European Journal of Cardiovascular Medicine

Acute hypoxemic respiratory failure (AHRF) is a frequent and critical presentation in emergency departments, necessitating prompt and effective respiratory support to prevent invasive mechanical ventilation and reduce mortality [1]. High-flow nasal oxygen (HFNO) has emerged as an advanced oxygen delivery method that improves oxygenation, enhances patient comfort, and reduces work of breathing compared to standard oxygen therapies [2]. While noninvasive ventilation (NIV) has traditionally been the go‑to noninvasive respiratory support, recent evidence has begun to challenge its superiority in hypoxemic patients without hypercapnia or specific underlying conditions [3–5].

Notably, a landmark randomized clinical trial (RENOVATE) demonstrated that HFNO is noninferior to NIV in treating a wide range of adults with acute respiratory failure, showing comparable rates of endotracheal intubation or death within seven days and acceptable safety profiles [6]. Complementary meta-analyses and real-world evaluations have found similar efficacy between HFNO and NIV in ICU settings, though data specific to undifferentiated AHRF in emergency contexts remain limited [4,5,7]. A recent ED-based study reported that HFNO significantly improved respiratory distress and patient compliance over NIV within the first hour of use, highlighting its potential utility in acute care environments [8].

HFNO has also been associated with a reduced risk of intubation when compared to standard oxygen therapy, and its applicability appears broader and more patient-friendly than NIV, especially in settings where rapid triage and comfort are essential [9]. Nonetheless, some comparative trials have documented higher failure rates and intubation incidence among HFNO-treated patients, indicating the need for careful patient selection and monitoring [10].

Given these evolving insights and the paucity of robust emergency department data, our study aims to evaluate the impact of HFNO compared to NIV in adult patients presenting with acute hypoxemic respiratory failure, with respect to key clinical outcomes including intubation rates, respiratory parameters, and patient tolerance

This prospective and observational study will be conducted in the Department of Emergency Medicine at Sheth LG Hospital, affiliated with Narendra Modi Medical College, Ahmedabad. The study period will span from 1st August 2024 to 31st October 2024, during which data will be gathered from patients presenting to the Emergency Department with acute hypoxic respiratory failure. The research aims to compare the impact of High Flow Nasal Oxygen (HFNO) therapy with Non-Invasive Ventilation (NIV) in terms of clinical outcomes and patient response.

The study population will include adult patients aged 18 years and above who present with acute dyspnea and hypoxemia, characterized by a respiratory rate greater than 24 breaths per minute and oxygen saturation (SpO₂) less than 94% on room air. Eligible participants will be enrolled only after obtaining informed consent from the patient or their legal representative. Patients requiring immediate invasive mechanical ventilation, those with a decreased level of consciousness (Glasgow Coma Scale <13), hemodynamic instability, hypercapnic respiratory failure, or pregnancy will be excluded from the study to ensure homogeneity of the hypoxic group and minimize confounding variables.

For each enrolled participant, a detailed clinical evaluation will be performed, and findings will be recorded in a structured case record form. The collected data will include demographic details, clinical presentation, etiology of respiratory failure, respiratory and hemodynamic parameters at presentation, relevant laboratory and radiological investigations, and treatment modality (HFNO or NIV) employed. The primary outcomes assessed will be the requirement for escalation to invasive mechanical ventilation, improvement in oxygenation, patient comfort, and in-hospital mortality.

All data will be compiled and entered into Microsoft Excel, and subsequently analyzed using appropriate statistical software. Quantitative variables will be expressed as mean ± standard deviation or median with interquartile range depending on the data distribution, and categorical variables will be presented as frequencies and percentages. Comparative analysis between the HFNO and NIV groups will be conducted using the chi-square test or Fisher’s exact test for categorical variables and Student’s t-test or Mann-Whitney U test for continuous variables. A p-value of less than 0.05 will be considered statistically significant.

This methodology is designed to provide a robust framework for evaluating the role of HFNO in the acute emergency setting and to assess whether it offers a clinically meaningful advantage over traditional NIV therapy in terms of both physiological improvement and overall patient outcome.

In this study, the mean heart rate on arrival was similar between patients treated with NIV (124.04 bpm) and those on HFNC (121.77 bpm), with no statistically significant difference observed (p = 0.4318). However, at 12 hours, the HFNC group showed a significantly greater decrease in heart rate compared to the NIV group (99 vs 119 bpm, p = 0.001), reflecting better cardiovascular adaptation. At 24 hours, both groups showed further decline, but the difference was statistically insignificant (p = 0.1753) as shown in Table 1.

