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Sept 2022

Early use of NHF in infants and children


In this Pediatric edition of Flow Matters, we review the literature and provide an evidence-based approach to implementation of NHF in pediatric patients.


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Summary
  • NHF therapy at 2 L/kg/min is well established in pediatric care areas across the hospital, including the PICU, ED and other general care areas.1-14
  • In the ED, the use of NHF as a primary treatment for infants with bronchiolitis resulted in a significantly lower rate of therapy failure compared with standard oxygen therapy.1
  • In the PICU, the use of NHF as a primary treatment for acutely-ill children was non-inferior to CPAP, and resulted in lower use of sedation, nasal trauma and shorter durations of PICU and hospital stay14

Review of the literature

A systematic search of the available literature shows there are over 220 peer-reviewed papers investigating the use of nasal high flow (NHF) therapy in infants and children. These figures exclude papers investigating the use of NHF in the neonatal population. Of these, 30 are randomized controlled trials (RCTs) – 16 of which compared NHF with standard oxygen therapy, 10 with continuous positive airway pressure (CPAP) and four with alternative treatments. A further 12 are in the form of systematic reviews.
Review of literature
 
NHF therapy in infants and children


These studies represent application of NHF therapy in infants and children in a range of respiratory conditions in the pediatric intensive care unit (PICU), emergency department (ED) and other general care areas in the hospital.



 

The body of literature helps to define the role of NHF in pediatric respiratory care and supports:
 
  • the use of NHF early in the course of respiratory distress, which is associated with improved physiological outcomes compared with standard oxygen therapy, including: 1-6
     
    • improved breathing patterns and rapid unloading of the respiratory muscles
    • significant reduction in the work of breathing
    • rapid improvement to respiratory distress
    • improved mucosal function and secretion clearance through the delivery of heated and humidified gas

  • the early use of NHF outside of the PICU can lead to reduced intubation rates and PICU admissions.5, 7-11
 
Use of F&P Optiflow™ systems in RCTs


The weight of evidence is from studies which used an F&P Optiflow system, including an F&P Optiflow Junior interface and an F&P humidity delivery system.

17 out of 21 RCTs used an F&P Optiflow System
The systematic review conducted showed that 24 out of 30 RCTs (80%) used an F&P Optiflow system.
17 out of 21 RCTs used an F&P Optiflow System
Of the 4,398 total participants on NHF in RCTs, 3,957 participants (90%) were treated using an F&P Optiflow system.

Key:     F&P Optiflow Systems
Other Systems


Landmark Study

The largest NHF RCT was conducted by Franklin et al.1 This multi-center RCT supports the use of NHF in the ED and general care areas in young infants with bronchiolitis, and used the F&P Airvo™ with an Optiflow Junior interface.
Bronchiolitis Patients
Emergency Departments and Wards
The primary outcome of the study was that the use of NHF at 2 L/kg/min as a primary treatment in the ED and general care areas resulted in a significantly lower rate of therapy failure compared with standard oxygen therapy (12 vs. 23%, p < 0.001). Therapy failure was defined as therapy escalation or PICU admission.
Therapy failure (%) in patients who received NHF at 2 L/kg/min vs. those who received standard oxygen therapy
There were no significant differences between the secondary outcomes (PICU admissions, intubation rates and adverse events). It is important to note that the study design allowed patients on standard oxygen therapy who met the therapy failure criteria to escalate to NHF; 61% of the patients who failed on standard oxygen therapy were rescued by NHF and avoided PICU admission.

 
Landmark Study

The FIRST-ABC Trial

First-line Support for Assistance in Breathing in Children (FIRST-ABC) was designed as a master protocol of two pragmatic noninferiority RCTs by Ramnarayan et al.13

These RCTs investigated the safety and efficacy of NHF and CPAP when used as:

Post-extubation support in critically ill children (Step down)
First-line support in acutely ill children (Step up)


 
Treatment Algorithm. A standardized treatment protocol was used to ensure the consistency of treatment across the multiple centers involved in the study.
CPAP (7 – 8 cmH2O) or NHF starting at 2 L/kg/min
Weaning therapy


Stopping therapy


Success: ≥ 48 hours free from respiratory support
 
Primary Outcome: Time to liberation from respiratory support
Key findings




For post-extubation support in critically ill children (Step down)
Patients in PICU transition to CPAP or NHF post-extubation. 553 participants (0 – 15 years, median age: 3 months). 22/28 PICUs in the UK.
When used for post-extubation, NHF did not meet noninferiority criteria compared with CPAP for time on respiratory support.
Patients on NHF required an average of 7.6 hours longer of respiratory support (NHF: 50.5 hours vs. CPAP: 42.9 hours; adjusted hazard ratio: 0.83 (95% CI: 0.70 – 0.99))


