Drug Presentation
On
Surfactant Replacement Therapy
Presenter - Submitted To-
Diksha Dr. Poonam Joshi
M Sc Nursing 1st year Associate Professor
CON, AIIMS CON, AIIMS
Introduction to lung Surfactants
Surfactant is the lipid:protein complex that coats the alveolar surface and greatly reduces surface
tension, allowing for efficient inspiration. Surfactant is produced exclusively by alveolar type II
epithelial cells and stored in specialised organelles called lamellar bodies (LBs) until it is secreted
into the lumen of the alveolus. The proteins and lipids that make up the surfactant have both
hydrophilic and hydrophobic regions. By adsorbing to the air-water interface of alveoli, with
hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid
component of surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.As a
medication, pulmonary surfactant is on the WHO Model List of Essential Medicines, the most
important medications needed in a basic health system.
Composition of Lung surfactant
Pulmonary surfactant is a complex mixture of lipids and proteins. The main active component is
dipalmitylphosphotidylcholine (DPPC) which is responsible for reducing surface tension and
maintaining alveolar stability.
Phospholipids 80%
Dipalmitoylphosphatidylcholine (DPPC). Lecithin 60%
Phosphatidylglycerol (PG) 20%
Neutral Lipids 10%
Mostly cholesterol
Surfactant Proteins 10%
SP-A , SP-D. (Hydrophilic)
SP-B , SP-C. (Hydrophobic)
DPCC PG Lipid Surface proteins
10%
10%
20% 60%
Production Of Natural Lung Surfactant
Surfactant production in humans begins in type II cells during the alveolar sac stage of lung
development. Lamellar bodies appear in the cytoplasm at about 20 weeks gestation. These lamellar
bodies are secreted by exocytosis into the alveolar lining fluid, where the surfactant forms a
meshwork of tubular myelin. Full term infants are estimated to have an alveolar storage pool of
approximately 100 mg/kg of surfactant, while preterm infants have an estimated 4–5 mg/kg at birth.
Surfactant production is stimulated by -
• Cortisol
• thyroxin
• prolactin
Surfactant production is inhibited by -
• Insulin (diabetic mother)
Function
• To increase pulmonary compliance.
• To prevent atelectasis (collapse of the alveoli or atriums) at the end of expiration.
• To facilitate recruitment of collapsed airways.
Compliance
Compliance is the ability of lungs and thorax to expand. Pulmonary surfactant greatly reduces
surface tension, increasing compliance allowing the lung to inflate much more easily, thereby
reducing the work of breathing. It reduces the pressure difference needed to allow the lung to
inflate.
Alveolar size regulation
As the alveoli increase in size, the surfactant becomes more spread out over the surface of the
liquid. This increases surface tension effectively slowing the rate of expansion of the alveoli. This
also helps all alveoli in the lungs expand at the same rate, as one that expands more quickly will
experience a large rise in surface tension slowing its rate of expansion. It also means the rate of
shrinking is more regular as if one reduces in size more quickly the surface tension will reduce
more, so other alveoli can contract more easily than it can. Surfactant reduces surface tension more
readily when the alveoli are smaller because the surfactant is more concentrated.
Prevention of fluid accumulation and maintenance of dryness of airways
Surface tension draws fluid from capillaries to the alveolar spaces. Surfactant reduces fluid
accumulation and keeps the airways dry by reducing surface tension.
Innate immunity
Surfactant immune function is primarily attributed to two proteins: SP-A and SP-D. These proteins
can bind to sugars on the surface of pathogens and thereby opsonize them for uptake by phagocytes.
It also regulates inflammatory responses and interacts with the adaptive immune response.
Surfactant inactivation may contribute to enhanced susceptibility to lung inflammation and
infection.
