RESPIRATORY DISTRESS SYNDROME

RDS, also known as hyaline membrane disease, is a common cause of respiratory disease in
the premature infant. RDS is also seen in infants whose mothers have diabetes in pregnancy. RDS is
caused by a deficiency of alveolar surfactant, which increases surface tension in alveoli, resulting in
microatelectasis and low lung volumes. RDS affects 40,000 infants each year in the US and accounts
for approximately 20% of neonatal deaths. RDS typically affects infants < 35 weeks gestational age
(GA) but may affect older infants who have delayed lung maturation. Low GA is the greatest risk
factor for RDS, and its incidence varies inversely with birth weight among AGA infants (Edwards et al,
2013).
The primary cause of RDS is inadequate pulmonary surfactant. The structurally immature
and surfactant-deficient lung has decreased compliance and a tendency to atelectasis; other factors
in preterm infants that increased the risk of atelectasis are decreased alveolar radius and weak chest
wall. With atelectasis, well perfused but poorly ventilated areas of lung lead to V/Q mismatch (with
intra-pulmonary shunting) and alveolar hypoventilation with resultant hypoxemia and hypercarbia.
Severe hypoxemia and systemic hypoperfusion result in decreased O2 delivery, anaerobic
metabolism and subsequent lactic acidosis. Hypoxemia and acidosis may further impair oxygenation
by causing pulmonary vasoconstriction, resulting in right-to-left shunting at the levels of the foramen
ovale and ductus arteriosus. Other factors, such as baro/volutrauma and high FIO2, may initiate
release of inflammatory cytokines and chemokines causing more endothelial and epithelial cell
injury. The injury results in reduced surfactant synthesis and function as well as increased
endothelial permeability leading to pulmonary edema. Leakage of proteins into the alveolar space
further exacerbates surfactant deficiency by causing surfactant inactivation. Macroscopically, the
lungs appear congested, atelectatic and solid. Microscopically, diffuse alveolar atelectasis and
pulmonary edema are seen. An eosinophilic membrane composed of a fibrinous matrix of materials
from the blood and cellular debris (the hyaline membrane) lines the visible airspaces that usually
constitute dilated terminal bronchioles and alveolar ducts (Hibbard et al, 2010).
Signs of RDS appear immediately after birth or within 4 hours. RDS is characterized by
tachypnea (>60 breaths/min), intercostal and subcostal retractions, nasal flaring, grunting, and
cyanosis in room air. Tachypnea is due to an attempt to increase minute ventilation to compensate
for a decreased tidal volume and increased dead space. Retractions occur as the infant is forced to
generate a high intrathoracic pressure to expand the poorly compliant lungs. Grunting results from
the partial closure of the glottis during forced expiration in an effort to maintain FRC. After an initial
improvement with resuscitation and stabilization, an uncomplicated course is often characterized by
a progressive worsening for 48 to 72 h. Recovery usually coincides with a diuresis after an initial
period of oliguria. Other clinical features may include hypotension, acidosis and hyperkalemia. The
typical chest radiograph shows low lung volumes and a bilateral, reticular granular pattern (ground
glass appearance) with superimposed air bronchograms. In more severe cases, there is complete
“white out” of the lung fields. Application of positive airway pressure may minimize or even
eliminate these radiographic findings. Acute complications include air leaks and intracranial
hemorrhage. Long-term, RDS has been associated with an increased incidence of chronic lung
disease, ROP, and neurologic impairment (Mahoney and Jain, 2013).
The goals of management of an infant with RDS are to avoid hypoxemia and acidosis,
optimize fluid management (avoid fluid overload and resultant body and pulmonary edema while
averting hypovolemia and hypotension), reduce metabolic demands and maximize nutrition,
minimize lung injury secondary due to volutrauma and oxygen toxicity. The three most important
advances in prevention and treatment of RDS have been antenatal glucocorticoids, continuous
positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP), and surfactant
replacement therapy. These have dramatically decreased morbidity and mortality from RDS (Carlo et
al, 2011).
