RESPIRATORY DISTRESS SYNDROME

Moderator : Dr. NIRANJAN

Presenter : Dr. M.A. RAHEEM

Introduction• Respiratory distress syndrome

(RDS) – the most common respiratory disorder in preterm neonates

• Once the major cause of mortality in premature neonates

• The incidence and severity of RDS is inversely related to the gestational age and birth weight of infant

• The Severity peaks at 24-48 hours, resolution by 72-96 hours (even without surfactant therapy)

• HMD is the most common cause of respiratory failure during the first days after birth

DEFINITION• Acute lung disease of the

newborn caused by surfactant deficiency

• RDS is the clinical expression of surfactant deficiency and its histologic counterpart, hyaline membrane disease (HMD)

INCIDENCE• 60-80% of <28wk GA ; 15-30% of 32-36wk GA ;

5% of 37wk-term

• In a report from the NICHD Neonatal Research Network, Fanaroff and coworkers reported that 71% of infants between 500 and 750 g had RDS 54% between 751and 1000 g, 36% between 1001 and 1250 g, and22% between 1251 and 1500 g

• Incidence of RDS varies from 6.8 to 14.1%

in preterm live births in our country with

the incidence being about 58% in infants <

30 wks, 32% in infants b/w 30-32 wks and

10% in infants b/w 33-34 wks gestation

• 2003 report of National Neonatal Perinatal

Database (NNPD), the incidence of RDS

in our country was 1.2 % of all live births

DEVELOPMENT OF LUNG• Typically lung development has been divided

into five stages:

• Embryonic (3.5-7 weeks)

• pseudoglandular (5-17 weeks )

• Canalicular (16-26 weeks )

• Saccular ( 24-38 weeks )

• alveolar period (32 weeks to 2years post

natally)

• The alveolar period has been split in two and a

sixth stage has been defined as the period of

microvascular maturation (birth to 3 years post

natally )

• The human lung originates as a

ventral endodermal pouch from the

primitive foregut during the fourth

week of embryonic life

• The endodermal bud will then

elongate, growing caudally, where it

will bifurcate into the primary left and

right lung buds

• The two lung buds (primary bronchi) will then

grow out in a posterior-ventral direction into the

splanchnic mesenchyme, where they will branch

again, with the left bronchi forming two

secondary bronchi and the right bronchi forming

three secondary bronchi

• Each of these secondary bronchi represents a

future lobe of the mature lung, and will undergo

further branching, thus expanding the major

airways within each lobe of the lung

LUNG MATURATION

• Lung maturation is a complex process requiring

establishment of highly branched tubes that lead

to a gas exchange area capable of supporting

respiration following birth

• By 24 weeks gestation during the canalicular-

saccular transition of lung morphogenesis,

respiratory epithelial cells in the lung periphery

begin to undergo differentiation marked by

accumulation and then utilization of glycogen

stores for lipid synthesis

• During the saccular stage of development,

structural and biochemical maturation of the lung

proceeds, associated with increasing

vascularization of peripheral airspaces and

thinning of the pulmonary mesenchyme

• Interactions between mesenchymal fibroblasts

and the epithelium result in the differentiation of

type II epithelial cells, with their characteristic

lamellar body inclusions, a storage granule for

pulmonary surfactant

• Type II cells differentiate to produce the highly

differentiated squamous type I epithelial cells

that form an increasing proportion of the

saccular-alveolar surface of the lung with

advancing gestation

• In the normal lung, differentiation of the type II

epithelial cell begins at 24–26 weeks gestation

and can be precociously induced by hormonal

stimulation with glucocorticoids

• Avery and Mead in 1959 were the first to

demonstrate that surfactant is deficient in the

lungs of infants dying of HMD

• Surfactant is identifiable in fetal lung as early as

16 weeks, though its proper secretion begins

after 24 weeks gestation and is synthesized

most abundantly after the 35th week of gestation

• Pulmonary Surfactants are phospholipids

synthesized in the type II cells lining the alveoli

Surfactant• Phospholipid produced

by alveolar type II cells

• Lowers surface tension.

