use of early nasal continuous positive airway …
TRANSCRIPT
USE OF EARLY NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN PRETERM NEONATES
WITH HYALINE MEMBRANE DISEASE (NEONATAL RESPIRATORY DISTRESS
SYNDROME)
By Dr. NAZEER AHMAD
Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
In partial fulfillment of the requirements for the degree of
DOCTOR OF MEDICINE in
PAEDIATRICS
Under the Guidance of Dr.H.VEERBHADRAPPA
M.D. (Paed)
Professor
DEPARTMENT OF PAEDIATRICS M.R. MEDICAL COLLEGE, GULBARGA-585 105
2009
i
ii
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation entitled “USE OF EARLY
NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN PRETERM
NEONATES WITH HYALINE MEMBRANE DISEASE (NEONATAL
RESPIRATORY DISTRESS SYNDROME)” is a bonafide and genuine
research work carried out by me under the guidance of
Dr.H.VEERBHADRAPPA, Professor, Dept. of Paediatrics.
Date:
Place: GULBARGA Dr. NAZEER AHMAD
i
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation entitled “USE OF EARLY
NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN PRETERM
NEONATES WITH HYALINE MEMBRANE DISEASE (NEONATAL
RESPIRATORY DISTRESS SYNDROME)” is a bonafide research work
done by Dr. NAZEER AHMAD in partial fulfillment of the requirement
for the degree of DOCTOR OF MEDICINE in PAEDIATRICS.
Date:
Place: GULBARGA Dr.H.VEERBHADRAPPA Professor Dept. of Paediatrics, M.R. Medical College, Gulbarga
ii
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
ENDORSEMENT BY THE HOD, PRINCIPAL/ HEAD OF THE INSTITUTION
This is to certify that the dissertation entitled “USE OF
EARLY NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN
PRETERM NEONATES WITH HYALINE MEMBRANE DISEASE
(NEONATAL RESPIRATORY DISTRESS SYNDROME)” is a bonafide
research work done by Dr.NAZEER AHMAD under the guidance of
Dr.H.VEERBHADRAPPA Professor, Department of Paediatrics.
Dr.Shrikant.S.W, MD, Dr.Mallikarjun B. Prof. & Head of the Dept. Principal & Dean Dept. of Paediatrics M.R. Medical College, Gulbarga Date: Date:
Place: GULBARGA Place: GULBARGA
iii
COPYRIGHT
DECLARATION BY THE CANDIDATE
I here by declare that the Rajiv Gandhi University of
Health Sciences, Karnataka shall have the rights to
preserve, use and disseminate this dissertation in print or
electronic format for academic/ research purpose.
Date:
Place: GULBARGA Dr.NAZEER AHMAD
© Rajiv Gandhi University of Health Sciences, Karnataka.
iv
ACKNOWLEDGEMENT
With a deep sense of gratitude and thankfulness, I acknowledge my indebtedness to my reverend and learned teacher Dr.H.Veerbhadrappa, Professor, Department of Paediatrics, M.R. Medical College, Gulbarga for his constant guidance and encouragement throughout my post-graduate career and for his kind help and guidance given to me right from the selection of the topic till the completion of this dissertation, without which this work would not have been completed. Its my privilege to have worked under the able guidance and supervision of my respected teacher Dr.Shrikant.S.W, Professor & HOD, Department of Paediatrics, M.R. Medical College, Gulbarga. I pay my respect and thanks for his keen interest in the study and his guidance for the preparation of this dissertation. I gratefully acknowledge the kind permission granted by Dr.Mallikarjun B., Dean., M.R.Medical College, Gulbarga to carry out the present study. My sincere thanks to I take this opportunity to extend my sincere thanks to my beloved teachers Dr.G.D.Sidhram, Professor for his guidance during my study. I am also thankful to Dr.Shivanand B., Dr.Sharangowda Patil, Dr.Basawaraj Patil, Dr.Roopa M, Dr.Arundhati Patil, Dr.Rohit Bhandar, Dr.Sandeep V.H., Dr.Prabhushetty, Dr.Darshan Singh Thakur, Dr.Govind Malu, Dr.Shivakumar Sangolgi for their help during my study. I remain grateful to my friends especially and my colleagues for their support and encouragement during the course of this dissertation and for excellent cooperation at all times. I would be failing in my duties, if I would not mention my gratitude to my beloved parents, my brothers, sisters and other family members for their constant support, prayers, encouragement and inspiration throughout my career. And finally, I thank the Almighty for making all these wonderful people happen to me and pray for continued benison and fruition. Date:
Place: Dr.Nazeer Ahmad
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LIST OF ABBREVIATIONS USED
BPD......................Bronchopulmonary dysplasia
CDP......................Continuous distending pressure
CLD......................Chronic lung disease
CNP......................Continuous negative pressure
CPAP....................Continuous positive airway pressure
ELBW ..................Extremely low birth weight
ET.........................Endotracheal tube
FRC......................Functional residual capacity
HMD ....................Hyaline membrane disease
IFD .......................Infant Flow Driver
IPPV.....................Intermittent positive pressure ventilation
MV .......................Mechanical Ventilation
NNPD...................National Neonatal Perinatal Database
PDA......................Patent ductus arteriosus
PEEP ....................Positive end expiratory pressure
RDS......................Respiratory distress syndrome
SAS ......................Silverman-Anderson Score
VLBW..................Very low birth weight
vi
ABSTRACT
Background & Objective: Mechanical ventilation is the standard treatment for hyaline membrane disease (HMD) and has increased neonatal survival. However this increased survival has come at the expense of increased morbidity in the form of chronic lung disease, longer duration of hospital stay and at the cost of expensive technology. Alternate form of respiratory support is early nasal CPAP. Hence present study aims at managing increasing number of preterm babies with HMD with a non-invasive approach in the form of early nasal CPAP. Methods: 50 babies of 28-34 weeks gestational age admitted in Neonatal ICU of Basaveshwar & Sangameshwar Teaching & General Hospital, Gulbarga, with clinical diagnosis of HMD, requiring respiratory support were treated with early nasal CPAP and studied prospectively from 01.12.2007 to 31.05.2009. Statistical analysis: Chi-square and other appropriate tests. Results: We found a success rate of 80% in babies with HMD, who were managed with early nasal CPAP alone. Remaining 20% needed intubation and higher mode of ventilation. Mild and moderate grade HMD were effectively managed with early nasal CPAP (P<0.05). It was also found to be effective in babies of mothers who have received antenatal steroids (P<0.05). Conclusion: Prematurity is the commonest predisposing cause for HMD. Early nasal CPAP is safe, inexpensive and effective means of respiratory support in HMD. It is useful in mild and moderate grade disease. It may not be a replacement for assisted ventilation in severe disease. It is also found to be effective in babies of mothers who have received antenatal steroids. Key words: Hyaline membrane disease; Nasal CPAP.
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LIST OF CONTENTS
1. Introduction........................................................................01
2. Objectives ..........................................................................05
3. Review of Literature ..........................................................06
4. Methodology......................................................................40
5. Results................................................................................44
6. Discussion..........................................................................55
7. Summary ............................................................................62
8. Conclusion .........................................................................64
9. Bibliography ......................................................................65
10. Annexures ..........................................................................76
Proforma ............................................................................76
Master Chart.......................................................................80
viii
LIST OF TABLES
Sl. No. Title Page
No.
1. Advantages and Disadvantages of various CPAP Delivering Devices 25
2. Nasal CPAP treatment outcome among babies 45
3. Gender distribution of the study group 46
4. Distribution of babies based on gestation age and results 47
5. Distribution and outcome of babies based on birth weight 48
6. Distribution of mean age at the time of initiation of treatment 49
7. Mean duration of treatment (hours) in success and failure group 49
8. SA Score in study group before and after treatment 50
9. Distribution of SA score in study group before and after 6 hours treatment
51
10. Comparison of ABG parameters before and after treatment in success and failure group
52
11. Distribution of babies based on radiological grading of HMD and outcome
53
12. Antenatal steroids and outcome 54
13. Studies for outcome of HMD 55
14. Gender-wise distribution of success rate in HMD 56
15. Studies for outcome of HMD depending on gestational age 57
16. Studies for outcome of HMD depending on birth-weight 58
17. Studies for radiological outcome of HMD 60
18. Studies for outcome with use of antenatal steroids 61
ix
LIST OF FIGURES
Sl. No. Title Page
No.
1. Timeline for fetal and postnatal lung development that incorporates silent events in the development of airway and alveolar and vascular components
6
2. Composition of surfactant recovered by alveolar wash 8
3. Contributing factors in the pathogenesis of hyaline membrane disease
9
4. X-ray of a neonate with HMD showing reticulogranular pattern admitted in our NICU
10
5. A baby with HMD put on nasal CPAP in our NICU 32
6. Outcome of nCPAP treatment among study group 45
7. Gender distribution among success and failure group 46
8. Distribution of babies based on gestational age and results 47
9. Distribution of birth weight of the babies among success and failure group
48
10. Mean duration of treatment (hours) among success and failure group
49
11. Comparison of mean values of ABG parameters in success and failure group
52
12. Results of early nasal CPAP based on radiological appearance 53
13. Antenatal steroids and results 54
x
INTRODUCTION Neonatal respiratory distress syndrome (neonatal RDS), previously
called hyaline membrane disease, is a developmental disorder of mainly
preterm infants. Structural immaturity of the lungs, surfactant deficiency and
surfactant dysfunction are main problems of preterm newborns, leading to
respiratory distress. Despite of new preventive strategies neonatal RDS is still
the leading causes of mortality and morbidity in neonatal intensive care1.
Respiratory distress syndrome (RDS) is the single most important
cause of morbidity and mortality in infants. According to the year 2002-03
report of National neonatal Perinatal Database (NNPD)2 involving 151436
intramural deliveries, the incidence of RDS in our country was 1.3% of all live
births and it was the primary cause of death in 13.5%. The incidence of RDS
is inversely related to gestational age. In babies born at 28-32 weeks, RDS
occurs in up to 50% of live births3.
Intermittent positive pressure ventilation (IPPV) with surfactant is the
standard treatment for RDS. Initial attempts at artificial ventilation were done
with negative pressure ventilators and subsequently with intermittent positive
pressure ventilators. In 1960s, mechanical intermittent positive pressure
ventilation became widely accepted as the standard treatment of RDS in
newborn4. Although varying degrees of success was reported with assisted
ventilation as therapy for RDS, in all series mortality was high when infants
were less than 1500 grams or required ventilation before 24 hours of age5,6.
Therefore another method for improving oxygenation in infants with RDS was
1
sought and in 1971 Gregory et al7 used continuous positive airway pressure
(CPAP) in the treatment of idiopathic respiratory distress syndrome. It was
though that application of CPAP might overcome atelectasis and improve
arterial oxygenation. The effect of grunting respiration on arterial
oxygenation also suggested that CPAP might be useful. Infants who grunt
exhale against a partially closed glottis which increases transpulmonary
pressure and probably decreases or prevents atelectasis. If grunting is
prevented by insertion of endotracheal tube, arterial oxygen tension (PaO2)
decreases; however when tube is removed and grunting is resumed PaO2 rises.
This was welcomed as a missing link between the oxygen and ventilatory
therapy with great enthusiasm.
The major difficulty with IPPV is that it is invasive and contributes to
airway and lung injury including the development of chronic lung disease.
The advent of less invasive CPAP has permitted early treatment of RDS in
neonates with aims to intervene as early as possible and to avoid intubation
and reduced mucociliary flow and risk of mucosal injury or secondary
infection and to minimize volutrauma to the airways and lung parenchyma. In
1976 Wung et al8 stated that “introduction of continuous distending pressure
(CDP) was a major breakthrough and remained an important modality of
treatment in RDS”. This view was supported by number of studies which
indicate that early intervention with CDP might modify the course of illness
and lower the need for more aggressive therapy.
Continuous distending pressure (CDP) has been used for the
prevention and treatment of RDS as well as the prevention of apnea, and in
2
weaning from IPPV. CPAP results in progressive recruitment of alveoli,
inflates collapsed alveoli and reduces intrapulmonary shunt9,10. it increases
the FRC and inturn gaseous exchange. It reduces inspiratory resistance by
dilating the airways. This permits a larger tidal volume for a given pressure,
so reducing the work of breathing11. It reduces the compliance of very
compliant lungs and in these lungs, reduces the tidal volume and minute
volume. It regularizes and slows the respiratory rate. It increases the mean
airway pressure and improves ventilation perfusion mismatch. It conserves
surfactant on the alveolar surface12,13,14.