Antenatal glucocorticoids accelerate fetal lung maturity by increasing formation and release
of surfactant and maturing the lung morphologically. Physiologic stress levels of corticosteroids
administered to the mother initiate a receptor-mediated induction of specific developmentally
regulated proteins in the fetus. Administration of glucocorticoids at least 24 to 48 h (and no more
than 7 days) before preterm delivery decreases both incidence and severity of RDS. They are most
effective before 34 weeks. However, antenatal steroids should still be considered when therapy is
less than 24 h before anticipated delivery because a reduction in neonatal mortality and RDS can still
occur in this time frame. Repeated (>3) courses of corticosteroids have been associated with
decreased fetal growth and poorer neurological outcomes. Antenatal steroids also reduce the
incidence of intraventricular hemorrhage, an effect that is independent of lessened pulmonary
morbidity and that may be secondary to stabilization of cerebral blood flow or maturation of
cerebral vasculature. The effects of antenatal steroids and surfactant have been demonstrated to be
additive in improving lung function (Abbasi et al, 2010).
It has been shown in multiple randomized controlled trials that the use of exogenous
surfactant in preterm infants improves oxygenation, decreases air leaks, reduces mortality due to
RDS, and decreases overall mortality. Several studies have shown that two doses, 12 h apart, may be
more effective than single dose therapy. More than 2 doses is rarely required and is rarely effective.
The dose of surfactant is: Infasurf™ 3mL/kg or Survanta™ 4 mL/kg. Two approaches have been used
for surfactant delivery: prophylactic and rescue treatment (Bahadue an Soll, 2012).
 Prophylactic administration involves giving surfactant soon after birth, as soon as the infant
has been stabilized. The theoretical benefit of this approach is that replacement of surfactant before
RDS develops will avoid or ameliorate lung injury. Animal studies have shown that the lung
epithelium of very premature subjects can be damaged within minutes of onset of ventilation. The
damage can result in protein leak which subsequently interferes with surfactant function. For
prophylactic administration, the position of the endotracheal (ET) tube should be verified by two
people before surfactant is given. Attach the surfactant syringe to the side port of the ET tube,
occlude end of ET tube, and administer surfactant as a single aliquot over ≈ 5 sec (Bahadue et al,
2012).
Rescue administration involves giving surfactant to infants who have established RDS and
require mechanical ventilation and supplemental O2. The advantage of this approach is that patients
are not treated unnecessarily. Because surfactant currently can only be given via an endotracheal
tube, this would prevent intubation and mechanical ventilation of infants who would do well
without surfactant and avoid unnecessary baro/volutrauma, adverse physiological effects of
laryngoscopy, and possible inadvertent hyperventilation. Past studies have shown greater reduction
in neonatal mortality with prophylactic administration versus rescue, especially in infants greatest at
risk for RDS (i.e., with the advantages of avoiding mechanical ventilation and volutrauma. For rescue
therapy, obtain chest radiograph to confirm tube position. Administer surfactant through a feeding
tube inserted to (but not past) the end of the ET tube. Administer in same manner as with
prophylactic treatment. Slower administration may interfere with its efficacy. After administration,
the infant should be hand ventilated and may transiently require higher ventilatory support. Rescue
treatment with surfactant should be given to preterm infants who have respiratory distress,
necessitating intubation and assisted ventilation; no radiological evidence of another disease
process; a mean airway pressure ≥7 cmH2O (Bahadue and Soll, 2012)
Although surfactant administration is relatively safe, complications include obstruction of
the endotracheal tube, transient increases in O2 requirement and ventilatory settings, and
pulmonary hemorrhage, an infrequent adverse effect reported in 2-6% of infants given surfactant.
