Slide 1

Non-Invasive Positive Pressure Ventilation evidence base in preterm infants

Slide 2

And he went and lay upon the child.. Put his mouth upon his mouth.. And the flesh of the child waxed warm Kings 4:32 Lord Leighton Elisha reviving the Shunammite child Methods used to avoid tracheal intubation

Slide 3

OUTLINE 1. Why does non-invasive support matter? endotracheal intubation damages airway mucosa from top to bottom Long term adverse effects of BPD 2. Some relevant physiology 3. Methods to avoid intubation NIPPV Evidence from randomized trials

Slide 4

Sato K Ann Otol Rhinol Laryngol. 2006 115:816 Grossmann G, Eur J Pediatr 1986 145:361 Necrotizing TracheoBronchitis Kirpalani H CCM1985 Reyburn M. Am J Respir Crit Care Med. 2008 Control Ventilation no SFTVentilation + SFT

Slide 5

(n=910) Baseline Risk Probability of a poor outcome at 18 months Number of Morbidities at 36 weeks: BPD, ROP, Brain Injury

Slide 6

Objectives 1. Why does non-invasive support matter? BPD and endotracheal intubation Long term effects of BPD 2. Physiology 3. Methods to avoid intubation CPAP, NIPPV Evidence from randomized trials

Slide 7

Historical Surgical Therapy for HMD: Sternal traction Warley & Gairdner Arch Dis Child 1962; 37: 464

Slide 8

Newborn chest wall and lung pressure-volume curves Agostino E and Mead J 1964; Handbook of Physiology Chest Wall Adult Newborn Pressure Lung

Slide 9

90 135 Normal or abnormal chest wall-abdominal movements 45 Ped Pulmonol 1998; 25; 175

Slide 10

Synchronized Effects of Synchronization During Nasal Ventilation Hung-Yang Ang C Pediatr Res 69: 84, 2011 Non - Synchronized Synchronization did not affect tidal volumes; phase angles; apnea spells; hypoxemic spells

Slide 11

Moretti C: Comparing nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nCPAP) after extubation in VLBW. Early Hum Dev. 1999;56:167

Slide 12

Objectives 1. Why does non-invasive support matter? BPD and endotracheal intubation Long term effects of BPD 2. Physiology of NIPPV 3. Methods to avoid intubation CPAP, NIPPV Evidence from randomized trials

Slide 13

Repetitive themes in ventilation Spiral philosophy: The progress.. raises to each next stage of determination the whole content, and enriches and concentrates itself... G.F.Hegel Science of Logic; The Absolute Idea; 812; Circular philosophy: The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun Ch 1, v9 Ecclesiastes

Slide 14

1889 ALEXANDER GRAHAM BELL: Presented results to a meeting of the American Association for the Advancement of Science at Montreal his invention met with little enthusiasm. Stern L: Symposium on Artificial Ventilation Paris 1969; Biol. Neonate 16: 2429 (1970)

Slide 15

Drinker P, Shaw LA. J Clin Invest. 1929 Jun;7(2):229-47. 1890s Wilhelm Schwake: Pneumatic Chamber

Slide 16

Simple device for producing continuous negative pressure in infants with IRDS. Bancalari E, Gerhardt T, Monkus E. Pediatrics. 1973;52:128

Slide 17

NEGATIVE PRESSURE ISOLETTE NPV: RCTs (i)Silverman WA Pediatrics 1967 Sequential RCT: NPV vs IPPV in >1000 g BW; Stopped early for no benefit after 27 pairs. (ii)Fanaroff AA J Pediatr 1973 Sequential analysis RCT: NPV vs IPPV; benefit in oxygenation (iii)Alexander G: AJDC:1979 RCT n=36; NPV vs CPAP: equivalent HEAD

Slide 18

Slide 19

Treatment of RDS CPAP Gregory GA: N Engl J Med. 1971; 284:1333

Slide 20

P :In infants VLBW or ELBW in DR I : does randomization to nCPAP C :compared to intubation IMV O :increase survival without BPD T :at 36 weeks PMA? PICOT CPAP

Slide 21

N Engl J Med 2008;358:700

Slide 22

Wright CL, Kirpalani H 2011: 128: 111 0.91 (0.83, 1.00 ) Primary Outcome Death or BPD 36 weeks

Slide 23

Mortality similar Nevertheless we encountered complications stomach distension... Oedema of the face RCT of ventilation using oro-nasal mask Llewellyn MA, Tilak KS, Swyer PR: 1970; Arch Dis Child 45:453

