MuScle WastIng and DysphaGia iN CriticAlly IlL Patients (SIGNAL)

The Relationship Between Oral and Suprahyoid Muscle Wasting and Dysphagia in Critically Ill Patients

The goal of this study is to find out how muscle wasting in the mouth and throat affects swallowing (dysphagia) in adults who are critically ill and being treated in intensive care units.

The main aims of this research study are to understand: how much and how quickly the oral and suprahyoid muscles waste in critically ill participants, and whether muscle wasting causes problems with swallowing. The investigators will compare critically ill participants with non-critically ill participants to determine if muscle wasting is linked to swallowing problems.

In this study, participants will have the size and strength of their mouth and throat muscles measured at four different times during their critical care admission and hospital stay. Tests will also be performed to check how well and how safely participants can swallow. Tongue strength will be measured, and participants will answer questions about their experience with swallowing and eating using patient-reported outcome measures.

This study may help identify better ways to diagnose and treat swallowing problems in people who are critically ill, to support safe eating and drinking and promote faster recovery.

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.

Inclusion Criteria:

• Adults >18 years
• Receiving mechanical ventilation via endotracheal tube and/or tracheostomy. Expected to receive ventilation for at least 72 hours.
• Expected to survive admission and spend more than 7 days in the intensive care unit.

Control participants

• Adults >18 years
• Receiving ward-based care.
• Expected to survive hospital admission. Present with a primary medical diagnosis of acute medical or surgical illness, not requiring critical care admission.

Exclusion Criteria:

Applies to both critically ill and control participants.

• Pregnancy
• Patients with a diagnosis of a primary neuromuscular pathology (e.g., motor neurone disease), central nervous system disease (e.g., stroke, Guillain barre), traumatic brain injury, connective tissue disease (e.g., scleroderma), head and neck cancer, previous surgery or radiotherapy to the head and neck.