Oxygen should be administered to preterm infants in concentrations sufficient to maintain PaO2
between 50-70 mmHg or saturation (by pulse oximetry) between 85-92%. Higher O2 concentrations
may exacerbate lung injury and will increase the risk of retinopathy of prematurity. The initial
decision in respiratory management of an infant with RDS is whether the infant can be adequately
managed with nasal CPAP (i.e., no treatment with surfactant) or should receive endotracheal
intubation, surfactant therapy and mechanical ventilation. The goals of ventilatory management in
the intubated infant are to maintain adequate oxygenation and ventilation while minimizing
ventilator induced lung injury. To achieve these aims, utilize a strategy of permissive hypercarbia,
maintaining PaCO2 between 45- 55 mmHg, theoretically reducing volutrauma and preventing
deleterious effects of hypocarbia. To reduce further the risk of volutrauma, adjust ventilatory
pressures to maintain tidal volume between 4-5 mL/kg (Hibbard et al, 2010).
Administration of surfactant improves lung mechanics (increase lung compliance) and
increases oxygenation by reducing atelectasis and increasing FRC. It is extremely important to
recognize the time frame of these changes. After surfactant administration, there may be very rapid
improvements in pulmonary function that necessitate rapid weaning of ventilator settings. Close
attention must be paid to tidal volume, blood gas tensions, transcutaneous CO2 and pulse oximetry
values in order to avoid inadvertent hyperventilation, hyperoxia and overdistension of the lung, all
of which can result in lung injury. Although it may be necessary to wean FIO2, inspiratory pressure
and ventilator rate, one should decrease PEEP with extreme caution. Infants in the early phases of
RDS will rarely maintain adequate lung inflation if PEEP is < 5 cmH2O, even after administration of
surfactant (Mahoney et al, 2013).
Recently, much effort has been directed towards other, less invasive modalities of
respiratory support to prevent lung injury, specifically nasal CPAP. CPAP, as treatment for RDS, was
first described in 1971 by George Gregory at UCSF. Modifications in the nasal CPAP delivery system
have generated renewed interest in nasal CPAP for the ventilatory management of RDS. Randomized
controlled trials have shown a decreased need for mechanical ventilation in VLBW infants treated
with nasal CPAP, although the impact on mortality and chronic lung disease have not been defined.
Furthermore, recent reports indicate that approximately 70% of infants with birth weight < 1,000 g
will not be adequately managed with nasal CPAP and will require intubation and mechanical
ventilation. Nevertheless, in order to minimize ventilator-induced lung injury, early extubation to
nasal CPAP is a reasonable strategy. Criteria for extubation to nasal CPAP in the first week of life are
adequate respiratory drive, mean airway pressure < 7 cmH2O, and FiO2 < 0.35 (Edward et al, 2013).
Nasal CPAP is delivered via a specialized nasal mask or prongs, utilizing a patient demand
flow system. CPAP is administered between 4 and 6 cmH2O. Lower pressures do not maintain lung
inflation and higher pressures often cause gastric distension. Limitations to the use of nasal CPAP
include hypercarbia, frequent episodes of apnea, gastric distension and breakdown of nasal skin and
mucosa from the mask/prongs. The method and timing of further weaning, from nasal CPAP to
supplemental O2 via nasal cannula, varies with gestational age, post-natal age, weight and stability
of the individual patient. Some infants require a gradual transition to nasal cannula through
“sprinting,” a process in which infants are trialed on nasal cannula for a portion of the day and then
returned to nasal CPAP. As the infant demonstrates increased tolerance of these trials, the length of
these trials is slowly extended.. The time of these trials often coincides with feeds, in order to
minimize handling of VLBW infants (e.g., if feedings are q3 hours, trials of nasal cannula are usually
increased in 3 hour intervals) (Hibbard et al, 2010).
The clinical and radiographic features of pneumonia may be indistinguishable from RDS at
birth. As a result, all infants with RDS should have blood cultures and CBC drawn, and should receive
empiric antibiotic therapy (Ampicillin and Gentamicin). Generally, antibiotics may be discontinued if
the blood culture has no growth after 48 hours, unless prenatal history or clinical scenario warrants
extended treatment (Mahoney et al, 2013).