Analysis of respiratory rate at different intervals demonstrated a significant advantage of HFNC over NIV. On arrival, HFNC patients had a slightly lower respiratory rate than NIV patients (28.85 vs 31.30, p = 0.0266). This difference became more pronounced at 12 hours (22.29 vs 28.37, p = 0.001), suggesting faster clinical improvement in the HFNC group. Although respiratory rate was still lower in the HFNC group at 24 hours, the p value of 0.0985 indicated no significant difference at that point (Table 2).

The improvement in oxygenation was assessed using the P:F ratio. The HFNC group, despite having a lower P:F ratio on arrival (150 vs 167.65), showed significantly better improvement by 12 hours (286 vs 242.91, p = 0.001) and by 24 hours (372 vs 336.47, p = 0.0289). This emphasizes the faster oxygenation recovery associated with HFNC, as presented in Table 3.

As per the diagnostic profile of the study population, pneumonia was the leading cause of acute hypoxic respiratory failure (37 cases), followed by heart failure (18 cases), pulmonary tuberculosis (10 cases), and other conditions such as ILD, sepsis, and lobar pneumonia. The breakdown of diagnoses is summarized in Table 4.

Dyspnea scores showed a remarkable improvement in the HFNC group. At admission, severe dyspnea was observed in 96% of HFNC patients and 91% of NIV patients. However, after 12 hours, 83% of HFNC patients reported mild dyspnea compared to only 31% in the NIV group, a highly significant difference (p = 0.0001). At 24 hours, 96% of HFNC patients and 79% of NIV patients had mild dyspnea, further reinforcing the superiority of HFNC in symptom relief (Table 5).

Discomfort scores also favored HFNC. Initially, high discomfort was experienced by almost all patients in both groups. At 12 hours, however, 94% of HFNC patients rated their discomfort as low compared to only 18% in the NIV group (p = 0.0001). This trend continued at 24 hours, where 96% of HFNC users experienced low discomfort compared to 18% in the NIV group, indicating better patient compliance and comfort with HFNC therapy (Table 6).

Table 1: Comparison of Heart Rate at Arrival, 12 Hours and 24 Hours

Table 2: Comparison of Respiratory Rate at Arrival, 12 Hours and 24 Hours

Table 3: Comparison of P:F Ratio at Arrival, 12 Hours and 24 Hours

Table 4: Distribution of Study Subjects by Primary Diagnosis

Table 5: Severity of Dyspnea at Different Time Points

Table 6: Discomfort Scores at Different Time Points

The findings of this study reinforce the growing evidence supporting the efficacy and tolerability of High Flow Nasal Cannula (HFNC) therapy in managing patients with acute hypoxic respiratory failure. In the current study, patients on HFNC showed a more rapid improvement in respiratory rate and oxygenation (P:F ratio), along with greater patient comfort and reduced dyspnea scores compared to those receiving Non-Invasive Ventilation (NIV). These results align closely with recent multicentric analyses highlighting HFNC as a non-invasive modality with superior clinical outcomes in terms of oxygenation indices and patient-reported comfort scores [11]. The significant improvement in P:F ratio observed in our HFNC group by 12 and 24 hours mirrors the findings by van Beurden et al., where HFNC use was associated with sustained improvements in arterial oxygenation in the early treatment window [12].

Another critical aspect of this study is the subjective relief of dyspnea. HFNC patients reported a faster transition from severe to mild dyspnea within 12 hours, which has also been observed in trials comparing HFNC to CPAP in emergency settings [13]. It has been hypothesized that the constant flow and humidified air delivered by HFNC reduce respiratory drive and improve alveolar recruitment, thereby enhancing the sensation of breathlessness relief more rapidly than NIV. The discomfort scores further corroborate this as HFNC patients experienced significantly lower discomfort at 12 and 24 hours, consistent with the comfort-oriented design advantages of HFNC interfaces [14].

Importantly, the early use of HFNC in our cohort showed a promising trend toward decreased respiratory distress without requiring escalation to mechanical ventilation. This is consistent with the findings by Crimi et al., who demonstrated that HFNC reduced the need for intubation in selected patients with hypoxic respiratory failure when applied early and monitored effectively [15]. This highlights the critical role of triaging patients appropriately in the emergency department to benefit from less invasive interventions. Collectively, these findings suggest that HFNC not only offers physiological advantages in terms of gas exchange but also translates to perceptible clinical benefit from the patient's perspective.

This study demonstrates that High Flow Nasal Cannula (HFNC) therapy is associated with faster improvement in oxygenation, reduced respiratory effort, and superior patient comfort compared to Non-Invasive Ventilation (NIV) in cases of acute hypoxic respiratory failure. Early application of HFNC in emergency settings may reduce patient distress and improve outcomes, making it a favorable first-line option in appropriately selected patients.

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