Treating preterm infants with Surfactant: an overview of application techniques and results Angela 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:  23 infants enrolled ( g, 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: 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:

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: Nebulization of surfactant - Data

Neonatologie Mazela et al. Curr Opin Pediatr 19: 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: 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):

Neonatologie Standard of delivery room management  Covering the baby with a polyurethrane wrap  Suction of the mouth  Positioning of a face mask with high- flow- CPAP (Benveniste valve), FiO2 0,4, PEEP 8-14 cmH2O  Positioning of a pulsoxymeter  Observation of:  SO2 ( >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 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 ( ) 25,7 ( ) 25,2 ( ) 25,3 ( ) 25,1 ( ) Birth weight (gramm) 714 ( ) 667 ( ) 705 ( ) 690 ( ) 668 ( ) Apgar 5‘7 (2-9)7 (3-10)8 (2-9)8 (3-9)8 (1-9) Gender male / female23/1523/2426/1916/1216/19 SGA (<10.Perc.)9 (23,7%)10 (21,3%)10 (22,2%)6 (21,4%)11 (31,4%) Sepsis at birth12 (31,6%)13 (27,7%)17 (37,8%)12 (42,9%)15 (42,9%) PPROM < 23 weeks3 (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 steroids32 (84,2%)44 (93,6%)45 (100%)27 (96,4%)30 (85,7%)

Neonatologie Respiratory management of RDS (n=155) %

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

Neonatologie Mechanical ventilation vs. CPAP as initial respiratory support Demographic data and prenatal risks Ventilation N=23 CPAP N=132 Significance Gestational Age (weeks)24,825,4P=0,038 Birth weight (gramm)662686n.s. Apgar 5 min.4,77,6P<0,001 gender male / female11/1263/69n.s. Any antenatal steroids21 (91,3%)125 (94,7%)n.s. SGA < 10. Perc.4 (17,4%)40 (30,3%)n.s. Sepsis at birth15 (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 transfusion5 (21,8%)9 (6,8%)P=0.037

Neonatologie CPAP + Surfactant: Responder vs Non Responder Demographic data and prenatal risks Responder N=90 Non Responder N=38 Significance Gestational Age (weeks)25,525,2n.s. Birth weight (gramm)691666n.s. Apgar 5 min.7,77,4n.s. gender male / female44/4619/19n.s. Any antenatal steroids87 35n.s. SGA < 10. Perc. 2614n.s. Sepsis at birth2615n.s. PPROM < 23 weeks of gestational age 20 7n.s. Twin to twin transfusion 4 5n.s.

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

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