INDIAN PEDIATRICS VOLUME 35-FEBRUAKY 1998

ROLE OF EARLY POSTNATAL DEXAMETHASONE IN

RESPIRATORY DISTRESS SYNDROME
Kanya Mukhopadhyay, Praveen Kumar and Anil Narang
From the Division of Neonatology, Department of Pediatrics, Postgraduate Institute of Medical
Education and Research, Chandigarh 160 012.

Reprint requests: Dr. Anil Narang, Additional Professor, Head, Neonatology Division,
Department of Pediatrics, PGIMER, Chandigarh 160 012.

Manuscript received: June 5,1997; Initial review completed: July 31,1997;

Revision accepted: September 23,1997.

Objective: To study the effect of early postnatal dexamethasone therapy on severity of hyaline
membrane disease. Design: Prospective, randomized, controlled, unblinded study.
Setting: Neonatal Intensive Care Unit. Methods: 19 babies who had hyaline membrane disease
were included in this study. The inclusion criteria were clinical and radiographic diagnosis of
RDS, requiring mechanical ventilation and FiO2 >0.3. Ten babies received injection
dexamethasone 0.5 mg/kg/dose 12 hourly for 3 days starting within 6 hours of birth. The control
group did not receive any drug. Babies with active infection, bleeding tendency and congenital
malformation were excluded. None of the babies received surfactant. The duration of ventilation
and AaDO2 and FiO2 requirements from day one to five were calculated. Results: The initial
AaDO2 were similar in both the groups but on day 3, 4, 5 AaDO2 were low in study group (201,
85, 70) compared to control group (236, 209, 162). The initial FiO2 were 0.66 and 0.63 in
dexamethasone and control groups, respectively and remained high till day 2 and came down in
study group on days 3, 4 and 5 (0.41, 0.27, 0.27) compared to control group (0.53, 0.34, 0.42).
The mean duration of ventilation was shorter in dexamethasone group (87 hours) vs control
group (120 hours). Conclusion: Early use of postnatal dexamethasone reduces the disease
severity and oxygen requirement in RDS and hence would be useful in the Indian context.

Key words: Alveolar arterial oxygen gradient, C-reactive protein, Fraction of inspired oxygen,
Respiratory distress syndrome.

M ORTALITY and morbidity related to

hyaline membrane disease (HMD) is
high in our country. Surfactant is the well
shown to improve short term lung
function(l,2). We report a prospective,
randomized, controlled trial of early post-
established modality of therapy in HMD in natal dexamethasone treatment in preterm
West. However, the cost is a prohibitive babies with HMD.
factor for routine use in our country. On Subjects and Methods
the other hand many mothers may report
too late in labor making antenatal steroid This study was conducted in the Neo-
ineffective or may have a contraindication natal Intensive Care Unit at PGIMER,
to postpone the delivery, e.g., antepartum Chandigarh over 6 months period (from
hemorrhage, eclampsia, etc. Glucocorti- February 1996 to July 1996). Infants of less
coids administered postnatally have been than 34 weeks and less than 2000 grams

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MUKHOPADHYAY ET AL. POSTNATAL DEXAMETHASONE & RDS

who could be provided ventilation were tension, hyperglycemia, Gl bleeding) were

included in the study. The inclusion also recorded.
criteria were: clinical (retraction, grunt,
poor air entry) and radiographic (bilateral The primary outcome measures were:
reticulo-granular or whiteout appearance) (i) Duration of ventilation; (ii) Disease se-
evidence of respiratory distress syndrome verity as measured by: (a) AaDO2 = {FiO2 x
(RDS), requiring mechanical ventilation (760-47)-PACO2-PaO2} and (b) Oxygen re-
and FiO 2 > 0.3. Babies with evidence quirement. Statistical analysis was done by
of infection, e.g., history of chorioamnio- using Student's "t" test for comparison of
nitis in mother and any two positive rapid means of continuous variables.
diagnostic tests (micro-ESR, CRP, absolute Results
neutrophil count and gastric aspirate for
Forty three babies developed HMD
polymorphs) in the baby were excluded.
during the study period who were less
Presence of bleeding in the baby and con-
than 34 weeks and 2000 grams but only 28
genital malformations were also taken as
could be provided ventilation. Eight babies
exclusion criteria. were excluded subsequently due to
After initial stabilization, the babies nonavailability of blood gases due to tech-
were randomly assigned to either dexa- nical fault and 1 baby who had complete
methasone or control group. The study congenital heart block was also excluded.
group received injection dexamthasone So a total of 19 babies were studied of
starting within 6 hours of birth in a whom 10 babies received injection
dose of 0.5 mg/kg/dose 12 hourly for 3 dexamethasone and 9 babies did not re-
days. The control group did not receive ceive any steroid. Table I shows the baseline
any drug. No baby received surfactant. All characteristics of two groups. No signifi-
babies received intermittent mandatory cant difference was found except that the
ventilation (IMV). Ventilatory and other control group had more males. The mean
managements of these babies were done Apgar score at 5 minutes and per cent of
as per the unit protocol by the treating babies receiving antenatal steroid were
physician. similar. The initial severity of disease is
shown in Table II. There was no significant
Data collection included baseline difference between two groups.
patient characteristics (birth weight, gesta-
tional age, sex, Apgar score), obstetric data, The initial AaDO2 were similar and re-
use of antenatal steroid, severity of initial mained so till 48 hours but on days 3, 4 and
disease (age at mechanical ventilation, ini- 5, AaDO2 were low in the study group; the
tial AaDO2, initial FiO2 (fraction of inspired values on the consecutive days being 201,
oxygen) maximum AaDO2 (alveolar arterial 85, 70 and 236, 209, 162 in the dexa and
oxygen gradient) and age at maximum control groups, respectively (Fig. 1). How-
AaDO2), AaDO2 and oxygen requirement ever, the differences were statistically not
from day one to five. AaDO2 and FiO2 were significant (p>0.05). The initial FiO2 were
calculated in the beginning of ventilation 0.66 and 0.63 in dexamethasone and con-
and subsequently at the end of 24 hours, 48 trol groups, respectively and remained
hours, 72 hours and at the end of 4th and high in both the groups till day 2 and FiO2
5th day. Mortality rate, incidence of sepsis, requirement came down in study group on
patent ductus arteriosus (PDA), pneumo- days 3, 4 and 5 (0.41, 0.27, 0.27) compared
thoraces and side effects of steroid (hyper- to control group (0.53, 0.34, 0.42) (Fig. 2)

