Steroids Final - Postnatal

8/15/2019 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 infectioninflammation' oxidative stress'

barotraumavolutrauma' 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) Deamet!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+gday for 0 days' $ith

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

3s per the recommendations of the /"." 3merican 3cademyof Pediatrics 1 4"%/ mg+gday) of Deamet!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 asubstantial 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 $ell7establishedlong7term 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 "%,0@

;-# 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+gday

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

2nterestingly' alsh et al (/""? b) reported decreasing postnatalcorticosteroids 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 reardin %teroid Aderse 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 .%A.@;-# 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 thenumber 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 Fventov7riedman'/"";)' demonstrating

significantly increased ris+ of neuro7developemental impairment

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

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

postmenstrual age at the time of dexamethasone exposure

(ilson7ostello et al' /"";)%

Thus' the avoidance of postnatal dexamethasone is prudent'

given $hat is +no$n about the ris+s and benefits and there are

significant data to support the use of any other systemic steroid

at this point in time%


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In!aled steroids:

3lthough inhaled steroids initiated in the first / $ee+s of life have been

studied for prevention of BPD' there are no data suggesting either immediate

or later clinical improvement $ith this intervention' although there is a trend

to$ard decreased systemic steroid use in these infants (8hah et al' /"",)%

3 pilot study of budesonide $ith beractant (8urvanta' 3bbot' olumbus' 6hio)

compared to beractant alone for treatment of RD8 resulted in a significantly

lo$er rate of death or BPD at 0? $ee+s (0/# vs% ?.#)' $ithout evidence of

substantial adverse effects (Eeh et al' /""A)%

These findings are some$hat surprising' given that the maCority of infants

received only a single dose of study medication%


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Ot!er

Indications


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1se prior to etu+ation :

8ome babies $ith RD8 $ho re*uire intubation can develop lung

inCury and inflammation and become dependent on ventilator%

Dexamethasone is effective at facilitating extubation and

reducing BPD but is associated $ith significant long7term

adverse effects' including an increased ris+ of cerebral palsy

$hen used during the first $ee+ of life%

The greater the ris+ of BPD' then the more li+ely it is that

benefits of steroids $ill out$eigh the ris+s %


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Reime prior to etu+ation

: Three doses of Dexamethasone G "%/- mg+gdose every ./

hours starting A to ./ hours before the next extubation%

(or attenuation of postextubation air$ay edema' $ith stridorous

obstruction leading to respiratory failure)

There is also evidence from case series that much lo$er doses

of dexamethasone ("%"- mg+gday) might be effective infacilitating extubation%

3 rapid tapering course of 2 Dexamethasone' starting at "%/-

mg+gday and lasting for -7, days' $as advised%


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1se prior to etu+ation (Ctd….) :

3lthough this regimen has not been tested in clinical trials' a short

course and relatively lo$ dose of hydrocortisone has been used

successfully to potentially reduce ventilator settings and facilitate

extubation as it is claimed to have less potential for adverse

effects%

2nhaled Betamethasone does not prevent BPD but does decrease

the need for systemic steroids and facilitate earlier extubation ofventilated infants $ith BPD%


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Rescue lucocorticosteroid t!erap$ &or

Re&ractor$ #$potension:

Refractory hypotension commonly occurs in premature ne$borns

and is associated $ith a high mortality rate' an increased

incidence of intraventricular hemorrhage and periventricularleu+omalacia and poor neurodevelopmental outcomes%

onsider lo$ dose hydrocortisone ( G 0 mg+gday) for /7- days in three

divided doses)

8tudies support the efficacy of Hydrocortisone in raising BP $ithin / hours of

administration' yet the long term neurologic effects of this treatment in &Bs

remain to be investigated%


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-idence:

There are several retrospective trials regarding rescue glucocorticosteroid

therapy to treat neonatal refractory hypotension% Ho$ever' there are

insufficient numbers of $ell7designed randomi9ed controlled trials (RTs)

regarding glucocorticosteroid therapy for refractory hypotension in

preterms%

3mong the four RTs included in a recent ochrane Revie$ ' :aissmaier

et al% used dexamethasone (DFI) and >g et al% used hydrocortisone' are

intended to treat early neonatal refractory hypotension by glucocorticoid

therapy% The authors in both of the trials concluded that glucocorticoid

therapy significantly reduced the use of inotropes in the management of

refractory hypotension% Ho$ever' their study designs $ere not sufficient to

determine the safety of rescue use of glucocorticoid%


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-idence (Ctd…..) :

ith regard to studies using hydrocortisone as the primary

treatment of hypotension (not for hypotension unresponsive to

inotropes)' Bourchier et al% compared hydrocortisone versusdopamine in a randomi9ed controlled manner $ith a relatively

small sample si9e' and found no significant advantage of

hydrocortisone against dopamine use%


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In Meconium Aspiration %$ndrome :

The use of corticosteroids in M38 is generally not recommended

although this approach has been proposed to reduceinflammation induced by meconium and minimi9e prostaglandin7

mediated pulmonary vasoconstriction%


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In re&ractor$ !$pol$cemia :

Hydrocortisone (G- mg+gday) is generally indicated $hen

neonate cannot maintain its glucose levels $ithin normal range

despite receiving :DR of ./7.- mg+gmin%

2t reduces peripheral glucose utili9ation' increase

gluconeogenesis and increases the effects of glucagon%

Before administrating Hydrocortisone' it is important that a cortisol

level be dra$n and sent to the laboratory%


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Ta,e !ome messae :

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 othertherapies in BPD%

The steroids may be used routinely prior to extubation but only in

cases of refractory hypotension' refractory hypoglycemia (notresponding to multiple drugs) and generally not recommended in

meconium aspiration syndrome%


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Ta,e !ome messae : (Ctd…)

There are significant data to support the use of systemic

steroids at this point in time hence' these should be preferred

over inhaled steroids%

The steroid treatment should be given after , days of life to

minimi9e the potential adverse effects%


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Steroids Final - Postnatal