“Reclutamento alveolare in sala

parto: la sustainedlung inflation”

Gianluca Lista, Francesco Cavigioli, Francesca Castoldi

Direttore SC Neonatologia e TINOspedale dei Bambini “V.Buzzi”, ICP,

Milano, Italy

Lung fluid secretion during foetal life and at birth

Lung fluidproduction(> 20wks; 5ml/Kg) byepithelial lung ; fluidleaves lung bytrachea inducing aninternal distendingpressure

At birth: there is neverdistending effect and the superface tension in the lung induces lungcollapse by anintrapleural P (-)

20-30 ml/Kg

- Alveolus liquid/air interface : liquid molecules exert a

strenght towards the internal site ( ( surfacesurface tensiontension), ),

tendency to LUNG COLLAPSE

P= 2T/r

Birth : transition

Birth : transition

After the umbilical cord is tied and the neonate begins his first breaths:

• fast increase of sistemic Raw• resistance to pulmonary blood flow drops sharply blood flow trough lungs increase of pulmonary venous flow, pressure increased in left atrium : closure of F.O.

• After birth : closure of ductus venosus• After 12-24 hrs : functionally closure of ductus arteriosus ( anatomically at 10 days of age)

Clear separation between left from right heart ( switch from parallel circuits to in series)

"Immediately after the umbilical cord is tied, the fetus ceases its dependent existance and the neonate becomes independent."

Bland, J Appl Physiol, 1986

Epithelial sodium channel = ENaC

Bland, Miami 2007

Summary :

•In the developing pulmonary epitheliumNa+ channels can be rapidly and reversiblyactivated, a property which has not beenreported in other epithelia

How is the “real “mechanism of lungliquid clearance and lung aereation at birth ?

by te Pas,Monza 2010

2007

Rabbit pups delivered at term by CS and killedimmediately after birth or at different times

Physiology of the first breaths in a newborn

FRC

Aeration rate :

3 ml/Kg/breath over the first 5 breaths

FRC: createdwithin secondsto minutes

Vtml/Kg

TIME

sec

0

4

2

1

6

10

12

8

0 32 4

First breath

30 sec

10’,60’,90’

days

Fig. 1.14 Schematic representation of the average spiro gramof the first breat and those at 10’,30’and at few day s after birth

Term newborn

Karlberg P, J Pediatr 1960, vol.56, 585-604

94±1.4 % aeration during inspiration

Inspiration…..DP…airway liquid removal…initial FRC…… ..EBMs …maintain FRC

by te Pas,Monza 2010

Premature delivery :a failure of transition tocreate an early FRC

Many preterm babies breathe at birth,but:• Poor respiratory muscle strenght ( e.g. diaphragm)• Poor inspiratory pressure• High chest wall compliant• Low lung compliance ( surfactant deficiency)• Neurological impairment• Inefficient fluid clearance

Frequent need of respiratory support ( e.g. CPAP)

N=103 preterm infants, < 32 wks ( mean 29±1.9 wks , BW 1220 ± 412g)

Pediatr Res 64:281-285, 2008

Expiratory hold pattern(most frequently)

Slow Expiratory pattern

Crying /grunting

pattern

Panting pattern

Pediatr Res 64:281-285, 2008

Which neonatal resuscitation forpreterm infants ?

• Actual recommendations: based on dogma’s

• Preterm lung : at high risk for “lung injury”• Respiratory support : to avoid tracheal

intubation ; non-invasive asap but it is notalways …….easy

te Pas et al., Curr Ped Rev 2007

by te Pas,Monza 2010

What have we do “ IN PRIMIS “ in the delivery room for babies with reduced respiratory effort ? The role of the SUSTAINED LUNG INFLATION….

Preterm infant Asphyxiated infant

Initial pressure applied and maintained at 30 cm/H 2O for approximately 5”

A

B

D

C

1’’

3’’

7’’

Expired tidal volume

10- and 20-s SI increased the inspiratory volume and p roduced a greater FRC,and a 20-s SI uniformly aerated the lung before ventilation started

Time to need areate 90% of the lung = 14 ± 4.1 sec ( r ange = 8.6-20 sec)

Respir Res. 2009 Mar 10;10:19.

te Pas et al Pediatrics 2007; 120: 322-29

• Oropharyngeal and nasal suctioning• Sustained lung inflation (SLI) by face mask

immediately after delivery early CFR (15”-20”, CDP at 25 cmH2O by NeoPuff, plus PEEP at 5 cmH2O), 1 or 2 times

• Good spontaneous breathing ?• Nasal CPAP (4 - 6 cmH2O) or SiPAP or N-SIPPV using

nasal pharyngeal tube or nasal prongs• Tracheal intubation if : HR < 100/min and SpO2 < 80%

at 5’ (FiO2 >0.5 too) , apnea or marked and increasingdyspnea

• Surfactant: < 26 wks

Delivery room protocol for VLBW infantswith respiratory failure from 2007 (Buzzi)

Lindner W, Pediatrics 1999,103:961-967

Nguyen An T et al., Pediatrics 2003,112:208-211

Does sustained lung inflation at birth improve outcome of preterm infants at risk for respiratory distress syndrome ?