• As alveoli radius decreases, surfactant’s ability to lower surface tension increases

• The half-life of surfactant is 30 hours

Insert fig. 16.12

Figure 16.12

Production and release

Type ll cell

Alveolar air

space

Hypophase

Type I cell

Basal lamina

Capillaryendothelium

Monolayer Hypophase

Alveolar gas

LMVB

Golgi

RERDMVB

Type I cell

Tubular myelinLamellar

bodies

Fig. 1. B, type II cells produce surfactant, which is stored in lamellar

bodies(1)and secreted into the alveolar space (2). The surfactant is

transformed (3) into tubular myelin (4),from which the monolayer (5) is

formed. After the surfactant is used, it is taken up again (6) by the type

II cells and reused (7).

Composition

12 3 4 5 6

7

DPPC - dipalmitoylphosphatidylcholine 50%*

• Reduces alveolar surface tensionPG - phosphatidylglycerol

7%*• Promotes the spreading ofsurfactant throughout the lungs

Apoproteins or surfactant

specific proteins 2%*

1. Serum proteins 8%*2. Other lipids 5%*3. Other phospholipids 3%*4. Phosphatidylinositol 2%*5. Sphingomyelin 2%*6. Phosphatidylethanolamine 4%*7. UnsaturatedPhosphatidylcholine 17%*

* By molecular weight

Endogenous Surfactantcomposition and functions

• Major Lipids (~90%) Saturated Phosphatidylcholine DPPC (Lecithin) 60-80%

Unsaturated Phosphospholipids

Phosphatidylglycerol (PG) ~10%

• Proteins (~10%)

SP-A

Hydrophilic, Host defence

Surfactant homeostasis

SP-B

Hydrophobic, Spreading, surface tension

SP-C

Hydrophilic , Adsorption

SP-D: ? Phagocytic function

SURFACTANT

Function of the Surfactant:-

Decrease the surface tension

To promote lung expansion during inspiration

To prevent alveolar collapse and loss of lung volume at

the end of expiration

SURFACE TENSION

• The cohesive forces among liquid

molecules are responsible for

phenomenon of surface tension

• In the bulk of liquid each molecule is

pulled equally in every direction by

neighboring liquid molecules resulting in

net force of zero

• Molecules at the surface do not have

other molecules on all sides of them

and therefore are pulled inwards

• This creates some internal pressure

and forces liquid surfaces to contract

to minimal area

Surface TensionWater has a VERY HIGH surface tension

Water will attempt to minimize its surface

area in contact with air

An air-filled sphere coated with water has a

tendency to collapse (reach a minimum

volume) due to the pulling force of water

surface tension

Alveoli are coated with lung surfactant in order

to reduce the surface tension of water, thus

preventing collapse (atelectasis) upon

exhalation and decreasing the force necessary

to expand the alveoli upon inhalation

Lipids form a monolayer at the air-water interface

Surface tension decreases as lipid monolayer is

compressed

Law of Laplace• Pressure in alveoli is

directly proportional to

surface tension and

inversely proportional to

radius of alveoli

• Pressure in smaller

alveolus greater

Insert fig. 16.11

Figure 16.11

SURFACTANT

• Diminished surfactant :

Progressive Atelectasis

Loss of functional residual capacity

Alterations in ventilation perfusion ratios

Uneven distribution of ventilation

• Instability of terminal airspaces due to

elevated surface forces at liquid-gas

interfaces

• Stable alveolar volume depends on a

balance between: 1)surface tension at the

liquid-gas interface, and 2) recoil of tissue

elasticity

pathophysiology

Pathophysiology

• Reduced lung compliance (1/5th -1/10th)

• Poor lung perfusion ( 50-60% not perfused),

decreased capillary blood flow

• R--> L shunting ( 30-60% )

• Alveolar ventilation decreased

• Lung volume reduced

• Increased work of breathing

• Hypoxemia, hypercarbia, acidosis

Pathology• Characteristic injury to terminal airways beginning

within the first few breaths

• Lungs are solid, congested, with destruction of

epithelium of terminal conducting airways

• Hyaline membranes: coagulum of sloughed cells

and exudate, plastered against epithelial

basement membrane

• Photograph of an autopsy specimen demonstrates small atelectatic lungs with focal hemorrhage (arrow) visible on the pleural surface.

