Treating preterm infants with Surfactant: an overview of application techniques and resultsAngela Kribs, Children‘s Hospital, University of Cologne

Neonatologie

Application techniques

Classical way: endotracheal intubation and application of surfactant via endotracheal tube

Intubation, surfactant application and rapid extubation (INSURE)

Application of surfactant into the nasopharynx immediately after birth

Application of surfactant via a laryngeal mask

Nebulization of surfactant

Application of surfactant via a thin endotracheal catheter during spontaneous breathing

Neonatologie

Background

Association of surfactant administration and mechanical ventilation is meanly a historical phenomena.

Outcome of ELBW infants treated with CPAP as primary respiratory support is comparable to that of infants treated with primary intubation, mechanical ventilation and surfactant administration.

Mechanical ventilation has the risk to induce lung injury and may perhaps influence the development of brain lesions.

But: Surfactant usually related to intubation and mechanical ventilation has improved the prognosis of preterm infants more than any other therapy.

>>>>> Surfactant without any mechanical ventilation but with CPAP could be the combination of two effective principles !!!!

Neonatologie

Application of surfactant into the nasopharynx immediately after birth - Data

Kattwinkel et al.

Technique for intrapartum administration of surfactant without requirement for an endotracheal tube. J Perinatol. 2004;24:360-365.

23 infants enrolled (560-1804 g, 27-30 w)

Instillation of 3,0-4,5 ml Infrasurf into the nasopharynx before birth of the shoulders

CPAP of 10 cmH2O after birth, than reduced to 6 cmH2O

No further treatment of RDS in 13 of 15 vaginally delivered infants

Need for endotracheal intubation and endotracheal surfactant in 5 of 8 infants delivered by cesarian section

Neonatologie

Application of surfactant into the nasopharynx immediately after birth – potential Pros and Cons

Pros

Avoidance of intubation

Avoidance of any positive pressure ventilation

Active inspiration of surfactant

Cons

Failure after cesarian section

Neonatologie

Application of surfactant via a laryngeal mask - Data

Brimacombe et al. The laryngeal mask airway for administration of surfactant in two neonates with respiratory distress syndrome.

Paediatr Anaesth. 2004;14:188-190.

Two case reports of successfull use of this technique in two infants with RDS (1360g and 3200g)

Neonatologie

Application of surfactant via a laryngeal mask - Data

Trevisanuto D et al. Laryngeal mask airway used as a delivery conduit for the administration of surfactant to preterm infants with respiratory distress syndrome. Biol Neonate. 2005;87:217-220.

Neonatologie

Application of surfactant via a laryngeal mask – potential Pros and Cons

Pros

Avoidance of intubation

In some cases avoidance of any positive pressure ventilation

In some cease active inspiration of surfactant

Cons

Technical limitations in the smallest infants

Neonatologie

Mazela et al. Curr Opin Pediatr 19:155-162

Nebulization of surfactant - Data

Neonatologie

Mazela et al. Curr Opin Pediatr 19:155-162

Nebulization of surfactant - Data

Neonatologie

Nebulization of surfactant – potential Pros and Cons

Pros

Avoidance of intubation

Avoidance of any positive pressure ventilation

Active inspiration of surfactant

Cons

Technical problems (particle size, stability of the substance)

High loss of substance >>>

expensive

Neonatologie

Application of surfactant via a thin endotracheal catheter during spontaneous breathing - Data

Kribs A et al. Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age </=27 weeks). Paediatr Anaesth. 2007;17:364-369.

Kribs A et al. Early surfactant in spontaneously breathing with nCPAP in ELBW infants--a single centre four year experience.Acta Paediatr. 2008;97(3):293-298.

Neonatologie

Standard of delivery room management

Covering the baby with a polyurethrane wrapSuction of the mouthPositioning of a face mask with high- flow- CPAP (Benveniste valve), FiO2 0,4, PEEP 8-14 cmH2O Positioning of a pulsoxymeterObservation of:

SO2 (<80% after 10 min. >>increase FiO2)Silverman- Score (5 min.) (> 5 after 10 min. >> increase PEEP)Heart rate (no increase within 2 min. >> ventilation with mask and

bag using PEEP- ventil and a pressure limitation. )

Neonatologie

Indications for endotracheal intubation in the delivery room

Persistent apnea and bradycardia with need for resuscition

Prenatal diagnosis of severe malformation with imminent respiratory failure

(need for transport over a long distance)

Neonatologie

Indications for surfactant administration

FiO2 > 0,3 for SO2 > 80% after optimization of CPAP for infants with a gestational age <26 completed weeks or FiO2 >0,4 for infants with a gestational age >26 weeks

