1. Non Invasive Ventilation
Dr Julian Eason
Chair Neonatology
Corniche Hospital
Abu Dhabi

2. Corniche Hospital 64 bed NICU, 1000 admission/year
High Risk obstetric and Fetal medicine referral centre in
UAE

3. Non-invasive support

4. History of Preterm infants and RDS
1970’s – nCPAP
1972 – Antenatal Steroids
1980’s – Exogenous Surfactant
1990’s – SIMV and HFOV
2000’s – nCPAP, NIPPV, INSURE
2007 – mINSURE
HHFNC

5. Learning Points
1. Recognise that the basic element of all noninvasive strategies is to develop Positive End Expiratory Pressure.
2. Be aware that there are uncertainties in the relative benefits of different types of noninvasive ventilation.
3. Acknowledge that noninvasive strategies to avoid intubation and mechanical ventilation do not prevent the development of bronchopulmonary dysplasia in most infants.

8. Is CLD in LBW infants preventable? Avery et al, Pediatrics 1987
Survey of 8 level 3 NICU in USA
Birth weight 700g to 1500g
Columbia New York
Used Hudson nCPAP ~ 5 cm H2O soon after birth, half in the Delivery Unit
PaCO2 up to 60 mmHg before intubation.
The Dr Cheng factor

9. What’s wrong with Ventilation?
Barotrauma / Volutrauma / Rheotrauma / Atelectotrauma
Increases resistance to breathing.
Injures airways, Increases infection.
Risk of hypocarbia. Low PaCO2 ?→ PVL
Many doctors don’t really know how to use ventilators
when to start
which mode
how to wean
when to stop.
Options confusing

10. PEEP is very effective Helps clear lung fluid at birth
Helps establish and maintain lung aeration
Improves oxygenation
Conserves surfactant
Decreases upper & lower airway resistance
Improves the compliance of stiff lungs
Regularises and slows respiratory rate
Reduces apnoea
Reduces lung injury and inflammation
Reduces energy expenditure
Reduces the need for ventilation

11. Why NIV?

12. Types of CPAP nCPAP, nSiPAP and nBiPAP Assisted CPAP (NIPPV-SNIPPV)
Humidified High Flow Nasal Cannula (HHFNC)
HFOV (Oscillation)(via nasal prong)

13. Comparisons nCPAP v NIPPV - BPD same ?Apnoeas
Lemyre B. Cochrane Review 2001
SiPAP v nCPAP - No Difference
Ricotti et al, J Matern Fetal Neonatal Med. 2013
HHFNC v nCPAP - Similar
Bradley A. Yoder, Pediatrics 2013
Neotech RAM Cannula Versus Conventional Binasal Prong Continuous Positive Airway Pressure (CPAP) to Treat Respiratory Distress in Low Birth Weight Neonates – recruiting 2014 Minnesota

14. Apnoea’s
Lin randomised 34 infants and showed decrease in freq of apnoeas (event/hr) with NIPPV v CPAP
Lin CH et al. Pediatric Pulmonol p
Cochrane meta-analysis NCPAP v NIMV
54 infants to 4-6 hours
Only one infant on CPAP required intubation
Lemyre B. Cochrane Review 2007

15. NIPPV Post extubation
Pooled 3 RCT’s showed dec in extubation failure using NIPPV.
More infants on NIPPV remained extubated at hours
All used sync NIPPV
Dec CLD favoured NIPPV
Davis PG et al. Cochrane Systematic Review 2007

16. CPAP

17. Initial Rx of RDS
COIN showed 55-60% infants at weeks gestation fail initial CPAP NEJM 2008 Feb (7) 700-8
Bhandari et al. RCT of infants receiving surfactant compared rapid extubation to NIPPV with ongoing ventilation
No difference in duration of intubation or oxygen.
Reduced CLD 52% to 25% in NIPPV group
No differences at 22 months J Perinatol 27 (2007) p

18. 76 neonates 28-34 weeks randomised at 6 hrs NIPPV or CPAP
RCT from India
76 neonates weeks randomised at 6 hrs
NIPPV or CPAP
Failure rate at 48 hours and 7 days less with NIPPV
Most benefit in smaller infants not receiving surfactant
Kishore M et al. Acta Paediatr p
Ramanathan 110 infants born before 30 weeks requiring surfactant. NIPPV suggested dec CLD compared to CPAP
Ramanathan R et al. J Perinatol 2012 May (5) p336-43

19. CPAP Failure assingned to:
Noninvasive positive pressure ventilation or conventional mechanical ventilation for neonatal continuous positive airway pressure failure.
Int J Prev Med Aug;5(8):
55 Newborns weeks
CPAP Failure assingned to:
NIPPV bpm at 20cm
IPPV bpm PIP 12-20cm
74% CPAP failures improved on NIPPV and not ventilated
More failure in low 5 min apgar and inc surfactant use
Less LOS and oxygen in NIPPV but not significant

20. CPAP: Generators

21. Delivery

22. High Flow Nasal Cannula (HFNC)
Heated humidified high flow nasal cannula (HHHFNC)
HHFNC can donate more than
1 l/min flow
Used as initial mode of respiratory
support or after extubation
More comfortable and easy to maintained
than CPAP, avoid intubation, easy to clear
secretion, less trauma and more liked by
nursing staff
Garg S, J Clin Neonatol. 2013

23. Optiflow Nasal Cannula

24. More people are now using HHFNC but…………
“The main drawback of using HHFNC is that the pressure generated is not measurable and cannot be regulated.”
Really? Do you think you regulate CPAP?

