disease [5, 6, 7]. Accordingly, we use postnatal
corticosteroids selectively, aiming to reduce mortality in those infants with
established or evolving lung disease.
A preparation of dexamethasone that includes sulphite as a preservative has been
reported to increase the risk of adverse outcome [8, 9]. The dexamethasone in use
at Liverpool Women’s Hospital is sulphite-free.
Short term side effects (hypertension, hyperglycaemia, septic episodes) may be
associated with high doses of postnatal steroids [1-3]. These side effects do not
appear to be a major issue with the low doses in use at LWH, which are based on
the DART study .
Any decision to commence steroids will be made by a Consultant, who will inform
the family of the risk-benefit analysis that underlies the decision to give
corticosteroids. The parents should be given a copy of the relevant Parent
1/ Very early systemic steroids (<7days) - not indicated in infants with respiratory
distress syndrome owing to difficulty recognizing which infants will be at high risk of
chronic lung disease and concerns about acute side-effects in unstable infants,
including intestinal perforation.
2/ At 7-14 days - Infants weighing less than 2000g who are ventilator dependent, are
receiving high concentrations of inspired oxygen and in whom the consultant feels
there is little prospect of improvement may receive dexamethasone. The initial dose
is 150 microgrammes / Kg 12 hourly of dexamethasone. This will usually be given for
3 days, followed by 3 days of 100 microgrammes / Kg 12 hourly of dexamethasone,
followed by 50 microgrammes mg/kg 12 hourly of dexamethasone. The duration of
each dose level may be adjusted in the light of clinical response, by the Consultant.
Contraindications may include sepsis, gastrointestinal bleeding, major malformation,
hypertension, and suspected NEC. Patent ductus arteriosus as a cause of ventilator
dependency should be excluded.
At present there is no strong evidence that prolonged courses of systemic steroids in
ventilator dependent infants are beneficial.
3/ After 14 days, steroids may be considered for those babies who are ventilator
dependent in high concentrations of oxygen and who considered to be at high risk of
chronic lung disease. The initial dose is 150 microgrammes / Kg 12 hourly of
dexamethasone. This will usually be given for 3 days, followed by 3 days of
100 microgrammes /Kg 12 hourly of dexamethasone, followed by 3 days of 50
microgrammes / Kg 12 hourly of dexamethasone. Thus the duration of the standard
course will be 9 days. The duration of each dose level may be adjusted in the light of
clinical response by the Consultant.
Occasionally, an infant with established CLD on maximal nasal CPAP or
headbox oxygen support may be given corticosteroids to avoid reintubation.
If the infant’s respiratory status rebounds significantly after stopping steroids, a
second course of dexamethasone may be considered with slower tapering of the
dose. (Any decision to commence steroids will be made by the consultant).
4/ After failed extubation - Infants with evidence of laryngeal swelling either seen on
direct laryngocoscopy or suggested clinically by stridor should receive three doses
of 200 micrograms/kg of dexamethasone base at 8 hourly intervals with the first
dose being given 4 hours prior to extubation.
All infants receiving postnatal steroids should have their blood pressure recorded
12 hourly and urine tested daily for sugar.
1. Halliday HL, Ehrenkranz, RA, Doyle, LW. Early postnatal (<96 hours)
corticosteroids for preventing chronic lung disease in preterm infants.
Cochrane Database Syst Rev 2003;CD001146.
2. Halliday HL, Ehrenkranz, RA, Doyle, LW. Delayed (>3 weeks) postnatal
corticosteroids for chronic lung disease in preterm infants. Cochrane
Database Syst Rev 2003;CD001145.
3. Halliday HL, Ehrenkranz, RA, Doyle, LW. Moderately early (7-14 days) postnatal
corticosteroids for preventing chronic lung disease in preterm infants. Cochrane
Database Syst Rev 2003;CD001144.
4. Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in
the preterm infant: a systematic review of RCTs. BMC Pediatr 2001;1:1.
5. Doyle LW, Halliday, HL, Ehrenkranz, RA, Davis, PG, Sinclair, JC. Impact of
postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants:
effect modification by risk for chronic lung disease. Pediatrics 2005;115:655-61.
6. Onland W, Offringa M, Jaegere AP, van Kaam AH. Finding the optimal postnatal
dexamethasone regimen for preterm infants at risk of bronchopulmonary dysplasia:
a systematic review of placebo-controlled trials. Pediatrics 2009;123:367-77.
7. Watterberg K. Policy Statement – postnatal corticosteroids to prevent or treat
bronchopulmonary dysplasia. Pediatrics 2010;126:800-8.
8. Baud O, Laudenbach, V, Evrard, P, Gressens, P. Neurotoxic effects of fluorinated
glucocorticoid preparations on the developing mouse brain: role of preservatives.
Pediatr Res 2001;50:706-11.
9. Baud O, Foix-L'Helias, L, Kaminski, M, Audibert, F, Jarreau, PH, Papiernik, E, et
al. Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very
premature infants. N Engl J Med 1999;341:1190-6.
10. Doyle LW, Davis PG, Morley, CJ McPhee A, Carlin JB. Low-dose
dexamethasone facilitates extubation among chronically ventilator-dependent
infants: a multicenter, international, randomized, controlled trial. Pediatrics
April 1st 2011 (version 7-NICU75)
MANAGEMENT AND OPERATION OF ST. CYRIL & METOD HEALTH CENTRE Management Team In order to streamline the management of the hospital it was recently decided that the hospital should be registered as a trust deed under trustees. This was done and the following is the current composition of the caretaker management committee; Lions representatives – 2No Local catholic churc