Careful temperature control is imperative in all VLBW infants and is especially important in
infants with RDS to minimize metabolic demands and oxygen consumption. RDS can limit oxygen
uptake leading to hypoxia which limits the ability of an infant to increase their metabolic rate when
cold stressed, resulting in a fall in body temperature. An incubator or radiant warmer must be
utilized to maintain a neutral thermal environment for the infant (Mahoney et al, 2013).

Edwards MO, Kotecha SJ, Kotecha S. Respiratory distress of the term newborn infant. Paediatr Respir
Rev. 2013;14(1):29–36
Hibbard JU, Wilkins I, Sun L, et al; Consortium on Safe Labor. Respiratory morbidity in late preterm
births. JAMA. 2010;304 (4):419–425
Mahoney AD, Jain L. Respiratory disorders in moderately preterm, late preterm, and early term
infants. Clin Perinatol. 2013;40(4): 665–678
Carlo WA, McDonald SA, Fanaroff AA, et al; Eunice Kennedy Shriver National Institute of Child Health
and Human Development Neonatal Research Network. Association of antenatal corticosteroids with
mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation.
JAMA. 2011;306 (21):2348–2358
Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory
distress syndrome. Cochrane Database Syst Rev. 2012;11:CD001456
Abbasi S, Oxford C, Gerdes J, Sehdev H, Ludmir J. Antenatal corticosteroids prior to 24 weeks’
gestation and neonatal outcome of extremely low birth weight infants. Am J Perinatol. 2010;27(1):
61–66
KANGAROO MOTHER CARE
Kangaroo mother care (KMC) is a method of care of preterm or low birth weight (LBW)
infants by placing them in skin to skin (STS) contact with mother or other caregiver in order to
ensure optimum growth and development of the infant. It has proved effective in meeting a baby’s
needs of warmth, breastfeeding, protection from infection, stimulation, safety and love. Its key
features include early, continuous, and prolonged skin-to-skin contact between the mother and the
baby, and exclusive breastfeeding (ideally) or feeding with breaastmilk. The World Health
Organization defines KMC with 4 components: early, continuous, and prolonged skin-to-skin contact
(SSC) between the newborn and mother, exclusive breastfeeding, early discharge from the health
facility, and close follow-up at home (Uyanage, 2005)
The aim is for early initiation of KMC and for continuous performance (over 18 hours per
day), but initiation, continuity and duration may vary according to the stability of the infant and the
context of care. Other key components of KMC are support for exclusive and early breastmilk
provision and timely discharge from the hospital with appropriate follow-up. KMC was first
developed and scientifically evaluated in Colombia over three decades ago as an alternative to
incubator care. The evidence generated in Colombia allowed authorities to gradually include KMC in
national LBW guidelines and spread the practice to a large number of health facilities. Recently, with
preterm birth becoming the leading cause of under-five mortality, and additional evidence on KMC’s
mortality benefit, more attention has been focused on scaling up the practice (Boundy et al, 2016).
There were two type of KMC, continuous and intermittent. Continous KMC is defined as the
practice of skin-to-skin care continuously throughout the day without breaking the contact between
mother and baby. While intermittent KMC is the practice of skin-to-skin care alternated with the use
of either a radiant warmer or an incubator care for the baby (Boundy et al, 2016).
KMC does not need special equipment or facilities. Baby, dressed in nappy, is placed upright
against mother’s bare chest, between her breasts and inside her blouse (figures 1). Baby’s head is
turned to a side so that ear is at the same level as the mother's heart. Both mother and the baby
should be covered in with blanket if it is cold (Uyanage, 2005).
Figure 1 Kangaroo Mother Care (KMC) position (uyanage, 2005)

Babies can be breast fed while in kangaroo care. If baby is not mature enough to suck from
breast alternative methods such as tube feeding and cup feeding can be practised in this position.
Monitoring of temperature, breathing and colour is important till KMC is well established and
mother is confident (Vessel et al, 2015).
