Where does HFNC fit in the spectrum of non-invasive ventilation?

OR

“THE FACTS MA’AM, JUST THE FACTS”

CPAP

The Gold Standard

RECOMMENDATION

•CPAP immediately after birth with later selective surfactant

administration is an alternative to routine intubation and

surfactant administration in preterm infants (Level of

Evidence: 1, Strong Recommendation)

•If it is likely that respiratory support with a ventilator will be

needed, early administration of surfactant followed by rapid

extubation is preferable to prolonged ventilation (Level of

Evidence: 1, Strong Recommendation)

NCPAP immediately after extubation for preventing morbidity in preterm infants

Outcome: Failure

Study NCPAP Headbox RR (fixed) RR (fixed)or sub-category n/N n/N 95% CI 95% CI

Engelke 1982 0/9 6/9 0.08 [0.00, 1.19] Higgins 1991 7/29 23/29 0.30 [0.16, 0.60] Chan 1993 19/60 22/60 0.86 [0.52, 1.42] Annibale 1994 15/40 17/42 0.93 [0.54, 1.59] So 1995 4/25 13/25 0.31 [0.12, 0.81] Tapia 1995 7/29 2/30 3.62 [0.82, 16.01] Davis 1998 16/47 27/45 0.57 [0.36, 0.90] Dimitriou 2000 15/75 25/75 0.60 [0.34, 1.04] Peake 2005 16/49 24/48 0.65 [0.40, 1.07]

Total (95% CI) 363 363 0.62 [0.51, 0.76]Total events: 99 (NCPAP), 159 (Headbox)Test for heterogeneity: Chi² = 17.93, df = 8 (P = 0.02), I² = 55.4%Test for overall effect: Z = 4.58 (P < 0.00001)

0.1 0.2 0.5 1 2 5 10

Favours NCPAP Favours Headbox

Treat 6 babies to prevent 1 failure

HFNC

The Contender

The battleground

• Primary therapy: prophylaxis/treatment of RDS• Post-extubation care• (Apnea)• (Weaning from CPAP)

WHO IS USING HFNC?

2/3 of US academic unitsHochwald, J of Neonatal-Perinatal Medicine, 2010

2/3 of Australia and NZ NICUs Hough, J Paediatr Child Health, 2012

>80% of UK NICUsNath, Pediatrics International, 2010

50% of level 2 and 33% of level 1 SCNs in the UK use HFNC (either humidified or not)

Nath, Pediatrics International, 2010

Some tertiary NICUs have stopped using nasal CPAP as routine therapy

AUSTRALIA NZ NEONATAL NETWORK

First included data on HFNC use in 2009Blended air and oxygen, >1 L/min, ≥4 hours

2009 2010 2011 20120%

10%

20%

30%

40%

50%

All registrants

<28 weeks' GA

WHY ARE HFNC BEING USED?

‘easy to use’

‘safe’

‘decreases WOB’

‘nurses love it’

‘babies more settled’

‘less “CPAP belly”’

‘less nasal trauma’

‘no pneumothoraces’

Nursing PerceptionsPerceptions of HFNC in comparison to NCPAP

Roberts, Journal of Paediatrics and Child Health, 2014

Nursing PerceptionsWhich mode of post-extubation support would you rather use for these infants?

24-week, 500g 26-week, 750g 28-week, 1kg 30-week, 1.2kg0

10

20

30

40

50

60

70

80

90

100

NCPAPHFNC

Perc

enta

ge o

f nur

ses

Parental Preference

Klingenberg, ADC 2013

COCHRANE REVIEW (2011) WILKINSON, ANDERSEN, O’DONNELL AND DE PAOLI

“Insufficient evidence to establish the safety or effectiveness of HFNC… in preterm infants”

COCHRANE REVIEW (2011) WILKINSON, ANDERSEN, O’DONNELL AND DE PAOLI

“Further adequately powered RCTs should be undertaken in preterm infants comparing HFNC with NCPAP…”