In extremely low birth weight babies (ELBW), the chest wall is very
complaint and tends to collapse with descent of diaphragm (paradoxical
respiration). This results in small and ineffective tidal volumes. CPAP helps
by splinting the chest wall and the airways, which increase in caliber. This
decreases the airway resistance and improves the ventilation of lung segments
supplied by airways. Thus, permitting a larger tidal volume for a given
pressure, thus reducing the work of breathing. The work of breathing is
further reduced by constant flow of gas directed to the patient does part of the
work. Furthermore, it has been shown that both inspiratory and expiratory
times increases with CPAP13,14.
CDP has been applied as a continuous positive airway pressure
(CPAP) or as a continuous negative pressure (CNP). CNP is applied
externally to the thorax using a negative pressure chamber with the seal
around the neck; it produces lung distension as a result of negative
intrathoracic pressure. CPAP is applied via a face mask, nasopharyngeal tube,
3
or nasal prongs, using a conventional ventilator, bubble circuit or CPAP
driver. Application of positive compared with negative pressure might have
different results in terms of effectiveness and complications.
Bubble CPAP is a newer CPAP delivering system. It is CPAP
delivered by CPAP system with underwater seal. It has been shown that
CPAP delivered by underwater seal causes vibration of the chest due to gas
flow under water, which is transmitted to infant’s airway. These vibrations
simulate waveforms produced by high frequency ventilation15. Bubble CPAP
has also been shown to reduce need for intubation and mechanical
ventilation16, postnatal steroids and trend towards decreased incidence of
chronic lung disease17. With an underwater blow off system, sufficient flow
creates continuous bubbling from the end of the underwater tube, placed at a
specified depth underwater, to ensure that circuit pressure is maintained. A
comparison of underwater bubble endotracheal (ET) CPAP with conventional
ventilator derived (ET) CPAP in preterm neonates suggests that such
oscillation contributes to gas exchange15. It is relatively a simple and
inexpensive way of generating CPAP. It also has the advantage that if there is
inadequate pressure owning to a large leak the bubbling can be seen to stop.
Present study is a hospital based study and aims at managing increased
number of babies with hyaline membrane disease with a non-invasive
approach in the form of early nasal CPAP.
4
OBJECTIVES
1. To find the incidence of premature neonates (less than 37 weeks) in
our hospital.
2. To find the incidence of hyaline membrane disease in premature
neonates with gestational age between 28-34 weeks.
3. To evaluate the effectiveness of early nasal CPAP in these premature
neonates with hyaline membrane disease.
5
REVIEW OF LITERATURE Hyaline Membrane Disease (Neonatal Respiratory Distress Syndrome)
Etiology/ Pathophysiology
Although prematurity is the main risk factor to develop HMD,
additional risk factors are: male sex, white race, twin pregnancy, maternal
diabetes, maternal pre-ecclampsia, delivery by cesarean section and prenatal
and perinatal asphyxia1.
Central in the pathogenesis of HMD are structural pulmonary
immaturity and immaturity of the surfactant metabolism.
Structural pulmonary immaturity can be expected after preterm birth,
because normal lung development occurs throughout pregnancy and continues
after birth till 2 to 3 years of age1,18.
Figure-1: Timeline for fetal and postnatal lung development that incorporates silent events in the development of airway and alveolar and
vascular components aa, vv, arteries, veins19
6
During the embryonic phase (0-7 weeks) the lung bud, stemming from
the embryonic foregut, undergoes repetitive branching to form the proximal
structures of the tracheo-bronchial tree. In the following pseudoglandular
phase (7-17 weeks) branching of the airways and concomitant blood vessels
continues. The forming of acinar structures (respiratory bronchioli, alveolar
ducts and primitive alveoli) takes place in the canalicular phase (17-27 weeks).
Only after 27 weeks of gestational age, in the saccular phase (28-36 weeks),
the peripheral airways enlarge and the gas-exchanging surface enlarges by
thinning of the arterial septa. The process of formation of definitive alveoli
continues from 36 weeks gestational age till 2 to 3 years after birth. Therefore
structural pulmonary immaturity leads to impaired diffusion of oxygen and
carbon dioxide, which leads, among others, to the clinical characteristics of
HMD.
In preterm infants the surfactant metabolism is also immature. In the
embryonic phase, undifferentiated columnar epithelium lines the airways.
During the canalicular phase differentiation of the epithelium in flat alveolar
type I cells, which line the alveolar surface and cuboid type II cells takes
place. From 20 weeks of gestational age the type II cells contain lamellar
bodies which are the intracellular storage places of surfactant. Surfactant
contains 70-80% phospholipids, about 10% protein and 10% neutral lipids.
The main phospholipid is phosphatidylcholine, in saturated form it is the most
important surface-active component of surfactant20.
7
Figure-2: Composition of surfactant recovered by alveolar wash21
Therefore phosphatidylcholine concentration in amniotic fluid is used
as marker for the amount of available active surfactant. During the second
half of gestation synthesis of surfactant increases linearly22.
From about 35 weeks of gestational age surfactant is released to the
alveoli by exocytosis from the type II cells and forms, after unraveling to
tubular myelin, a monolayer on the air-liquid interface. Catecholamines,
calcium and alveolar stretch stimulate release of surfactant23.
In term newborns an active re-uptake and recycling process of the
secreted surfactant takes place. Surfactant stabilizes the alveoli by decreasing
the surface tension at the air-liquid interface inside the alveoli and it plays an
important role in the water clearance from the alveoli. Another function of
surfactant lies in the host defense of the lungs24-26.
8
Surfactant deficiency will therefore lead to alveolar collapse and
atelectasis. Alveolar collapse leads to distension of the proximal airways
because they have a higher compliance. Over-distension of the proximal
airways injures the epithelium and causes necrosis of the airway epithelium
and desquamation. The resulting epithelial lesions allow leakage of proteins
into the small airways and alveolar space. Intra-alveolar proteins interfere
with the formation of the surfactant monolayer and can interfere with the
biophysical activities of surfactant27,28. This can lead to further alveolar
collapse and atelectasis.
Furthermore, the protein leakage also causes an increased osmotic
pressure in the alveolar spaces, attracting fluids or interfering with the normal
fluid clearance from the alveoli which will result in protein rich edema in the
alveoli. Therefore, HMD is a disease characterized by hampered diffusion,
alveolar collapse and pulmonary edema.
Figure-3: Contributing factors in the pathogenesis of hyaline membrane
disease29
9
Clinical Manifestations
Understanding the pathophysiology of HMD, one can explain the
typical clinical signs. Alveolar collapse results in a decrease of functional
residual capacity and leads to cyanosis of the patient. Progressive alveolar
collapse also causes a decrease of compliance of the lung. Clinically
intercostals retractions and tachypnea can appreciate this as the infant tries to
compensate for a low tidal volume and tries to maintain an adequate minute
volume. Expiratory grunting is an effort of the infant to avoid alveolar
collapse. The vocal cords are simultaneous closed, so that a resistance of the
expiratory flow is created that is counteracting alveolar collapse.
The chest X-ray of infants suffering from HMD is characterized by a
typical reticulogranular pattern with an air bronchogram, due to collapsed
alveoli and distended gas filled larger airways30. The more opaque the X-ray
the more severe the disease.
Figure-4: X-ray of a neonate with HMD showing reticulogranular pattern admitted in our NICU
10
Typical for HMD is that the clinical signs develop gradually in the first
hours after birth. It is assumed that breathing movements of the surfactant
deficient lung generate shear forces to the epithelium of the terminal
bronchioli, resulting in epithelial lesions. Subsequently fibrinogen and other
serum proteins leak through the epithelial lesions into the alveolar space.
These proteins inhibit surfactant function and hence cause progressive alveolar
collapse. Depending on the severity of the disease, respiratory failure occurs
and artificial ventilation is indicated. When the natural course proceeds
uncomplicated, respiratory signs diminish from the second to third day after
birth leading to recovery31,32.
However, complicated HMD will prolong the infant’s need for
ventilatory support with high oxygen concentrations and high inspiratory
pressure and may led to chronic lung disease and prolonged respiratory
support33.
Treatment
The treatment of HMD consists of general supportive care and specific
treatment that includes respiratory support for developing hypoxemia and
hypercapnia and the endotracheal supplementation of surfactant.
General Supportive care
The initial stabilization of the infant is critical; the smaller the infant
the more important this becomes. The infant should not be allowed to become
hypothermic, hypoglycemic or hypovolemic. Hypovolemia can be avoided by
not clamping the umbilical cord immediately after delivery. In this way the
11
risk of metabolic acidosis is reduced and hence the risk of pulmonary
vasoconstriction. Fluid administration is to be directed to meet insensible
water losses and urine production.
Specific Treatment
In mild cases with cyanosis as the only symptom of HMD,
predominantly in neonates born after a gestation of 32-36 weeks, the
administration of supplementary oxygen is sufficient to restore hypoxemia.
When the infant needs more than 30-40% oxygen to obtain adequate
oxygenation generally more features of HMD occur: tachypnea, inercostal
retraction, grunting and nasal flaring. Then the application of nasal
Continuous Positive Airway Pressure (CPAP) is indicated. Gregory et al7
introduced this therapy for neonates with HMD in 1971.
Infants born at a gestational age of less than 30 weeks are prone to
develop severe HMD and as the gestation is shorter, the risk for respiratory
failure is higher. For these patients mechanical ventilation is indicated. This
technique was initiated in the early years 1950. Introduction of polyvinyl
nasotracheal tubes by Brandstadter in 1962 eliminated the need for
tracheotomy and made mechanical ventilation a more feasible therapy34.
The most important development in the treatment of HMD is the
endotracheal instillation of surfactant. Since the discovery of Avery and Mead
that surfactant deficiency was a key factor in the pathogenesis of HMD, many
investigators were stimulated to find ways to supplement this missing
compound in the lung35.
12
In the year 1980 a large number of randomized clinical trials have been
published. The majority of these studies indicate that mortality of infants, who
are treated with surfactant, is reduced significantly. The impact on the
development of chronic lung disease is less clear. This therapy has become
routine treatment for HMD in developed countries all over the world.
With progress in neonatal care, including antenatal glucocorticoids,
surfactant and new ventilatory strategies, the preterm infants born after a
gestational age of 28 weeks, less frequently developed BPD.
Lung maturation is influenced by multiple factors. Antenatal
glucocorticoids induce structural maturation and induce the surfactant
system36,37.
Prevention
The best prevention of HMD would be the prevention of preterm birth.
Preventive strategies aiming at prevention of HMD after (inevitable) preterm
birth, have been directed at acceleration of lung maturation and maturation of
surfactant synthesis. Meta-analysis of antenatal glucocorticoid administration
to the mother has shown that this is really effective in reducing the incidence
and severity of HMD in preterm infants (over all odds ratio 0.5, 95%
confidence interval 0.40-0.65)38.
Glucocorticoids stimulate the production of surfactant proteins and
phospholipids. They also stimulate lung maturation by enhanced maturation
of cell differentiation, especially of type II cells and fibroblasts, by inhibition
13
of DNA synthesis and thereby inhibition of cell synthesis, but consequently
stimulation of cell differentiation. Glucocorticoids also cause a decrease in
interstitial tissue in the alveolar septa, which makes the alveolar septa thinner
which facilitates gas-exchange39.
Other preventive strategies have been tried, such as antenatal thyroid
releasing hormone administration40. Thyroid hormone increases synthesis of
surfactant phospholipids and accelerates structural development of the
connective tissue matrix of the lung41-43.
Recent multicenter trials showed no additional effects of antenatal
thyroid hormone administration to antenatal glucocorticoid administration or
postnatal surfactant administration40. Antenatal thyroid releasing hormone
still could be considered in those situations where surfactant is not available44.
EARLY NASAL CPAP:
Historical Background
Poultan and Oxan45 used positive pressure therapy in 1936 for acute
ventilatory insufficiency. They used facemask for positive pressure therapy.