25. Use of HHFNC in NICUs J Neonatal-Perinatal Med 2010
A survey of 97 training directors in USA
60% responded.
Of these 69% used heated humidified HHFNC.
Used flows from 1 to 6 L/min
Indications for use varied: to give CPAP, after extubation, nasal injury, weaning CPAP, for apnoea
Weaned by reducing the flow
No adverse effects reported

26. Use of HHFNC in Australasian NICUs J Paediatrics and Child Health 2011
Survey to all 167 neonatologists
67% completed questionnaire
HHFNC used in 93% of NICU
Uses: reduce nasal trauma 91%, CPAP 62%
Perceived benefit: easier care of infant and better tolerance by infant.
Problem: Rainout in prongs

27. HHFNC increasingly used because of
Simplicity
Ease of use – nurses and mothers like it
Much easier to move and handle baby
Effective
Minimal nasal trauma
More convenient and effective than head box,
Much better than gas bubbled through cold water

28. Research in high flow therapy: Mechanisms of action Dysart
Research in high flow therapy: Mechanisms of action Dysart Respiratory Medicine 2009
Washout of nasopharyngeal dead space lowers CO2
Reduces inspiratory and expiratory resistance in nasopharynx, areducing work of breathing.
Improves pulmonary compliance and conductance compared to dry, cool gas.
Warm, humidified gas through nasopharynx reduces metabolic work associated with gas conditioning.
High flow through nasopharynx increases pressure.
This all happens with nCPAP!

29. The high flow of gas flushes out nasopharyngeal dead space
Reduces CO2
Reduces work of breathing

30. Mouth closed CPAP pressure Mouth open 2 pharyngeal pressures 510
Mouth closed
Mouth open
2 pharyngeal pressures
CPAP pressure
De Paoli Arch Dis Child F & N 2005; 90(1):F79-F81.

31. Pharyngeal pressure compared with set CPAP pressure with mouth open and closed
Mouth closed
Pharyngeal pressure (cmH2O)
Mouth open 3 4 5 6 7 8
Set CPAP pressure (cm H2O)
De Paoli Arch Dis Child F & N 2005; 90(1):F79-F81.

32. So n CPAP has……… Low and variable pharyngeal pressure
A high gas flow through nasopharynx
nCPAP and HHFNC are very similar
HHFNC is easier and has less nasal trauma

33. Overall outcomes from four RCTs of nCPAP vs HHFNC
Nasal trauma significantly reduced (except Chinese trial)
Similar extubation failure rates for CPAP and HHFNC.
No significant differences in mortality and morbidity.

34. NIPPV
May be more effective than nasal CPAP in treating apnoea without influencing long-term outcomes
Ramanathan 2012
A trial of NIPPV can be considered to reduce the risk of extubation failure in babies failing on CPAP

35. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation
Cochrane Database Syst Rev Sep 4;9:CD003212
Lemyre B, Davis PG, De Paolli AG, Kirpalani H.
NIPPV reduces the incidence of symptoms of extubation failure and need for reintubation within 48 hours to one week more effectively than NCPAP; however, it has no effect on chronic lung disease or mortality.
Synchronisation may be important in delivering effective NIPPV. The device used to deliver NIPPV may also be important; however, there are insufficient data to support strong conclusions. NIPPV does not appear to be associated with increased gastrointestinal side effects.

36. A RCT of HHFNC vs NIPPV for RDS
To compare rate of intubation
< 35 weeks, >1000g with RDS
HHFNC (n = 38) 1 – 5 L/min
NIPPV with SLE ventilator (n = 38)
Result: no significant difference in intubation rate and morbidities
Conclusion: HHFNC may be as effective as NIPPV in preventing intubation in primary treatment of RDS
Kugleman Ped Pulm 2014

37. When to Ventilate Perinatal depression Hypoxaemia requiring >40%O2
Acute hypoventilation with rising CO2
Frequent apnoeas with intervention
Severe distress
?<26 weeks
Clinical Judgement

38. Conclusions
There are few differences between nCPAP and HHFNC and nIPPV.
HHFNC is easier for nurses, and mothers, and and causes less nasal trauma.
NIPPV is perhaps more promising demonstrating better success after extubation
Use which suits you, the babies and staff.