POPULARITY OUTSTRIPPED THE EVIDENCE

HIGH FLOW AS PRIMARY THERAPY

Yoder, Pediatrics 2013

• Multicentre RCT• 141 infants (primary therapy) ≥28 weeks and

≥1000g• Randomized in 1st 24 hrs

• HFNC: Comfort Flo, Vapotherm, F&P• NCPAP: Bubble, ventilator, SiPAP

• No significant difference in intubation <72 hours: 9/75 for NCPAP, 6/66 for HFNC

Kugelman, Pediatr Pulmonol 2014

• Single centre RCT• 76 infants <35 weeks’ gestation • Randomised to HFNC or NIPPV from birth• No significant difference in intubation

– 13/38 (34.2%) for NIPPV, 11/38 (28.9%) for HFNC

HIGH FLOW FOR POST EXTUBATION CARE

Collins, J Pediatr 2012

• Single centre RCT• Device: Vapotherm vs Hudson binasal

prongs• Subjects: 132 infants <32 weeks, post-

extubation• Primary outcome: No significant difference

in extubation failure within 7 days• HFNC caused less nasal trauma

Yoder, Pediatrics 2013

• Devices: Comfort Flo, Fisher and Paykel, Vapotherm vs Bubble CPAP, Infant Flow, Ventilator

• Subjects: 432 infants 28 weeks – term, primary therapy or post-extubation

• Primary outcome: No significant difference in intubation <72 hours

• HFNC caused less nasal trauma

NON-INFERIORITY TRIALS

• Most RCTs are superiority trials• Non-inferiority trials: does the new treatment (eg. HFNC) have efficacy that is similar to or no worse than an established therapy (eg. NCPAP)• The premise: the new treatment has some other benefit and might be favoured over the standard treatment, even if the efficacy is the same or lower

Piaggio et al, JAMA 2006

NON-INFERIORITY TRIALS

•Non-inferiority is based on the risk difference (95% CI) for the primary outcome between the two treatments •‘Margin of non-inferiority’ is definedWe defined the margin as 20%If the risk difference for treatment failure and upper

limit of its 95% CI is ≤20%, then HFNC is ‘non-inferior’

Piaggio et al, JAMA 2006

SUPERIOR

NON-INFERIOR

INCONCLUSIVE

INFERIOR

High-Flow Nasal Cannulae as Post-Extubation Respiratory Support in Premature Infants:

A CPAP Equivalent?

A multicenter, randomized, non-inferiority trialNEJM 2013

The HIPERSPACE Trial

INTERVENTION

HFNC

Fisher & Paykel ‘Optiflow’ circuitFisher & Paykel prongs

Extubated 5-6 L/min

Max 6-8 L/minMin 2 L/min

Could use NCPAP only if already failed HFNC

NCPAP

Ventilator or ‘Bubble’ CPAPHudson/midline binasal prongs

Extubated 7 cm H2O

Max 8 cm H2O

Min 5 cm H2O

+/- Non-synchronised NIPPV

Discouraged any use of HFNC during the admission

Caffeine <24 hours prior to extubation

INTERVENTION

HFNC

Fisher & Paykel ‘Optiflow’ circuitFisher & Paykel prongs

Extubated 5-6 L/min

Max 6-8 L/minMin 2 L/min

Could use NCPAP only if already failed HFNC

NCPAP

Ventilator or ‘Bubble’ CPAPHudson/midline binasal prongs

Extubated 7 cm H2O

Max 8 cm H2O

Min 5 cm H2O

+/- Non-synchronised NIPPV

Discouraged any use of HFNC during the admission

Caffeine <24 hours prior to extubation

INTERVENTION

HFNC

Fisher & Paykel ‘Optiflow’ circuitFisher & Paykel prongs

Extubated 5-6 L/min

Max 6-8 L/minMin 2 L/min

Could use NCPAP only if already failed HFNC

NCPAP

Ventilator or ‘Bubble’ CPAPHudson/midline binasal prongs

Extubated 7 cm H2O

Max 8 cm H2O

Min 5 cm H2O

+/- Non-synchronized NIPPV

Discouraged any use of HFNC during the admission

Caffeine <24 hours prior to extubation

PRIMARY OUTCOME

Failure of the assigned treatment within 7 days

Defined as receiving maximal support and satisfying one or more of the following criteria:

1. Increased oxygen: increase of 20% (0.2) above pre-extubation baseline

2. Apnea: more than 6 requiring stimulation in 6 hours or 2 episodes of positive pressure ventilation in 24 hours

3. Respiratory acidosis: pH <7.2 and pCO2 >60 mm Hg4. Emergency intubation: at physician discretion

FAILURE

HFNC

FAIL

NCPAP 7 cm H2O (+/- nsNIPPV)

FAIL

RE-INTUBATED

FAILURE

HFNC

FAIL

NCPAP 7 cm H2O (+/- nsNIPPV)

FAIL

RE-INTUBATED

‘Rescue CPAP’

FAILURE

HFNC

FAIL

NCPAP 7 cm H2O (+/- nsNIPPV)

FAIL

RE-INTUBATED

NCPAP

FAIL

RE-INTUBATED

INFANT DEMOGRAPHICSHFNCN=152

NCPAPN=151

GA, weeks, mean (SD) 27.7 (2.1) 27.5 (1.9)

Birth weight, grams, mean (SD) 1041 (338) 1044 (327)

Antenatal corticosteroids 93% 95%

Surfactant treatment 93% 95%

Median age at extubation, hours 43 38

Mean FiO2 prior to extubation 0.23 0.23

PRIMARY OUTCOME (N=303)FAILURE OF THE ASSIGNED TREATMENT WITHIN 7 DAYS

HFNC52/152

34%

NCPAP39/151

26%

Risk difference 8%95% CI (-2, 19) %

819-2

NON-INFERIOR

<26 WEEKS’ GA (N=63)FAILURE OF THE ASSIGNED TREATMENT WITHIN 7 DAYS

HFNC26/32

81%

NCPAP19/31

61%

Risk difference 20%95% CI (-2, 42) %

INCONCLUSIVE

26 WEEKS’ GA (N=240)FAILURE OF THE ASSIGNED TREATMENT WITHIN 7 DAYS

HFNC26/120

22%

NCPAP20/120

17%

Risk difference 5% 95% CI (-5, 15) %

5-5 15

NON-INFERIOR

SECONDARY OUTCOMES:

RE-INTUBATION WITHIN 7 DAYS

HFNC27/152

18%

NCPAP38/151

25%

Risk difference -7%95% CI (-17, 2) %

SECONDARY OUTCOMES:

RE-INTUBATION WITHIN 7 DAYS

HFNC27/152

18%

NCPAP38/151

25%

HALF OF INFANTS IN WHOM HFNC FAILED WERE ‘RESCUED’ BY NCPAP

No difference in:

• Death or BPD • Time on resp

support• Steroids for BPD • Days in oxygen • Pneumothorax

• Laser for ROP• Proven sepsis• NEC stage 2 or 3• IVH grade 3 or 4• Cystic PVL• Days in hospital

NASAL TRAUMAHFNC NCPAP P value

Nasal trauma- Any recorded- Due to assigned treatment

39%19%

55%53%

0.008<0.001

CONCLUSIONSHFNC was non-inferior to NCPAP as post-extubation support in very preterm infants

About half of very preterm infants in whom HFNC therapy failed were ‘rescued’ from re-intubation by NCPAP

HFNC is feasible, but should be used with caution in infants born <26 weeks’ GA

HFNC was not associated with any increased risk of morbidity, and caused less nasal trauma than NCPAP

HFNC vs CPAP/NIPPV as Primary TherapyNeed for intubation

HFNC vs CPAP post-extubationExtubation failure

But what does it mean for us?

• Moved from sceptics to cautious adopters– More mature babies– CPAP back up

• We like it for– Kangaroo care (from week 1)– Establishment of breast feeding (and boosting maternal

supply) from 32 weeks• We like it enough to start a trial of HFNC for initial

therapy of RDS in babies >28 weeks (HipsterTrial)

Thank you to the

Hipsters