Later it was abandoned when mechanical ventilation became feasible.
In 1960s mechanical intermittent positive pressure ventilation became
widely accepted as standard treatment of respiratory distress syndrome (RDS).
When it became evident that low volume was a consequence of the disease,
continuous distending pressure (CDP) was developed as a means of increasing
lung volume and improving oxygenation7. They applied CPAP to 20 infants
14
(birth weight 930-3800 grams) with idiopathic respiratory distress syndrome
through endotracheal tube (in 18 infants) and plastic pressure chamber (in 2
babies). They found no difference in the effects of CPAP applied through an
ET tube or by a plastic chamber. 17 of the 20 infants treated with CPAP
recovered from RDS. Arterial oxygenation increased in all infants after the
application of CPAP permitting to lower inspired oxygen concentration to an
average of 37.5% within 12 hours.
However, several workers utilized cautious approach to deliver CPAP
due to inherent risks of endotracheal tube.
In 1973 Agostino et al46 reported the first small series of infants with
RDS treated with nasal canula CPAP. This was based on the fact that most
infants were nasal breathers and would spontaneously form a seal between the
palate and tongue. In case of too high pressure the mouth could act as a
natural popoff valve. Over subsequent years variety of non-nasal CPAP
devices were developed including pressurized plastic bag fitted over infant’s
head47, face chamber48 and face masks49.
The role of CPAP in preterm infants with RDS has long been debated
in neonatal literature with early interest focused on a multicenter study by
Avery et al. Avery et al50 published a paper in 1987 that compared the
respiratory outcome in 1625 infants born with a birth weight between 700 and
1500 g from eight NICUs across North America. The incidence of CLD,
defined as need for oxygen at 28 days, was relatively consistent between seven
units but the rate was much lower in the eighth. This centre, Columbia
15
University Medical Center in New York City, appeared to have similar patient
demographics and the survival rate was comparable but they quite clearly had
better respiratory outcomes. Each of the eight centers was then asked to
describe their practices regarding respiratory management. Again, Columbia
stood out as being different from the rest. It was therefore reasonable to
hypothesize that their low incidence of CLD resulted from their unique
approach to respiratory support of very low birth weight neonates.
These distinctive elements of their approach included:
• The provision of nasal CPAP shortly after birth to any infant showing
signs of respiratory distress.
• Tolerance of a PaCO2 as high as 60 mm Hg before intubating
• For those babies requiring intubation and ventilation: the avoidance of
hyperventilation, prohibition of muscle relaxants and the supervision
of ventilatory management by one clinician.
Although it is not easy to tease out which aspects of the ‘Columbia
approach’ contributed most to the reduction in CLD, the avoidance of
endotracheal intubation and mechanical ventilation is likely to be one of the
most important elements, the early and liberal use of nasal CPAP being used
to achieve this.
Whereas CPAP was first introduced in the 1970s as a treatment for
preterm babies with established RDS or to facilitate extubation, the group at
Columbia and their disciples advocate the elective application of nasal CPAP
soon after birth. The rationale for this is that the CPAP will help to establish
16
the functional residual capacity and promote the release of surfactant, thereby
creating and maintaining an adequate air-liquid interface in the lung. They
allow the PaCO2 and FiO2 to rise, tolerate apnoeic spells and reserve
intubation for only those infants who demonstrate, without a doubt, that they
require ventilation to survive.
The first few minutes after birth represent the most profound period of
physiological adaptation that humans must undergo. The transition from intra-
uterine life requires major changes to the respiratory and circulatory systems
to allow a neonate to maintain adequate respiratory gas exchange without the
benefits of the placental circulation. Inflation of the lungs with air, the release
of surfactant, the establishment of functional residual capacity, the
reabsorption of lung liquid, increases in pulmonary blood flow and the
establishment of a regular respiratory pattern are necessary for successful
postnatal adaptation. Although any infant can have difficulty with these
complex processes, those born preterm are particularly vulnerable to
respiratory problems during this critical period. Within neonatal intensive
care units, these babies are often provided with various types of support to
compensate for inadequate respiratory drive, abnormalities in their surfactant
system and/ or difficulties with the reabsorption of lung liquid. Assisted
ventilation, continuous positive airway pressure (CPAP) and surfactant-
replacement therapy are often used to support lung expansion and adequate
gas exchange.
17
CPAP Delivering Devices
The goal of any CPAP delivering device is to prevent atelectasis and
airway closure. An ideal CPAP delivery system should include a patient
system interface that is easy and rapid to apply, remove and remain connected
to the airway, is non-traumatic to the neonate, efficiently maintains pressure at
the desired levels, allows easy humidification of gases and oxygen control, has
low resistance to breathing, minimal dead space, is easily sterilized and is safe
and cost effective.
Fundamentally the delivery of continuous positive airway pressure
requires three components:
1. Flow generation
2. An airway interface
3. A positive pressure system.
Flow Generation
Two major varieties exist; constant flow and variable flow (demand).
The flow generator usually also warms and humidifies the inhaled gases.
Constant flow is usually provided by an infant ventilator, which because it can
be used in two ways, may limit expenditure on hardware. Most often, the
amount of flow is set by the clinical team. Alternatively, variable flow
devices use a dedicated flow generator. Here the ‘expiratory’ limb of the
circuit is open to the atmosphere and the infant can draw extra gas from this
limb to support inspiratory efforts. This device has gained widespread
acceptance in Europe and North America. Despite the theoretical advantages
18
of the variable flow device, there are no consistent data showing clinical long-
term meaningful benefit over constant flow devices51.
Airway Interface
Different types of interfaces between the circuits and the infant’s
airway are in use: single prongs, binasal prongs (short and long),
nasopharyngeal prongs, endotracheal tubes, head boxes, pressurized plastic
bag, nasal cannulae and face masks. The most commonly used route today –
nasal CPAP, was introduced in the early 1970s. Nasal prongs are very easy to
apply and comparatively non-invasive to the airways. The infant can still be
nursed and handled with uninterrupted CPAP.
Non-nasal Devices
Endotracheal Tube
Gregory et al7 applied CPAP in 18 out of 20 patients through
endotracheal tube. An endotracheal tube bypasses the larynx so PEEP should
be applied to reduce loss of lung volume. Endotacheal CPAP may be used
just before extubation, to ensure the baby does not become apnoeic without
intermittent inflation.
Endotracheal CPAP should preferably not be used due to its
invasiveness and increased risk of infection. It increases the work of breathing
by increasing the resistance and baby can tire out.
Cochrane52 review 2003 was performed to study the results of
extubation from low-rate intermittent positive airway pressure versus
extubation after a trial of endotracheal continuous positive airway pressure in
19
intubated preterm infants. Results of the review shows direct extubation from
low rate ventilation is associated with a trend towards increased chance of
successful extubation when compared to extubation after a period of
endotracheal CPAP; RR 0.45 (0.19, 1.07), RD – 0.103 (-0.200, -0.006), NNT
10 (5,167).
Facemask
Rhodes and Hall49 studied the use of CPAP delivered by facemask in
infants with idiopathic RDS. A significant difference in survival (p<0.05) was
noted in treated compared with control patients. Complications were confined
to difficulties with mask fit and local skin care.
Facemask provides a positive pressure but it is difficult to get a good
seal on the baby’s face. Pressure is lost when the mask is removed. It is
difficult to use a nasogastric or orogastric tube.
Head Box with a Seal
Used first by Gregory et al7 (1971) to deliver CPAP in 2 out of 20
patients treated with CPAP. There was no difference between endotracheal
tube or pressure chamber. This is a head box which seals round the baby’s
neck and has a valve to control the pressure. It is difficult to get a good seal,
and there is poor access to the baby’s face. Attention to the face causes loss of
pressure, and the high gas flow cools the baby; it is also noisy.
Negative Pressure Box
This is a negative pressure cuirass around the baby’s chest and
abdomen. It is difficult to get a good seal, and there is poor access to the baby.
20
Handling the baby causes loss of pressure, and the high gas flow cools the
baby.
The use of tight-fitting facial masks and devices requiring a neck seal
declined as a consequence of serious complications associated with their
application, including an increased incidence of cerebellar hemorrhage53 and
post-hemorrhagic hydrocephalus54. Nasal devices remained popular as they
facilitated better access to the infants9.
Nasal CPAP Devices
Nasal CPAP is widely used for a range of neonatal respiratory
conditions. In Australia and New Zealand a massive upsurge in the popularity
of nasal CPAP has seen its use, increase four-fold over the past decade. It is
established as an effective method of preventing extubation failure, is used in
the management of apnea of prematurity, and is increasingly seen as an
alternative to intubation and ventilation for the treatment of respiratory distress
syndrome (RDS).
Devices in common use for the delivery of nasal CPAP include single
and double (binasal) prongs, nasal canula and long (nasopharyngeal) forms.
Nasal Prongs
This is the most effective and least unsatisfactory method of delivering
CPAP. As neonates are nose breathers, nasal CPAP is easily facilitated. One
or two prongs are inserted into the nostrils and attached to a ventilator or a
device for delivering CPAP.
21
Single versus Double Prong Devices
Single prong CPAP, using a cut down endotracheal tube, continues to
be used widely despite evidence of better results using short binasal devices.
A randomized trial in more mature preterm infants with early respiratory
distress reported better oxygenation, respiratory rate, and weaning success
with a short binasal device when compared with single prong nasopharyngeal
CPAP55.
There are several short binasal prongs available to the clinician
including the Argyle prong56, Hudson prong57,58, infant flow driver55 and
INCA prongs.
In vitro resistance of different devices used for the delivery of nasal
continuous positive airway pressure (NCPAP) were compared in neonates.
Flows of 4-8 liters/ min were passed through a selection of neonatal NCPAP
devices (single prong, Duotube, Argyle prong, Hudson prong, Infant Flow
Driver), and the resultant fall in pressure measured using a calibrated pressure
transducer. Study showed large variation in the potential fall in pressure using
different devices. Devices with short double prongs had the lowest resistance
to flow59.
Kamper J et al56 studied early treatment of idiopathic respiratory
distress syndrome using binasal continuous positive airway pressure at
department of pediatrics, Odense University Hospital, Denmark. During a 3-
year period (1979-81) 85 premature infants with idiopathic respiratory distress
(IRDS) were treated early with an easily applicable light weight CPAP-system
22
with a binasal tube and a gas jet. They used conservative criteria for ventilator
treatment. CPAP treatment was initiated as soon as a concentration of oxygen
in the inspired air of atleast 40% was needed to prevent PO2 values below 60
mm Hg and/or general cyanosis. The treatment proved sufficient in 18 out of
25 infants with a birth weight less than or equal to 1500 g and in 53 out of 60
infants with a birth weight greater than 1500 g. Seven infants developed
pneumothorax during CPAP treatment. Seventy-four infants survived all
without bronchopulmonary dysplasia. With the criteria used, early CPAP
proved effective in the majority of infants with idiopathic RDS.
Kamper J et al60 performed another study of early treatment with nasal
continuous positive airway pressure in very low-birth-weight infants at
Department of Pediatrics, Diagnostic Radiology, Odense University Hospital,
Denmark. During 1988 and 1989, a regional cohort of 81 infants with birth
weight less than 1501 g were treated with oxygen only (n=11), early
continuous positive airway pressure (CPAP) (n=68) or mechanical ventilation
from birth (n=2). They used an easily applicable light weight CPAP system
with nasal prongs and a gas jet supplemented with ventilator treatment if
necessary, but with conservative criteria for ventilator treatment with tolerance
of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom
were supported solely with CPAP or oxygen. No survivors had
bronchopulmonary dysplasia.
The results suggested that treatment by early CPAP with nasal prongs
with tolerance of high PCO2 may be effective and lenient in most infants more
than 25 weeks’ gestation.
23
In a prospective study from South Africa, Pieper et al61 conducted a
quasi-randomized control trial of CPAP for infants weighing between 775-
1160g who were denied access to NICU compared to the standard therapy of
headbox oxygen. Although the CPAP was initially placed by respiratory
therapists, the ongoing care was continued by nursing staff with no intensive
care or CPAP experience. The infants who received CPAP in these
circumstances had a significantly improved short-term survival (at 24 hours),
with trends towards improved long-term survival.