Gross : Lung firm, red, liverlike

• Microscopic : Diffuse atelectasis, pink

membrane lining alveoli & alveolar ducts.

Pulmonary arterioles with thick muscular

coat, small lumen. Distended lymphatics

• Electron microscopic : Damage / loss of

alveolar epithelial cells, disappearance of

lamellar inclusion bodies, swelling of

capillary endothelial cells

Lung Function in HMD

• Reduction in FRC from 30 ml/kg, to as low as 4-

5 ml/kg

• Caused by loss of volume and interstitial edema

• FRC mirrors changes in oxygenation

• Improvements can be due to distending

pressure, surfactant replacement, or clinical

resolution

• Lung Compliance is also reduced: from 1-2 to

0.2 -0.5 ml/cmH2O/kg

• Reduction due to decreased number of

ventilated alveoli, and increase in recoil pressure

of ventilated airspaces

• Lung resistance is significantly increased

Clinical presentation

• Signs usually develops before the neonate is 6

hours old and persist beyond 24 hours

• progressive worsening until day 2-3 and onset

of recovery by 72 hours

• Respiratory rate above 60/min

• Grunting expiration

• Indrawing of the chest, intercostals spaces and

lower ribs

• Cyanosis without oxygen

• The diagnosis of HMD by NNPD requires all of

the following three criteria:

Preterm neonate

Respiratory distress having onset within 6 hours

of birth

Amniotic fluid L/S ratio of <1.5, or negative

gastric aspirate shake test, or X ray evidence

OR Autopsy evidence of HMD

• Risk factors:

• Prematurity

• Maternal diabetes, perinatal asphyxia, C-section

without labor

• White race, male sex

• Hypothermia, hypothyroidism

• Familial predisposition (AR)

• 2nd twin

Genetic Predisposition to RDS

• Susceptibility to RDS is interaction between genetic,

environmental and constitutional factors

• Very preterm infants

• Common allels preddicts RDS: SP- A 642, Sp-B121, Sp-

C 186 ASN.

• Near Term:

Rare alleles increase the risk: SP-A 643.

• Term Infants: Loss of function mutation of SP-B, SP-C,

ABCA3

• Protective factors

• STEROIDS

• Chronic PIH

• IUGR

• Maternal narcotic addiction

• PROM

• Sickle cell disease

• Chronic Renal disease

• Catecholemines, prolactin, thyroxine, estrogen

Antenatal Corticosteroid Effects on lung and Surfactant production

• lung structure changes within 1 day – the

mesenchyme thins, the potential airspace

increases, and the epithelium is more resistant

to injury and the development of pulmonary

edema

• The corticosteroid-exposed preterm lung may be

surfactant-deficient and both therapies might

have additive effects to improve lung function

• The surfactant from the corticosteroid-treated

lambs is less sensitive to inhibition by plasma

proteins in vitro

• The clinical literature also supports the benefits

of antenatal corticosteroid treatment followed by

surfactant treatments for those infants with RDS

• Corticosteroids are indicated in all women in

preterm labour 24-34 week of gestation who are

likely to deliver a fetus within one week

• 2 doses of bethmethasone 12mg IM

seperated by 24hour interval or 4

doses of dexamethasone 6mg IM at

12 hourly intervals

• Repeated weekly doses of

betamethasone till 32 week gestation

may reduce neonatal morbidities

• Secondary surfactant deficiency may occur in infants with the following:

Pulmonary infections e.g. group B Strep

Pulmonary hemorrhage

Meconium aspiration pneumonia

Oxygen toxicity; barotrauma or volutrauma to the lungs

Congenital diaphragmatic hernia and pulmonary

hypoplasia

Investigations• CBC WITH BLOOD CULTURE

• GRBS

• CHEST X RAY

• ABG

• Gastric aspirate

• To confirm diagnosis:

• Shake test on gastric aspirate

• Amniotic fluid : L / S ratio, SPC, PG

• The X-ray appearances depend on the severity of the disorder, with poorly inflated lungs being the cardinal feature

Grade 1 - mild disease, the lungs show fine homogeneous

reticulogranular pattern

Grade 2 - more severe, widespread air bronchograms

become visible

Grade 3 - development of confluent alveolar shadowing

Grade 4 - severe case, complete white-out of the lung fields

with obscuring of the cardiac border

• L/S ratio

Separates lecithin (PC) and sphingomyelin from

amniotic fluid by TLC

L/S > 2 indicates mature lung

>2.5 = 0.5%, >2 =10% ,

1.5-2 = 15-20%, <1.5 = 60% risk

• Blood & meconium depress mature L/S ratio and may

elevate immature ratio

• Exceptions : IDM ( L/S>3.5 ), Asphyxia, Hydrops, IUGR,

Abruptio, Toxemia

• Saturated Phosphatidylcholine (SPC) > 500 ug/dl(latex agglutination)

• Fluorescence polarization(TDx) measures surfactant – albumin ratio ; >45mg/dl – mature lungs

• Lamellar body count – packages of phospholipids produced by type II alveolar cells, no. ↑ with gestational age

>50,000 lamellar bodies/μlit – lung maturity

• Shake test on gastric aspirates – 0.5ml of NS + 1ml of 95% ethyl alcohol + 0.5ml gastric aspirate in a test tube, shake for 15 min & allow to stand for 15min

Bubbles < 1/3rd – 60% risk

>2/3rd – mature lungs, risk < 1%

Differential Diagnosis• Bacterial pneumonia

• TTNB

• Congenital anomalies

• Massive pulmonary haemorrhage

• Aspiration syndrome e.g. Meconium

• Pulmonary air leaks e.g. Pneumothorax

• Diaphragmatic hernia

• Cardiac anomalies

Differential Diagnosis

• Pulmonary hypoplasia

• PPHN

• Birth asphyxia

• Primary neurological or muscle disease

• Hypothermia

Management• Concepts

• Respiratory

• Prevent hypoxia and acidosis

• Prevent worsening atelectasis, edema

• Minimize barotrauma and hyperoxia

• Supportive management

• Optimize fluid and nutrition management

• Perfusion, Infection, Temperature control

• Respiratory management• Surfactant replacement therapy

• Ventilatory Assistance

Oxygen therapy

• CPAP ( Nasal, ET, Face-mask )

• Positive pressure ventilation

• High-frequency ventilation

• ECMO

• Liquid ventilation

Initial Care• Maintain warmth- cold stress will mimic other

causes of distress

• Monitor blood glucose levels- assure they are

normal

• Provide enough oxygen to keep the baby pink

Temperature Control

• Body Temperature that is too high or too low will

increase metabolic demands

• Servo controlled warmers are very helpful

Initial CareEnsure adequate hydration:

• Start fluids at 80 ml/kg/day 10% glucose solution

• Smaller babies may need more fluid

• Add electrolytes by the 3rd day

• On day 3-4 watch for diuresis as spontaneous diuresis

occurs preceding improvement in pulmonary function

Surfactant replacement therapy

• Fujiwara in 1980 reported the 1st successful clinical

trial of tracheal applications of surfactant in infants

with RDS ,showing that surfactant replacement

therapy improved oxygenation, ventilatory

requirements, x-ray abnormalities, acidosis and

hypotension in 10 preterm infants with RDS

• Commercial preparations of surfactant were

subsequently approved by the FDA in the USA in

1989

Surfactant replacement therapy

• When: Prophylaxis (prevention) vs. Treatment (rescue) ;

Early vs. Late

• What: Synthetic preparation (Exosurf) vs. Natural

(Survanta)