For first-line support in acutely ill children (Step up)
Patients admitted to PICU receive CPAP or NHF as first-line therapy. 573 participants (0 – 15 years, median age: 9 months). 24/28 PICUs in the UK.
When used as first-line therapy, NHF met the noninferiority criteria when compared with CPAP for time on respiratory support.
Patients on NHF required an average of 5 hours longer of respiratory support (NHF: 52.5 hours vs. CPAP: 47.9 hours; adjusted hazard ratio: 1.03 (95% CI: 0.86 – 1.22))
Therapy failure occurred more frequently in the CPAP group compared with the NHF group.


Predominantly due to discomfort


Predominantly due to clinical deterioration
Of the secondary outcomes, the NHF group had significantly:


Lower use of sedation

NHF 27.7% vs. CPAP 37.0%


Fewer occurrences of nasal trauma

NHF 2.0% vs. CPAP 6.5%


Shorter mean duration of PICU stay

Mean difference -3.1 days


Shorter mean duration of acute hospital stay

Mean difference -7.6 days

An evidence-based approach to implementation of NHF in pediatric patients


This information collates data from published guidelines and the body of evidence. It does not overrule expert clinical judgment in individual patient management.

 

Flows

 
Weight (kg) ≤12 13-15 16-30 31-50 >50
Starting flow rate 2 L/min/kg 25 – 30 L/min 35 L/min 40 L/min 50 L/min

 

Humidity
Heating and humidification of gases during respiratory support (including NHF and standard oxygen therapy):

  • enables maintenance of airway defenses and mucociliary transport
  • promotes efficient gas exchange
  • reduces respiratory effort for the patient
  • enables conservation of energy for growth and development.

O2

  • PARIS 2 Protocol and FIRST-ABC group implemented the titration of FiO2 to achieve a target SpO2 of ≥ 92%.

Monitoring

  • Non-responders can be identified within the first 60 minutes of NHF initiation, by the monitoring of physiological parameters such as heart rate, respiratory rate, and work of breathing.

Weaning off NHF therapy

ED (PARIS)

  • Reduce the FiO2 to maintain SpO2 at target levels without reducing flow.
  • Once the FiO2 has been reduced to 21% (room air) and the patient is stable at this concentration, NHF therapy can be stopped.

PICU (FIRST-ABC)

  • When FIO2 < 40% and respiratory distress is not severe, use weaning flow rates
  • When FIO2 < 30% and/or mild respiratory distress, stop NHF
 
Weight (kg) ≤12 13-15 16-30 31-50 >50
Weaning flow rate 1 L/min/kg 13 - 15 L/min 18 L/min 20 L/min 25 L/min
Definitions
F&P Optiflow system: An F&P system developed for the delivery of NHF. An F&P Optiflow interface (e.g., F&P Optiflow Junior 2) with either:
  • an integrated flow source, humidifier and breathing set (e.g., F&P Airvo™ with AirSpiral™ tube and chamber kit)
  • a separate flow source combined with an F&P humidifier and breathing set (e.g., MR850 and RT-series circuit kit).
 
Infants and children: This search included literature concerning the use of NHF in infants and children only, defined by the US Food and Drug Administration (FDA) as between 1 month to 2 years postnatal age and 2 to 12 years of age, respectively. Papers regarding the use of NHF in neonates (birth to 1-month postnatal) were not included, as indications for NHF are different in this population.
 
Nasal high flow (NHF): NHF is a mode of noninvasive respiratory support that delivers high flows of heated and humidified blended air and oxygen through an unsealed nasal interface.

Standard oxygen therapy: A form of oxygen therapy that is delivered through a nasal cannula at low flow rates (< 2 L/min) and is typically unheated and unhumidified. May also be referred to as conventional oxygen therapy.

Systematic search of the available literature: Conducted on July 21, 2022 using predefined search terms on PubMed, Embase & Cochrane Library, with data extraction and screening performed via DistillerSR (Evidence-Based Partners, Ottawa, Ontario) by internal F&P clinical researchers.
 


For further information, please view https://www.fphcare.com/hospital/infant-respiratory/nasal-high-flow/ or the hyperlinked references below.

 
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