Nasal Cannulae
Nasal cannulae are used to deliver oxygen into the nose at low flow,
usually with no intention of generating positive pressures in the airway.
However, nasal cannulae with an outer diameter of 3 mm and flows up to 2
liter/min, have been reported to deliver CPAP62. A study of CPAP via nasal
cannulae found it as effective in the treatment of apnoea of prematurity as
conventional CPAP prongs63. No studies have examined its role in the
treatment of RDS or in the post-extubation settings. It has been shown that
CPAP pressures are unlikely to be delivered effectively to the airway, because
flows used are low and leaks around the cannulae are large. Monitoring of the
pressure generated by a given flow and achieving adequate humidity are
problematic.
Nasal Masks
Nasal masks were an early means of applying CPAP to neonates64.
They lost favour because of the difficulty in maintaining an adequate seal and
24
a tendency to obstruct the nasal airway65. Recently a new generation of nasal
masks have been developed which anecdotally have been noted to deliver
CPAP effectively while causing minimal nasal trauma. These promising
devices have not yet been subject to proper clinical comparisons with nasal
prongs.
Nasopharyngeal Prongs
Prongs inserted up to nasopharyngeal level has been shown to deliver
effective CPAP66. They received early criticism because they were perceived
to be poorly tolerated and difficult to insert46. However, nasopharyngeal
prongs were continued to be used and featured in trial, which examined
binasal67 and single forms68.
Table-1: Advantages and Disadvantages of various CPAP
Delivering Devices
Method Advantages Disadvantages Endotracheal tube Patent airway, easy
attachment to respirator; easily stabilized and controlled
Complications associated with intubation, high airway resistance.
Head box Easy to apply; eliminates intubation
Leaks, compression of neck vessels, tissue necrosis and infant accessibility is difficult
Mask Easy to apply and eliminates intubation
Leaks, dangers of aspiration, CO2 retention if flow is inadequate
Nasopharyngeal tube Easily inserted and eliminates intubation
Loss of PEEP; high airway resistance, abdominal distention from swallowed air
Nasal prongs Easy to apply; flexible and infants position can be changed. Eliminates intubation, low airway resistance.
Nasal septum erosion and necrosis; abdominal distension from swallowed air
25
Circuit for Flow of Inspiratory Gases
Oxygen and compressed air sources provide the required inspired
gases and oxygen blender enables to deliver appropriate FiO2. The rate of
flow of inspired gases is controlled by a flow meter. The amount of gas flow
through the CPAP circuit is important. Insufficient set flow limits the flow
available for inspiration, increasing airway pressure fluctuation, and raising
the work of breathing. The flow required is affected by the degree of ‘leak’ of
gas from the infants’s nose and mouth. If the mouth is open the pressure in
the pharynx will fall and the flow will need to be increased to maintain it. If
the mouth is tightly closed and the nasal prongs are a good fit (that is, minimal
‘leak’) the flow reqired will be less. The flow required and its dynamics are
also affected by the system used to generate the CPAP.
The bubble CPAP pressure generating system used in our study has the
advantage that the adequacy of flow can be seen and heard. If the leak is high
the flow causing the bubbling is too low and the bubbling stops. If the flow is
too high the bubbling becomes very vigorous.
The minimum flow rate should be two and half times the infants
minute ventilation and should also compensate for the inherent leaks around
the apparatus. Usually flow rates of 5 to 10 liters per minute is sufficient. The
gases should be humidified prior to delivery to the infant.
26
Positive Pressure System
Infant Flow Driver System
Infant flow driver system uses ‘fluidic flip’ mechanism, which is
claimed to provide a more stable CPAP throughout the respiratory cycle (both
inspiration and expiration) so that there is less variation in airway pressure69.
Altering the flow into the CPAP device directly changes the delivered pressure
with the IFD. It needs flows in excess of 8 liters/ min to generate pressures
around 5 cm H2O. The actual flow delivered to the airway and the effect of
leaks, using ‘variable flow’ devices such as the IFD, has not been studied.
The ‘expiratory’ limb of the IFD is unusual among CPAP devices in
that it is open to the atmosphere. Potentially, the baby can inspire with a
higher flow than that delivered through the inspiratory limb. This extra gas
can be drawn from the expiratory limb (‘variable flow’). This reduces the
possibility of the pressure falling with large inspirations and therefore may
reduce the work the baby expends to take large breaths.
Mazzella et al56 have shown superiority of IFD over nasal CPAP in
terms of decreased oxygen requirement and respiratory rates and lesser need
for mechanical ventilation. Babies who failed nasal CPAP could be rescued
by IFD and mechanical ventilation could be avoided. IFD treated patients also
had higher extubation rates, shorter duration of ventilation and fewer
extubation failures. However, others have not observed this superiority of IFD
over NCPAP70.
27
Benveniste Device
The Benveniste device71 requires high gas flows with up to 14 liter/
minute to generate pharyngeal pressures of between 3 and 10.5 cm H2O.
Comparisons with other flow sources for CPAP generation are lacking. As
with the IFD, altering the flow to the Benveniste device directly alters the
pressure at the level of the attached nasal prongs. Benveniste device in
conjunction with a binasal tube has been shown a simple and effective nasal
CPAP system for the treatment of RDS.
Bubble CPAP
As evident from the above description there exists a multiplicity of
CPAP delivery systems. Not all are similar and success with nasal CPAP
depends on specific device used to deliver CPAP. Bubble CPAP is an
inexpensive and a simple mode for delivering CPAP. Bubble CPAP delivers
mechanical oscillatory vibrations which are transmitted into the chest
secondary to the non-uniform flow of gas bubbles across a downstream
underwater seal. Its proponents point to generated waveforms, in the airway
similar to those produced by high-frequency ventilation15.
Lee et al15 performed a randomized cross over study in 10 premature
infants ready for extubation to test whether bubble CPAP contributes to gas
exchange compared to conventional ventilator-derived CPAP. Measurements
of tidal volume and minute volume were made using the Bear-Cub neonatal
volume monitor, and gas exchange was measured using an oxygen saturation
monitor and a transcutaneous carbon dioxide (tcp CO2) monitor. Authors
28
found 39% reduction in minute volume (p<0.001) and 7% reduction in
respiratory rate (p=0.004) with no change in tcp CO2 or O2 saturation for
infants supported with bubble versus ventilator-derived CPAP. They
concluded bubble CPAP might offer an effective and inexpensive option for
providing respiratory support to premature infants.
There are not many studies that have examined the effectiveness of
bubble CPAP via the nasal route. Narendran v et al17 studied outcomes in
extremely low birth weight babies with early application of bubble CPAP.
Study was performed at Division of Neonatology, Cincinnati Children’s
Hospital Medical Center, Cincinnati. Outcomes of all infants weighing 401 to
1000 g born in a level 3 neonatal intensive care units between July 2000 and
October 2001 (period 2) were compared using historical controls (period 1). It
was shown that delivery room intubations, days on mechanical ventilation and
use of postnatal steroids decreased (p<0.001) in period 2, while mean days on
CPAP, number of babies on CPAP at 24 hours (p<0.001) and mean weight at
36 weeks corrected gestation also increased (p<0.05) after introduction of
early bubble CPAP.
They concluded that early bubble CPAP reduced delivery room
intubations, days on mechanical ventilation, postnatal steroid use and was
associated with increased postnatal weight gain with no increased
complications.
29
De Klerk and De Klerk16 studied effects of Bubble CPAP on
respiratory and non-respiratory outcomes in preterm infants at Department of
Pediatrics, Middlemore Hospital, South Auckland, New Zealand.
Outcomes in two groups of preterm infants with a birth weight of
1000-1499 g were compared retrospectively over a 5-year period before
(period I; n=57) and after (period II; n=59) the introduction of a primarily
nasal CPAP-based approach to respiratory support. From period I to period II,
there was a decline in the number of infants ventilated (65 vs 14%,
respectively) and receiving surfactant (40 vs 12%, respectively) and in the
median days of ventilation (6 vs 2, respectively) and oxygen (4 vs 2,
respectively).
Recent study by Jobe et al72 has sown bubble CPAP in preterm lambs
results in lower indicators of acute lung injury (neutrophils and hydrogen
peroxide) than mechanical ventilation in the first two hours of life.
With this background we intended to study early nasal CPAP in the
treatment of preterm babies with HMD.
Equipments used to Set-up Bubble CPAP
1. Fisher and paykel nasal prongs
2. Container with lid, filled with sterile water to a depth of 10 cm
H2O.
3. Column to fit through the lid of this container with graduated scale
from 0-10 cm H2O.
4. Oxygen blender with flow meter attached.
30
5. Oxygen tubings
6. Humidifier
7. Inspiratory and expiratory circuits.
8. Cap or stockinette
Bubble CPAP is delivered through Fisher and Paykel nasal prongs.
They are soft, pliable and gentle on the baby’s nares and are automatically
curved for a comfortable fit. They are available in 9 sizes based on prong
diameter and width of septum. Fisher and Paykel nasal prongs have the
largest bore possible to reduce resistance to flow and work of breathing
(WOB).
Oxygen tubing is connected to the flow meter and attached to the inlet
port of the humidifier. Flow rates of oxygen is between 5-7 liters/min. The
flow rate will provide adequate pressure to wash out carbon dioxide in the
system, compensate for the normal air leakage from the tubings and generate
adequate CPAP pressure. Connect one light weight non-kinking corrugated
tube to the humidifier. Choose appropriate size nasal prongs as mentioned
above and attach one side to the corrugated tubing coming from the
humidifier. Prongs should fit the nares snugly without pinching the nasal
septum. If the prongs are too small there will be increase in the airway
resistance and increases air leak from the system. Fill the container with
sterile water to 10 cm H2O and place the container below the level of the
infant. The column should be fitted into the container through the lid and
placed under the fluid level to desired pressure i.e., initially 6-7 cm H2O; the
31
expiratory circuit from the infant is connected to the column. The expiratory
circuit will need a port and pressure tubing leading to a calibrated manometer.
Figure-5: A baby with HMD put on nasal CPAP in our NICU
Technique of Application
• Position the baby with head end elevated to 30 degrees. Place a small
roll under the baby’s neck.
• Place the stokinette over the head to hold CPAP in place. The needed
length and width varies with size of the baby.
32
• Gently suction the mouth and nose of the baby to remove any
secretions.
• Place the nasal prongs curve side down into the baby’s nose. It is
important to have the prongs and tubing to be positioned properly to
reduce nasal irritation. When they are properly positioned tubings will
not be touching the baby’s skin, there will be no lateral pressure on
baby’s nasal septum and prongs should not rest on the philtrum.
• Once every thing is in place double check the system to ensure smooth
working of the system.
Maintaining Bubble CPAP
• Baby is evaluated with SAS scoring, SpO2 and regular arterial blood
gas (ABG) analysis.
• Oxygen blender is set at appropriate amount of oxygen. FiO2 will vary
according to SpO2 and ABG analysis.
• Underwater bubbling is constantly checked. It indicates that there is
enough flow in the system.
• Carefully inspected the nasal septum for signs of irritation since nasal
erosion is a potential complication of CPAP.
• The CPAP is started at pressure of 5 cm of water with FiO2 of 0.4 to
0.5. If respiratory distress does not improve with this, or worsens
further or oxygenation is impaired, pressure is increased in steps of 1
to 2 cm of H2O to reach a maximum of 8 cm of H2O. if still the
oxygenation is compromised, FiO2 is then increased to 0.6.
33
Monitoring of a Baby on CPAP
Continuous monitoring of respiratory rate, respiratory distress by
Silverman Anderson score, oxygen saturation monitoring and blood gas
analysis should be done as and when required. Aim is to maintain saturation
between 90-93%, PaO2 between 60-80 mm Hg and PaCO2 between 35 to 45
mm Hg of water.
Weaning from CPAP
The patient should be weaned from CPAP after the natural course of
disease is expected to be improving. There should be no respiratory distress
on this setting, minimal or no need for vasopressor support, normal blood gas
and an improving X-ray chest. Once it is decided to wean off CPAP, FiO2
should be decreased in steps of 0.05 to FiO2 of 0.25. Then pressures should be
decreased in steps of 1-2 cm H2O until a pressure of 3-4 cm H2O is reached.