Surfactant Replacement Therapy
Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in
preterm neonates.Pulmonary surfactant is a complex mixture of phospholipids and proteins that
creates a cohesive surface layer over the alveoli which reduces surface tension and maintains
alveolar stability therefore preventing atelectasis. Surfactant deficiency is a recognised cause of
respiratory distress syndrome in the preterm neonate. Secondary surfactant deficiency also
contributes to acute respiratory morbidity in late-preterm and term neonates with meconium
aspiration syndrome, pulmonary haemorrhage, and pneumonia/sepsis. Many clinical trials have
demonstrated that surfactant replacement therapy is a safe, effective and beneficial treatment as it
significantly reduces respiratory morbidity, ventilatory requirements and mortality in these
neonates. Indications for surfactant therapy
Clinical indications
Surfactant replacement is done mainly for RDS. But it can be used in other conditions where
surfactant is inactivated such as
• meconium aspiration syndrome,
• pneumonia,
• pulmonary haemorrhage,
• congenital diaphragmatic hernia
• acute respiratory distress syndrome.
In RDS, surfactant can be administered either prophylactically or as rescue therapy.
ContraIndications
Hypersensitivity to active substance or any of the excipients.
No specific contraindications are yet known.
Special Precautions of use
Prior to starting the treatment with surfactant infants’s general condition should be stabilised.
Correction of acidosis , hypotension , anaemia, hypoglycemia and hypothermia is also
recommended.
In the event of reflux administration of surfactant should be stopped.
Type of surfactants
There are a number of types of pulmonary surfactants available. Like their natural counterparts,
pulmonary surfactant preparations consist of phospholipids (mainly DPPC) combined with
spreading agents such as SP-B and SP-C.
Natural / Animal derived Surfactant
• Beractant
- Alveofact - extracted from cow lung lavage fluid
- Survanta - extracted from minced cow lung with additional DPPC, palmitic acid and
tripalmitin.
- Beraksurf- extracted from minced cow lung with additional DPPC, palmitic acid and
tripalmitin.
• Calfactant (Infasurf) - extracted from calf lung lavage fluid
• Poractant alfa (Curosurf) - extracted from material derived from minced pig lung
Synthetic pulmonary surfactants:
• Colfosceril palmitate (Exosurf) - a mixture of DPPC with hexadecanol and tyloxapol added as
spreading agents
• Pumactant (Artificial Lung Expanding Compound or ALEC) - a mixture of DPPC and PG
• Lucinactant (KL-4) - composed of DPPC, palmitoyl-oleoysl phosphatidylglycerol, and palmitic
acid, combined with a 21 amino acid synthetic peptide (sinapultide) that mimics the C-terminal
helical domain of SP-B.
• Venticute - DPPC, PG, palmitic acid and recombinant SP-C
• Lucinactant (trade name Surfaxin) is a liquid medication that contains DPPC, POPG as the
sodium salt, and palmitic acid.
Dosages
Initial recommended dose is 200 mg/kg/dose (2.5 mL/kg), up to 2 repeat doses of 100 mg/kg may
be considered at 12 hourly intervals.
Initial
Weight ⃰ Initial Curosurf® Volume Surfactant
dose
< 600g 2.5 mL /kg 200mg / kg
600g -> 200mg/ kg ->
1.5 mL (1 vial)
1.2 kg 100mg / kg
1.2 kg -> 200mg / kg ->
3 mL (2 vials)
2.4 kg 100mg / kg
2.4 kg -> 150mg / kg ->
4.5 mL (3 vials)
3.6 kg 100mg / kg
Consider the indications for
> 3.6 kg
surfactant use in this population
For example a baby weighing 555g could be given 1 vial (2.7 mL /kg, 216mg /kg) and a baby
weighing 1250g could receive 1 vial (1.2 mL /kg, 96mg /kg)
Common brands of surfactant and their dosage
Surfactant Survanta Curosurf Neosurf
preparations (Abbvie) (Nicoholas) (Cipla)
Dose (phospholipids) 4 mL/kg (100 mg/kg) 2.5 mL/kg (200 mg/ 5 mL/kg (135 mg/kg)
kg)
Available 4 mL and 8 mL 1.5 mL and 3 mL 3 mL and 5 mL
Formulation
1. Prophylactic surfactant:
Surfactant is administered within15- 30 min of birth, irrespective of the presence of symptoms of
RDS. Prophylactic SRT is given in preterm neonates <28 weeks of gestation, if no or incomplete
antenatal steroids to mother or if requiring intubation and mechanical ventilation at birth.