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INDIAN PEDIATRICS VOLUME 35-FEBRUARY 1998

group and 55% in control group. Four ba-

though the differences were statistically not bies died in dexamethasone group within 4
significant (p>0.05). FiO2 and AaDCX, at the days due to pneumothorax. In the control
points of study were the lowest values group 2 babies died due to pneumothorax,
achieved on that day. 1 due to persistent hypoxia and one due to
grade 4 intraventricular hemorrhage. Two
Mean duration of ventilation was short- babies in each group died subsequently
er in dexamethasone group (87±42 hours) after 7 days due to sepsis.
vs control group (120±46 hours). One baby
in dexamethasone group needed reventila- Discussion
tion at 32 hours of life who was initially Alveolar-arterial oxygen gradient
extubated at 22 hours of life. Only 1 had (AaDO2) is used as an indicator of disease
culture positive sepsis in dexamethasone severity(3) which quantifies the O2 gradient
group and 2 in control group. Dexa- between alveoli and blood and indicates
methasone did not produce any significant the level of gas exchange through the
side effect. Three babies in dexamethasone lungs. We used AaDO2 and FiO2 require-
group and 1 baby in control group had ment as clinical indicators of disease severi-
PDA. None of the babies had ty. Though mean airway pressure (MAP)
bronchopulmonary dysplasia (BPD). can be used as a parameter for assessing
Four babies had pneumothorax in the severity of disease, AaDO2 and oxygen-
dexamethasone group and 3 in control ation index are considered better means of
group. Pneumothorax developed at a assessing the disease severity(3). In con-
significantly lower pressure in dexa- ventional ventilation, higher positive end
methasone group compared to the control expiratory pressure (PEEP) is used by some
group. There was no significant difference which results in higher mean airway
of pressure in the dexamethasone group pressure (MAP), but this may not be entire-
who had pneumothorax compared to those ly indicative of disease severity.
who did not have pneumothorax (Table III). Our study shows that dexamethasone
In the control group, pneumothorax administration to preterm babies with RDS
occurred only when babies received signifi- decreased the disease severity starting
cantly higher pressure. from day 3 till day 5 as compared to un-
Overall survival was 60% in treated treated group. The treated group required

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INDIAN PEDIATRICS VOLUME 35-FEBRUARY 1998

improved survival and shorter duration of

hospital stay. In 1996, a multicenter trial(7)
used a three day postnatal dexamethasone
trial in RDS and showed that there was re-
duction in requirement of ventilation at 3
days in the treated group. Though none of
our babies had BPD, the present study was
focussed on the initial one week differences
due to dexamethasone therapy.
We conclude that use of steroid had
some beneficial effect during the first 5
less oxygen and less hours of ventilation days of life and in Indian set up when sur-
than the control group. factant is still not available to us for routine
The mechanism proposed for the im- use, this modality of therapy should be of-
provement of lung function after dexa- fered. However, our number of patients are
methasone therapy are increase in surfac- too small and hence a multicenter trial with
tant synthesis and its secretion(4) and a larger number of patients is required
decrease in inflammatory changes in venti- before recommending it for routine use.
lated lungs(5). Previous reports of the use
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MUKHOPADHYAY ET AL. POSTNATAL DEXAMETHASONE & RDS

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