The infant should then be transferred to oxygen hood or incubator oxygen.
The patients’ condition will guide the speed of weaning.
Clinical Application of CPAP
CPAP has been used in infants with respiratory distress resulting from
HMD, transient tachypnea of newborn, PDA, chronic pulmonary insufficiency
of prematurity. It is also used in apnea of prematurity and weaning infants
from mechanical ventilation.
The effects of CPAP in managing RDS have been evaluated in several
trials and fall into following groups:
34
Prophylactic CPAP in HMD
Cochrane review73 2005 updates on role of prophylactic nasal CPAP
commenced soon after birth regardless of respiratory status in the very preterm
or very low birth weight infant in reducing the IPPV and the incidence of
chronic lung disease (CLD). All trials using random or quasi-random patients
allocation of very preterm infants 32 weeks gestation and/ or <1500 gms at
birth were studied. Comparison was made between prophylactic nasal CPAP
commencing soon after birth regardless of the respiratory status of the infant
versus ‘standard’ methods of treatment where CPAP or IPPV is used for a
defined respiratory condition. They found no statistically significant
differences in any of the outcomes reported. There was a trend towards
increase in the incidence of BPD at 28 days [RR 2.27 (0.7, 6.65)], death [RR
3.63 (0.42, 31.08)] and any IVH [RR 2.18 (0.84, 5.62)] in the CPAP group.
There is currently insufficient information on prophylactic CPAP to make
recommendations for clinical practice.
Early Treatment of HMD
Initial experience with CPAP was obtained by observing clinical
condition and arterial blood gases of infants with RDS before and after
applying CPAP. Three RCTs74,75 evaluated effect of CPAP vs no CPAP in
treatment of RDS. These trials included total 136 babies with moderately
severe distress based on clinical and radiological criteria and provided CPAP
by facemask or ET tube. They showed that CPAP improves oxygenation,
reduced need for subsequent ventilation and reduced death rate. However,
35
applicability of these results in current practice is difficult to assess given the
outdated methods of CPAP delivering devices.
Use of early CPAP establishes and maintains an adequate functional
residual capacity (FRC) by preventing collapse of unstable alveoli and
opening up some already collapsed alveoli. This is crucial for gas exchange,
stabilization of air spaces and promotion of release of surfactant stores.
Numerous studies have sown the fact that early use of CPAP reduces the need
for subsequent intubation and mechanical ventilation in RDS.
Gittermann MK et al76 tested the hypothesis that the use of early nasal
CPAP (applied as soon as signs of respiratory distress occurred, usually within
15 min after birth) reduces the need for intubation, the duration of intermittent
mandatory ventilation and the incidence of bronchopulmonary dysplasia. The
study was performed at Division of Neonatology, University Women’s
Hospital, Bern, Switzerland. All live born VLBW infants (birth weight <1500
g) admitted to neonatal intensive care unit in 1990 (historical controls) and in
1993 (early nasal CPAP group) were the subjects of the study.
The intubation rate was significantly lower after introduction of nasal
CPAP (30% vs 53%, p=0.016). Median duration of intubation was 4.5 days
(interquartile range 3-7 days) before versus 6 days (2.8-9 days) after nasal
CPAP was introduced (p=0.73). The incidence of bronchopulmonary
dysplasia was not reduced significantly (32% vs 30%, p=0.94).
They concluded that early nasal CPAP is an effective treatment of
respiratory distress in VLBW infants, significantly reducing the need for
36
intubation and intermittent mandatory ventilation without worsening other
standard measures of neonatal outcome.
Cochrane review77 (2002) was performed to determine if continuous
distending pressure (CDP) reduces the need for IPPV and associated morbidity
without adverse effects. The standard search strategy of the Neonatal Review
Group was used. This included searches of the Oxford Database of Perinatal
Trials, Cochrane Central Register of Controlled Trials (The Cochrane Library,
Issue 3, 2004), MEDLINE (1966 August, 2004), and EMBASE (1980 August,
2004), previous reviews including cross references, abstracts, conference and
symposia proceedings and expert informants.
All trials using random or quasi-random allocation of preterm infants
with RDS were eligible. Interventions were continuous distending pressure
including continuous positive airway pressure (CPAP) by mask, nasal prong,
nasopharyngeal tube, or endotracheal tube, or continuous negative pressure
(CNP) via a chamber enclosing the thorax and lower body, compared with
standard care. It is seen that CDP is associated with a lower rate of failed
treatment (death or use of assisted ventilation) [summary RR 0.70 (0.55, 0.88),
RD – 0.22 (-0.35, -0.09), NNT 5 (3, 11)] overall mortality [summary RR 0.52
(0.32, 0.87), RD – 0.15 (-0.26, -0.04), NNT 7 (4, 25)], and mortality in infants
with birth weights above 1500 g [summary RR 0.24 (0.07, 0.84), RD – 0.281
(-0.483, -0.078), NNT 4 (2,13)].
It was concluded that in preterm infants with RDS the application of
CDP either as CPAP or CNP is associated with benefits in terms of reduced
37
respiratory failure and reduced mortality. Where resources are limited, such
as in developing countries, for RDS may have a clinical role.
Early versus Late Initiation of CPAP
Cochrane review78 2002 determines if early compared with delayed
initiation of CDP result in lower mortality and reduced need for intermittent
positive pressure ventilation. It was a trial among pre-term infants with
respiratory distress syndrome spontaneously breathing at trial entry, which
used random or quasi-random allocation to either early or delayed CDP. They
found early use of CPAP (at onset of respiratory distress) was associated with
decreased need for intermittent positive pressure ventilation (IPPV) by about
50%, but it had not effect on mortality, or chronic lung disease at 28 days of
life, when compared to late initiation of CPAP i.e., when FiO2 requirement of
baby is more than 60%.
Recent study by Sandri F et al79 published in arch dis child 2004
evaluates the benefits and risks of prophylactic nCPAP in infants of 28-31
weeks gestation. It was a multicenter randomized controlled clinical trial
conducted at seventeen Italian Neonatal Intensive Care Units. A total of 230
newborns of 28-31 weeks gestation, not intubated in the delivery room and
without major malformations, were randomly assigned to prophylactic or
rescue nCPAP. Prophylactic nCPAP was started within 30 minutes of birth,
irrespective of oxygen requirement and clinical status. Rescue nCPAP was
started when FiO2 requirement was >0.4, for more than 30 minutes, to
maintain transcutaneous oxygen saturation between 93% and 96%.
38
Exogenous surfactant was given when FiO2 requirement was >0.4 in nCPAP
in the presence of radiological signs of respiratory distress syndrome.
Results were surfactant was needed by 22.6% in the prophylaxis group
and 21.7% in the rescue group. Mechanical ventilation was required by 12.2%
in both the prophylaxis and rescue groups. The incidence of air leaks was
2.6% in both groups. They concluded that in newborns of 28-31 weeks
gestation, there is no greater benefit in giving prophylactic nCPAP than in
starting nCPAP when the oxygen requirement increases to a FiO2>0.4.
39
METHODOLOGY
The study was conducted at Neonatal ICU, Sangameshwar &
Basaveshwar Teaching & General Hospitals, Gulbarga. 50 cases of clinically
diagnosed HMD with gestational age 28-34 weeks admitted to Neonatal ICU
were subjects of this study. These babies requiring respiratory support were
treated with early nasal CPAP (within 6 hours of onset of respiratory distress)
and studied prospectively from December 2007 to May 2009. The period of
collection of data was one and half year.
Design of the study: Hospital based observational study.
Duration of the study: One and half year i.e., from December 2007 to May
2009.
Definitions:
Hyaline membrane disease: The baby should meet all of the following three
clinical criteria80:
1. Preterm neonate
2. RDS having onset within 6 hours of birth.
3. Amniotic fluid L/s ratio of <1.5 or negative gastric aspirate shake test
or Skiagram of chest showing either poor expansion with air
bronchogram or reticulogranular pattern or ground glass opacity.
40
CPAP is successful when: The saturation is >85%; PaO2 of 60-80 mm Hg,
PaCO2 of 25 to 45 mm Hg and pH of 7.3 to 7.4 with FiO2 <0.6. Baby has no
respiratory distress.
CPAP failure is defined as:
• PO2 < 50 mm Hg or PCO2 > 60 mm Hg with FiO2 >0.6.
• SAS score >6.
• Recurrent apnea.
Inclusion criteria for cases:
• All preterm neonates born in our hospital with gestational age between
28-34 weeks with diagnosed HMD after taking consent from parents/
guardians.
Exclusion criteria for cases:
1. All term neonates
2. Neonates with congenital malformations.
3. Babies born to mothers receiving general anesthesia, phenobarbitone,
pethidine and other drugs likely to depress the baby.
4. Preterms born outside our hospital
5. Babies with meconium aspiration syndrome.
6. Babies with birth asphyxia.
Method of collection of data:
50 babies with gestational age between 28-34 weeks admitted with
clinical diagnosis of HMD requiring respiratory support were treated with
41
early nasal CPAP (within 6 hours of onset of respiratory distress) and studied
prospectively from December 2007 to May 2009.
All babies with HMD were evaluated using SA scoring, blood gas
analysis and pulse oxymetry. Babies with SA score of >4 or requiring FiO2 >
0.4 to maintain PaO2 above 50-60 mm Hg were treated with early nasal CPAP
and effectiveness was judged using SA scoring and blood gas analysis. If
symptoms progress and FiO2 requirement is >0.6 to maintain SpO2 above
85%, babies were ventilated.
Method of Statistical Analysis
After the completion of the study, data was analyzed using appropriate
statistical methods to find out the effectiveness of early nasal CPAP in the
treatment of preterm infants with HMD.
Babies treated with nasal CPAP treatment were classified into two
groups namely success and failure group and comparison between the groups
were carried out as follows:
1. Proportions were compared using chi-square (χ²) test of significance.
Proportion of cases belonging to specific group of parameter or having
a particular problems was expressed in absolute number and
percentage.
2. The results were averaged (mean±standard deviation) for each
parameter (duration of treatment, age at admission, age at treatment
and ABG parameter) between the groups. Student’s ‘t’ test used to
find a significant difference between two means.
42
Student’s t test is as follows:
21
21
11nn
s
xxt
+
−= ~~~~~ tn1+n2-2
Where s² = )2(
)1()1(
21
222
211
−+−+−
nnsnsn
In all above test, “p” value of less than 0.05 was accepted as indicating
statistical significance.
43
RESULTS
Total number of deliveries and preterm births (<37 weeks) and
incidence of Hyaline Membrane Disease (HMD) in both Basaveshwar
Hospital and Sangameshwar Hospital attached to M.R. Medical College
during the study period i.e., from December 2007 to May 2009 were
determined.
Total number of deliveries ...........................................................................4050
Total number of preterm neonates (<37 weeks) ............................................503
Incidence of preterm neonates ................................................................ 12.42%
Total number of diagnosed HMD cases.........................................................130
Incidence of HMD in neonates with gestational age between 28-34
weeks........................................................................................................... 3.2%
50 babies admitted with clinical diagnosis of HMD requiring
respiratory support were treated with early nasal CPAP and studied
prospectively from December 2007 to May 2009. Out of total 50 babies who
were managed with nasal CPAP, it proved effective in 40 babies (80%),
remaining 10 babies (20%) had to be intubated and required ventilation.
44
Table-2: Nasal CPAP treatment outcome among babies
Success Failure Total number of babies treated Number Percent Number Percent
50 40 80.00 10 20.00
The above table shows the outcome in study group after early nasal
CPAP. Among 50 babies, 40 improved with success rate of 80%, whereas 10
babies (20%) failed requiring higher mode of ventilation.
Figure-6: Outcome of nCPAP treatment among study group
20.00%
80.00%
Success Failure
45
Table-3: Gender distribution of the study group
Success Failure Gender Total
Number Percent Number Percent
Male 32 24 75.00 8 25.00
Female 18 16 88.88 2 11.11
Total 50 40 80.00 10 20.00
χ²= 1.38 df = 1 p>0.05 Not significant
Table-3 analyses in which group of babies success rate was more. We
found a success rate of 75% in males and 88.88% in females (p>0.005).
