MuScle WastIng and DysphaGia iN CriticAlly IlL Patients (SIGNAL)

Background:

Dysphagia is a common and serious complication among critically ill patients admitted to intensive care units (ICUs). Up to 62% of patients who require mechanical ventilation experience dysphagia, which can lead to aspiration pneumonia, malnutrition, longer hospital stays, and increased mortality. Muscle wasting is a known consequence of critical illness and is associated with poor functional outcomes. The contribution of oral and suprahyoid muscle wasting to dysphagia in critically ill participants is poorly understood. This study aims to prospectively evaluate muscle wasting and its impact on swallowing function in critically ill adults.

Ethical Approval:

This study has Research Ethics Committee and Health Research Authority approval.

Study Objectives:

Primary Objective:

To measure the extent and rate of change in the cross-sectional area of the oral and suprahyoid muscles in critically ill adults using bedside ultrasound at four time points, and to relate these changes to swallowing physiology and safety.

Secondary Objectives:

To compare muscle mass and swallowing function between critically ill and non-critically ill participants.

To measure electrophysiological features of swallowing muscles using high-definition surface electromyography.

To assess patient-reported outcomes related to swallowing and eating.

To compare changes in the rectus femoris (thigh) muscle to those in the oral and suprahyoid muscles as a reference for general muscle wasting.

Study Design:

This is a prospective observational study. Critically ill participants admitted to the ICU will be recruited and compared with non-critically ill controls. The study includes repeated measures of muscle size and swallowing function over time.

Study Procedures:

Ultrasound Assessments:

The cross-sectional area of the tongue, geniohyoid, mylohyoid, and anterior belly of digastric muscles will be measured using bedside ultrasound at four time points during the participant's ICU stay. The rectus femoris muscle will also be measured as a reference for general muscle wasting.

Swallowing Evaluation:

Instrumental assessments of swallowing physiology and safety will be performed using gold standard assessments (e.g., videofluoroscopy or fiberoptic endoscopic evaluation of swallowing).

Tongue Strength:

Tongue strength will be measured using tongue dynamometry.

Electromyography:

High-definition surface electromyography will assess muscle activation patterns at rest and during swallowing.

Patient-Reported Outcomes:

Participants will complete patient reported outcome measures on swallowing, eating, and quality of life.

Data Management and Quality Assurance:

Data will be collected and managed according to Good Clinical Practice (GCP) and UK data protection regulations. Data will be collected using an online database (RedCap). Monitoring and auditing will be conducted by the sponsor to ensure protocol adherence and data integrity.

Sample Size and Statistical Analysis:

The sample size is calculated to detect clinically meaningful differences in muscle wasting and swallowing outcomes, based on expected rates in critically ill patients. Sample size was calculated based on a proof-of-conduct study completed by the investigators.

The primary analysis will use mixed-effects models to evaluate changes in muscle size and their association with swallowing function over time. Secondary analyses will compare critically ill patients with non-critically ill controls and explore associations between muscle wasting, swallowing outcomes, and patient-reported measures. Missing data will be addressed using appropriate statistical methods, such as multiple imputation or sensitivity analyses, as detailed in the statistical analysis plan.

Safety and Adverse Event Reporting:

The study involves only non-invasive assessments; risks are minimal and mainly relate to patient discomfort during swallowing tests. Adverse events and serious adverse events will be monitored and reported according to regulatory requirements.

Patient and Public Involvement:

Patients with experience of dysphagia in critical care contributed to the design of the study and the selection of outcome measures.

• Measure electrophysiological features of swallow muscle activity [Time frame: Day 1, 3, 7 and 10 of intensive care unit admission]
• Compare relationship between muscle mass and swallow physiology [Time frame: Day 1, 3, 7 and 10 ultrasound assessments, swallow evaluation completed following day 10 ultrasound or when patient is extubated and clinically appropriate]
• Patient reported outcomes: Sydney Swallow Questionnaire [Time frame: Within two weeks of day 10 ultrasound measurement or when clinically appropriate (e.g., ICU delirium resolved if present), up to 1 month]
• Patient reported outcomes: Swallowing Quality of Life (SWAL-QoL) Score [Time frame: Within two weeks of day 10 ultrasound measurement or when clinically appropriate (e.g., ICU delirium resolved if present), up to 1 month]
• Patient reported outcomes: Functional Oral Intake Scale [Time frame: Within two weeks of day 10 ultrasound measurement or when clinically appropriate (e.g., ICU delirium resolved if present), up to 1 month]
• Patient reported outcomes: Eating Assessment Tool-10 (EAT-10) [Time frame: Within two weeks of day 10 ultrasound measurement or when clinically appropriate (e.g., ICU delirium resolved if present), up to 1 month]
• Compare the extent of muscle wasting in critically ill versus non-critically ill patient [Time frame: Day 1, 3, 7 and 10 ultrasound evaluation vs single timepoint in non-critically ill patients]