high flow nasal cannulae: evidence base in preterm infants peter davis melbourne australia
TRANSCRIPT
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