Pharm Ch 10 Surfactant Agents

Front 1

Primary indication for pulmonary surfactant

Back 1

Membrane Disease (HMD)/ARDS

-Preterm baby= 30-32 weeks normally

Front 2

Treatment strategies include

Back 2

Oxygen: enhances oxygenation directly, and by decreasing intrapulmonary shunting

***CPAP (Continuous Positive Airway Pressure) preterm babies

(Stabilize FRC..answers usually CPAP!)

Mechanical Ventilation

Surfactant Replacement Therapy

(Have to intubate them but don't have to go on mechan vent)

IMPORTANT: Consider

Extra-pulmonary causes:

- Hypovolemia, Anemia

- Acidosis, Hypoglycemia, Hypothermia

- CNS hemorrhage, drugs, neuromuscular disease

- Heart disease

Front 3

It has been shown that surfactant treatment at less than ______of life significantly decreases the _____________

Back 3

2 hrs

rates of death, air leak, and death or bronchopulmonary dysplasia in preterm infants.

Front 4

When should we intubate to administer surfactant?

Back 4

IN-SUR-E Trial/Method

Intubation (Early)

Surfactant (Early)

Extubation (Early)With or without nCPAP

Front 5

INSURE method

Back 5

(INtubation-SURfactant-Extubation)

in early and late premature neonates with respiratory distress:

factors affecting the outcome and survival rate.

Front 6

RDS and Surfactant Replacement TherapyGoals

Back 6

○Prevent progression of disease process

○Intervene early to establish FRC in the delivery room and the NICU

-CPAP

-Appropriate Mechanical Ventilation

Techniques/Management

-Surfactant replacement

Front 7

Physical principles of surfactant administration

Back 7

Administered to replace missing pulmonary surfactant in respiratory distress syndrome (RDS) of newborn

Front 8

Define surfactant

Back 8

Surface-active agent that lowers surface tension (detergents)

Front 9

Define surface tension

Back 9

Force caused by attraction between like molecules that occurs at liquid–gas interfaces and holds liquid surface intact

Front 10

LaPlace’s Law

Physical principle describing and quantifying:

Back 10

-The relation between internal pressure of drop or bubble

-Amount of surface tension

-Radius of drop or bubble

-For bubble, which is liquid film with gas inside and out, LaPlace’s Law is:

Pressure = (4 × surface tension)/radius

Front 11

In alveoli there is only one single air–liquid interface, LaPlace’s Law would be:

Back 11

Pressure = (2 × surface tension)/radius

Front 12

The higher the surface tension of the liquid, the greater is the _______, Which can what ______

Back 12

compressing force inside the alveolus, which can cause collapse or cause difficulty in opening the alveolus

Front 13

Lowering the surface tension will have what effect?

Back 13

ease the alveolar opening

allow for maintenance of recruitment

Front 14

Exogenous surfactants are clinically indicated for

Back 14

treatment or prevention of RDS in newborns

Front 15

Clinical Indications for Exogenous Surfactants

Back 15

-treatment or prevention of RDS in newborns

-Prophylactic treatment

-Rescue treatment:

Front 16

Prophylactic treatment:

Back 16

Prevention of RDS in very-low-birth-weight infants

Infants with higher birth weights, but with evidence of immature lungs

Infants who are at risk for developing RDS

Front 17

Rescue treatment:

Back 17

Retroactive or “rescue” treatment of infants who have developed RDS

Front 18

Composition of pulmonary surfactant

Back 18

Lipids

85 to 90% of surfactant by weight

-Mostly phosphatidylcholine

-Dipalmitoylphosphatidylcholine (DPPC)

(Other 10% is cholesterol)

Proteins

-Surfactant protein A (SP-A)

(Reuptake)

-Surfactant proteins B and C (SP-B, SP-C)

(Spreading of surfactant)

-Surfactant protein D (SP-D)

Front 19

Production and regulation of surfactant secretion:

Synthesized in?

Major stimulus?

Key feature?

Back 19

●Synthesized in type II alveolar cells and stored in vesicles termed lamellar bodies

●Major stimulus for secretion of lamellar bodies into alveolar space appears to be inflation of the lung

(Exception C-sect- don't get all amniotic fluid squeezed out)

●10% of the intracellular pool is secreted every hour

●Key feature: recycling activity (Re-uptake)

Front 20

Types of exogenous surfactant preparations

Back 20

●Natural/modified natural surfactant

Survanta (Bovine), Curosurf

(Porcine), Infasurf

●Synthetic surfactant

Lucinactant (Surfaxin)

Clinical trials in Latin America were criticized for protocol based in potentially unethical principles.

