Evolution of Muscle Function, Breathlessness and Quality of Life Following Intra or Extra-Abdominal Sepsis in ICU Patients

Sepsis Clinical Trial

— EMBLemAticS  

Official title:

Evolution of Muscle Function, Breathlessness and Quality of Life Following Intra or Extra-Abdominal Sepsis in ICU Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06010186
• Other study ID #: EMBLemAticS
• Status: Recruiting
• Phase: N/A
• Start date: July 28, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Fondation Hôpital Saint-Joseph
• Contact: Johan WORMSER
• Phone: 144123085
• Email: jwormser[@]ghpsj.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sepsis is organ dysfunction secondary to an inappropriate host response to infection. In the most severe cases, circulatory failure necessitating the introduction of vasopressor therapy is called septic shock. Sepsis and septic shock are life-threatening systemic organ dysfunctions requiring hospitalization in a critical care unit. According to several studies, sepsis accounts for around 30% of patients in these units. In this patient population, mortality in the critical care unit or in hospital is 25.8% and 35.3% respectively. Among the organ dysfunctions associated with sepsis, striated skeletal muscle damage is frequent and possibly severe. The literature refers to this as sepsis-induced myopathy, and describes three main mechanisms: mitochondrial dysfunction, exacerbated proteolysis and altered muscle membrane excitability. Of all the striated skeletal muscles that can be affected, the diaphragm and the muscles of the thoracic and abdominal wall play a major role in breathing. The diaphragm remains the main muscle involved in breathing. Its physiology is twofold. Firstly, through its contraction, the diaphragm is responsible for the lateral movement of the lower ribs, thus increasing the transverse diameter of the thorax. This first action is commonly referred to as "insertional". At the same time, lowering the phrenic center of the diaphragm increases abdominal pressure. Its distinctive upwardly convex domed appearance means that it is intimately in contact with both the chest wall and the abdominal cavity. This particular area of contact is called the apposition zone. It is on this zone, under the action of the abdominal compartment, that positive pressure also generates an outward thrust from the medial face of the lower ribs, a second action commonly referred to as "appositional". A number of studies, including that carried out by our team (US_DIAMONDS, NCT 02474797), have identified a high prevalence of diaphragmatic damage in patients with sepsis or septic shock. This can be as high as 60%. This diaphragmatic dysfunction would then be associated with a higher mortality rate in hospital and at D90 of discharge. The clinical evolution of post-resuscitation patients remains a little-studied subject. However, patients may present muscle dysfunctions in the longer term after a stay in intensive care. In our study, we demonstrated that less than half of patients recovered from diaphragmatic dysfunction on discharge from the critical care unit. In addition, Borges RC et al. found a significant decrease in the cross-sectional area of the rectus femoris at discharge, compared with the same measurement taken at D+2 of admission to the critical care unit. Finally, the impact of muscle dysfunction on dyspnoea during sepsis and after its resolution is uncertain. Similarly, the impact of muscle dysfunction and dyspnoea on quality of life is unknown. Sepsis is associated with muscle dysfunction of multiple mechanisms. The aim of this study is to assess the immediate and longer-term impact of muscle dysfunction on muscle, dyspnea and quality of life in patients with abdominal sepsis ("Abdominal sepsis" group) and patients with extra-abdominal sepsis ("Extra-abdominal" group). Depending on the location of sepsis, this study will enable us to assess and potentially confirm the preferential effect of abdominal sepsis on diaphragm function.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 86
• Est. completion date: December 31, 2025
• Est. primary completion date: July 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient over 18 years of age,
• Patient admitted to a critical care unit at Paris Saint-Joseph Hospital,
• Sepsis or septic shock (defined by the international consensus conference "sepsis-3"),
• Sepsis/septic shock less than 72 hours old,
• Patient affiliated to a health insurance scheme,
• French-speaking patient,
• Patient or relative who has given free, informed and express consent.

Exclusion Criteria:

• History of documented chronic muscular disease, whatever the cause (neuromuscular damage, abdominal or diaphragmatic hernia, muscular damage of inflammatory origin, myopathies, etc.),
• Moribund patients,
• Patient already included in a type 1 interventional research protocol (RIPH1),
• Patient under guardianship,
• Patient deprived of liberty,
• Patient under court protection,
• Pregnant patient.