• How: Administration : Indications, Dosage, Technique

Indications• 3 main indications for surfactant administration in newborns

1. Prophylactic therapy

a. Neonates with gestation < 30 weeks of gestation

b. Surfactant given within 15 minutes of birth before a

diagnosis of RDS is made

2. Early Rescue therapy

a. Neonate with RDS (confirmed clinically & radiologically).

b. Surfactant given within first 2 hours of life

3. Late Rescue therapy

a. Neonate with RDS and requiring ventilation with a MAP of

at least 8 cms of water and/or an FiO2 > 30% ( or a/A ratio

< 0.22) Or PEEP > 7

b. Surfactant given after 2 hours of birth

Timing of surfactant• Surfactant may be given as:

Prophylactic therapy

Early rescue therapy

Late rescue therapy

• In reference to decreasing the incidence of air leaks and

mortality, prophylactic therapy is better than early rescue

which in turn is better than late rescue

NomenclatureAt risk baby born

Surfactant given at < 15

min age before

respiratory distress=

“Prophylactic”

Signs of RDS

develop

Nevertheless, if

baby develops

signs of RDS

Multiple doses

Described as part of

“prophylaxis” regime

If baby continues to have

signs of RDS

Multiple doses

Described as part of “rescue” regime

Surfactant given at

<2 hrs, after resp

distress starts but

before obvious

HMD =

“Early rescue”

Surfactant given at

>2 hrs, after

obvious HMD =

“Late rescue” or

“Selective”

Is early rescue better than late?

Early rescue

reduces

Pneumothorax

PIE

BPD

Neonatal mortality

Give surfactant within 2 hours of birth;

the earlier the better

Benefit much more in 29 wks

• Continued post-surfactant intubation and

ventilation are risk factors for BPD

• Early surfactant administration with brief mechanical

ventilation (< 1 hour) was followed by extubation to

nasal CPAP

INSUREIntubation,Surfactantadministration, Extubation

INSURE reduces

Need for mechanical

ventilation

BPD

Number of surfactant

doses/patient

Air leak syndromes

Repeat doses• 2nd or subsequent doses of surfactant are

given if the infant with RDS is requiring

ventilation and has a FiO2 requirement of

> 30%

• A minimum duration of 6 hours is

recommended between any 2 doses of

surfactant. Surfactant is usually not

continued beyond 3 days of life (72 hours)

Benefits of multiple doses

Multiple doses

reduce

Pneumothorax

Mortality

How many doses & how often?

• Current guidelines

• If extubated or on FiO2 <0.4, no more doses

• If improved after 1st dose but worsened again, give

repeat dose irrespective of time gap

• Generally no more than 2 doses required

• Rarely 3, never 4

• Have lower threshold for re-treatment if complicated by

asphyxia or sepsis

Surfactant preparations are of basically 3 types:

• Natural surfactant (animal derived by either

lung mince extract or by lung lavage extract)–

phospholipids with surfactant proteins

• Synthetic surfactant – only phospholipds

• Newer surfactant –synthetic surfactants with

synthetic peptides modelled on surfactant

proteins, Aerosolized surfactants

Exogenous Surfactants• Natural

• Natural: from animal

lungs

• Examples:

• Bovine (beractant):

SURVANTA, NEOSURF

• Porcine (poractant):

CUROSURF

• Animal lung extract +

extra DPPC + palmitate

• Has natural SP-B &

SP-C

• Synthetic

• DPPC + hexadecanol

+ tyloxapol

• Examples:

• Without proteins

(colfosceril):

EXOSURF, SURFACT

• With proteins

(lucinactant): SURFAXI

Naturals Vs Synthetics

Survanta Vs Exosurf

Survanta reduces

Pneumothorax

BPD

ROP

Death

Brand Source Vol Conc Dose MRP (Rs)

Curosurf Porcine

minced

1.5 ml 1 ml= 80 mg 200 & 100

mg/k (1st &

2nd resp.)

