nasal high flow therapykfafhconferences.com/neonate/images/8-lavizzari_anna_jeddah_ho… · > 5...
TRANSCRIPT
Nasal High Flow
Therapy
in preterm infants
Anna Lavizzari, MD NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
University of Milan, Italy
Disclosures
I received travel grants from Vapotherm, Fisher&Pykel and
Chiesi S.p.A.
I have been consultant for Chiesi S.p.A.
Clin Perinat 2015
Hendrik S. Fischer and Christoph Bührer
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
REDUCTION INCIDENCE DEATH/BPD < 30 wks’ GA NNT 35
DOI: 10.1542/peds.2013-1880; originally published online October 21, 2013; 2013;132;e1351Pediatrics
Hendrik S. Fischer and Christoph BührerMeta-analysis
Avoiding Endotracheal Ventilation to Prevent Bronchopulmonary Dysplasia: A
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
REDUCTION INCIDENCE DEATH/BPD < 32wks’ GA NNT 25
2017
Research on non-invasive
respiratory support
from 2000 to 2011
0
200
400
600
800
1000
1200
1400
1600
NCPAP HFNC BiPAP NIPPV/SNIPPV nHFV
Number of studies in the National Library of Medicine (PubMed)
from 2008 to 2019
The increasing clinical use of nHFT
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
%
0
10
20
30
40
50
60
Mangiagalli
Italia VON
Europa
Nasal High Flow Therapy (nHFT)
“Small, thin, tapered binasal tubes that deliver oxygen or blended oxygen/air at gas flows of more than 1 L/min.”
Wilkinson et al, Cochrane Database Syst Rev 2011
• Flow rates greater than 1 L/min
• The gas is heated to near body temperature and humidified
• The respiratory gas is delivered at a flow rates that meet or exceed the patient's inspiratory flow rate
• nHFT provides positive end-expiratory pressure
Locke 1993, Frey 2001, Sreenan 2001
High Flow Therapy
NCPAP High Flow NC Low Flow NC
Flow 0-14 L/min 1-8 L/min 1-2 L/min
Humidifier PASS Over
Humidifier
Membrane Humidifier/
PASS over Humidifier
Contact, bubbling
Humidifier
Interface prongs fit snugly into the
infant’s nostrils with minimal leakage
NC do not occlude
nostrils and have a large
leak around (preferred
cannula/nare ratio 0.5,
should be <0.8)
Standard nasal cannula
FiO2 0.21 - 1.0 0.21 -1.0 < 0.4
Nasal High Flow Therapy
Matching physiology!!
The ideal Non-Invasive Respiratory
Support should… Provide alveolar
recruitment,
maintain an adequate
end-expiratory volume
and airway patency
Enhance the wash out
Reduce the
Work of Breathing
Decrease the
metabolic cost
for gas conditioning
Positive distending
pressure
Adequate bias flow,
↓ the dead space
↓ the patient’s load
Optimal gas
conditioning
nCPAP
Matching Physiology
Provision of distending pressure
• Patient circuit with
inspiratory and
expiratory lines
• Pressure determined
by the resistance on
the expiratory line
Servo-controlled valve CPAP provided
by mechanical ventilator Water immersion Bubble CPAP
Respiratory flow Expiratory flow
Bias Flow
nHFT
Matching physiology
Provision of distending pressure
Flow out
Flow from the device Flow from the device
Flow out
Respiratory Flow Respiratory Flow
R = space between the cannula and the nares
Pressure = R * Flow out
nHFT
Matching physiology
Provision of distending pressure
Flow out
Flow from the device Flow from the device
Flow out
Respiratory Flow Respiratory Flow
P = R * Flow out
Flow out = Flow device – Resp flow Flow out = Flow device + Resp Flow
P = R * Flow out
Provision of distending pressure
Nasal High Flow Therapy
Provision of distending pressure
Nasal High Flow Therapy
Wilkinson DJ et al, J Perinat 2008
The distending pressure in
HHHFNC depends on :
• flow rate not linear!!
• infant size
• amount of leak around the
cannula
It is highly variable and not
easily to be monitored
Preterm infants receiving
HFNC at flow rates of 2 to 8 lpm
can receive clinically relevant
transmitted
pharyngeal pressures similar to
nCPAP
P phar (cmH2O) = 0.7 + 1.1 F
(F = flow per kg in l min -1 kg -1)
1
2
3
Provision of distending pressure
Nasal High Flow Therapy
Pressure delivered may be affected by
different devices, in particular for higher
flow rates
Collins et al. J Pediatr Child Health 2013
4
Lavizzari et al,
Arch Dis Child Fetal Neonat 2014
5 In addition to the intersubject and
intrasubject variability in the
amount of pressure developed,
there may also be large between-
centre variability.