Silverman Score > 5 after optimization of CPAP

Neonatologie

Indications for endotracheal intubation during the first 72 hours of live

FiO2 > 0,5 for SO2 > 80% for more than two hours after optimization of CPAP and after appplication of surfactant

Persistant Silverman Score > 5

More than one apnea with need for intervention within 2 hours

Resp. acidosis with pH < 7,15

Neonatologie

period 0

(N=38)

period 1

(N=47)

period 2

(N=45)

period 3

(N=28)

period 4

(N=35)

Gestational age (weeks)

25,7

(23+2-27+6)

25,7

(23+0-27+6)

25,2

(23+0-27+6)

25,3

(23+0-27+6)

25,1

(23+0-27+6)

Birth weight

(gramm)

714

(347-1000)

667

(350-1000)

705

(430-1000)

690

(430-1000)

668

(400-990)

Apgar 5‘ 7 (2-9) 7 (3-10) 8 (2-9) 8 (3-9) 8 (1-9)

Gender male / female 23/15 23/24 26/19 16/12 16/19

SGA (<10.Perc.) 9 (23,7%) 10 (21,3%) 10 (22,2%) 6 (21,4%) 11 (31,4%)

Sepsis at birth 12 (31,6%) 13 (27,7%) 17 (37,8%) 12 (42,9%) 15 (42,9%)

PPROM < 23 weeks 3 (7,9%) 10 (21,3%) 10 (22,2%) 6 (21,4%) 11 (31,4%)

Twin to twin transfusion

2 (5,3%) 6 (12,8%) 5 (11,1%) 2 (7,1%) 1 (2,9%)

Any antenatal steroids 32 (84,2%) 44 (93,6%) 45 (100%) 27 (96,4%) 30 (85,7%)

Neonatologie

Respiratory management of RDS (n=155)

0102030405060708090

100

period 0 period 1 period 2 period 3 period 4

CPAP

CPAP + Surf

mech. Ventilation

CPAP failure as %of CPAP startersmech. vent. due toRDS

%

Neonatologie

Outcome of preterm infants </= 1000 g and </=27 weeks (data are given in %)

0102030405060708090

100

period0

period1

period2

period3

period4

survival

survival withoutBPD

survival withoutBPD, IVH>II°, PVL

survival withoutBPD, IVH>II°, PVL,ROP>II°

Neonatologie

Mechanical ventilation vs. CPAP as initial respiratory supportDemographic data and prenatal risks

Ventilation

N=23

CPAP

N=132

Significance

Gestational Age (weeks) 24,8 25,4 P=0,038

Birth weight (gramm) 662 686 n.s.

Apgar 5 min. 4,7 7,6 P<0,001

gender male / female 11/12 63/69 n.s.

Any antenatal steroids 21 (91,3%) 125 (94,7%) n.s.

SGA < 10. Perc. 4 (17,4%) 40 (30,3%) n.s.

Sepsis at birth 15 (65,2%) 43 (32,6%) P=0.004

PPROM < 23 weeks of gestational age

10 (43,5%) 27 (20,5%) P=0.031

Twin to twin transfusion 5 (21,8%) 9 (6,8%) P=0.037

Neonatologie

CPAP + Surfactant: Responder vs Non ResponderDemographic data and prenatal risks

Responder

N=90

Non Responder

N=38

Significance

Gestational Age (weeks) 25,5 25,2 n.s.

Birth weight (gramm) 691 666 n.s.

Apgar 5 min. 7,7 7,4 n.s.

gender male / female 44/46 19/19 n.s.

Any antenatal steroids 87 35 n.s.

SGA < 10. Perc. 26 14 n.s.

Sepsis at birth 26 15 n.s.

PPROM < 23 weeks of gestational age

20 7 n.s.

Twin to twin transfusion 4 5 n.s.

Neonatologie

Outcome of preterm infants </= 1000 g and </=27 weeks (data are given in %)

0102030405060708090

100

23 24 25 26

survival

survival without BPD

survival withoutBPD, IVH>II°, PVL

survival withoutBPD, IVH>II°, PVL,ROP>II

Neonatologie

Application of surfactant via a thin endotracheal catheter during spontaneous breathing – potential Pros and Cons

Pros

Minimization of trauma by intubation

Avoidance of any positive pressure ventilation

Active inspiration of surfactant

Cons

New procedure with „learning curve“

Still need for laryngoskopie

Neonatologie

Summary

There is an obvious need for alternative ways to administer surfactant to premature infants with RDS

With this alternative ways it should be possible to:Avoid intubation

Avoid mechanical ventilation

Allow active inspiration of surfactant

Data from feasibility studies are available and promising but large prospective randomized trials are needed