[2.5 & 1.25

ml/kg]

10,680

Neosurf Bovine

lavage

3 ml & 5 ml 1 ml= 27mg 135 mg/kg

(5 ml/kg)

3 ml= 4,900

5 ml= 8,000

Survanta Bovine

minced

4 ml & 8 ml 1 ml= 25 mg 100 mg/kg

(4 ml/kg)

4 ml= 7,260

8 ml= 12,000

Cost at diff wt groups

Brand 750 gm 1 kg 1.25 kg 1.5 kg

Curosurf: 1st

2nd

21,360

10,680

21,360

10,680

31,740

10,680

31,740

21,360

Neosurf 8,000 8,000 13,000 13,000

Survanta 7,260 7,260 12,000 12,000

What does surfactant not achieve?

Surfactant generally does not reduce

• ROP

• Severe IVH

• NEC

• Sepsis

Dose

• Survanta 100mg/kg for the first and subsequent

doses.

• Curosurf 200mg/kg for the first dose and 100mg/kg

for the subsequent doses or 100 mg/kg for all the

doses.

Administration of surfactant

• Technique of administering intratracheal surfactant

vary from preparation to preparation

• Entire dose is administered in a single instillation or

aliquots through a feeding tube that is cut to a

length just slightly longer than that of the

endotracheal tube

• Multiple aliquots could be administered

through a feeding tube or side adapter

• A more uniform distribution has been

reported if the aliquots are restricted to 4

and they are administered in the supine

position with interposed ventilations

between aliquots

What to Monitor?

• Before administration

• ETT position

• During administration

• Ventilator settings

• Surfactant reflux

• Chest wall movements

• Vitals

• After

administration

– ABG

– CXR

– Vitals

– Ventilator

settings

– BP

Contraindications to surfactant

• Major malformations

• HIE III

• B/L Grade 4 IVH

• Lab evidence of lung maturity

• Pulmonary haemorrhage.(??)

POOR RESPONSE TO SURFACTANT THERAPY

• Delayed administration

• Leakage of proteinaceous materials into the

alveolar space

• High FiO2 or PIP at entry

• High MAP

• Additional neonatal pulmonary conditions like

pneumonia and perinatal asphyxia

COMPLICATIONS OF SURFACTANTS• Transient hypoxia, bradycardia and fluctuating BP

• Rapid changes in lung compliance leading to

barotrauma if not monitored

• Pulmonary hemorrhage - more with natural(5-6%)as

compared to synthetic(1-3%)

• Theoretical risk of immunological reactions to foreign

proteins

• Theoretical risk of transmission of infective agents such

as prions and virions

Additional Support

• Oxygen

• Continuous Positive Airway Pressure

• Mechanical Ventilation

• Bag and mask / endotracheal tube

• Ventilator if available

• First used by mask in 1936 for acute

insufficiency in ventilation

• First used in 1940s in high altitude flying

• Introduced in treatment of Adult

Respiratory Distress Syndrome in 1967

• First applied to infants with HMD in 1971

CPAP• Indication: Significant respiratory distress, FiO2 >

0.40

• INSURE therapy

• Start with Nasal prong CPAP, 5 cm H2O pressure,

flow 5-10 lpm, FiO2 0.40-0.60

- Mechanism of action• CPAP prevents collapse of unstable alveoli upon

expiration

• Facilitates recruitment of unventilated alveoli

• Reduces right to left shunting across foramen

ovale

• Reduces left to right shunting across the Ductus

Arteriosus, improving cardiac output and blood

pressure

CPAPConcept:

Prevents atelectasis

Reduces pulmonary edema

Improving Functional residual capacity

Correcting ventilation-perfusion abnormalities

Reducing intrapulmonary shunting

Problems:

• High CPAP may decrease venous return

• High CPAP may decrease minute ventilation

• Abdominal distension

CPAP Delivery• Endotracheal tube: simple and efficient, but

increased work of breathing

• Face mask: Easy to apply, inexpensive, but difficult to regulate, causes abdominal distention

• Nasopharyngeal prongs

• Nasal cannulae

• Nasal Prongs: Simple to apply and use, minimal cost, mouth leaks hampers efficacy. Usually the preferred method

