Effect of High Flow Nasal Therapy (HFNC) Weaning Protocols vs Standard of Care on Respiratory Outcomes in Patients With Acute Respiratory Failure

University of Milan148 enrolled

Overview

High-flow nasal cannula (HFNC) is a widely used noninvasive respiratory support technique for patients with acute respiratory failure (ARF). It provides heated and humidified oxygen at high flow rates, improving oxygenation, reducing respiratory effort, and enhancing patient comfort. International guidelines recommend HFNC over conventional oxygen therapy in hypoxemic ARF. However, there is significant variability in clinical practice regarding HFNC discontinuation, and no standardized weaning criteria currently exist. Prolonged HFNC use may increase hospital stay and healthcare costs, while premature discontinuation may lead to respiratory deterioration and the need for further ventilatory support. Previous studies suggest that successful HFNC weaning may be predicted by a Fraction of inspired oxygen (FiO₂) ≤40% and a Respiratory rate-Oxygenation index (ROX index) ≥9.2. The ROX index is calculated as the ratio of peripheral oxygen saturation (SpO₂) divided by fraction of inspired oxygen (FiO₂) to respiratory rate. The primary objective of this study is to compare a standardized HFNC weaning strategy based on ROX index and FiO₂ thresholds with usual clinical practice based on physician judgment. The primary outcome is weaning failure at the first attempt, defined as the need for HFNC reinstitution, noninvasive or invasive mechanical ventilation, or death within 48 hours after discontinuation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

148

Conditions

Acute Respiratory Failure (ARF)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years * Presence of acute respiratory failure (ARF) * Receiving HFNC treatment for ≥24 hours Exclusion Criteria: * Post-extubation HFNC use or tracheostomized patients * Respiratory acidosis (pH \<7.35) or clinically significant acute hypercapnia (pCO₂ \>50 mmHg with worsening from baseline) * Long-term home NIV or home CPAP use * Do-not-intubate (DNI) orders precluding escalation to invasive mechanical ventilation * Life expectancy ≤48-72 hours due to terminal non-respiratory disease * Neurological impairment or deep sedation preventing safe HFNC use (e.g. coma or severe uncontrolled delirium) * Technical contraindications to HFNC (i.e. facial trauma, maxillofacial surgery, severe nasal obstruction) * Refusal to participate or inability to provide informed consent

Outcomes

Primary Outcomes

Weaning failure

To compare the percentage of patients who fail HFNC weaning within 48 hours after the first separation attempt using a protocolized HFNC weaning strategy based on ROX index and FiO₂ cut-offs versus standard clinical practice guided by physician judgment.

Time frame: Within 48 hours after the first separation attempt

Secondary Outcomes

Second-attempt weaning success

To compare the percentage of patients who fail HFNC weaning within 48 hours after the second separation attempt using a protocolized HFNC weaning strategy based on ROX index and FiO₂ cut-offs versus standard clinical practice guided by physician judgment.

Time frame: Within 48 hours after the second separation attempt

Length of hospital stay

Comparison of total hospital stay and post-weaning hospital stay between the two study arms.

Time frame: From the day of hospital admission until the day of hospital discharge, assessed up to 60 days; and from the day of HFNC discontinuation until the day of hospital discharge, assessed up to 60 days.

In-hospital and 30-day mortality

Comparison of in-hospital mortality and 30-day mortality after discharge between the two study arms.

Time frame: From the day of admission to the day of discharge or death (in-hospital mortality) and from the day of admission to 30-day after discharge (30-day mortality)

Predictors of weaning success

Identification of clinical and respiratory variables associated with successful HFNC weaning.

Time frame: From enrollment through hospital discharge, an average of 10 days.

Number of days of HFNC treatment from initiation to definitive discontinuation

Time frame: From the date and time of HFNC initiation until the date and time of definitive HFNC discontinuation, assessed up to 30 days.

Predictors of HFNC treatment duration

Demographic, clinical, radiological and laboratory variables associated with HFNC treatment duration

Time frame: From HFNC initiation through hospital discharge, an average of 10 days

Prevalence of diaphragmatic dysfunction assessed by diaphragm thickening fraction (DTF) and diaphragmatic excursion measured by ultrasound between the two study arms.

Comparison of the prevalence of diaphragmatic dysfunction assessed by diaphragmatic ultrasound between patients with successful HFNC weaning and those with weaning failure. Diaphragmatic function will be evaluated using diaphragm thickening fraction (DTF) and diaphragmatic excursion measured by ultrasound.

Time frame: 30 minutes before HFNC weaning initiation and 24 hours after weaning completion.

Changes in diaphragmatic function

Evaluation of diaphragmatic ultrasound parameters before and after HFNC discontinuation.

Time frame: Before HFNC discontinuation and within 48 hours after weaning attempt