●Synthetic natural surfactantNone at this time

Front 21

Signs NB gives you: unstable FRC

Back 21

Increase RR

Grunting

Nasal flaring

Chest recoil

Front 22

Beractant (Survanta)

Indications:

Back 22

A modified natural surfactant (bovine)

Indications for use:

Prophylactic therapy of premature infants less than 1250 gram birth weight or with evidence of surfactant deficiency and risk of RDS

Agent should be given within 15 minutes of birth or ASAP

Rescue treatment of infants with evidence of RDS

Agent should be given within 8 hours of birth

Front 23

Beractant (Survanta)

Dosage

Administration

Back 23

Dosage

4 mg/kg of birth weight

Administration

Do not shake

Let stand at room temperature for 20 minutes

Instilled into trachea through a 5-French catheter placed into the endotracheal tube (ETT)

Give in quarter doses from a syringe

During each quarter dose the infant is placed in a different position

Front 24

How to ensure homogenous distribution of SURVANTA?

Back 24

Front 25

Calfactant (Infasurf)

Indications:

Treatment:

Back 25

Modified natural surfactant (bovine)

Indications for use:Prevention (prophylaxis) of RDS in premature infants less than 29 weeks of gestational age and at high risk for RDS

Preferably administered no more than 30 minutes after birth

Treatment (rescue) of premature infants less than or equal to 72 hours of age who develop RDS and require endotracheal intubation

Front 26

Calfactant (Infasurf)

Dosage

Administration

Back 26

Dosage

3 mL/kg body weight at birth, delivered over two doses

Repeat doses, up to total of three doses; can be given 12 hours apart

Administration

Side-port adaptor

Catheter administration (5 F)

Front 27

Poractant Alfa (Curosurf)

Indications

Unlabeled use

Back 27

Natural surfactant (porcine)

*most commonly used

Cow based

Indications for use:

Treatment (rescue) of premature infants with RDS thus reducing mortality and pneumothoraces

Unlabeled uses:

Severe meconium aspiration syndrome in term infants

Respiratory failure caused by group B streptococcal infection in neonates

Front 28

Poractant Alfa (Curosurf)

Dosage

Administration

Back 28

Dosage

2.5 mL/kg birth weight; subsequent doses of 1.25 mL/kg birth weight can be given twice at 12-hour intervals if needed

Maximum recommended total dose is 5 mL/kg

Administration

Warm to room temperature

No need to reconstitute

Administered in one dose or two aliquots through a 5-French catheter in ETT

Front 29

Mode of Action

Back 29

Replace and replenish deficient endogenous surfactant pool in neonatal RDS

Can be recycled into type II cells and form a surfactant pool to regulate surface tension

Front 30

Clinical outcomes

Back 30

-Dramatic improvement in oxygenation

-Increase in functional residual capacity (FRC) or increased compliance

Clearing of chest x-ray

Blood gas (gas exchange) improvements

Increased lung volumes (FRC & RV)

Improved static compliance

Front 31

Hazards and complications

Back 31

Airway occlusion, desaturation, bradycardia

High arterial oxygen (PaO2) values

(Have to wean)

Overventilation and hypocapnia

(Have to wean)

Apnea

Pulmonary hemorrhage- (treat: ice cold saline- vasoconstriction. Push epi. **go up on PEEP until blood stops coming out**)

Typically: younger, smaller, PDA (patent ducts arternosis)

Front 32

AEROSURF

Back 32

(Not yet approved)

Deliver surfactant without intubation! Delivered with aerosol

Front 33

Assessment

Back 33

Monitor pulse/cardiac rhythm

(During and after administration)

Signs of airway occlusion

Color/activity level

Chest rise

Arterial oxygen saturation

(Prevent hyperoxia Prevent hypoxia)

Front 34

Before treatment assess

Back 34

Assess the need for surfactant therapy.

Front 35

During treatment and short term assess

Back 35

●Monitor pulse and cardiac rhythm during and after administration.

●Monitor the infant for signs of airway occlusion

(desaturation and bradycardia) during and after administration;

if obstruction is evident, remove the infant from the ventilator and manually ventilate;

in addition, saline lavage and aggressive suctioning to clear the airway may be needed.

●Monitor color and activity level of the infant.

●Monitor chest rise for level of ventilation, or use electronic monitor if available.

●Monitor arterial oxygen saturation and adjust Fio2 accordingly to prevent hyperoxia or hypoxia.

●Monitor transcutaneous Pco2 if possible, and be prepared to adjust level of ventilation as needed to prevent hypercarbia or hypocarbia.

Front 36

Long term assessment

Back 36

●Assess lung mechanics (exhaled volumes or peak inspiratory pressures) during mechanical ventilation to determine effectiveness of the exogenous agent in normalizing lung compliance. The instilled drug may cause changes within minutes in some cases.

●Assess the need for repeat dosing.Consider possible hazards if pulse, cardiac rhythm, or arterial/transcutaneous blood gas values deteriorate.