Matching physiology Washout of nasopharyngeal dead space
Matching physiology
Washout of nasopharyngeal dead space
pCO2
pO2
Pediatric Pulmonology, 2017
Large prongs/large nares Small prongs/small nares
Arch Dis Child Fetal Neonat 2019
Nasopharingeal End-Expiratory CO2 - pEECO2 • Crossover, CPAP 6 cmH2O vs HFNC 8-2 lpm,
in 44 infants of 3 groups: <1000 g, 1000–1500 g and >1500 g
• pEECO2 was markedly attenuated at higher
flows with a strong, negative correlation
between pEECO2 and weight-corrected flow
rate (rs=−0.323, p<0.0001). • Open mouth state was associated with
greater washout effect, not statistically
significant
• The reduction of pEECO2 was greatest in
infants weighing <1000 g,
• The mean nCPAP pEECO2 was higher than
HFNC across all flows, but only achieved
significance at 6–8 L/min (p<0.05).
The ideal Non-Invasive Respiratory
Support should… Provide alveolar
recruitment,
maintain an adequate
end-expiratory volume
and airway patency
Enhance the wash out
Reduce the
Work of Breathing
Decrease the
metabolic cost
for gas conditioning
Providing an adequate
positive distending
pressure
Adequate bias flow,
↓ the dead space
↓ the patient’s load,
pressure stability,
synchronization
Adequate gas
conditioning
Matching physiology
Reduction of WOB
INCLUSION CRITERIA
• GA between 28+0 and 32+6
weeks
• Postnatal age < 96 h
• Receiving either NCPAP or
HHHFNC for mild to
moderate RDS
• Parental consent
EXCLUSION CRITERIA
• Intraventricular haemorrhage
• Major congenital abnormalities
Study objective: To compare the effect of HHHFNC and NCPAP on lung function and
mechanics in preterm infants with respiratory distress syndrome at the same level of
retropharyngeal pressure (Prp)
Arch Dis Child Fetal Neonat 2014
Work of breathing
at equal distending pressure
NCPAP
2 cmH20
4 cmH20
6 cmH20
HHHFNC
2 l/min
4 l/min
6 l/min
Cross-
over trial
Face mask
pneumotachography
Oesophageal
balloon
Retropharyngeal
catheter + pressure
transducer
PtcO2 , PtcCO2
SpO2
RIP bands
Lavizzari et al, Arch Dis Child Fetal Neonat 2014
Breathing pattern, lung mechanics, gas exchange, WOB at equal Prp
Breathing pattern
Mechanical properties
Gas Exchange
WOB
Prp of 2 cmH2O Prp 4 cmH2O
Lavizzari et al, Arch Dis Child Fetal Neonat 2014
WOB associated with upper airways
Cross-over trial,
20 preterm infants
HHHFNC at 6-8 lpm
versus
NCPAP at 6 cmH2O
Shetty et al, Arch Dis Child Fetal Neonat 2017
Pediatr Pulmonol. 2015
De Waal et al, Arch Dis Child Fet Neonatal 2017
Williams et al, Crit Care Med 1996
Humidity, temperature of inspired gas and
function of airway mucosa
MTV= mucus transport velocity
BTPS= body temperature, atmospheric pressure and saturation with water vapor
ACQUA CALDA
ACQUA CALDA
GAS RISCALDATO & UMIDIFICATO
Gas flow
Circuit
Vapor transfer
cartridge Flow Temperature
> 5 lpm 37-38°C
< 5 lpm 35-36°
Setting
Nasal High Flow Therapy
Clinical Efficacy!!
nCPAP or nHFT
Post- extubation
N.
