High flow nasal cannula vs non-invasive ventilation in pediatric ARDS : an RCT

Introduction: Pediatric Acute Respiratory Distress syndrome (PARDS) has been re-defined (2015) as per the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. The use of high flow nasal cannula is a promising treatment but its efficacy compared with non invasive ventilation (NIV) is not known. 
Aims and Objectives: The current study was undertaken to study the efficacy of high flow nasal cannula compared with NIV in PARDS. 
Methods: This was a pilot randomized controlled trial done in the PICU of a tertiary care teaching hospital over 10 months (December 2017 – September 2018). All patients aged 1-18 years of age, who presented with or developed ARDS during their course of hospitalization, and who fulfilled the inclusion criteria, were randomized to receive HFNC and Continuous Positive Airway Pressure (NIV) as the initial respiratory support.Details were noted in a pre-designed standardized data collection form, entered into MS-EXCEL worksheet 2013 and analyzed using the Epi info software version 7.2.0.1. 
Results: A total of 40 patients were enrolled, 20 in each arm.Of these majority (25/40=62.5%) were boys. Majority of these patients were from rural or semi-urban areas (28/40=70.0%) and belonged to low socio-economic class (33/40= 82.5%) patients.Underlying diagnosis was sepsis in the majority (27/40=67.5%) patients.Twenty one (23/40=57.5%) patients had co-existent pneumonia.Development of hemodynamic instability approached statistical significance in being low in HFNC group compared with the CPAP group (p=0.07; OR 0.206, 95% CI 0.036-0.159).Subsequent requirement of invasive ventilation was also low in HFNC group compared with CPAP group and approached significance (p=0.09; OR 1.653, 95% CI 0.074-1.246). Total duration of respiratory support (p=0.62) was comparable in both the groups. 
Conclusion: HFNC is efficacious in managing PARDS. Subsequent requirement of invasive ventilation and hemodynamic deterioration was significantly low with HFNC compared with NIV (CPAP).


Introduction
Acute Respiratory Distress syndrome (ARDS) is characterized by hypoxemia, dyspnea and a marked increase in work of breathing [1]. It has been re-defined (2015), in children, as per the final recommendations of the Pediatric Acute Lung Injury Consensus Conference (PALICC) [2]. Prevalence of PARDS (Pediatric acute respiratory Distress Syndrome) as it is now known as, has been found to be upto 9.9% in a recent study [3]. The use of high flow nasal cannula is a promising treatment but its efficacy compared with non invasive ventilation (NIV) in management of PARDS or acute hypoxemic respiratory failure [4] is not known [5,6].

Discussion
High Flow Nasal Cannula oxygen therapy is effective in management of pediatric ARDS, when compared with Non-Invasive Ventilation (CPAP).
ARDS was seen in this study was found to be 15.07% of the 324 patients admitted to the PICU, during the study period.
A prevalence of 9.9% was found in another study [3], which enrolled patients fulfilling the PARDS criteria defined by the PALICC [2].
Underlying etiology of ARDS was sepsis in majority (67.5%) of the pediatric patients in our study, of whom 57.5% patients had co-existent pneumonia. In another study, done in adult patients, pneumonia accounted for the majority (82%) of cases of ARDS [7].
A recent study of 75 patients, >13 years of age, from an urban tropical setting in India, found that Leptospirosis was the most common (18.7%) underlying etiology, and concluded that tropical infections are the major etiological component of ARDS in a developing country like India [8].
Therapeutic effect of HFNC oxygen therapy was evaluated in treating an adult patient of Middle East Respiratory syndrome (MERS) in whom respiratory function improved and the complication of ARDS was prevented [9].
Another single centre observational study in adult patients (mean age 57.9 years), concluded that HFNC may be considered as first-line therapy in acute respiratory failure, including patients with ARDS [7].
To the best of our knowledge, there has been no trial to compare the efficacy of high flow nasal cannula oxygen therapy with non invasive ventilation in ARDS per se in children.
However, an observational study comparing the efficacy of sequential application of oxygen therapy via HFNC and NIV, found that HFNC was better tolerated than NIV and allowed for significant improvement in oxygenation and tachypnea compared with standard oxygen therapy in subjects with AHRF (Acute Hypoxemic Respiratory Failure), and advocated the use of HFNC in between the NIV sessions [10].
Mean P:F ratio was 237.7 in our study. A low mean P:F score between 200-300 (which was earlier classified as "Mild" ARDS in children, as per the Berlin definition [11]) might be one of the possible reasons why HFNC proved to be efficacious in management of ARDS, in this study.
Even NIV application is to be limited only to mild forms of ARDS, as its use is associated with higher rates of treatment failure and mortality in severe forms [12].
The study was limited in not comparing the final outcome or survival to discharge in both the groups, as this was not the primary objective. Also, results are approaching statistical significance and are not clearly significant, which might be attributed in part to small number of patients in both the groups.
Hence more robust studies are required to prove efficacy of HFNC over NIV in ARDS in future. Similar conclusion was drawn by Wolfler A et al [5], who evaluated the use of HFNC and NIV in infants with severe bronchiolitis.

Conclusion
HFNC is efficacious in managing PARDS. Subsequent requirement of invasive ventilation and hemodynamic deterioration was significantly low with HFNC compared with NIV (CPAP).

What this study adds?
This study proves that high flow nasal cannula oxygen therapy is better than non invasive ventilation, in managing patients with PARDS.

Author contribution
 Surabhi Chandra -Conceived the idea, devised methodology and prepared the manuscript