Muscle Ultrasound Study in Shock Patients

Study Overview
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Brief Summary
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Intensive Care Unit (ICU) patients are known to lose muscle mass and function for many reasons, ranging from prolonged immobilization, to the effects of ICU treatments such as mechanical ventilation (MV), to the critical illness itself. Ultrasonography (US) is widely used in the ICU setting and has greatly evolved in the last decades, since it allows the non-invasive assessment of different structures, using radiation-free and user-friendly technology; its application for the assessment or the skeletal muscle is a promising tool and might help detecting muscle changes and thus several dysfunctions during early stages of ICU stay. By using skeletal muscle ultrasound at both diaphragm and peripheral levels, the overall aim of this study is to improve knowledge in the early detection of muscle dysfunction and weakness , and their relationship with mechanical ventilation weaning and muscle strength, in critically ill patients suffering from septic shock.

Official Title
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Diaphragm Dysfunction and Peripheral Muscle Wasting in Septic Shock Patients: Exploring Their Relationship Over Time Using Ultrasound Technology

Conditions
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Septic Shock

Intervention / Treatment
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* Other: Diaphragm ultrasound (DUS)
* Other: Peripheral Muscle Ultrasound (PMUS)
* Other: Airway occlusion pressure (P0.1)
* Other: Medical Research Council (MRC) sum score


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients (> 18 years old) admitted to the ICU with a diagnosis of septic shock a SOFA score equal or superior to 8 points, at ICU admission blood lactate concentration above 2 mmol/L, at ICU admission expected to have more than 48h of mechanical ventilation (estimated by the attending physician) expected to stay more than 5 days in the unit (estimated by the attending physician) able to walk prior to ICU admission / walking aids accepted; Exclusion Criteria: pregnancy lower limb amputation, fixators or open wounds thoracic fixators or open wounds diagnosed neuromuscular or central nervous system diseases being transferred from another ICU spinal cord injury diaphragm pacemaker palliative goals of care cancers derived sarcopenia cachexia anorexic disorders (protein-energy malnutrition) intellectual or cognitive impairments, limiting the ability to follow instructions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Septic Shock<br> | Other: Diaphragm ultrasound (DUS)<br>* DUS assessments of diaphragmatic thickness (TDI), thickness fraction (TFDI) and shear modulus (SMDI), this last measured by shear-wave elastography (SWE), will be performed for both right and left hemi-diaphragms. A landmark between the 8th and 10th intercostal space in the mid-axillary or antero-axillary line, 0.5-2 cm below the costophrenic sinus, will be used. Here, the diaphragm can be seen as the less echogenic structure between two echogenic lines; TDI (cm) will be the calculated as the distance between the two lines at the end of expiration and TFDI as the rate of change between end-expiration and end-inspiration thicknesses (TFDI = thickness at end inspiration - thickness at end-expiration / thickness at end-expiration, %). SMDI will assess muscle's stiffness. For each image, a region of interest covering the widest possible surface of diaphragm and allowing an acquisition frequency of 2Hz will be set; results will be retrieved in kilopascals (kPa).<br>* Other names: Diaphragm ultrasonography;Other: Peripheral Muscle Ultrasound (PMUS)<br>* PMUS assessments of quadriceps rectus femoris (RF) muscle cross-sectional area (CSARF), echogenicity (ECHORF) and shear modulus (SMRF), this last measured by shear-wave elastography (SWE), will be performed. Probe will be placed perpendicularly to the anterior plane of the thigh, in 2 anatomical points, as follows: (i) in the midpoint between the anterior superior iliac spine and the upper pole of the patella and (ii) the border of the lower 1/3 and upper 2/3 between the anterior superior iliac spine and the upper pole of the patella. CSARF (cm2) will be calculated by outlining the area under the muscle hyperechoic line (aponeurosis). For ECHORF (differences in grey-scale images), the analysis of a region of interest (ROI) of 2cm x 2cm will be performed. For SMRF (kPa), a ROI covering the widest possible area of the RF and allowing an acquisition frequency of 2Hz will be set for analysis. All assessments will be performed with minimal compression and a copious amount of water-gel.<br>* Other names: Muscle ultrasonography;Other: Airway occlusion pressure (P0.1)<br>* P0.1 is the pressure developed in the occluded airway 100 milliseconds after the onset of inspiration. Its use doesn't require any additional equipment since it can be easy measured by using patient's ventilator. For the measurement itself, patients will be in semi-recumbent position (head elevation between 30° and 45°) with knee extended in neutral position and will be asked to stay as relaxed as possible. After 5 minutes breathing without any interruption or disturbance, 4 measurements will be observed and recorded as displayed on the ventilator screen.<br>Other: Medical Research Council (MRC) sum score<br>* This is a manual muscle strength testing tool, used very often in the ICU setting. It's based on the assessment of the following muscle groups: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and dorsiflexion of the ankle, all scored bilaterally. Muscle strength is graded as follows: 0, no visible/palpable contraction; 1, visible/palpable contraction without movement of the limb; 2, movement of the limb, but not against gravity; 3, movement against gravity; 4, movement against gravity and some resistance; 5, normal. The sum score ranges between 0 and 60 (between 0 and 5, in 12 muscle groups), with a score <48 indicating the presence of weakness.<br>* Other names: MRC muscle strength score;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Baseline (at 24 hours after ICU admission) | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Day 2, after ICU admission | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Day 3, after ICU admission | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Day 4, after ICU admission | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Day 5, after ICU admission | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Extubation day, approximately 7 days | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Weekly (1x/week), counting from day 6 of ICU stay until ICU discharge (approximately 10 days) | 
| Association between SWE assessment and other muscle ultrasound markers. | To explore the existence of an association between SWE assessment and other muscle ultrasound markers (TDI, TFDI, CSARF and ECHORF) for each muscle (diaphragm and quadriceps rectus femoris muscles) over the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | ICU discharge, approximately 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between the rate change (%) in DUS and PMUS assessments. | The association between the rate change (%) in DUS (TDI, TFDI and SMDI) and PMUS (CSARF, ECHORF and SMRF) markers over time, during the ICU stay, in adult patients (> 18 years old) admitted for a septic shock. | Time-points of assessment relating to baseline (ICU admission) values. | 
| Weaning success/failure predictive model. | The analysis of a combined model comprising, among other ICU variables, one DUS marker (TDI, TFDI and SMDI) and one PMUS marker (CSARF, ECHORF and SMRF) to predict weaning success/failure, in adult patients (> 18 years old) admitted to the ICU for a septic shock. | Between ICU admission and extubation moment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle ultrasound, Intensive care unit-acquired weakness, Diaphragm dysfunction, Mechanical ventilation, Weaning, Sepsis, Critical illness