Figure-7: Gender distribution among success and failure group
75
25
88.88
11.11
0
10
20
30
40
50
60
70
80
90
100
Success Failure
Per
cent
age
Male Female
46
Table-4: Distribution of babies based on gestation age and results
Success Failure Gestational age in weeks Total
Number Percent Number Percent
28-30 12 5 41.67 7 58.33
31-32 30 28 93.30 2 6.67
33-34 8 7 87.50 1 12.50
Total 50 40 80.00 10 20.00
χ² = 14.50 df=2 p>0.001
Table-4 depicts distribution of babies based on gestational age and
outcome after using nasal CPAP. Out of 50 babies, 12 belonged to gestation
age of 28-30 weeks, 30 babies were in 31-32 weeks gestation and remaining 8
in 33-34 weeks gestational age. In babies who were between 28-30 weeks<
there is 41.67% success and 58.30% failure rate. Outcome in babies of 31-32
weeks gestation is 93.30% and 6.67% success and failure rates respectively.
Among 33-34 weeks, success rate is 87.5% and failure rate is 12.5%. There is
statistically significant difference between success and failure groups with
respect to gestational age (p<0.001). Higher the gestational age more is the
success rate.
Figure-8: Distribution of babies based on gestational age and results
41.67
93.387.5
58.33
6.6712.5
0
10
20
30
40
50
60
70
80
90
100
28 -30 31 - 32 33 -34
Gestational age
Per
cen
tag
e
Success Failure
47
Table-5: Distribution and outcome of babies based on birth weight
Success Failure Birth weight (gms) Total
Number Percent Number Percent
<999 4 3 75.00 1 25.00
1000-1500 36 29 80.50 7 19.50
1501-2000 10 8 80.00 2 20.00
Total 50 40 80.00 10 20.00
χ²=0.071 df=2 p>0.05 Table-5 shows results based on birth weight. Out of 50 babies, 4
belonged to <999 g, 36 in 1000-1500 g and remaining 10 were in >1501 g. In
babies who were <999 g 75% were managed with early nasal CPAP alone and
25% failed. Outcomes in 1000-1500 g group were 80.5% and 19.5% success
and failure rates respectively. In babies >1500 gm success and failure rates
were 80% and 20% respectively (p>0.05). Success and failure rates are not
significantly different with respect to birth weight.
Figure-9: Distribution of birth weight of the babies among success and
failure group
7580.5 80
2519.5 20
0
10
20
30
40
50
60
70
80
90
<999 1000-1500 1501-2000
Birth weight
Per
cen
tag
e
Success Failure
48
Table-6: Distribution of mean age at the time of initiation of treatment
Number of babies Mean age at initiation
of treatment±SD (hours)
Range (hours)
50 4.16±1.639 0.5 – 6 hours The mean age for initiation of treatment is 4.16 hours with range 0.5-6
hours.
Table-7: Mean duration of treatment (hours) in success and
failure group
Group Number Mean±SD Range (hours) Success 40 38.5±15.40 10 – 72 Failure 10 9.0±1.70 8 – 12
Table-7 analyses the duration of treatment in success and failure
groups. The mean duration in success group was 38.5±15.4 hours with range
being 10-72 hours. Similarly mean duration of treatment in failure group was
9.0±1.7 hours range being 8-12 hours.
Figure-10: Mean duration of treatment (hours) among success and failure
group
38.5
9
0
5
10
15
20
25
30
35
40
45
Mea
n du
rati
on o
f tr
eatm
ent
(hrs
)
Success Failure
Table-8: SA Score in study group before and after treatment
49
SA Score
Before treatment
(n=50) After 6 hours
(n=50) After 12 hours
(n=40)
Number Percent Number Percent Number Percent
1 -- -- -- -- 13 32.5
2 -- -- 7 14.0 26 65.0
3 -- -- 25 50.0 1 2.5
4 16 32.0 8 16.0 -- --
5 31 61.2 -- -- -- --
6 3 6.0 9 18.0 -- --
7 -- -- 1 2.0 -- --
Table-8 shows distribution of babies based on SA score. 61.2% were
in score 5, 6% in score 6 and 32% in score 4 before institution of CPAP.
Nasal CPAP was started when SA score was 4 or more.
50
Table-9: Distribution of SA score in study group before and after 6 hours
treatment
SA score after 6 hours after CPAP Total babies
SA Score before CPAP 2 3 4 6 7
16 4 5 (31.2%)
7 (43.8%)
0 (0.00%)
4 (25.00%)
0 (0.00%)
34 ≥5 2 (5.90%)
18 (52.9%)
8 (23.5%)
5 (14.7%)
1 (2.90%)
50 Total babies
7 (14.00%)
25 (50.00%)
8 (16.00%)
9 (18.00%)
1 (2.00%)
χ² = 24.50 df = 8 p<0.005
Table-9 depicts effect of nasal CPAP on SA score before and 6 hours
after application of nasal CPAP. Out of 16 babies who were in SA score 4, 5
(31.2%) babies improved to score 2, 7 (43.8%) babies to score 3 and
remaining 4 babies (25%) worsened to SA score of 6 and required ventilation.
Out of 34 babies who had a score of ≥5 before nasal CPAP, 2 (5.9%) babies
improved to score 2, 18 (52.9%) babies improved to score 3, 8 (23.5%) babies
improved to score 4. 5 (14.7%) babies deteriorated to score 6 and 1 (2.9%)
baby deteriorated to score of 7 after 6 hours of nasal CPAP (statistically
significant, p<0.005).
51
Table-10: Comparison of ABG parameters before and after treatment in
success and failure group
Before early nasal CPAP (mean±SD)
After early nasal CPAP (mean±SD) ABG
Parameter Success group
Failure group
Success group
Failure group
pH 7.268±0.079 7.314±0.1099 7.379±0.05 7.319±0.1188‘t’ value 1.4333 2.00 ‘p’ value 0.178 0.073 PO2 57.66±10.58 55.93±10.96 80.48±7.52 42.16±18.83 ‘t’ value 0.451 6.309 ‘p’ value 0.659 0.00* PCO2 41.31±11.14 36.99±10.42 30.62±6.67 38.40±9.73 ‘t’ value 1.147 2.389 ‘p’ value 0.270 0.036*
HC −3O 18.377±0.97 18.56±0.81 20.507±1.149 17.15±0.83
‘t’ value t=0.64 10.82 ‘p’ value >0.05 <0.001 Figure-11: Comparison of mean values of ABG parameters in success and
failure group
7.268
57.66
41.31
18.37
7.379
80.48
30.62
20.507
7.314
55.93
36.99
18.56
7.319
42.1638.4
17.15
0
10
20
30
40
50
60
70
80
90
pH-b
efor
e
PO2-
befo
re
PCO
2-be
fore
HCO
3-be
fore
pH-a
fter
PO2-
afte
r
PCO
2-af
ter
HC
O3-
afte
r
Per
cent
age
Success Failure
52
Table-10 shows effect of nasal CPAP on blood gas parameters. It
shows significant increase in oxygenation (p<0.05) after application of nasal
CPAP.
Table-11: Distribution of babies based on radiological grading of HMD
and outcome
Success Failure HMD grading Total
Number Percent Number Percent Mild 6 6 100.00 -- -- Moderate 29 27 93.10 2 6.9 Severe 15 7 46.67 8 53.33 Total 50 40 80.00 10 20.00 χ²=15.3 df=2 p<0.005
Table-11 shows in which group of babies based on radiological
appearance of early nasal CPAP proved more effective. It is found that in
moderate grade HMD, success rate is 93.1% (statistically significant p<0.005)
and only 6.9% failed. In severe grade HMD 53.3% failed and 46.67% was the
success.
Figure-12: Results of early nasal CPAP based on radiological appearance
10093.1
46.67
06.9
53.33
0
20
40
60
80
100
120
Mild Moderate Severe
Per
cen
tag
e
Success Failure
53
Table-12: Antenatal steroids and outcome
Success Failure Steroids received Total
Number Percent Number Percent
Yes 28 26 92.86 2 7.14
No 22 14 63.63 8 36.37
Total 50 40 80.00 10 20.00
χ² =6.5 df =1 p<0.05
Table-12 show outcomes in babies who received antenatal steroids. It
is found that success rate was 92.86% in babies of mothers who had received
antenatal steroids, whereas only 63.63% of the babies improved whose
mothers did not receive antenatal steroids (statistically significant p<0.05).
Hence, antenatal steroids in mother had definite role in better outcome of
HMD.
Figure-13: Antenatal steroids and results
92.86
7.14
63.63
76.37
0
10
20
30
40
50
60
70
80
90
100
Success Failure
Per
cent
age
Yes No
54
DISCUSSION
The incidence of prematurity in our study is 12.42% as compared to
National Statistics of 10-12% in India80.
The incidence of HMD in this study is 3.2%. According to NNPD
2002-03 report2 involving 151,436 intramural deliveries, the incidence of
HMD in our country was 1.3% of all live births.
50 preterm babies with gestational age 28 – 34 weeks with HMD were
treated with early nasal CPAP. Out of 50,40 babies (80%) were effectively
managed with early nasal CPAP alone. Remaining 10 (20%) had to be
intubated and required more invasive mechanical ventilation.
Table-13: Studies for outcome of HMD
Study Success rate (%)
Present 80.00
Kamper et al 84.00
Urs et al 80.00
Literature review shows varying results with administration of CPAP
in managing HMD and results differ based on different modes of CPAP used.
Kamper et al56 found success rate of 84% in HMD with CPAP system used
with a binasal tube. Failure rate of 16% was the lowest reported with any
CPAP system till then.
55
In a recent study by Gitterman et al76 early use of nasal CPAP in
VLBW showed significant reduction in intubation rate after introduction of
nasal CPAP (30% vs 53%, p=0.016). Another study by Narendran V et al17
showed early bubble CPAP reduced the need for mechanical ventilation
(p<0.001) with no increased complications. One study by Nair et al81 showed
failure rates of 10.7% in newborns with respiratory disease. They used nasal
CPAP using Benveniste’s valve.
In another recent study by Urs et al82 CPAP proved to be effective in
80% cases with HMD.
Out of 50 babies who were treated with early nasal CPAP, 64% were
males and 36% were female babies. The results were analyzed based on
gender characteristics and found no statistically significant difference in the
outcome between the two groups (p>0.005).
Table-14: Gender-wise distribution of success rate in HMD
Success rate (%) Study
Males Females
Present study 75.00 88.88
Urs et al 78.80 82.40
Study by Sandri F et al79 has shown higher need for respiratory
assistance in male infants. Urs et al82 have found no statistically significant
difference in outcome between males and females. The evidence of a worse
prognosis in boys has been widely reported in the literature.
56
The study was analyzed, which group of babies had better outcome
based on gestational age at the inclusion. Out of 50 babies, 12 belonged to
gestational age 28-30 weeks, 30 babies were in 31-32 weeks gestation and
remaining 8 in 33-34 weeks gestational age. In babies who were between 28-
30 weeks, we found overall success of 41.67%, babies between 31-32 weeks
gestation showed 93.3% success rates. Out of 10 babies who required
ventilation 90% of the babies were less than 32 weeks gestation age;
remaining 10% were between 33-34 weeks. Analysis of these results shows
that outcome is better with increase in gestational age (statistical significance
p<0.05). Jacobsen et al have shown better outcome in babies with gestational
age of <33 weeks. They found significant reduction in mechanical ventilation
from 76% to 35% (p=0.00001). Urs et al82 have found better outcome in
gestational age of 32-34 weeks (p<0.001).
Table-15: Studies for outcome of HMD depending on gestational age
Study Better outcome in gestational age group
Present study 31-32 weeks (93.3% success rate)
Urs et al 32-34 weeks (81.5% success rate)
Jacobson et al <33 weeks
We looked into effect of birth weight of the babies and overall
outcome. Out of 50 babies, 4 belonged to weight of <999 g, 36 in 1000-1500
g and remaining 10 were >1501 g. We found an overall success rate of 75%
in babies <999 g, 80.5% in 1000-1500 g and 80% in babies >1500 g. Out of
10 babies who failed 80% were <1500 g and remaining 20% above 1500g.
