Minimally invasive surfactant Application

1 December 7th 2015 Hot Topics_Kribs Minimally invasive surfactant Application Angela Kribs Childrens Hospital, University of Cologne Germany December 7th 2015 Hot Topics| Kribs Seite 2 Background I Most preterm infants start spontanuous breathing after birth and therefor do not obligatory need intubation and mechanical ventilation. Spontaneous patterns of breathing are important for lung recruitment. Larynx plays an important role in lung recruitment immediately after birth. Intubation inactivates laryngeal function. Mechanical ventilation has the risk to induce lung injury and may also influence the development of brain lesions. Association of surfactant administration and mechanical ventilation is meanly a historical phenomena. But: surfactant usually related to intubation and mechanical ventilation has improved the prognosis of preterm infants more than any other therapy.

2 December 7th 2015 Hot Topics| Kribs Seite 3 Background II Outcome of ELBW infants treated with nasal or pharyngeal CPAP as primary respiratory support is comparable to that of infants treated with primary intubation, mechanical ventilation and surfactant administration . >>>>> surfactant without any mechanical ventilation but with CPAP supported spontaneous breathing could be the combination of two effective principles !!!! December 7th 2015 Hot Topics| Kribs Seite 4 Non randomized trials First Author Type of study Number of LISA-patients Reference Mean results Kribs Observational, single centre 29 Paediatr Anaesth 2007; 17:364-9 Lower mortality, less IVH>II , less PIE compared to historical control Kribs Observational, single centre 150 Acta Paediatr 2008; 97:293-8 less CPAP failure after introduction of method, lower mortality in infants with CPAP success regardless whether with or without surfactant Kribs Observational, multi-centre 319 Klin Paediatr 2010; 222:13-7 Lower prevalence of mechanical ventilation, less BPD compared to standard care Dargaville Observational, single centre 25 Arch Dis Child Fetal Neonatal Ed 2011.

3 96:F243-8 Increase of SpO2 after the procedure, reduction of FiO2 and CPAP pressure Porath Observational, Follow-up 31 Acta Paediatr 2011; 100:352-9 No differences in outcome at early school age compared to historical control Mehler Observational, single centre 164 Acta Paediatr 2012; 101:1232-9 Improved survival and reduced morbidity in infants with a gestational age below 26 weeks after introduction of the procedure December 7th 2015 Hot Topics| Kribs Seite 5 Non randomized trials First Author Type of study Number of LISA-patients Reference Mean results Dargaville Feasibility study 61 Arch Dis Child Fetal Neonatal 2013; 98:F122-6 Increase of SpO2 after the procedure, reduction of FiO2 and CPAP pressure Klebermass-Schrehof Observational, single centre 224 Neonatology 2013; 103:252-8 lower mortality after introduction of LISA, esspecially in infants with a gestational age 23+0 - 25+6, less IVH, less severe IVH, less cystic PVL but more ROP and severe ROP, more PDA, less Death or BPD Aguar Observational, single centre 44 Acta Paediatr 2014; 103: 229-33 Procedure is feasibily without differences in any observed outcome compared to INSURE Canals Candela Observational single centre 19 An Pediatr (Barc) 2015 S1695-4033 Procedure is feasible without adverse events, less intubation during the first 72 hours of life compared to historical control G pel Matched pairs from German neonatal network 1103 Acta Paediatr 2015; 104:241-6 Lower rates of mechanical ventilation and BPD Krajewski Observational single centre 26 J Matern Fetal Neonatal Med 2015.

4 10:1161-4 Procedure is feasible and is associated with less intubation and mechanical ventilation compared to INSURE December 7th 2015 Hot Topics| Kribs Seite 6 Published randomized , controlled trials First Author Type of study Number of LISA-patients reported Reference G pel RCT (AMV-trial) 65 Lancet 2011; 378:1627-34 Kanmaz RCT ( Ta ke care trial) 100 Pediatrics 2013; 131:e502-9 Kribs RCT (NINSAPP) 107 JAMA Pediatr 2015; 169:723-30 Mohammadizadeh RCT 19 J Res Pharm Pract 2015; 4:31-6 Bao RCT 47 BMC Pediatr 2015; 1415:21 December 7th 2015 Hot Topics| Kribs Seite 7 Published randomized , controlled trials Study Gestational age Control group Primary outcome AMV 26+0 28+6 Any kind of standard care Need for any MV or being not ventilated but having a pCO2 >65 mmHg or a FiO2 > or both for more than 2 h between 25 and 72 hrs of age Take Care <32+0 InSurE Need for early MV NINSAPP 23+0 - 26+6 Intubation and mechanical ventilation Survival without BPD at 36 weeks Mohammadizadeh </= 34+0 InSurE Need for MV and duration of oxygen therapy Bao 28+0 -32+6 InSurE feasibility December 7th 2015 Hot Topics| Kribs Seite 8 Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised controlled trial G pel, Kribs et al.

5 Lancet 2011; 378:1627-34 December 7th 2015 Hot Topics| Kribs Seite 9 surfactant administration via a thin catheter during spontaneous breathing. Randomized controlled trial Kanmaz et al. Pediatrics 2013; 131:e502-9 December 7th 2015 Hot Topics| Kribs Seite 10 Nonintubated surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A randomized Clinical Trial Kribs et al. JAMA 2015; 169(8):723-30 December 7th 2015 Hot Topics| Kribs Seite 11 Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: Feasibility ans outcome Mohammadizadeh et al. J Res Pharm Pract 2015; 4(1):31-6 December 7th 2015 Hot Topics| Kribs Seite 12 A pilot study of less invasive surfactant administration in very preterm infants in a Chines tertiary center Bao et al. BMC Pediatr 2015; 15:21 December 7th 2015 Hot Topics| Kribs Seite 13 Summary The increasing use of CPAP as initial respiratory therapy of preterm infants with RDS raises the question, whether surfactant Application during CPAP is possible.

6 A number of observational studies demonstrate the feasibility of surfactant Application during CPAP via a thin endotracheal catheter lead to the hypothesis that the method may be beneficial. First RCTs demonstrate an effect on the need for mechanical ventilation. An reduction of neonatal complications seems possible. Further large RCT s are needed