Surfactant Agents

I. Definitions
a. Surfactant: A surface-active agent that lowers surface tension
i. Examples
1. soap
2. detergent
. Surface !ension: "orce caused # attraction etween li$e molecules
that occurs at li%uid-gas interfaces and that holds the li%uid surface
intact
i. &nits of 'easure: d#nes(centimeter )d#n(cm*
1. the force re%uired to cause a 1 cm rupture in the
surface film
ii. a droplet forms ecause a li%uid+s molecules are more
attracted to each other than the surrounding gas
c. ,a-lace+s ,aw: -h#sical principle that descries and %uantifies the
relationship etween the internal pressure. amount of surface
tension and the radius of a drop or ule
i. In the alveoli where there is a single air-li%uid interface.
,a-lace+s ,aw is: -ressure/)2 x S!*( r. where
1. S! / surface tension
2. r / radius of the alveoli
II. Application to the ,ung
a. Increased surface tension can cause collapse or difficult# opening
the alveoli
i. Surfactant lowers the surface tension to decrease the
pressure needed to open the alveoli
. In pulmonar# edema. the surface tension of the li%uid allows the
formation of a ul# froth
i. ,owering the surface tension will cause the foam ules to
collapse and li%uef#
III. 0linical Indications for Exogenous Surfactants
a. -roph#lactic !reatment
i. -revention of 1DS in ver#-low-irth-weight infants and infants
with higher irth weights who have evidence of immature
lungs. at ris$ for developing 1DS
. 1escue !reatment
i. 1etroactive or 2rescue3 treatment of infants who have
developed 1DS
1. the asic prolem in 1DS is lac$ of pulmonar#
surfactant as a result of lung immaturit#
2. increased ventilating pressure is re%uired to expand the
alveoli during inspiration. which will lead to respirator#
failure
I4. -revious Surfactant Agents in 1espirator# 0are
a. Eth#l alcohol
i. Application
1. used for treating pulmonar# edema
2. was given # neuli5er
a. 6 - 7 ml. of 68 - 789 solution
ii. 'ode of Action
1. alcohol lowered the surface tension of the foam#
exudate. reducing it to a li%uid. clearale state
iii. Disadvantages
1. efficac# not proven
2. toxic to memranes
6. etter alternatives are availale toda#
. 'ucus :etting Agents )Detergents*
i. Examples
1. Alevaire
2. !ergamist
ii. Indication
1. to improve water penetration and facilitate transport
and expulsion of adhesive mucus
iii. 'ode of Action
1. these agents ma# interact with mucus to produce
emulsification
a. !he mucus will dissolve or disperse into smaller
molecules
iv. Efficac#
1. efficac# in vivo is not proven
c. -hospholipids
i. 0oating of the airwa# epithelium # phospholipids ma# serve
as a luricant for mucus transport
ii. 'a# offer another alternative to normali5ing mucociliar#
transport and mucus clearing in disease states causing mucus
h#persecretion or decreased clearance of secretions
iii. !here are no agents in general clinical use at this time
4. Exogenous Surfactants
a. Exogenous
i. ;riginating outside the od#
1. other humans
2. animals
6. laorator# s#nthesis
. 0linical &se
i. to replace missing or immature surfactant in premature
infants
ii. investigated for use in adults with disease processes that
have low surfactant )A1DS*
c. <istor# and Development of Exogenous Surfactants
Year Event
1=2= 4on 'eergaard showed that lungs were more difficult to inflate
with air than with fluid
1=7> 0lements measured the surface tension of lung fluid extracts
1=7? Dipalmito#lphosphatid#lcholine )D--0* is identified #
0lements and associates as the main surface-active component
of pulmonar# surfactant
1=7= Aver# and 'ead showed that surface tension is higher in the
lungs of infants with h#aline memrane disease than in the
lungs of normal infants
1=>@ Aerosols of s#nthetic D--0 are attempted in 1DS. with little
success
1=A2 Enhorning and 1oertson demonstrate the effectiveness of
surfactant replacement in premature animals
1=?8 "uBiwara and associates report success in exogenous surfactant
therap# in infants. using 2l#ophili5ed artificial surfactant3
)ovine extract. Surfactant !A*
1==8 0olfosceril palmitate )Exosurf Ceonatal. Durroughs :ellcome*