All stable LBW babies are eligible for KMC. However, sick and very small babies (<1200 gm)
needing special care should be cared under radiant warmer initially. KMC should be started after the
baby is hemodynamically stable. Short KMC sessions can be initiated during recovery with ongoing
medical treatment (IV fluids, oxygen therapy). KMC can be provided while the baby is being fed via
orogastric tube or on oxygen therapy (Boundy et al, 2016).
The distinction between KMC and skin-to-skin care should be clear. Skin-to-skin care for
term newborns - where babies are placed on their mothers chest directly after birth as part of basic
newborn care and intermittently thereafter - helps to promote warmth, bonding and breastfeeding
as part of a continuum of woman and baby-centred care. KMC is intended for infants < 2000 g with
the aim of thermal regulation achieved through continuous skin-to-skin contact in the KMC position.
KMC may be required for weeks and is carried out alongside other aspects of care for the preterm
baby (Vessel et al, 2015).
When held skin-to-skin at mother’s breast, temperature quickly becomes sufficient to
maintain infant's body temperature. Therefore KMC provides effective thermal control and reduces
risk of hypothermia. It is the only effective and affordable method to prevent neonatal hypothermia
in health care units with limited resources. Many studies show that these babies had better weight
gain and earlier hospital discharge. Furthermore randomised controlled trials carried out in
lowincome countries showed that this method increased the prevalence and duration of
breastfeeding (Vessel et al, 2015)
 KMC should be encouraged as soon as possible after birth because it improves bonding
between mother and baby and reduces maternal stress . Some studies have shown that mothers
prefer skin-to-skin contact to conventional incubator care since it increases their confidence, self-
esteem, and feeling of fulfilment. In addition KMC has a significant positive impact on the infant’s
cognitive and motor development (Boundy et al, 2016).
When compared with conventional care, KMC is associated with decreased mortality among
newborns who survive to receive it, particularly among LBW infants. KMC also increases likelihood of
exclusive breastfeeding up to 4 months of age and decreases risk of newborn sepsis, hypothermia,
hypoglycemia, and hospital readmission. Additionally, infants receiving KMC have improved vital
signs, greater head circumference growth, and lower pain scores. There were no evidence of harm
related to KMC. Although the improvements in respiratory rate, oxygenation, and temperature that
we found associated with KMC exposure may each be of modest clinical significance, when taken
together they support the hypothesis that KMC improves overall physiologic regulation in the
neonate, which could have important effects on other longer-term outcomes. Lower pain measures
among infants receiving KMC may also provide additional benefits for LBW infants who experience
numerous injections during hospitalization (Boundy et al, 2016)
When the mother and baby are comfortable, KMC is continued for as long as possible, at the
institution and then at home. Often this is desirable until the baby's gestation reaches term or the
weight is around 2500 g. She starts wriggling to show that she is uncomfortable, pulls her limbs out,
cries and fusses every time the mother tries to put her back skin to skin. This is the time to wean the
baby from KMC. Mothers can provide skin-to-skin contact occasionally after giving the baby a bath
and during cold nights (Vessel et al, 2015).
Close follow up is a fundamental pre-requisite of KMC practice. Baby is followed once or
twice a week till 37-40 weeks of gestation or till the baby reaches 2.5 to 3 kg of weight. Thereafter, a
follow up once in 2-4 weeks may be enough till 3 months of post-conception age. Later the baby
should be seen at an interval of 1-2 months during first year of life. The baby should gain adequate
weight (15- 20 gm/kg/day up to 40 weeks of post-conception age and 10 gm/kg/ day subsequently).
More frequent visits should be made if the baby is not growing well or his condition demands
(Boundy et al, 2016)

Boundy EO, Dastjerdi R, Spiegelman D, et al. Kangaroo Mother Care and Neonatal Outcomes: A
Meta-analysis. Pediatrics. 2016;137(1):e20152238
Liyanage G. Kangaroo mother care. Sri Lanka Journal of Child Health, 2005; 34: 13-5
Vesel et al.: Kangaroo mother care: a multi-country analysis of health system bottlenecks and
potential solutions. BMC Pregnancy and Childbirth 2015 15(Suppl 2):S5.