Rationale: Administration of surfactant to a previously unventilated or minimally ventilated lung
will diminish acute lung injury. Acute lung injury results in alveolar- capillary damage, leakage of
proteinaceous fluid into the alveolar space and release of inflammatory mediators, resulting in
decreased response to surfactant replacement.
2. Early rescue:
Surfactant is administered in preterm neonates with RDS within 2 hours of birth. Early
administration of surfactant is advantageous as the presence of lung fluid helps in uniform
distribution of the surfactant. It also ensures that surfactant is administered before widespread
atelectasis develops in the lungs. Early rescue surfactant therapy following a trial of CPAP is
preferred over prophylactic therapy because the immediate outcomes are comparable and the
amount of surfactant used is reduced.
3. Late rescue:
Surfactant is administered after 2 hours. It is done usually in out-born neonates who are transported
late to referral centres.
Procedure for surfactant administration
Standard method of surfactant administration is through the endotracheal tube after intubation
Prepare equipment/supplies:
▪ Continuous cardiovascular monitoring equipment
▪ Transcutaneous CO2 monitor (TCM) or end tidal CO2 monitor (etCO2) if appropriate
▪ Surfactant
▪ Size 5 Fr feeding tube
▪ 3ml or 5ml syringe (dose dependent)
▪ Large gauge needle (18g, 19g or 20g)
▪ Alcohol swab 70%
▪ Sterile towel or drape
▪ Tape measure
▪ Sterile scissors
▪ Emergency equipment: Neopuff and mask, suction
• A physician or a nurse experienced in surfactant administration should administer the surfactant.
• Record baseline observations: heart rate, respiration rate, oxygen saturation, TCO2/etCO2, plus a
blood gas if required
• Warm the surfactant prior to administration (for at least 8 minutes if the vial is held between the
palms of the hands or for 20 minutes at room temperature.) The vial should not be heated and it
should not be kept on radiant warmer. It should not be kept in room air for more than 30 min as it
increases viscosity.
• Do not shake the surfactant.
• Intubate the baby with appropriate size endotracheal tube.
• Assess breath sounds for equality. Chest x ray is not mandatory for confirmation of ET tube
position.
• The neonate should be connected to a pulse oximeter and oxygen saturation and heart rate have
to be monitored throughout the procedure.
• Administer the surfactant through the feeding tube inserted in the ET tube or through the side
port of the ET tube(if available)
• Surfactant is given as bolus instillation in four aliquots of the total dose.
• No position change is required between the aliquots.
• Connect the neonate to ventilator or the resuscitation bag or T piece resuscitator with set PIP and
PEEP and ventilate carefully till saturation and heart rate stabilises before administering next
aliquot.
• Increase PIP by 10 % for at least 5 min after surfactant administration and frequency of 60
breaths/min for uniform distribution
• Suctioning of ET tube should be avoided at least 2hrs following surfactant administration
• Monitor neonate’s vital signs closely every 10 minutes for 30 minutes then resume normal
frequency of monitoring. A repeat blood gas may be necessary 30-60 minutes post
administration.
Potential complications and management
• During administration, transient bradycardia, oxygen desaturation and ETT blockage can
occur – temporarily stop surfactant administration, provide ventilation or oxygen as necessary,
and resume administration after patient is stable
• ETT obstruction – if suspected, observe saturations and chest wall movement. Call for medical
assistance if obstruction is not alleviated and ventilation is impaired
• Pneumothorax – can occur due to sudden changes in pulmonary compliance if ventilation
settings are not appropriately changed
• Pulmonary haemorrhage – notify medical officer immediately. Ensure the PEEP remains above
5cm H2O
Methods of surfactant administration
Surfactant preparations must spread uniformly throughout the lung into the air-liquid interface once
instilled in the proximal airways.
