The PARIS Trial: HFNC in Infants with Bronchiolitis

09 Apr
April 9, 2018

Background: Bronchiolitis is an acute inflammatory injury of the distal smaller airways, most commonly caused by viral infections.  There have been a host of medications studied in the treatment of bronchiolitis, including steroids, albuterol, epinephrine, and  inhaled hypertonic saline, with none proving to be effective in treatment.  Oxygen therapy via high-flow nasal cannula (HFNC) as opposed to standard nasal prongs provides some positive airway pressure which decreases work of breathing, improves oxygenation, and rates of intubation.  The trial we are going to review today (The PARIS Trial) evaluated early high-flow oxygen therapy vs standard oxygen therapy in infants with bronchiolitis and hypoxemia in both the emergency department and general pediatric ward settings.

What They Did:

  • Paediatric Acute Respiratory Intervention Study (PARIS)
  • Multicenter, randomized, controlled trial
  • Infants <12 months of age with bronchiolitis and need for supplemental oxygen therapy
  • High-flow oxygen therapy (High-flow group) vs standard oxygen therapy (Standard therapy group)
    • Infants in standard therapy group could receive rescue high-flow O2 if their condition met criteria for treatment failure

Treatments:

  • High Flow Oxygen Therapy:
    • Heated & humidified high-flow oxygen at a rate of 2L/kg/min via Optiflow system
    • Fraction of inspired oxygen (FiO2) adjusted to obtain O2 sat levels between 92 – 98% or 94 – 98% at some of the treatment hospitals as they had a higher minimum oxygen threshold
  • Standard Therapy Oxygen:
    • Supplemental oxygen through nasal cannula up to 2L/min
    • Maintain oxygen saturation level between 92 – 98% or 94 – 98% at some of the treatment hospitals as they had a higher minimum oxygen threshold

Outcomes:

  • Primary: Escalation of care due to treatment failure (defined as meeting ≥3 out of 4 clinical criteria
    • Persistent tachycardia
    • Persistent tachypnea
    • Hypoxemia
    • Medical review triggered by a hospital early-warning tool
  • Secondary:
    • Duration of hospital stay
    • Duration of oxygen therapy
    • Rates of transfer to a tertiary hospital
    • Rate of ICU admission
    • Rate of intubation
    • Rate of adverse events

Inclusion:

  • Infants <12 months of age
  • Clinical signs of bronchiolitis
  • Need for supplemental oxygen therapy to keep oxygen saturation between 92 – 98% (or 94 – 98% at some hospitals who had higher saturation thresholds)

Exclusion:

  • Critically ill infants who had immediate need for respiratory support and ICU admission
  • Cyanotic heart disease
  • Basal skull fracture
  • Upper airway obstruction
  • Craniofacial malformation
  • Receiving oxygen therapy at home

Results:

  • 1472 infants
  • Escalation of Care:
    • High-Flow Group: 12%
    • Standard Therapy Group: 23%
    • P <0.001
    • NNT = 9
    • Fragility Index = 51
  • No difference in:
    • Duration of hospital stay
    • Duration of oxygen therapy
  • Adverse Events: 1 infant in each group suffered a pneumothorax (<1% of infants) – no drainage needed in either case
  • 167 infants who had treatment failure with standard therapy
    • 102 (61%) had a response to high flow oxygen therapy

Strengths:

  • Protocol published previous to enrollment and completion of trial
  • Clinically important primary endpoint particularly in hospitals without pediatric ICUs
  • Investigators were unaware of trial outcome until the trial was completed
  • High-flow equipment for trial was donated by Fisher and Paykel Healthcare, who had no involvement in the design, analysis of data, or preparation of manuscript
  • Pre-specified subgroups were evaluated for heterogeneity of the studies results audemars piguet replica

Limitations:

  • Unblinded study – masking of the assigned treatment was not possible due to visually obvious differences between the two interventions. This may minimize the validity of the results of this paper due to placebo effect/bias or effect on physician decisions.
  • Clinicians could escalate therapy if they were concerned for other clinical reasons, which is a subjective decision – this occurred in 34% of the patients who did not meet 3 out of the 4 criteria for escalation of care
  • The respiratory rate was quite a bit higher in the HFNC group vs Standard therapy group (62.6 +/- 15.2 vs 54.6 +/ 12.4), which could potentially mean that the HFNC group was a bit sicker and therefore the results of this study would underestimate the true benefit of HFNC vs Standard therapy

Discussion:

  • Respiratory Syncytial Virus (RSV) was the most common virus detected in this study at approximately 55% of cases
  • Approximately 18% of the included patient population had premature (<37weeks) birth
  • Non-study treatment and medications received:

  • Escalation rates were quite higher in the peds hospital with an ICU. The escalation rate was also closer between HFNC and standard O2 groups in hospitals with an ICU as well. It is possible, that HFNC may be of greatest advantage at places that would have to transfer for escalation of care. Interestingly at the sites that did not have an ICU, the treatment failure rate was significantly lower in the HFNC group vs standard therapy group: 7% vs 28% (NNT = 5) compared to sites that did have an ICU 14% vs 20% (NNT = 17)

Author Conclusion: “Among infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy.”

