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

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