G. Lista, P.Fontana, F. Castoldi, F.Cavigioli, C.DaniNeonatology 2010, in press

• Objectives To verify if the application of a SLI of preterm infants < 32 wks with respiratory failure at birth may reduce the need for mechanical ventilation and improve their respiratory outcome.

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

2004-2006 (control group) n=119retrospectively studied

Suctioning

CPAP (5 cmH2O) or intermittent ventilation by mask(Peak pressure 20-25 cmH2O, PEEP 5 cmH2O, RR 60/min)T-piece ventilator (Neopuff Infant Resuscitator Fisher and Paykel, New Zealand)

• intubation and MV according to AAP

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

2007-2009 (SLI group) n=89prospectively studied

Suctioning

SLI 1 or 2 timespressure-controlled inflation(25 cm H2O) sustained for 15 ’’

CPAP (5 cmH2O) or intermittent ventilation by mask(Peak pressure 20-25 cmH2O, PEEP 5 cmH2O, RR 60/min)T-piece ventilator (Neopuff Infant Resuscitator Fisher and Paykel, New Zealand)

• intubation and MV according to AAP

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

the infants received NCPAP or MV (PTV+VG-Draeger Babylog 8000 plus) following NICU protocols.

Surfactant (Curosurf, Chiesi, Italy) was administered when FiO2 > 0.40 (INSURE procedure if assisted in NCPAP).

In the NICU

STATISTICAL ANALYSIS

Univariate statistical analysis :•Student “t” test for parametric continuous variables •Wilcoxon rank-sum test for non-parametric continuous variable•Fisher’s exact test for categorical variables

(p <0.05 , statistically significant)

Multiple logistic regression analysis (RR with profile likelihood-based 95% confidence limits)

Post hoc analysis, using the study’s sample size and observed variance98.3% statistical power of detecting as statistically significant a difference of 25% in the need for MV between SLI and control group ( α of 0.05 and β of 0.8).

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

0.1614.4+4.13.6+4.0CRIB score

0.4399 (83)78 (87)Antenatal Steroids(complete course)

0.1446.9+1.57.2+1.4Apgar 5’

0.63068 (57)47 (53)Male

0.9381080+3471084+390BW (grams)

1.00028.1+2.028.1+2.2GA (wks)

pControl Group(n=119)

SLI Group(n=89)

Mean+(SD), or number and (%)

Clinical characteristics of the groups

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

0.7929 (24)24 (27)PDA (n)

0.35917 (14)8 (9)Mortality (n)

0.2557 (6)10 (11)ROP > 3° (n)

0.29911 (9)4 (4)PVL (n)

0.3725 (4)1 (1)grade 3-4 IVH (n)

0.00425 (25)6 (7)BPD (n)

0.92010 (8)8 (9)PNX (n)

0.01030 (25)9 (10)Post-natal steroids (n)

0.01631 ± 3121 ± 27O2-therapy (d)

0.02773 (61)40 (45)Surfactant (n)

< 0.000129 (24)44 (49)Exclusive NCPAP

0.00811 ± 195 ± 11MV (days)

< 0.000190 (76)45 (51)MV (n)

0.0013 (3)14 (16)INSURE (n)

pControl (119)SLI (89)

Outcomes of the groups Mean+(SD), or number and (%)

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavi gioli, MD, C Dani, MD. Neonatology, 2010, in press

RESULTS:

Multiple regression analysis:

SLI (RR 0.49, 95% CI 0.34-0.72)CRIB <3 (RR 0.16, 95% CI 0.08-0.29)INSURE (RR 0.29, 95% CI 0.24-0.37)

GA 23-27 wks (RR 5.91, 95% CI 2.69-12.95)

BW<750g (RR 2.88, 95% CI 1.78-4.67)

Riskof MV

Riskof MV

Does sustained lung inflation at birth improve outc ome of preterm infants at risk for respiratory dist ress syndrome ?G Lista, MD, P Fontana, MD, F Castoldi, MD, F Cavigioli, MD, C Dani, MD. Neonatology, 2010, in press

BIAS:

This is not a RCT and its results need to be considered with caution…but our population is large enough to make our results relevant

The historical group constitutes a bias given the changes that occurred in time in the care of premies

…but very little has changed in the delivery room assistanceand no changes occurred in our NICU protocols in terms of indications to MV

Conclusion:

this study generates a good hypothesis for :• a multicenter RCT, since it suggests that the application of the SLI maneuver at birth in ELGAi with signs of RDS may decrease the need for mechanical ventilation• a RCT , since it suggests that SLI at birth may reduce the incidence of respiratory distress in late preterm infants or infants born near term after elective cesarean section

Work in progress ?

• “ Delivery room management with SLI in extremely preterm infants at risk forrespiratory distress : a RCT “

(proposal by Lista G and Dani C)

• SLI effect on cerebral oxygenation (rSO2-NIRS) ?

• SLI effect on oxidative stress ?

Conclusions

• Consider physiology from the DR• Initial SLI might be beneficial for infants

with less respiratory effort ( larger and earlier FRC, uniform lung aereation, consistent Vt)

• Use PEEP and CPAP for preterm infants ( e.g.VLGA-ELGA)

• We need to “monitor” from the delivery room and in NICU

Thanks to Te Pas and Hooper for their contribution