57
Table-16: Studies for outcome of HMD depending on birth-weight
Success rate (%) Birth weight (gms)
Present study Urs et al
<999 75.00 75.00
1000 – 1500 80.50 81.80
>1501 80.00 77.00
Studies have shown better outcomes in VLBW and ELBW. Aly H et
al83 studied outcome of nasal CPAP in ELBW. They found no significant
trends in mortality rate among the baseline group and the 3 groups after the
institution of the nasal CPAP practice. Nasal CPAP management increased in
the surviving infants over time, whereas the need for surfactant treatment
decreased.
Study by Narendran v et al17 has also shown better outcomes in
ELBW. Another study by Joris N et al84 has shown significant reduction in
intubation rate in babies <1500 g (from 72.1% to 30.8%; p<0.01). In our
study we did not find any significant difference in the outcome of babies based
on birth weight (p>0.005). Urs et al82 have shown better outcome in babies
with birth weight 1000-1500 gm (p<0.001).
In our study effectiveness of early nasal CPAP was judged based on
SA scoring and blood gas parameters. Out of 16 babies who were in SA score
4, 31.2% improved to score 2 and 43.8% to score 3 after 6 hours. These
58
babies improved further and were weaned off subsequently. Remaining 4
babies (25%) who were in SA score 4 worsened to SA score 6 after 6 hours
and had to be ventilated. Out of 31 babies who were in score 5 before early
nasal CPAP, 6.4% improved to score 2, 58.1% to score 3 and 16.1% to score 4
after 6 hours. Remaining 6 babies (19.3%) in this group worsened to score >6
and failed. 3 babies were in score 6 before treatment. All of them improved
to score 4 after 6 hours. We found statistically significant improvement
(p<0.005) in SA score after application of nasal CPAP. SA scoring also
helped us to predict which babies would go for ventilation. Recent study61
showed, infants who received CPAP in circumstances where NICU access was
denied had a significantly improved short-term survival (at 24 hours), with
trends towards improved long-term survival. Urs et al82 have shown
significant improvement in Downes score after application of bubble CPAP.
Blood gas analysis was the other parameter, which helped us to decide
success and failure on early nasal CPAP. In our study we found that babies on
CPAP had significant improvement in oxygenation (p<0.05), other parameters
varied. With this we could reduce FiO2 significantly and wean down the
babies. Among 10 babies who required ventilation, PO2 levels before CPAP
were (55.93±10.96) and remained low after CPAP (42.16±18.83).
There are very few studies, which have looked into the effect of CPAP
on oxygenation. First study by Gregory et al7 in HMD demonstrated
significant improvement in PO2; other parameters like PCO2 and pH did not
varied much. Another study by Harris H et al85 found a significant
improvement in mean PaO2 (from 47 to 80 mm Hg; p<0.001) with no
59
significant change in PaCO2 or pH. Improvement in PaO2 facilitated reduction
of FiO2 in less than 20 h.
Babies were classified as mild, moderate and severe grade HMD based
on radiological appearance86 and we studied in which group of babies early
nasal CPAP is more effective. Out of 50 babies, 6 babies showed mild HMD.
All of the improved on nasal CPAP (success rate of 100%). 29 babies
belonged to moderate grade HMD. We found a success rate of 93.1% in this
group (statistically significant p<0.005).
Table-17: Studies for radiological outcome of HMD
Success rate (%) Study
Mild Moderate Severe
Present 100.00 93.0 96.67
Urs et al 100.00 93.10 96.60
Out of 10 babies who failed on nasal CPAP, 80% of them had severe
grade HMD and 20% showed moderate HMD. With this we conclude that
early nasal CPAP is effective in mild and moderate HMD. It may not be a
replacement for assisted respiratory support (ventilation) in severe cases of
HMD. One study by Schmid R et al87 who analyzed data based on
radiological appearance and showed that CPAP was an effective method in
newborns with all grades except severe HMD. Another study by Urs et al82,
conclude that CPAP is effective in mild and moderate grade HMD.
60
Boo NY et al88 in a recent study determined the predictors associated
with failure of nasal continuous positive airway pressure (CPAP) in the
treatment of respiratory distress syndrome (RDS). They showed that only
three risk factors were significantly associated with failed CPAP. These were:
moderate or severe RDS (odds ratio 5.9; 95 percent; CI 1.5-50.7); and
pneumothorax during CPAP therapy (odds ratio 6.9; 95 per cent; CI 1.1-41.7).
In our study 80% of the babies who failed had severe RDS.
Whether antenatal steroid use has any effect on overall outcome of
babies treated with CPAP? We found that 26 (92.86%) of 28 babies whose
mothers had received antenatal steroids improved with nasal CPAP, whereas
out of 22 babies whose mothers had not received antenatal steroids only 14
(63.63%) improved and 8 (36.37%) failed. Statistical analysis showed p<0.05
(significant). Antenatal steroid administration helps us to predict the severity
of HMD and need for invasive respiratory support. Study by Sandri F et al79
has shown trend towards greater failure in babies who had not received
antenatal steroids (p=0.02). Urs et al82 have also shown that CPAP is more
effective in babies of mothers who have received antenatal steroids.
Table-18: Studies for outcome with use of antenatal steroids
Study Improvement with antenatal steroids (%)
Present study 92.86%
Urs et al 92.8%
61
SUMMARY
50 cases of clinically diagnosed HMD with gestational age between
28-34 weeks admitted to Neonatal ICU were subjects of this study. 50 babies
admitted with clinical diagnosis of HMD requiring respiratory support were
treated with early nasal CPAP (within 6 hours of onset of respiratory distress)
and studied prospectively from December 2007 to May 2009. After the
completion of the study data was analyzed using appropriate statistical
methods to find out the effectiveness of early nasal CPAP in the treatment of
preterm infants with HMD.
1. Incidence of prematurity in our hospital was 12.42%.
2. Incidence of HMD in our hospital in babies between gestational
age of 28-34 weeks is 3.2%.
3. Out of total 50 babies who were managed with early nasal CPAP, it
proved effective in 40 babies (80%), remaining 10 babies (20%)
had to be intubated and required ventilation.
4. The results were analyzed based on gender characteristics and
found no statistically significant difference in the outcome between
the two groups (p>0.005).
5. Babies were studied based on gestation age and birth weight at the
inclusion. Out of 10 babies who required ventilation 90% of the
babies were less than 32 weeks gestation age; remaining 10% were
between 33-34 weeks. Analysis of these results showed that
62
outcome is better with increased gestational age (p<0.005). Out of
10 babies who failed 80% were <1500 g and remaining 20% above
1500 g. In our study we did not find any significant difference in
the outcome of babies based on birth weight (p>0.005).
6. Effectiveness of early nasal CPAP was judged based on SA scoring
and blood gas parameters. We found statistically significant
improvement (p<0.005) in SA score after application of nasal
CPAP. We also demonstrated that babies on CPAP had significant
improvement in oxygenation (p<0.05), other parameters varied.
With this we could reduce FiO2 significantly and wean down the
babies.
7. Babies were studied based on radiological appearance and we
found a success rate of 93.1% in moderate grade HMD
(statistically significant p<0.005). Out of 10 babies who failed on
nasal CPAP, 80% of them had severe grade HMD and 20% showed
moderate HMD.
8. A success rate of 92.86% was found in babies of mothers who had
received antenatal steroids whereas only 63.63% of babies whose
mothers had not received antenatal steroids improved with early
nasal CPAP. Statistical analysis showed p<0.05 (significant).
63
CONCLUSION
1. Prematurity is the commonest predisposing factor for HMD. Its
incidence increases as gestational age decreases.
2. Early nasal CPAP is useful in mild and moderate grade HMD. It
may not be a replacement for assisted respiratory support
(ventilation) in severe HMD.
3. Nasal CPAP is found to be effective in babies of mothers who had
received antenatal steroids.
4. Nasal CPAP is safe, inexpensive and effective means of respiratory
support in HMD.
In developing countries like ours, there is high burden of prematurity
and sub-optimal use of antenatal steroid administration resulting in frequent
HMD. Use of early nasal CPAP which is simple, non-invasive, has low
capital outlay and does not require expertise, is the option for us where most
places cannot provide invasive ventilation.
64
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75
ANNEXURE
PROFORMA
Name of Baby: IP No.
Sex: Address:
Place of Birth: Mode of Delivery:
Date of birth:
APGAR Score: At 1 min
At 5 min
Obstetric history details:
1. Gravida
2. Bad obstetric history
3. Present pregnancy: Giddiness/ Pedal edema/ convulsions/ rashes
4. Drug intake
5. Any systemic illness
6. H/o antenatal steroid intake
