Steroids Final - Postnatal

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Role of postnatal steroids in

neonatology

Dr. Anirudha

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  Use of steroids in BPD

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  Introduction:

 The incidence of hronic lung disease (BPD) is

approximately !"# in extremely lo$ birth $eight infants and

is associated $ith mortality and poor neurodevelopmental

outcomes%

 The pathogenesis of &D is regarded as multifactorial'

including infectioninflammation' oxidative stress'

barotraumavolutrauma' genetic factors and the absence of

antenatal steroids %

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Introduction (cont.…)

 Recently' etterberg et al% proposed that early adrenal

insufficiency $as the basis of &D' based on their finding that

infants $ho subse*uently developed &D had significantly

lo$er cortisol secretion in response to adrenocorticotrophic

hormones than those $ithout &D%

 Based on these findings' glucocorticoids therapy has been

underta+en for prophylactic or therapeutic purposes for &D'

but its efficacy and safety have still not been fully clarified%

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  Treatment protocol :

 DART protocol:

(IV/PO) Deamet!asone"

"%",- mg+g per dose every ./ hourly for first 0 days'

  "%"- mg+g per dose every ./ hourly for 0 days'

  "%"/- mg+g per dose every ./ hourly for / days'   "%". mg+g per dose every ./ hourly for / days'

Bet$een Day , and Day .! of life%

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  Treatment protocol (Ctd….):

#$drocortisone1 started at - mg+gday for 0 days' $ith

$eaning over , to ." days% 2f no response by / to 0 days' stop treatment%

 3s per the recommendations of the /"." 3merican 3cademy of Pediatrics 1 4"%/ mg+gday) of Deamet!asone (in babies

$ho remain ventilator dependent after .5/ $ee+s of age)%

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Benefits:

 2n early trials' treatment $ith glucocorticoids (usually

dexamethasone) in infants' $ho remained ventilator dependent for /

to 0 $ee+s' resulted in increased rs (Dynamic compliance) '

decreased Rrs ( Respiratory system Resistance)' diminished 6/  re*uirement and earlier extubation%

 Ho$ever' treatment $ith glucocorticoids does not appear to have a substantial impact on long7term pulmonary outcomes' such as

duration of supplemental 6/ re*uirement' length of hospital stay or

mortality%

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  Benefits:

(Ctd…)  8ubse*uent trials of earlier treatment' recurrent pulses and

lo$er doses have yielded inconsistent results as either a

prophylactic or attenuating agent%

 Randomi9ed trials of inhaled glucocorticoids also did not

demonstrate improved pulmonary outcome%

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  %!ort term %ide e&&ects o& 'lucocorticoids :

  Transient adrenal suppression

  :astric ulceration' 2ntestinal perforation

  :lucose 2ntolerance

  8ystemic Hypertension

  Transient catabolic state

  2ncreased ris+ of sepsis

  Hypertrophic ardiomyopathy

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  on term dra*+ac,s:

 2n addition to these short7term side effects' long7term follo$

up of infants treated $ith postnatal corticosteroids' primarily

dexamethasone' has raised concerns about impairedneurodevelopement and gro$th%

 Because of this potential harm and lac+ of $ell7established long7term benefit' routine use of corticosteroids is

discouraged and reserved only for infants $ith progressive

respiratory failure that is refractory to all other therapies%

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  -idence

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  Mec!anism o& action :  Preterm infants $ho are given postnatal corticosteroids

demonstrate some decreased inflammatory mar+ers and

suppression of cyto+ine7mediated inflammatory reactions in their

tracheal aspirates ( :ronec+ et al' .;;0)%

 Proposed T!eories 1 The potential for increased surfactant

synthesis' enhanced

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  Mec!anism o& action (Ctd…..) :

 These potential benefits are balanced against the +no$ledge that

dexamethasone results in persistent decrease in alveolar

numbers in animal models (Massaro and Massaro' /""")%

 linical studies have demonstrated acute improvements in

dynamic compliance and pulmonary resistance after treatment

$ith postnatal corticosteroids' although small follo$7up studies

have demonstrated no differences in respiratory morbidity despite

fe$er children $ith abnormal pulmonary function at = - years of

age (>ixon et al' /"",)%

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  Timin o& e&&ect :

Based on t$o meta7analyses of treatment before and after , days of

age (Halliday et al' /"";a' /"";b)' postnatal dexamethasone has

similar beneficial effects on death or BPD at 0? $ee+s (RR "%,/ to "%,[email protected]

;-# 2s $ithin "%?.' "%A- for both treatment intervals) and decreased

need for mechanical ventilation' $ith no significant impact on survival to

hospital discharge%

The aggregation of studies comparing hydrocortisone administered in

the .st $ee+ of life to placebo demonstrates no effects on mortality or

BPD%

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!ic! +a+ies0  Potential criteria for treatment $ould be i6/ ="%?"' mean air$ay pressure

=./ to .! cm H/6 and age = , days%

  3t minimum' infants $ho might be candidates for dexamethasone therapy $ould be those $ith severe' persistent disease' treated under a protocol

$ith a short exposure (0 days)' $ith dosing initiated at 4 "%/- mg+gday

and after informing the family of the short and long7term effects%

 2nterestingly' alsh et al (/""? b) reported decreasing postnatal corticosteroids rates in three maCor >orth 3merican neonatal net$or+s

from /"". to /""0' follo$ing the societies statement' $ith no concurrent

change in the rate of BPD%

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  -idence reardin %teroid Aderse e&&ects

 MaCor concerns 1 Hypertension' Hyperglycemia' Hypertrophic

cardiomyopathy' 3drenal suppression and Decreased gro$th%

 ith administration of postnatal corticosteroids in the .st $ee+ of

life' the ris+ of gastrointestinal perforation is significantly

increased' regardless of $hich steroid is administered (RR1 .%[email protected] ;-# 21 .%00' /%!A)%This effect may be associated $ith concurrent

administration of indomethacin%

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  %ide e&&ects :(Ctd……)

 2ndividual studies have reported an increased ris+ of later cerebral

palsy (P) in children $ith dexamethasone in infancy (8hin$ell et

al' /"""@ Eeh et al' .;;A)%

 The meta7analyses support this concern $ith dexamethasone

initiated in the .st $ee+ of life ($ith no effect seen $ith

Hydrocortisone)' although the relationship $as not statistically

significant $hen treatment is initiated after , days of age (Halliday

et al' /"";a'/"";b)%

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  %ide e&&ects :(Ctd……)

 The lac+ of substantial beneficial effects and the concern

regarding adverse effects led the 3merican 3cademy of Pediatrics

and anadian Pediatric 8ociety to recommend against any routine

use of postnatal dexamethasone in /""/ (ommittee on the fetus

and ne$born' /""/)

  3 more recent assessment' $hile ac+no$ledging the uncertainty

around specific outcomes' does illustrate the overlap bet$een the number needed to treat ( prevent BPD) and the number needed to

harm (cause P) for early dexamethasone treatment (8chmidt et

al' /""A

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  %ide e&&ects : (Ctd……)

 This is further supported by an independent meta7analysis

(8hin$ell and Fventov7riedman'/"";)' demonstrating

significantly increased ris+ of neuro7developemental impairment

(>D2) and P $ith any dexamethasone exposure and a large cohort study demonstrating a dose7dependent increased ris+ of

death or >D2 at .A to // months corrected age' regardless of

postmen