approved for general use
1==1 Deractant )Survanta. 1oss ,aoratories* approved for general
use
1==? 0alfactant )Infasurf. "orest -harmaceuticals* approved for
general use
1=== -oractant alfa )0urosurf. De# ,as* approved for general use
4I. 0omposition of Surfactant
a. ,ipids )?7-=89*
i. -hospholipids )E=89*
1. -hosphatid#lcholine
a. Dipalmito#lphosphatid#lcholine )D--0*
i. most prominent in reducing surface tension
2. phosphotid#lgl#cerol
6. phosphatid#lethanolamine
@. phosphatid#lserine
7. phosphatid#linositol
>. spingom#elin
ii. Ceutral ,ipids )189*
1. cholesterol and others
. -roteins )189*
i. Surfactant protein A )S--A*
1. regulates secretion and reupta$e of surfactant to !#pe
II cell
ii. Surfactant protein D )S--D*
1. improves spreading of phospholipids in the alveolus
iii. Surfactant protein 0 )S--0*
1. improves spreading of phospholipids in the alveolus
iv. Surfactant protein D )S--D*
1. no clear role
4II. -roduction and 1egulation of Surfactant
a. -roduction
i. S#nthesi5ed in the t#pe II alveolar cells
ii. Stored in vesicles called lamellar odies
iii. Secreted # exoc#tosis into the alveolus
iv. !he maBor stimulus for secretion is inflation of the lung
. 1egulation
i. Endoc#tosis ac$ into the t#pe II cell
1. most surfactant )=8-=79* is ta$en ac$ into the t#pe II
cell. reprocessed. and resecreted
a. this is the reason that exogenousl# administered
surfactant is successful in replacing missing
surfactant with one or two doses
ii. 0learance(degradation # alveolar macrophages
4III. ;thers Denefits of Surfactant
a. 0ontriutes to host defense
i. Increased acterial $illing
ii. 'odifies macrophage function
iii. Down-regulates the inflammator# response
1. decreases mediator release
iv. enhances ciliar# eat fre%uenc#
IF. !#pes of Exogenous Surfactant -reparations
Category Description Examples
Catural Surfactant from
natural sources
)human or animal*
with addition or
removal of sustances*
Survanta )ovine*
Surfactant !A )ovine
0urosurf )porcine*
Infasurf )ovine*
Alveofact )ovine*
S#nthetic Surfactant that is
prepared # mixing in
vitro s#nthesi5ed
sustances that ma#
or ma# not e in
natural surfactant
Exosurf
A,E0
S#nthetic natural Surfactant prepared in
vitro with genetic
engineering
Cone at present
F. Specific Exogenous Surfactant -reparations
a. 0olfosceril palmitate )Exosurf Ceonatal*
i. Indications
1. -roph#lactic therap# of infants weighing less than
1678g irth weight
2. -roph#lactic therap# of infants with irth weights
greater than 1678g with evidence of pulmonar#
immaturit# and at ris$ for 1DS
6. 1escue treatment of infants who have developed 1DS
ii. Dosage
1. 7 ml($g of the reconstituted suspension %12G F 2 - 6
doses
iii. -reparation
1. availale as a dr# powder that is reconstituted with ? ml
sterile water prior to use
iv. Administration
1. instilled directl# into the endotracheal tue through a
side port adapter attached to E! tue. in 2 divided
ali%uots
a. 1
st
half of dose in midline position
i. infant rotated to the right and ventilated for
68 seconds
. 2
nd
half of dose in midline position
i. Infant rotated to the left and ventilated for
68 seconds
2. a single vial can treat up to a 1>88 g infant
a. 7 ml($g x 1.> $g / ? ml
. Deractant )Survanta*
i. Indications
1. -roph#lactic therap# of premature infants less than
1278g irth weight or with evidence of surfactant
deficienc# and ris$ of 1DS
2. 1escue treatment of infants with evidence of 1DS
ii. Dosage
1. @ ml($g )188 mg($g* of the suspension %>G
iii. -reparation
1. availale as a vial containing ? ml of suspension with
288 mg active ingredient )27 mg(ml*
iv. Administration
1. instilled directl# into the endotracheal tue through a 7-
"rench catheter. in @ divided ali%uots
2. the infant is placed in @ different positions and manuall#
or mechanicall# ventilated for 68 seconds
6. a single vial can treat up to a 2888 g infant
a. @ ml($g x 2 $g / ? ml
v. <andling
1. $eep refrigerated
2. warm at room air for at least 28 minutes prior to
administration
6. unopened vial ma# e returned for refrigeration within ?