Patients
GA, BW Study type and design Devices, NHFT flow
rates
Primary
outcome
Collins
132 preemies
< 32 wks
RCT of NCPAP vs HFNC
post-extubation
8 L/min to 4 L/min,
Vapotherm
Extubation
failure
within 7 days
Yoder 432 28-42
wks
RCT of NCPAP vs HFNC
either as primary therapy
for RDS or post-extubation
3-5 L/min wt-based;
Comfort Flo, Fisher and
Paykel, and
Vapotherm
Intubation
within 72 hrs
of applied
NIV mode
Manley 300 preemies
< 32 wks
Non-inferiority RCT of
NCPAP vs HFNC exclusively
as primary therapy for RDS
5-6 L/min;
Intubation
within 7 days
HFNC versus CPAP to prevent
extubation failure HFNC versus CPAP to prevent extubation failure, Death
HFNC versus CPAP to prevent extubation failure, CLD
Wilkinson et al.
Cochrane Database of Systematic Review 2016
HFNC versus CPAP to prevent extubation failure, Treatment failure
HFNC versus CPAP to prevent extubation failure, Nasal Trauma
HFNC versus CPAP to prevent extubation failure, Pneumothorax
NNTB 50
HFNC versus CPAP to prevent
extubation failure,
GI performation or NEC
NNTB 50
HFNC versus CPAP to prevent extubation failure, ROP
HFNC versus CPAP to prevent extubation failure, IVH
HFNC versus CPAP to prevent extubation failure, Sepsis
HFNC versus CPAP to prevent
extubation failure
nCPAP or nHFT - Primary treatment
for respiratory distress
N.
Patients
GA, BW Study type and design Devices, NHFT flow
rates
Primary
outcome
Iranpour [Arabic]
70 30-35
wks
RCT of NCPAP vs HFNC after
prophylactic surfactant
and early extubation to
NCPAP
HFNC F&P;
Flow (L/min) = 0.92 +
0.68x, X = weight in Kg
[Sreenan’s formula]
Intubation
within 7 days
Yoder 432 28-42
wks
RCT of NCPAP vs HFNC
either as primary therapy
for RDS or post-extubation
3-5 L/min wt-based;
Comfort Flo, Fisher and
Paykel, and
Vapotherm
Intubation
within 72 hrs
Kugelman 76 <35 wks,
>1,000 g
Pilot, RCT for CT of NIPPV vs
HFNC as primary therapy
for RDS
1-5 L/min;
Vapotherm
Mechanical
ventilation
within 72 hrs
Lavizzari 316 29-36
wks
Non-inferiority RCT of
NCPAP vs HFNC exclusively
as primary therapy for RDS
4-6 L/min;
Vapotherm
Intubation
within 72 hrs
nCPAP or nHFT - Primary treatment
for respiratory distress
N.
Patient
s
GA, BW Study type and design Devices, NHFT
flow rates
Primary
outcome
Roberts
750 ≥28 wks
Non-inferiority RCT on NCPAP
vs HFNC without prior
surfactant
treatment
6-8 L/min Intubation
within 72 hrs
Chen [chinese]
66 VLBW, GA not
specified in
abstract
RCT of NCPAP vs HFNC
after prophylactic
surfactant
not specified in
abstract
Intubation
within 7 days
Shin 87 30-35 wks
> 1250 g
Non-inferiority RCT on NCPAP
vs HFNC
Fisher & Paykel
Optiflow, 3-7L/min
Intubation and
mechanical
ventilation
Murki ≥28 wks
≥ 1000 g Non-inferiority RCT on NCPAP
vs HFNC
Optiflow Junior or
AIRVO 2, Fisher
and Paykel, 5-7
L/min
Intubation
within 72 hrs
HFNC versus CPAP for for primary
respiratory support after birth –
Secondary outcomes:
- nasal trauma,
- supplemental oxygen
- hospitalisation
- pneumothorax
- sepsis
HFNC versus CPAP for primary
respiratory support after birth HFNC versus CPAP for for primary
respiratory support after birth –
Treatment failure
HFNC versus CPAP for for primary respiratory support after birth - CLD
HFNC versus CPAP for for primary
respiratory support after birth –
Death
EXCLUSION CRITERIA
1) severe RDS
requiring early
intubation in DR
2) major congenital
anomalies
3) no parental
consent
INCLUSION CRITERIA
1) GA ≥ 29+0 and
< 37+0 weeks
1) inborn
2) parental consent
RDS with
Silverman score ≥ 5 or
FIO2 > 0.3 for target
SpO2 88-93%
Study enrollment
Methods – Intervention
Mechanical ventilation
1) FIO2 > 0.40 for SpO286-
93% after surfactant
2) Severe apnea (apnea
episodes > 4 in 1 hour or
> 2 in 1 hour requiring
PPV)
3) PaCO2>70 mmHg and pH
< 7.20
Chest XR, BG
Surfactant (INSURE)
(Curosurf, 200 mg/kg) if:
FIO2 > 0.35
to target SpO2 86-93%,
RDS with
Silverman score ≥ 5 or
FIO2 > 0.3 for target
SpO2 88-93%
HHHFNC
4-6 l/min
NCPAP (or
BiPAP)
4-6 cmH2O
Block-randomization;
stratification for GA
29+0-32+6 / 33+0-34+6
/35+0 36+6 weeks
Results - Primary outcome
Results – Primary outcome
Results – Secondary outcomes
Study design, primary outcome: same as HISTER trial
Study setting: non-tertiary centers
Inclusion: GA ≥31 weeks, birth weight >1200g
Patients enrolled n 754
Treatment failure intubation within 72h
ITT HFNC 78 of 381 infants (20.5%) vs CPAP 38 of 373 infants (10.2%)
(risk difference, 10.3 percentage points; 95%CI, 5.2 to 15.4).