Slide 24

Garland JS: Increased risk of GI perforations in neonates mechanically ventilated with either face mask or nasal prongs. Pediatrics,1985, 76:406 Retrospective Matched Case control study (1 case: 4 controls)

Slide 25

Post- Extubation BPD Death Un-intubated BPD Death Updated: Trials of NIPPV vs nCPAP Outcome NIPPV nCPAP Relative Risk n/N n/N (95% CI) 0.2 0.5 1 2 5 Favours NIPPV Favours nCPAP 26/93 3/56 3/80 5/79 38/88 3/55 10/80 9/85 0.2 (0.05, 0.87) 0.59 (0.22, 1.59) 0.97 (0.21, 4.44) 0.64 (0.44, 0.95) Lemyre B, DePaoli A, Kirpalani H, Davis P; and Salter S, Laughon M, Lemyre B, Bose C; Cochrane

Slide 26

V Rajadurai B Urlesberger P Maton G Dempsey D Millar E Boyle J Frank K Sankaran J Cairnie B Lemyre K Abubakar F Reiterer A Chaudhary M Roy R van Lingen S Rahman P Srinivasan E Asztalos P McNamara C ODonnell T Ibrahim W Marion M Finelli S Godambe B Simma W Stelzl B Jonsson P Gerhard R Roberts R Kim L Costantini I Herlihy P Dijk I Frantz I Hand M Hyndman J Miletin S Ranu A OSullivan L Legnevall R Whyte N Rashid C Thiel J Zupancic H Kirpalani NIPPV: The Nasal Intermittent Positive Ventilation for Prematures Trial

Slide 27

N Engl J Med. 2013 Aug 15;369(7):611-20

Slide 28

P : In infants

Primary Outcome Prior death or survival with BPD at 36 weeks PMA Definition of BPD: On respiratory support (IMV, nCPAP, NIPPV) or > 30% supplemental oxygen; or < 30% supplemental oxygen, and failed Oxygen Reduction test (ORT) ( J Perinatol 2003)

Slide 33

1009 infants randomized 504 NIPPV503 nCPAP Primary outcome BPD-ORT 497 98% 490 97% 2 withdrew consent Ascertainment of primary outcome

Slide 34

Mother NIPPV nCPAP Race White 56%57% Age Years 30.3 6.330.5 6.1 Antenatal Steroids92%91% Baseline Characteristics

Slide 35

Infant NIPPV nCPAP BW - g 802 131805 126 GA - wks 26.1 1.526.2 1.5 Male53%46% Multiples23%24% SNAP II 30.6 13.630.4 13.4 Baseline Characteristics

Slide 36

Primary Outcome: Death or BPD by ORT at 36 weeks NIPPV nCPAP 180 of 490 37% OR=1.1 95% CI 0.8 to 1.4 p=0.6 191 of 497 38%

Slide 37

sNIPPV nCPAP p = 0.6 108 of 279 39% NIPPV 36 of 101 36% 180 of 490 37% Sub-Group effects: Synchronization NIPPV adjusted Death or ORT-BPD

Slide 38

Number of post-randomization failures of respiratory support, requiring re-intubation and subsequent extubation by group NIPPV Median (IQR) 1 (0,1) nCPAP Median (IQR) 1 (0,1)

Slide 39

Death Cochrane: Greenough A 2008: Synchronised ventilation newborns Favours Synchronized Favours Control RR 1.19 (0.95,1.49)

Slide 40

Peak Trans-Diaphragm Electrical Potential

Slide 41

Slide 42

Brigitte Lemyre, Peter G Davis, Antonio G De Paoli, Haresh Kirpalani Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation Cochrane; 4 SEP 2014 CD003212.pub2

Slide 43

Some current barriers to sNIPPV 1. Available flow triggers rendered dependent on minimal- no leak nose and mouth 2. Devices for abdominal wall movement synchrisation no longer available (Graseby capsule) 3. Limited data on NAVA Needed now 1.Moderate to large scale trials with synchronizing devices, with a relevant primary outcome 2. Improved patient-device-interfaces C.T.Roberts, P.G.Davis, LS.Owen Neonatology 2013; 104:203 Bancalari E, Claure C Arch Dis Child (F&N): 2013: 98; F98

Slide 44

Leonardo Da Vinci (1452-1519) Notebook Conclusions: Non-invasive support using CPAP does reduce BPD Superior methods still needed Simple non-synchronized NIPPV does not improve BPD Synchronization for NIPPV needs further trials HFNVpromising trials needed

Slide 45

Diego Rivera (1886-1957) Hospital Mural Medicine for the People Technology marches on but is too often untested