Clinical Take Home Point: This is the largest trial to date evaluating the effectiveness of HFNC in bronchiolitis in infants <12months of age, hypoxemia, and either in the ED or pediatric ward.  Based on this well done study it appears that HFNC is superior to standard oxygen therapy with a NNT = 9.

References:

  1. Franklin D et al. A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis. NEJM 2018. PMID: 29562151

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)

The following two tabs change content below.

Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of R.E.B.E.L. EM
Tags: , ,
8 replies
  1. Chris Cole says:

    I think perhaps a more realistic summary of the take-home points from this study are:

    – High-flow oxygen treatment (HFOT) is safe.
    – HFOT makes _no_ difference to clinically relevant outcomes (reported as secondary outcomes in this study):
    — Admission to ICU (indeed, the HFOT group had _more_ admissions to ICU, 12% vs 9%)
    — ICU LOS
    — Hospital LOS
    — Duration of oxygen Rx

    – The reported difference in the (composite) primary outcome is entirely due to escalating kids from SOT –> HFOT.
    – The NNT = 9 –> you need to start 9 kids on HFOT immediately to avoid having to put 1 kid on it later.
    – This carries a significant logistic burden on resources (equipment, maintenance, nursing workload) without any clear clinically relevant benefit.

    It’s a good study. We recruited patients at our hospital for it. But the reported conclusion of “benefit” is sketchy, and the secondary outcomes are more clinically informative, I think.

    Chris Cole
    ED Staff Specialist
    Canberra, Australia

    Reply
    • Salim Rezaie says:

      Hello Chris,
      Appreciate you reading and commenting. Agree that HFNC is safe and can be a burden on resources. I found it interesting that escalation rates were quite higher in the peds hospital with an ICU. The escalation rate was also closer between HFNC and standard O2 groups in hospitals with an ICU as well. It is possible, that HFNC may be of greatest advantage at places that would have to transfer for escalation of care. Interestingly at the sites that did not have an ICU, the treatment failure rate was significantly lower in the HFNC group vs standard therapy group: 7% vs 28% (NNT = 5) compared to sites that did have an ICU 14% vs 20% (NNT = 17). Your point is well taken and appreciated.

      Salim

      Reply
  2. Ben symon says:

    As someone working in a NON tertiary hospital, I’d disagree that there’s no demonstrable benefit from High Flow based on this study. The possibility that 7% rather than 28% of my patients might need treatment escalation is actually a huge difference in our referral rate, and in doing so has significant impacts on the reputation of our hospital as ‘being able to cope’ with something, and a huge benefit to families and patients who might otherwise be moved further away from home.

    The demonstrable ability from this study that we can often safely treat bronchiolitis with high flow in our peripheral service is really important from my perspective. I’m not expecting HHFO2 to shorten the duration of illness, since highflow is not directly removing RSV from the lungs and the inflammatory processes involved are going to continue. But to be able to treat patients safely, in their local environment, is a great finding for me!

    Reply
    • Salim Rezaie says:

      Hello Ben,
      Appreciate you reading and your comments.

      Salim

      Reply
    • Suneth Jayasekara says:

      Hi Ben, but doesnt it mean that of 28% of patients who have their treatment escalated, the first step is to escalate to high flow therapy, and still managed in your non-ICU capable hospital. And only a smaller proportion of these would need to be referred elsewhere? (I.e the referral rate shouldn’t change whether your start high flow straight up, or start with standard oxygen, and then change to high flow)

      Reply
  3. Suneth Jayasekara says:

    The primary outcome of this trial confuses me. In my mind, standard oxygen therapy and high-flow oxygen therapy are not equivalent therapies – high flow oxygen being a more intensive therapy. Therefore I do not understand how you can compare the two directly. This is illustrated by the fact that the “treatment failures” in the standard oxygen therapy received high flow as their rescue therapy! And, high-flow was even successful in 61% of those cases!

    To me its like comparing using a Hudson mask in an adult vs NIV. Yes, NIV is more effective, but that does not mean that everyone should be started on NIV immediately as they are admitted.

    I’m not conviced that this data is evidence that every child with bronchiolitis should be started on high-flow first line. Why not take a stepwise approach, starting with standard oxygen, and in the 23% who fail, then escalating to high flow, and then to intubation etc?

    Reply
    • Salim Rezaie says:

      Hi Suneth
      Appreciate you reading and agree with your comments. I believe a pragmatic stepwise approach is the way to go in these patients. Certainly not advocating for HFNC in every bronchiolitis patient.

      Salim

      Reply

Trackbacks & Pingbacks

  1. […] [further reading] REBEL EM review […]

Leave a Reply

Want to join the discussion?
Feel free to contribute!

Leave a Reply

Your email address will not be published. Required fields are marked *

Time limit is exhausted. Please reload CAPTCHA.