7. Antepartum hemorrhage/ PV bleed
I) General Physical Examination
1. Any external congenital anomalies
2. Head shape
• Hair distribution
• Ant fontanelle
• Caput/ cephalhematoma
3. Eyes
4. Nose
5. Oral cavity
6. Ears
7. Neck
76
8. Thorax
9. Abdomen
10. Genitals
11. Anus
12. Lower limbs
13. Inspection of orifices
14. CFT
III) Anthropometry
• Head circumference
• Chest circumference
• Length
• Weight
IV) Vitals PR RR Temp NIBP
V) Systemic Examination 1. Cardiovascular system
2. Respiratory system
3. Per abdomen
4. CNS
VI) Investigations
• Hb%
• TC
• DC
• ESR
• PCV
• CRP
• Toxic granules
• Band cells
• Blood culture sensitivity
• Chext X-ray
• Shake test
77
MONITORING CHART AFTER INSTITUTION OF N-CPAP
Time of institution Time of discontinuation
Basal SpaO2 Total duration on CPAP
Respiratory rate Outcome
Basal Silverman Anderson score
ABG analysis Time SAS SpaO2
Supplemental O2
FiO2 Before CPAP
After CPAP
1st hr
2nd hr
3rd hr
4th hr
5th hr
6th hr
8th hr
12th hr
24th hr
36th hr
48th hr
60th hr
72nd hr
Signature of Candidate Signature of Guide
78
KEY TO MASTER CHART
DOB Date of birth
M Male
F Female
SA score Silverman-Anderson score
Hrs Hours
CPAP Continuous positive airway pressure
79
CASES 1
7.317
1 Hrs 2 Hrs 4 Hrs 6 hrs12 Hrs
24 Hrs
36 Hrs
48 Hrs
72 Hrs
1 Hrs 2 Hrs 4 Hrs 8 Hrs 12 Hrs 24 Hrs 36 Hrs 48 Hrs 72 Hrs pH PaO2PaCO
2HCO3 pH PaO2
PaCO2
HCO3
1 40258 Parvati M 5/1/2008 1.45 32 6 5 5 4 4 3 2 2 2 75% 90% 90% 91% 91% 92% 93% 95% 7.331 71.10 43.20 17.20 7.378 88.10 30.90 21.40 36.0 success
2 40610 Sridevi F 7/2/2008 1.49 32 4 5 5 4 3 2 1 1 1 1 77% 90% 91% 91% 92% 93% 95% 97% 97% 7.378 50.8 25.2 18.1 7.479 88.30 27.5 22.3 38 success
3 40684 Julekha Begum M 15/2/2008 1.97 34 2.5 5 5 5 4 3 2 2 2 1 1 70% 90% 90% 92% 93% 93% 93% 94% 96% 97% 7.202 61.30 30.70 19.20 7.351 92.10 27.50 21.40 72.00 success
4 265187 Bhagyashree M 6/4/2008 1.40 31 5 4 4 3 3 2 1 1 75% 90% 90% 93% 94% 96% 97% 7.347 70.2 22.1 16.2 7.32 98.2 24.1 22.3 18 success
5 266199 kaveri F 12/4/2008 2.00 34 5 5 5 4 4 3 2 2 2 1 72% 90% 91% 92% 94% 95% 95% 96% 98% 7.28 58.00 30.2 18 7.344 82 28.2 22.4 48 success
6 268383 Laxmi M 14/5/2008 1.30 31 6 5 5 5 6 6 7 70% 85% 80% 78% 65% 7.4 64.7 43.8 18.5 7.171 34.9 58.4 16.9 8 Failure
7 268530 Fahimunnissa F 16/5/2008 1.50 32 2 5 4 4 3 3 2 2 2 1 1 85% 90% 91% 93% 95% 95% 96% 97% 98% 98% 7.367 60.80 20.20 18.70 7.424 81.50 29.40 20.80 72.00 success
8 269490 Naseem F 29/5/2008 1.00 28 0.5 5 5 6 6 7 65% 85% 85% 82% 63% 7.216 63.2 43.7 18.8 7.22 20.2 46.2 16.8 8 Failure
9 269499 Mahadevi M 30/5/2008 1.05 29 4 5 5 5 6 6 70% 86% 85% 79% 60% 7.317 53.80 46.7 18.8 7.336 42.9 44.7 18.1 8 Failure
10 271356 kalpana M 25/6/2008 1.40 32 5 5 5 4 4 4 2 2 2 2 80% 90% 90% 91% 92% 94% 95% 97% 97% 7.117 48.30 56.4 18.5 7.376 82.2 41.3 22 48 success
11 42533 Safaira Begum F 3/7/2008 1.23 31 3 5 5 5 4 3 2 2 2 1 77% 90% 90% 91% 93% 95% 96% 97% 97% 7.225 36.80 35.7 18.8 7.364 88 32 20.3 40 success
12 42578 Laxmi M 5/7/2008 1.39 31 6 4 4 4 3 2 1 1 80% 90% 92% 94% 94% 95% 96% 7.14 83.50 33.5 19.5 7.34 82.3 22.6 22.1 24 success
13 42655 Merajunnissa --I F 12/7/2008 1.41 31 6 5 4 4 4 4 2 1 79% 90% 91% 92% 95% 97% 7.35 81.60 38.5 18.6 7.43 91.1 30.6 20.7 10 success
14 42750 Nafiz fatima M 18/7/2008 1.63 33 5 4 4 5 5 6 7 68% 85% 86% 85% 76% 67% 7.302 35.20 30.8 18.1 7.31 37.3 30.2 16.8 12 Failure
15 42869 Ahmadi Begum M 20/7/2008 2.14 34 4 5 5 4 4 3 1 1 1 70% 90% 90% 91% 92% 92% 94% 95% 97% 7.343 50.60 29.8 19.1 7.319 82.1 26.1 22.3 39 success
16 42717 Savita F 24/7/2008 0.85 28 3.5 5 5 5 6 6 7 60% 85% 78% 75% 69% 7.36 43.80 39.2 19.8 7.371 34.6 32.9 17.1 8 Failure
17 42869 Parveen Begum F 30/7/2008 1.48 31 5 4 4 4 3 3 2 2 2 1 71% 90% 90% 91% 93% 94% 95% 96% 98% 7.30 69.70 43.2 19.8 7.368 71.9 41.9 21.5 43 success
18 42817 Usha F 6/8/2008 2.15 34 1 5 5 5 4 4 3 2 2 1 75% 91% 91% 92% 93% 95% 96% 97% 98% 7.34 52.00 32 18.6 7.412 80.2 30 20.2 40 success
19 43001 Ashwini M 9/8/2008 1.05 28 5 5 5 4 4 3 2 2 1 69% 91% 91% 92% 94% 95% 97% 97% 7.263 52.00 57.2 20.4 7.349 82.2 37.4 22.4 36 success
20 43144 Laxmi M 19/8/2008 1.03 28 2 5 5 5 6 6 7 71% 85% 85% 80% 75% 60% 7.23 61.40 29.3 19.3 7.288 41 30.4 16.8 10 Failure
21 43280 Jayashre M 28/8/2008 1.57 32 6 4 4 5 5 6 7 68% 86% 80% 73% 70% 7.35 60.50 25.8 18.5 7.128 19.9 42.2 19.1 8 Failure
22 276174 Eramma F 2/9/2008 0.99 28 4 5 5 5 4 4 2 2 2 1 75% 92% 92% 92% 93% 95% 96% 98% 98% 7.165 58.30 47.3 18.5 7.28 80.2 37.3 19.3 48 success
23 43578 Danamma M 15/9/2008 1.49 32 6 5 5 5 4 3 1 1 1 74% 90% 91% 94% 95% 95% 96% 97% 7.271 61.00 30.6 18.6 7.295 80.1 19.7 20.4 34 success
24 43830 Vajreshwari M 3/10/2008 2.05 34 5 5 5 4 4 3 1 1 1 1 70% 90% 90% 92% 94% 95% 96% 97% 98% 7.33 58.80 40.8 17.3 7.34 82.2 37.7 19.4 44 success
25 44964 Bharati M 18/10/2008 1.46 32 3 6 5 5 4 4 2 1 78% 90% 91% 93% 95% 96% 97% 7.249 58.20 55.4 16.8 7.51 80.2 44.5 19.3 24 success
26 44136 Jagadevi M 23/10/2008 1.43 32 2 4 4 4 3 3 2 2 2 1 76% 90% 90% 91% 93% 95% 96% 98% 98% 7.222 52.300 38.3 18.8 7.34 82.3 30.4 20.3 48 success
27 279089 Radhika M 30/10/2008 1.27 31 6 5 5 4 4 3 2 2 2 70% 91% 91% 92% 93% 95% 96% 98% 7.249 51.20 41.1 19.6 7.312 81.6 36.6 20 36 success
28 44305 Syeda Tasleem F 3/11/2008 1.15 31 6 5 5 4 4 3 1 1 1 1 75% 90% 90% 92% 93% 95% 96% 98% 98% 7.086 48.70 66.3 18.6 7.515 78.9 18.9 20.2 40 success
29 44665 Shanta M 6/12/2008 1.19 31 5 5 4 4 3 3 2 1 76% 90% 92% 94% 95% 96% 96% 7.361 58.10 34.3 19.8 7.43 82.1 26.5 22.1 20 success
30 44669 Shweta M 7/12/2008 1.18 31 5 4 4 4 3 3 2 1 80% 91% 93% 95% 96% 98% 98% 7.31 42.20 38.6 18.6 7.43 82.3 26.5 21.7 18 success
31 44782 Afreen M 16/12/2008 1.28 31 3 6 5 5 4 4 2 2 2 82% 90% 92% 94% 96% 97% 98% 98% 7.30 49.90 38.6 16.7 7.399 80.3 30.6 19.8 36 success
32 286418 Parvati M 28/1/2008 1.68 33 6 5 5 4 4 4 2 1 78% 91% 91% 93% 95% 96% 97% 7.355 76.30 36.3 17.8 7.43 88.3 26.9 19.7 24 success
33 286578 Sunita--I M 30/1/2008 0.90 28 1 4 4 4 3 3 2 2 2 1 1 80% 90% 90% 91% 92% 93% 94% 96% 97% 98% 7.331 69.70 43.2 19 7.368 75.6 41.9 19.8 72 success
34 286579 Sunita--II M 30/1/2008 1.01 28 1.5 4 5 5 6 6 68% 87% 84% 77% 70% 7.552 68.30 28.7 18.9 7.521 70.1 26.9 17 8 Failure
35 286835 Syeda kishwar Sultana F 3/2/2009 1.09 31 4 4 4 4 3 3 2 1 76% 90% 91% 93% 95% 97% 98% 7.21 52.30 44.7 18 7.33 82.2 37.7 19.5 20 success
36 288405 Seema Anjum M 26/2/2009 1.06 29 4 5 5 5 6 6 7 69% 87% 86% 76% 67% 7.247 45.20 25.9 18.1 7.43 42.5 32 16.7 8 Failure
37 45649 Radhika F 9/3/2009 1.30 31 6 5 5 4 4 3 2 2 71% 90% 92% 93% 95% 97% 98% 7.259 42.00 41.3 19.8 7.334 81.1 30.9 20.8 22 success
Mother's Name
MASTER CHART - CASES
Sl. No.
Before CPAP
SAS SCORE
IP No. After CPAP
WEI
GH
T IN
KG ARTERIAL BLOOD GAS ANALYSIS
DOB OutcomeAfter CPAP After CPAPSex
Ges
tati
onal
Age
in
Wee
ks
Dur
atio
n of
C
PA
P in
Hrs
Age
At
inst
itu
tion
of
CP
AP
In
Hrs
Bef
ore
CP
AP Before
CPAP
SPO2
CASES 2
1 Hrs 2 Hrs 4 Hrs 6 hrs12 Hrs
24 Hrs
36 Hrs
48 Hrs
72 Hrs
1 Hrs 2 Hrs 4 Hrs 8 Hrs 12 Hrs 24 Hrs 36 Hrs 48 Hrs 72 Hrs pH PaO2PaCO
2HCO3 pH PaO2
PaCO2
HCO3
Mother's NameSl. No.
Before CPAP
SAS SCORE
IP No. After CPAP
WEI
GH
T IN
KG ARTERIAL BLOOD GAS ANALYSIS
DOB OutcomeAfter CPAP After CPAPSex
Ges
tati
onal
Age
in
Wee
ks
Dur
atio
n of
C
PA
P in
Hrs
Age
At
inst
itu
tion
of
CP
AP
In
Hrs
Bef
ore
CP
AP Before
CPAP
SPO2
38 289315 Rajeshwari M 11/3/2009 1.08 29 6 6 5 5 4 4 2 2 1 76% 90% 91% 93% 95% 96% 96% 97% 7.215 54.80 43.8 18.3 7.421 81.8 25.7 19.6 28 success
39 45852 Nasreen F 19/3/2009 0.86 28 2 4 4 4 4 3 1 1 1 67% 91% 91% 92% 94% 95% 96% 97% 7.08 56.50 66.1 17.8 7.41 66.8 18.9 19.3 36 success
40 45897 Pushpavathi --I F 22/3/2009 1.40 32 6 4 4 3 3 2 1 1 1 1 75% 90% 91% 92% 93% 94% 95% 96% 98% 7.165 48.30 58.9 17.5 7.334 71.1 30.9 19.1 48 success
41 45898 Pushpavati--II F 22/3/2009 1.20 31 5 5 5 5 4 3 2 1 1 78% 91% 92% 94% 95% 95% 96% 98% 7.31 52.10 36.4 17.3 7.422 66.1 24.1 20.2 28 success
42 290815 Jabeen Banu M 3/4/2009 1.81 33 3 5 5 4 4 3 2 1 69% 90% 91% 92% 94% 95% 96% 97% 7.262 61.20 48.2 16.2 7.357 76.1 35.7 19.7 36 success
43 290891 Sulochana M 3/4/2009 1.10 31 5 4 4 3 3 2 1 1 1 1 1 75% 90% 91% 92% 93% 95% 96% 96% 97% 97% 7.262 68.20 48.20 19.20 7.357 76.20 35.70 20.20 72 success
44 290970 Gouramma M 5/4/2009 1.00 28 2 4 4 5 6 6 7 69% 87% 89% 86% 80% 71% 7.173 63.20 56.3 16.8 7.26 78.2 40.1 16.2 12 Failure
45 291453 Jayashree M 12/4/2009 1.08 31 4 4 4 3 3 2 1 1 72% 90% 92% 93% 94% 95% 96% 7.322 66.20 43.1 18.6 7.409 82.3 23.4 19.3 24 success
46 46232 Ambika F 16/4/2009 1.37 32 5 4 4 4 3 3 1 1 1 81% 90% 91% 92% 93% 94% 95% 96% 7.331 69.70 43.2 20.2 7.368 82.1 41.9 21.5 30 success
47 291795 Sangeeta F 17/4/2009 1.12 31 3 5 5 4 4 3 2 2 2 78% 91% 92% 93% 94% 95% 96% 97% 7.215 54.70 41.9 17.3 7.412 82.8 25.7 18.4 32 success
48 46285 Jagadevi M 19/4/2009 1.43 32 2 5 5 4 3 3 2 1 1 1 72% 90% 91% 92% 94% 95% 95% 96% 97% 7.247 45.20 25.9 18.6 7.43 56.2 32 19.4 48 success
49 46808 Bhagyashree M 27/5/2009 1.52 32 6 5 5 5 4 3 2 2 2 2 1 70% 91% 92% 93% 94% 95% 96% 97% 97% 98% 7.165 49.30 58.9 16.6 7.32 82.1 30.2 18.9 60 success
50 46869 Bhagyashree M 30/5/2009 1.40 32 5 5 5 4 4 3 2 1 1 1 77% 92% 93% 94% 95% 96% 97% 97% 97% 7.215 54.80 44.8 18.9 7.41 68.1 25.3 20.3 48 success