CPAP delivery systems

Complications of CPAP

• Pulmonary air leaks - over distension of the

lungs caused by inappropriately high pressures

• Decreased cardiac output due to reduction in the

venous return, decreased right ventricular stroke

volume

• Impedance of pulmonary blood flow with

increased pulmonary vascular resistance

• Gastric distension and ‘CPAP belly syndrome’

• Nasal irritation, damage to the septal mucosa, or

skin damage and necrosis from the fixing

devices

Failure• Worsening respiratory distress

• Hypoxemia (PaO2 <50mmHg) /

hypercarbia (PaCO2 >60mmHg)

despite CPAP pressure of 7-8 cm

H2O and FiO2 of 0.8

• Recurrent episodes of apnea

Mechanical Ventilation• Indications:

• ABG criteria - respiratory acidosis with a pH of <7.20

to7.25 or severe hypoxemia with a PaO2 < 50 to 60

despite a highFiO2 (0.6 to 0.7)

• Clinical criteria - respiratory distress on CPAP, severe

respiratory distress with shock or severe apnea

• Severe apnea

• Decreasing “work of breathing”

• To give surfactant therapy

• Initial settings

• Continuous flow, pressure-limited,

ventilator conventional

• PIP 20-25 , PEEP 4-5 cm H2O

• Frequency 40-60/min

• Ti 0.3-0.5 sec

• FiO2 50-60%

• Rapid ventilator rates and short Ti are recommended because of the low pulmonary compliance and short time constant in neonatal RDS

• A/w a lower incidence of air leaks

• Following surfactant administration, oxygenation

improves rapidly because of an increase in functional residual capacity and is followed by a slower improvement in compliance

• Permissive hypercapnia, permissive hypoxemia, minimal peak pressures, rapid rates, early therapeutic CPAP, and rapid extubation help reduce ventilation induced lung injury (VILI) and possibly reduce BPD

• High Frequency vs. Conventional Ventilation

• Initial HiFi study disappointing - no reduction in BPD.

Increased IVH, PVL

• Subsequently,

• HFOV may decrease incidence of air leak

• HFOV does not increase BPD or IVH

• HFJV and HFFI similar to CMV: Mortality,

BPD, air leak incidence similar

• Use: Air leaks, Hypercapnia, ? R->L shunting

• Liquid Ventilation

• CONCEPT

• 1) Eliminate air-fluid surface tension by

converting alveoli to fluid filled structures.

• 2) Use fluid as a carrier for resp. gases.

• PFCs ( PerFluoroChemicals /

PerFluoroCarbons ) have O2 solubility 50-

53 ml gas / 100 ml liquid and CO2 solubility

140-210 ml gas / 100 ml liquid

• Undergoing trials, still experimental, very promising

Pharmacotherapy – beyond surfactant• Nitric oxide

• Inhaled nitric oxide (iNO)– a selective pulmonary

vasodilator improves oxygenation in preterm

infants with severe RDS.

• Nitric oxide may be a signaling molecule in

parenchymal lung growth & may reduce lung

injury and chronic lung disease

Complications

• Acute complications

• Air leak : Pneumothorax, PIE, Pneumomediastinum :

deterioration with hypotension, bradycardia, apnea,

acidosis

• ET complications : Blocked / dislodged ETT

• Infection : culture and treat rapidly

• Intracranial hemorrhage : monitor USG

• PDA : look for and treat aggressively

Complications & Outcome

• Long-term complications

• Bronchopulmonary dysplasia (BPD)

5-30%

• Retinopathy of prematurity (ROP)

7% of <1250 g

• Neurologic impairment

10-15% of survivors of RDS - associated with PVL, IVH,

degree of prematurity

• A meta-analysis of 13 RCTs to review neuro-developmental

outcome at 1 and 2 years of age following surfactant therapy

documented improved survival without an increase in

subsequent morbidity at 1 and 2 years of age

• Survival in RDS has varied from 25 to 84% in

different centers in India.

• RDS contributes to 13.5% of neonatal mortality in India

• High initial FiO2 >0.6, gestational age <34 weeks, birth weight

<1500 g, air leak syndromes have been a/w higher

mortality

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