Muscle Ultrasound Study in Shock Patients

Overview

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.

Full Title of Study: “Diaphragm Dysfunction and Peripheral Muscle Wasting in Septic Shock Patients: Exploring Their Relationship Over Time Using Ultrasound Technology”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: August 2022

Interventions

  • Other: Diaphragm ultrasound (DUS)
    • DUS assessments of diaphragmatic thickness (TDI), thickness fraction (TFDI) and shear-wave elastography (SWEDI), 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”, %). SWEDI will assess muscle’s stiffness. To its use, the ultrasound machine will be turned to the “Shear-wave mode” and an identical probe position will be used. For each image, a ROI of 2cm x 2cm will be set, and results will be retrieved in kilopascals (kPa).
  • Other: Peripheral Muscle Ultrasound (PMUS)
    • PMUS assessments of quadriceps rectus femoris (RF) muscle cross-sectional area (CSARF), echogenicity (ECHORF) and shear-wave elastography (SWERF) will be performed. Probe will be placed perpendicularly to the anterior plane of the thigh, in two 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 third and upper two-thirds 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’s hyperechoic line (aponeurosis), using the equipment’s cursor on a frozen image. For ECHORF (differences in grey-scale images, with values ranging from 0 to 255) and SWERF (muscle stiffness, kPa), a ROI of 2cm x 2cm will be defined. All assessments will be performed with minimal compression and with a copious amount of water-gel. Per landmark, three images for CSARF, ECHORF, and SWERF, will be recorded.
  • Other: Airway occlusion pressure (P0.1)
    • 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.
  • Other: Medical Research Council (MRC) sum score
    • 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.

Arms, Groups and Cohorts

  • Septic Shock

Clinical Trial Outcome Measures

Primary Measures

  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Baseline (at 24 hours after ICU admission)
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Day 2, after ICU admission
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Day 3, after ICU admission
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Day 4, after ICU admission
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Day 5, after ICU admission
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Extubation day, approximately 7 days
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: Weekly (1x/week), counting from day 6 of ICU stay until ICU discharge (approximately 10 days)
    • 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.
  • Association between SWE assessment and other muscle ultrasound markers.
    • Time Frame: ICU discharge, approximately 10 days
    • 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.

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. adult patients (> 18 years old) admitted to the ICU

2. with a diagnosis of septic shock

3. a SOFA score equal or superior to 8 points, at ICU admission

4. blood lactate concentration above 2 mmol/L, at ICU admission

5. expected to have more than 48h of mechanical ventilation (estimated by the attending physician)

6. expected to stay more than 5 days in the unit (estimated by the attending physician)

7. able to walk prior to ICU admission / walking aids accepted;

Exclusion Criteria

1. pregnancy

2. lower limb amputation, fixators or open wounds

3. thoracic fixators or open wounds

4. diagnosed neuromuscular or central nervous system diseases

5. being transferred from another ICU

6. spinal cord injury

7. diaphragm pacemaker

8. palliative goals of care

9. cancers derived sarcopenia

10. cachexia

11. anorexic disorders (protein-energy malnutrition)

12. intellectual or cognitive impairments, limiting the ability to follow instructions.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Geneva
  • Provider of Information About this Clinical Study
    • Principal Investigator: Karim Bendjelid, Professor – University Hospital, Geneva
  • Overall Official(s)
    • Karim Bendjelid, MD, PhD, Principal Investigator, Hôpitaux Universitaires de Genève (HUG) / Université de Genève (UNIGE)
  • Overall Contact(s)
    • Karim Bendjelid, MD, PhD, +41 22 382 74 46, karim.bendjelid@hcuge.ch

References

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Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, Vorona S, Sklar MC, Rittayamai N, Lanys A, Murray A, Brace D, Urrea C, Reid WD, Tomlinson G, Slutsky AS, Kavanagh BP, Brochard LJ, Ferguson ND. Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes. Am J Respir Crit Care Med. 2018 Jan 15;197(2):204-213. doi: 10.1164/rccm.201703-0536OC.

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Puthucheary ZA, Phadke R, Rawal J, McPhail MJ, Sidhu PS, Rowlerson A, Moxham J, Harridge S, Hart N, Montgomery HE. Qualitative Ultrasound in Acute Critical Illness Muscle Wasting. Crit Care Med. 2015 Aug;43(8):1603-11. doi: 10.1097/CCM.0000000000001016.

Dres M, Dubé BP, Mayaux J, Delemazure J, Reuter D, Brochard L, Similowski T, Demoule A. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients. Am J Respir Crit Care Med. 2017 Jan 1;195(1):57-66. doi: 10.1164/rccm.201602-0367OC.

Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC.

Bachasson D, Dres M, Niérat MC, Gennisson JL, Hogrel JY, Doorduin J, Similowski T. Diaphragm shear modulus reflects transdiaphragmatic pressure during isovolumetric inspiratory efforts and ventilation against inspiratory loading. J Appl Physiol (1985). 2019 Mar 1;126(3):699-707. doi: 10.1152/japplphysiol.01060.2018. Epub 2019 Feb 7.

Flatres A, Aarab Y, Nougaret S, Garnier F, Larcher R, Amalric M, Klouche K, Etienne P, Subra G, Jaber S, Molinari N, Matecki S, Jung B. Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients. Crit Care. 2020 Feb 3;24(1):34. doi: 10.1186/s13054-020-2745-6. Erratum in: Crit Care. 2020 Mar 5;24(1):79.

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