Monitoring Respiratory Muscle Function in Acute Respiratory Failure Patients on Non Invasive Respiratory Support

Background and Rationale Acute respiratory failure (ARF) is a common and life-threatening syndrome characterised by inadequate gas exchange, resulting in hypoxaemia with or without hypercapnia, and frequently necessitating hospital admission and escalation of respiratory support. ARF is associated with substantial short-term mortality and long-term morbidity, including prolonged hospitalisation, reduced functional capacity, impaired quality of life, and increased healthcare utilisation. Despite advances in supportive respiratory therapies, outcomes remain poor for a significant proportion of patients, particularly when clinical deterioration is not recognised early.

Non-invasive respiratory support (NRS), including high-flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP), has become first-line therapy for many forms of ARF. These modalities aim to improve oxygenation, reduce work of breathing, and prevent the need for endotracheal intubation and invasive mechanical ventilation. Avoiding invasive ventilation is associated with reduced risk of ventilator-associated pneumonia, ventilator-induced lung injury, diaphragm disuse atrophy, delirium, and long-term neuromuscular weakness. Consequently, NRS is increasingly delivered not only in intensive care units (ICUs) but also in emergency departments, high-dependency units, and general wards.

However, despite widespread use, NRS failure rates remain substantial. A significant proportion of patients deteriorate and require delayed intubation, which is consistently associated with worse outcomes compared with early escalation. One of the major challenges in managing patients receiving NRS is the limited ability to directly assess respiratory muscle workload and lung mechanics at the bedside. As a result, clinicians often rely on indirect clinical markers that may lag behind physiological deterioration.

The primary pathophysiological determinant of ARF progression and NRS failure is the imbalance between ventilatory load and respiratory muscle capacity. Excessive inspiratory effort can lead to respiratory muscle fatigue, impaired ventilatory efficiency, and patient self-inflicted lung injury due to high transpulmonary pressures during spontaneous breathing. Importantly, these processes may occur even when conventional oxygenation metrics appear stable.

Traditional bedside metrics, such as respiratory rate, peripheral oxygen saturation, arterial blood gas measurements, and composite indices including the ROX index or HACOR score, provide indirect and incomplete insight into respiratory effort. While these measures are useful for population-level risk stratification, they cannot reliably quantify work of breathing or identify early respiratory muscle overload at the individual patient level. Furthermore, these indices are influenced by multiple confounders, including sedation, oxygen delivery settings, and clinician intervention.

Oesophageal manometry remains the reference standard for assessing inspiratory effort and work of breathing. However, its invasive nature, poor patient tolerance, technical complexity, and limited availability render it impractical for routine use in awake, non-intubated patients receiving NRS, particularly outside the ICU environment. Consequently, there is a critical unmet need for practical, non-invasive tools that provide real-time physiological insight into respiratory muscle function and lung mechanics during NRS.

Two non-invasive bedside technologies-ultrasound (US) and electrical impedance tomography (EIT)-offer complementary and physiologically meaningful assessments of respiratory mechanics and lung function. Respiratory muscle ultrasound enables direct visualisation and quantification of diaphragmatic and parasternal intercostal muscle structure and activity, providing surrogate markers of inspiratory effort, muscle recruitment, and mechanical efficiency. Lung ultrasound enables serial assessment of lung aeration and consolidation, capturing dynamic changes that may not be apparent on conventional imaging.

Electrical impedance tomography provides continuous, breath-by-breath assessment of regional lung ventilation and changes in end-expiratory lung volume, offering insight into ventilation distribution, lung homogeneity, and dynamic lung mechanics during spontaneous breathing supported by NRS. Together, US and EIT have the potential to bridge the gap between physiological understanding and bedside decision-making.

Although both modalities are increasingly used in research and selected clinical settings, neither has been systematically evaluated for usability, feasibility, and clinical applicability in patients receiving NRS across diverse hospital environments. In particular, it remains unclear how clinicians interpret, trust, and integrate this information into real-world decision-making processes. Understanding these aspects is essential before advanced monitoring can be embedded into routine care or tested in interventional trials.

Study Objectives Primary Objective The primary objective of this study is to evaluate the usability of respiratory muscle ultrasound and electrical impedance tomography as clinical decision-support tools for patients with acute respiratory failure receiving non-invasive respiratory support. Usability will be assessed using the Healthcare System Usability Scale (HSUS), focusing on effectiveness, efficiency, and clinician satisfaction when interpreting and applying physiological monitoring data in routine care.

