Mechanical ventilation versus CPAP -what are the pros and cons Mechanical ventilation versus CPAP -what are the pros and cons? Anne Greenough Professor of Neonatology & Clinical Respiratory Physiology Division of Asthma, Allergy and Lung Biology King’s College, London, School of Medicine

Bronchopulmonary dysplasia PREDISPOSED INFANT Immaturity Family History RDS SEVERE LUNG DISEASE PDA/Fluid overload PIE CONTRIBUTARY FACTORS Infection Surfactant abnormalities Disturbance of elastase/protease HIGH LEVEL OF RESPIRATORY SUPPORT Baro/volutrauma Oxygen Support Bronchopulmonary dysplasia

Which ventilation strategy? Strategies to reduce the likelihood of baro/volutrauma: (i) Avoidance of intubation and mechanical ventilation - nasal continuous positive airways pressure (nCPAP) (ii) Respiratory support working synergistically with the infant’s respiratory efforts - patient triggered ventilation (iii) Minimisation of excessive “tidal” volumes - volume targeted ventilation - high frequency oscillation

Early nCPAP Reduced incidence of intubation and mechanical ventilation Jacobsen 1993, Poets 1996, Gitterman 1997 Eight centre comparison, the centre with the lowest occurrence of BPD used CPAP in preference to IPPV - avoided hyperventilation and muscle relaxants - used permissive hypercapnia - one individual supervised ventilatory care Avery 1987

Nasal CPAP or intubation at birth (COIN trial) 610 infants 25 to 28 weeks gestation IPPV CPAP O2 dep 28 days 63% 51% <0.001 Days of IPPV 4 3 <0.001 O2 dep at 36 weeks 29% 35% ns Pneumothorax 3% 9% =0.003 Morley et al NEJM 2008

Early surfactant and extubation to CPAP versus selective surfactant and IPPV Meta-analysis of six trials demonstrated CPAP: Reduced BPD 0.51(0.26-0.99) Reduced need for IPPV 0.67 (0.57-0.79) Reduced airleaks 0.52 (0.28,0.96) Surfactant 1.62 (1.41,1.86) Stevens et al Cochrane 2007 But early versus selective surfactant reduces airleaks and BPD/death and improves survival

Nasal trauma 20% infants on dual prongs affected Robertson et al ADC 1996 40 infants randomised nasaopharyngeal tube or binasal prong - similar trauma incidence Buettiker et al Intens Care Med 2004 89 infants randomised to binasal prong or mask -no significant difference in nasal trauma incidence - nasal injury (32%) related to CPAP duration Yong et al ADC 2005

PTV (ACV/SIMV) versus CMV Oxygen dependency: at 28 days 0.93 (0.77 - 1.14) at 36 weeks 0.91 (0.77 - 1.09) Severe IVH: 1.03 (0.75 - 1.43) Reduction in ventilation duration: - 45.2 hours (12.1 - 78.3) - only when PTV was started in the recovery phase Greenough et al Cochrane review 2007

Pressure support (PS) Infant triggers an inflation which is pressure supported at a preset level The beginning and end of inflation are triggered by the start and end of inspiration Inflation is terminated when the inspiratory flow is reduced to a certain level - 15% maximum flow (Draeger Babylog 2000 - PSV) - 5-25% maximum flow (Bird VIP - termination sensitivity)

Randomised trial of SIMV versus SIMV and pressure support (PS) 107 infants birthweight 500-1000gms >one week PS group SIMV rate reduced by 10bpm and PS added at 30-50% of the PIP-PEEP PIP decreased to PaCO2 and Vt: 3 and 5 ml/kg SIMV reduced to keep between 40-65mmHg Reyes et al Pediatr 2006

Randomised trial SIMV versus SIMV + PS all infants 700-1000 SIMV PS p SIMV PS p Age at final extubation (days) 44 35 .91 29 24 .366 IPPV (days) 34 22 .18 25 15 .118 IPPV 28 days (%) 69 47 .04 53 30 .116 O2 at 36wks (%) 48 33 .21 58 38 .142 O2 (days) 72 49 .11 86 58 .034

Work of breathing during SIMV with and without pressure support 20 infants mean gestational age 31 weeks, being weaned from mechanical ventilation SIMV SIMV + PS p PTP 141 (93) 112 (85) <0.001 PaO2 8.6 (2.6) 8.5 (1.8) 0.78 PaCO2 5.9 (1.3) 6.0 (1.6) 0.55 Resp rate 64 (13) 55 (11) 0.001 Patel et al ADC 2009