1. Slow infusion versus rapid bolus administration-
Surfactant can be administered either by slow tracheal infusion or rapid bolus administration.
Natural surfactant works best if given by a rapid bolus into the lungs as it leads to homogeneous
distribution of surfactant and also results in rapid improvement in oxygenation. But it can also cause
obstruction of the ET tube, transient bradycardia, hypotension and changes in cerebral blood flow.
Currently, rapid bolus technique is the recommended method of surfactant administration.
2. Less invasive surfactant administration (LISA) –
Because of the risk associated with ET tube placement and ventilation, newer techniques with less
invasive therapy have emerged. Surfactant is administered through a feeding tube (4-5 Fr catheter)
inserted into trachea using Magill forceps under direct laryngoscopy without intubation. During this
technique, CPAP is continued to facilitate alveolar recruitment which helps in the distribution of
surfactant and avoids positive pressure ventilation.
3. Minimally invasive surfactant therapy (MIST) -
Minimally invasive surfactant therapy (MIST) does not require sedation, minimises airway injury
and avoids placing positive pressure ventilation on an immature lung. Spontaneously breathing
preterm infants with RDS receive surfactant via a gastric tube placed in the trachea by direct
laryngoscopy with no sedation.Surfactant is delivered using a slightly stiff catheter like angiocath
16 G without using Magill forceps.
4. Through laryngeal mask airway-
Trials used LMA for surfactant therapy in neonates of more than 1000 g showed that there is less
need for mechanical ventilation. Surfactant reflux and coughing is more frequently seen with this
method.
5. Nebulised surfactant delivery-
It is truly non invasive technique. Practical issues like loss of surfactant in upper airway/
oesophagus, inactivation of surfactant and non-homogenous distribution need to be addressed
before this method can be recommended.
InSurE
InSurE stands for Intubate – Surfactant – Extubate to CPAP. InSurE comprises of intubation,
surfactant administration, brief period of ventilation (usually < 1 hour) and rapid extubation to nasal
CP AP to prevent ventilation induced lung injury (VILI). In neonates with signs and symptoms of
RDS, InSurE to nasal CPAP results in decreased duration of mechanical ventilation, air leak and
less incidence of BPD. InSurE technique may not be successful in the presence of severe birth
asphyxia, lack of complete course of antenatal steroids, extreme prematurity, delayed administration
of surfactant and shock.
Repeat dose of surfactant
Multiple doses had a stronger effect than single doses. Repeat doses of surfactant may be required if
the administered surfactant is inhibited by oedema fluid, soluble proteins and inflammatory
mediators which are present in the alveoli after lung injury due to mechanical ventilation and in
neonates with delayed surfactant administration or sepsis, lower gestation/ birth weight and male
sex. Neonates may require repeat doses of surfactant if they require FiO2 0.4 or more on CPAP and
mechanical ventilation to maintain a target saturation. Administering more than three doses has not
been shown to have a benefit.
Special considerations
• Storage and handling:
The product must be stored at 2 to 8 degree celsius, protected from the light.
Do not use any residual quantity left in the vial after the first aspiration.
Unopened, unused vials of Curosurf that have warmed to room temperature can be returned to
refrigerated storage within 24 hours of future use.
Do not warm to room temperature and return to refrigerated storage more than once.
• Infection control:
Ensure hand hygiene is performed, surgical aseptic technique is used and equipment is kept sterile/
clean to minimise risk of infection
Bibliography
• h t t p s : / / w w w. n e w b o r n w h o c c . o r g / 2 0 1 9 _ p d f /
Surfactant%20Replacement%20Therapy%20%20-%202019.pdf
• Kliengman RM.,et.al. Nelson Textbook Of Pediatrics. 21st edn. Canada: Elsevier;
2020.Page no. 4008-4009.
• https://www.drugs.com/drug-class/lung-surfactants.html