hours
@. used vials should e discarded
c. 0alfactant )Infasurf*
i. Indications
1. !he prevention of 1DS in premature infants H 2= wee$s
of gestational age at high ris$ for 1DS
2. 1escue treatment of premature infants less than or
e%ual to A2 hours of age who develop 1DS and re%uire
endotracheal intuation
ii. Dosage
1. 6 m,($g of the suspension %12 h up to 6 doses
iii. -reparation
1. availale as a vial containing > ml of suspension with
218 mg of active ingredient
iv. Administration
1. Side-port adapter
a. !he dose in given in two ali%uots
i. -osition the infant with either the right or
left side dependent
ii. Administer half the dose in small ursts to
coincide with the inspirator# c#cle. over 28
to 68 reaths
iii. 1eposition and administer the other half of
the dose in the opposite position
2. 0atheter
a. !he dose is given in four ali%uots. with the
catheter removed etween each instillation
. Each portion is given with the infant in a different
position
i. -rone
ii. Supine
iii. 1ight lateral
iv. ,eft lateral
c. !he infant is ventilated for 8.7 to 2 minutes
etween portions
6. a single vial can treat up to a 2888 g infant
a. 6 ml($g x 2 $g / > ml
d. -oractant alfa )0urosurf*
i. Indications
1. "or the treatment or rescue of 1DS in premature infants
2. &nlaeled &ses
a. -roph#laxis for 1DS
. A1DS resulting from viral pneumonia
c. <I4-infected infants with -neumoc#stis carinii
pneumonia )-0-*
d. A1DS after near-drowning
ii. Dosage
1. 2.7 m,($g
2. 1epeat doses of 1.27 m,($g irth weight %12h x 2
iii. -reparation
1. two preparations availale
a. a vial containing 1.7 ml of suspension containing
128 mg of active ingredient
. a vial containing 6.8 ml of suspension containing
2@8 mg of active ingredient
iv. Administration
1. instilled directl# into the endotracheal tue through a 7-
"rench catheter
a. !he dose is given in two ali%uots
i. Each portion is given with the infant in a
different position
1. right side dependent
2. left side dependent
ii. !he catheter is removed etween portions
and the infant is manuall# ventilated with
1889 ;2 for 1 minute
2. a single 6.8 ml vial can treat up to a 1288 g infant
a. 2.7 ml($g x 1.2 $g / 6 ml
FI. 'ode of Action
a. Exogenous surfactants replace and replenish a deficient endogenous
surfactant pool in neonatal 1DS
i. Increased "10
1. dramatic improvement in ox#genation
FII. <a5ards and 0omplications of Surfactant !herap#
a. During instillation
i. airwa# occlusion
1. relativel# large volumes are instilled into the E!!
ii. desaturation
1. impaired diffusion
iii. rad#cardia
1. heart rate H 188 pm in a neonate
a. normall# 128-1>8 pm
2. caused # h#poxia and vagal stimulation
. -ost-instillation
i. high arterial ox#gen )-a;2* values
1. wean ;2 to maintain -a;2 78-A8 torr
ii. over-ventilation and h#pocaria
1. decrease ventilating pressures as compliance improves
to prevent arotraumas
iii. apnea
1. irritation to the airwa# causes apnea in a neonate
iv. pulmonar# hemorrhage
1. factors that increase ris$
a. H A88 g irth weight
. #ounger
c. male
d. patent ductus arteriosus )-DA*
FIII. "actors in Surfactant Selection
Parameter Synthetic (Colfosceril) Natural (Beractant)
1esponse time Slower in onset )several
hours*
1apid in onset )7-68 min*
Administration During mechanic ventilator
reath
1emoved from ventilator
Drug preparation 'ust reconstitute efore
use
1efrigerated suspensionI
must warm prior to use
Side effects Co proteins to stimulate
immune responseI no
-roteins ma# elicit
immune responseI
infectious agents present concern over sterili5ation
effectiveness
0ost Similar Similar
FI4. Denefits of Surfactant !herap#
a. Improved survival in 1DS
. Increased ox#genation
c. Decreased da#s of ventilator# support and supplemental ;2