Volume targeted ventilation No significant reduction in death or death and BPD Reduced duration of ventilation 2.39 days Reduced pneumothoraces RR 0.23 Reduced 3-4 ICH RR 0.32 4 trials identified – 178 infants McCallion et al Cochrane database 2005

Volume targeted ventilation Volume support – desired volume is selected, the duration of inflation depends on the time taken for the volume to be delivered Bird VIP Volume limited – pressure support for any inflation is aborted if the measured volume exceeds the preset upper limit SLE 5000, Bearcub 750 Volume guarantee – preset expiratory tidal volume is delivered, but the preset Ti determines the duration of inflation Draeger Babylog Volume controlled – constant flow during inspiration – the required volume is delivered over the Ti Stephanie

Delivery depends on ventilator type Draeger positive pressure plateau Stephanie pressure increasing till Ti termination SLE and VIP Bird inflation terminating when the volume was delivered At the same settings – different MAP delivery Sharma et al Acta Ped 2006

Impact of VG on CO2 tensions Randomised trial of 40 infants 27 weeks gestation SIMV +/-VG 4mls/kg In infants > 25weeks VG halved the incidence of hypocarbia Ineffective in infants <26 weeks GA Cheema et al EHD 2006

Volume controlled vs pressure limited Randomised trial - 90 infants BW 600 to 1500gms, GA 24 –32 wks Bird VIP, volume controlled (VC) or pressure limited Success criteria oxygenation/MAP reached at 23 hrs VC versus 33 hrs (p=0.15) (BW<1000gms p=0.03) No significant differences in other outcomes Singh et al J Pediatr 2006 VT 4-6mls/kg

VG level and work of breathing 20 infants mean GA 28 weeks (10 ACV; 10 SIMV) PTP levels at VG levels of 4, 5 and 6 mls/kg VG level ACV SIMV 0 144 (47) 173 (88) 4 203 (82) 237 (100) 5 168 (59) 180 (78) 6 135 (47) 147 (51) Patel et al Pediatr 2009

Prophylactic HFO 13 published prophylactic trials ( < 12 hours) BPD at 36 weeks PMA or discharge in survivors RR 0.88 (0.79 – 0.99) Death by 36 weeks PCA RR 0.98 (0.83 – 1.16) Death or BPD at 36 weeks PMA or discharge RR 0.92 (0.85-1.00) Pulmonary airleak RR 1.14 (1.00-1.29) 3-4 IVH RR 1.11 (0.95-1.1.3) PVL RR 1.10 (0.84-1.44)

UKOS Trial Infants between 23 weeks and 28 +6 weeks gestational age, CMV or HFOV within 60 minutes of birth CMV HFO n 397 400 Died 26% 25% Survived O2 dependant at 36 weeks 41% 41% Airleak 18% 16% Cerebral abnormality 25% 17% Johnson et al NEJM 2002

Pulmonary function at one year Means and 95% CI of the differences in the means: CMV HFOV (95%CI diff) Respiratory rate (bpm) 31.2 33.9 (-6.1,0.7) TGV (mls/kg) 26.9 26.5 (-2.5,3.4) FRC (mls/kg) 24.1 23.5 (-2.1,3.2) FRC:TGV 0.90 0.90 (-0.06,0.06) Resistance (cmH2O/l/s) 33 34 (-8,6) Thomas et al ARJCCM 2003

V’maxFRC z-score Crown-heel length (cm) Effect of preterm delivery on airway function in first year of life V’maxFRC z-score Crown-heel length (cm) 24

Worsening V’maxFRC in infants with BPD 36 infants mean birthweight 837 (152) gms and gestational age 26.8 (1.7) gms BW < 1250gms, IPPV>7 days, BPD Initial ventilation: IPPV or HFOV in the youngest and smallest infants Evaluated at 6 and 12 months Maximum flow at functional residual capacity (V’maxFRC) Hofhuis et al AJRCCM 2002

Mechanical ventilation versus CPAP Current evidence: High volume HFO reduces BPD, but whether it improves long term lung function requires follow-up of infants entered into RCTs Weaning is best by modes supporting every breath –whether ACV or PSV is better merits testing Severe respiratory distress – a trial of rescue HFOV with long term outcomes is needed CPAP as the preferred mode?