39. Thank you

40. European Consensus Guidelines for RDS Management (2013 Update) {Endorsed by European Association of Perinatal Medicine)
Babies with RDS should be given a natural surfactant
Early Rescue Surfactant Rx if there is evidence of RDS or for ELBW infants whose mothers had not received AS or those intubated for stabilization.
< 26 wks with FiO2 >0.30 and >26 wks with FiO2 > 0.40 should be considered for early, rescue Surfactant
Poractant alfa 200 mg/kg is better than 100 mg/kg
Consider INSURE and early extubation to NCPAP/NIPPV
Caffeine should be considered for all babies < 1250 g BW, who are on NCPAP/ NIPPV
Sweet DG et al. Neonatology 2013; 103:

41. NIPPV: Settings

42. Simple HHFNC Guidelines
Prongs about 50% of nostril diameter
Gas heated to 37oC and 100% humidity
Flow 2 to 8 L/min for neonates
Mouth not actively closed
Blended oxygen to achieve SpO2
Wean by reducing FiO2 then flow rate
When flow <2 L/min consider off HHFNC
Failure criteria same as for CPAP

43. Future neonatal nCPAP and HFNC research
Investigate flow into nose on nCPAP vs HFNC
Calculate nasopharyngeal dead space
Investigate whether HFNC and nCPAP alter pCO2
Investigate effect of mouth position on gas flow with nCPAP and HFNC
Determine the optimal nasal gas flow?

44. The use of CPAP is well established
The use of CPAP is well established. There is evidence of a reduction in Chronic Lung Disease in some studies. Its practical application can be challenging and problems do occur. It has reduced our use of delivery room surfactant and also the amount of rescue surfactant. Despite the fact that we have studies demonstrating improved survival in infants receiving Surfactant, these were mechanically ventilated infants. We have seen no worse outcomes with the increasing use of CPAP. CPAP however is not the only way to generate PEEP and prevent alveolar atelactasis. The introduction of Humidified High Flow Nasal Cannulae as well as Synchronised Nasal Intermittent Positive Pressure Ventilation has increased our choices and brought out our biases to one treatment or another. Current studies show similar outcomes and certainly no harm can be demonstrated. This talk tries to help with understanding the differing physiological mechanisms allowing us to achieve acceptable stability in our premature population.

45. The Treatment of Idiopathic Respiratory Distress Syndrome with Continuous Positive Airway Pressure. NEJM June 1971
Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Bradley A. Yoder, Pediatrics 2013
Use of HHFNC in Australasian NICUs J Paediatrics and Child Health 2011
Does HHFNC create Pharyngeal Pressure? Wilkinson J Perinatology 2008
A RCT of HHFNC vs NIPPV for RDS. Kugelman. Ped Pulm 2014

46. Optiflow?

47. RCT HFNC v CPAP in prems - Collins trial
Infants <32 wk n=132 with 59 <28 wk.
Post extubation, treated with caffeine
CPAP 8 cm H2O if FiO2 >0.3 otherwise 7 cm H2O
8 L/min with Vapotherm
No escalation or weaning protocol
Composite outcome: Bad apnoea, or PaCO2 >66 mg, or FiO2 increased >15%, or intubated – within 7 days of starting

48. “No significance differences for composite outcome”
Primary outcome (Bad apnoea, or PaCO2 >66 mg, or FiO2 >15%, or intubated in first 7 days)
HFNC
nCPAP n 67 65
“Failure” 1st week
22%
34%
Intubated 1st week
10%
12%
“No significance differences for composite outcome”
Collins J Peds 2012

49. Secondary outcomes HFNC nCPAP n 67 65 Reintubated any time 21% 25%
Nasal trauma score
3 (7)
12 (11)
BPD 36 wk
36%
43%
Severe IVH 3% 6%
Days to full feeds
12.9 (0.7)
12.3 (0.7)
Died
1.5% 4%
Conclusion: No significant difference all outcomes between HFNC or NCPAP after extubation except HFNC significantly less nasal trauma.
Collins J Peds 2012

50. 423 infants 28 to 42 weeks
CPAP as either 1ry therapy or post-extubation
Excluded <1000g, <28 wks, air leak, abnormalities
Randomised to:
CPAP either bubble, ventilator, or SiPAP
HFNC either Vapotherm, F & P or Comfort Flo.
1ry outcome - intubation <72 h from start of treatment

51. Outcomes CPAP n = 216 HFNC n = 211 p Early failure 8.2% 10.8% NS
Days any PPS
4 (2-8)
6 (3-11)
<0.001
Days ventilated
2 (1-4)
2 (1-5)
Days O2
8 (5-24)
10 (5 – 27)
BPD in infants <33 w
16%
20%
Air leak 2% 1%
Nasal trauma 9%
<0.05
Death
Conclusion: For this population of infants > 28 wk, HFNC had similar efficacy and safety to nCPAP and less nasal trauma.

52. Infants <32 w post-extubation randomised to:
HFNC  at 5-6 L/min or NCPAP at 7 cm H2O.
1ry outcome = failure within 7 days.  
Those who failed HFNC could have CPAP 7 cmH2O.
Infants where CPAP failed were re-intubated. 
300 infants required to show non-inferiority of HFNC with 90% power

53. Outcomes HFNC CPAP P value 1ry Outcome 34% 25% NS Death 3% 4%
BPD – O2 36 w
39%
42%
Pneumothorax 1%
Reintubated
18%
Days resp support (median) 34 38
Days oxygen (median) 49
Nasal trauma
19%
53%
<0.001
IVH, PDA, home oxygen, NEC no signif differences