Per protocol
HFNC 49 of 339 infants (14.5%) vs CPAP 27 of 338 infants (8.0%)
(risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2).
NEJM 2019
Objective: to identify clinical and demographic variables that predict nasal
high-flow (nHF) treatment failure when used as a primary respiratory support for preterm infants.
Secondary analysis from the data of the HIPSTER trial on 278 infants
A multivariable logistic regression model was applied, where the dependent variable was nHF treatment failure within 72 hours of randomization.
J Pediatr 2017
Nasal HF treatment success was more likely in infants born at ≥ 30 weeks GA and with
prerandomization FiO2 <0.30 the “30/30” rule!
However, CPAP remains superior to nHF (without no rescue CPAP) in preventing
treatment failure, even when the 30/30 rule is applied.
Nasal High Flow Therapy
User friendly!!
2018
Nasal injury is common in preterm
infants born <30 weeks’ gestational age, receiving CPAP via binasal
prongs.
nurses
J Pediatrics and Child Health 2014
Infant Comfort & Parents Preference
Arch Dis Child Fet Neonat 2013
Does nHFT really improve comfort?
Salivary cortisol Premature Infant Pain Profile (PIPP)
Does nHFT improve feeding ability?
• RCT of 44 infants BW < 1500g and
GA <30 weeks with evolving BPD
• Randomization at 32 weeks, if still requiring CPAP
• Primary outcome: days taken to establish full oral feeds (oral
intake ≥120 mL/kg/day), aiming to demonstrate demonstrate a 7-day difference
Arch Dis Child Fet Neonat 2016
Nasal High Flow Therapy
In practice…
Journal of Perinatology 2017
Yoder BA et al, J Perinat 2017
Why do we need practice Guidelines?
• HHHFNC is widely used in high-resource countries
• Expanding international use
• Guidelines generally improve outcomes
• Assist in identifying areas to improve
Practice Guidelines on Nasal High-Flow Therapy
in newborn infants
Nasal High Flow Therapy
Arch Did Child Fetal Neonat 2018
Ped Pulmonology 2019
Conclusions
• Even though nasal CPAP is the most widely used form non-
invasive respiratory support in neonates, nasal HFT has been
increasingly applied to this population worldwide.
• The clinical use of nHFT has been supported by different
mechanisms of action, which has been evaluated both in
animal and human studies.
• Recent meta-analysis support the use of nHFT as an
alternative to nCPAP for post-extubation in infants ⩾28 weeks
of gestation in preventing treatment failure, death, and BPD.
Conclusions
• By contrast, HFNC is associated with higher failure rates than
NCPAP as primary support in premature infants, even though
it is not associated to increased rate of intubation.
• Infants > 30 wks of gestation and with FiO2 < 0.30 are more
likely to succeed with NHFT (30/30 rule)
• NHFT was safe and it was clearly associated with reduced
rates of nasal trauma compared to nasal CPAP. There may
also be a reduced incidence of pneumothorax.
Future Research
Agenda
Optimization of NHFT and nasal CPAP Best strategy for weaning Bed-side, non-invasive tools to individualize respiratory
management Implementation (O2-closed loop, high frequency,
heliox…) To assess the efficacy of NHFT in other neonatal lung
disorders (MAS, CDH…) To compare different devices and interfaces NHFT for delivery room stabilization, neonatal
transport, post-discharge… NHFT in resource-limited countries
Thank you!