Secondary Objectives

Secondary objectives are to:

* Assess the feasibility of performing repeated, protocolised ultrasound and EIT measurements across multiple time points during the early phase of NRS, including recruitment, retention, tolerability, data completeness, and technical reliability. * Quantify temporal changes in respiratory muscle function, including diaphragmatic and parasternal intercostal muscle activity, and lung aeration and ventilation patterns over the first 72 hours of NRS. * Examine the relationship between physiological measurements derived from US and EIT and NRS treatment settings, including flow rate, positive end-expiratory pressure (PEEP), and pressure support. * Explore associations between respiratory muscle and lung physiological patterns and clinically relevant outcomes, including escalation to invasive ventilation and in-hospital mortality. * Collect structured qualitative field notes describing workflow integration, interpretability, and real-world usability of advanced monitoring techniques from the perspective of the research team and clinical staff.

Study Design This is a prospective interventional study to be conducted across two hospital sites: the Royal London Hospital and the Newham University Hospital across Barts Health over 14 months. Data collection will be undertaken by the co-investigator, who is a member of the direct care team.

The study aims to obtain complete longitudinal physiological datasets from at least 50 adult patients. Up to 100 participants will be recruited to account for attrition due to early clinical deterioration, intolerance of monitoring, missing data, or withdrawal. In parallel, approximately 50 clinical staff members involved in the care of participating patients will complete usability assessments, and up to 20 may participate in optional semi-structured interviews.

For patients with acute respiratory failure requiring non-invasive respiratory supports serial measurements of respiratory muscle function will be taken across six time points within the first 72 hours (from day 1 to day 3) of commencing non-invasive respiratory support. Day 1 is defined as the first 24 hours from starting any non-invasive respiratory device.

The measurements taken from day 1 to day 3 are described below:

Ultrasound (US) data:

* Diaphragmatic excursion * Parasternal intercostal muscle cross-sectional area and thickness at end inspiration and end expiration * Diaphragmatic and parasternal thickening fraction * Parasternal intercostal muscle strain from the US video * Lung parenchyma aeration, consolidation and fluid burden following the recommended approach from current evidence of the Blue Protocol and the Lung Ultrasound score (as per literature).

Electrical Impedance Tomography (EIT) data:

The EIT lung imaging field will be divided into two regions of interest: from halfway down, the dependent dorsal lung region will be identified, and the other half represented the non-dependent ventral region. The following EIT parameters will be measured:

* Global and regional changes in end-expiratory lung impedance (corresponding to changes in end-expiratory lung volume) expressed in arbitrary units of impedance change from the baseline step (∆EELI, ∆EELInon-dep, and ∆EELIdep, respectively) * Lung compliance and inhomogeneity These measurements will also be collected at a variable time point defined as when the patient is liberated from non-invasive respiratory or when is intubated.

For completeness, from day 1 to day 3 and at a variable time point, basic routinely measured data will also be collected such as respiratory rate, heart rate, peripheral oxygen saturation, partial arterial oxygen pressure, partial arterial carbon oxide pressure, fraction of inspired oxygen, ROX index (Respiratory rate Oxygenation) defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) over respiratory rate (RR), pain score (numerical scale), conscious level. Breathlessness score (using the Borg scale) also be collected from day 1 to day 3 and at a variable time point if the patient is not intubated.

Data about the in NRS treatment settings (i.e. flow, PEEP and pressure support) will be collected; as well as outcome data regarding treatment failure such as intubation rate and death.

The initial assessment will take place at the earliest possible point in their admission (e.g., once the patient has been deemed eligible and consent has been received). Evaluation of respiratory muscle function (ultrasound and EIT), will be completed across six timepoints from day 1 to day 3. Please see Table 1 below.

Usability will be evaluated across two times points at day 1 and at a variable time point either at day 2 or day 3 as clinical workload allows. To evaluate the usability of data acquired with US and EIT (in monitoring respiratory muscle function) to guide clinical decision making, the co-investigator (BF) will undertake the following steps:

1. Present the data acquired with US and EIT, alongside basic routinely measured data and information about the NRS settings to clinical staff 2. Administer the Healthcare System Usability Score (HSUS) questionnaire will be administered to two clinical staff (i.e. a senior doctor in training or consultant and a nurse or allied health care practitioner) involved in making decisions about patients treatments. This will allow to evaluate the usability of the data in supporting clinical decision making. 3. In addition, we will collect field notes defined as written records of observations, experiences, and insights while conducting this research to evaluate usability in depth.

Only if additional manpower resources allow, semi-structured interview will be undertaken with up to 20 multidisciplinary clinical staff.

All data will be managed using secure and anonymised databases. Data will be reported using descriptive and inferential statistics.

The study is purely observational. The research team does not provide treatment recommendations or mandate changes to clinical management. Clinicians may view monitoring data as part of routine care but retain full autonomy over treatment decisions.

Eligibility criteria:

Inclusion criteria * Adult (≥18 years old) * with acute respiratory failure with hypoxia (i.e. arterial oxygen tension (PaO2) of \<8.0 kPa), and/or with or without hypercap

• Feasibility evaluation [Time frame: 72 hours]
• Observational evaluation [Time frame: 72 hours]