Related Conditions & MeSH terms

• Dyspnea
• Intraabdominal Infections
• Sepsis
• Septic Shock
• Toxemia

Intervention

Other:
• Ultrasound measurement of the diaphragm and intercostals
The specific research procedures correspond to the addition of : Two additional ultrasound examinations, i.e. at discharge from intensive care and 3 months after hospital discharge: non-invasive examination (duration 20 minutes). Ultrasound is a risk-free, painless procedure involving the placement of an ultrasound probe on the body part under investigation, without the need for a radius or puncture. Questionnaires to assess quality of life (SF-36) and functional impact (LCADL) of dyspnea, carried out at discharge from hospital and at 3 months (duration 15 minutes).

Locations

Country	Name	City	State
France	Hôpital Paris Saint-Joseph	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Fondation Hôpital Saint-Joseph

Country where clinical trial is conducted

France, 

References & Publications (15)

Borges RC, Soriano FG. Association Between Muscle Wasting and Muscle Strength in Patients Who Developed Severe Sepsis And Septic Shock. Shock. 2019 Mar;51(3):312-320. doi: 10.1097/SHK.0000000000001183. — View Citation

Bougle A, Rocheteau P, Sharshar T, Chretien F. Muscle regeneration after sepsis. Crit Care. 2016 May 19;20(1):131. doi: 10.1186/s13054-016-1308-3. — View Citation

Chen Y, Liu Y, Han M, Zhao S, Tan Y, Hao L, Liu W, Zhang W, Song W, Pan M, Jiao G. Quantification of diaphragmatic dynamic dysfunction in septic patients by bedside ultrasound. Sci Rep. 2022 Oct 15;12(1):17336. doi: 10.1038/s41598-022-21702-6. — View Citation

De Troyer A, Boriek AM. Mechanics of the respiratory muscles. Compr Physiol. 2011 Jul;1(3):1273-300. doi: 10.1002/cphy.c100009. — View Citation

Demoule A, Jung B, Prodanovic H, Molinari N, Chanques G, Coirault C, Matecki S, Duguet A, Similowski T, Jaber S. Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study. Am J Respir Crit Care Med. 2013 Jul 15;188(2):213-9. doi: 10.1164/rccm.201209-1668OC. — View Citation

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. — View Citation

Grassi A, Ferlicca D, Lupieri E, Calcinati S, Francesconi S, Sala V, Ormas V, Chiodaroli E, Abbruzzese C, Curto F, Sanna A, Zambon M, Fumagalli R, Foti G, Bellani G. Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study. Crit Care. 2020 Mar 12;24(1):85. doi: 10.1186/s13054-020-2761-6. — View Citation

Hadda V, Kumar R, Tiwari P, Mittal S, Kalaivani M, Madan K, Mohan A, Guleria R. Decline in diaphragm thickness and clinical outcomes among patients with sepsis. Heart Lung. 2021 Mar-Apr;50(2):284-291. doi: 10.1016/j.hrtlng.2020.12.014. Epub 2020 Dec 28. — View Citation

Laghi FA Jr, Saad M, Shaikh H. Ultrasound and non-ultrasound imaging techniques in the assessment of diaphragmatic dysfunction. BMC Pulm Med. 2021 Mar 15;21(1):85. doi: 10.1186/s12890-021-01441-6. — View Citation

Le Neindre A, Hansell L, Wormser J, Gomes Lopes A, Diaz Lopez C, Romanet C, Choukroun G, Nguyen M, Philippart F, Guinot PG, Buscher H, Bouhemad B, Ntoumenopoulos G. Thoracic ultrasound influences physiotherapist's clinical decision-making in respiratory management of critical care patients: a multicentre cohort study. Thorax. 2023 Feb;78(2):169-175. doi: 10.1136/thoraxjnl-2021-218217. Epub 2022 Mar 23. — View Citation

Le Neindre A, Wormser J, Luperto M, Bruel C, Misset B, Bouhemad B, Philippart F. Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study. Aust Crit Care. 2023 Mar;36(2):239-246. doi: 10.1016/j.aucc.2022.01.003. Epub 2022 Mar 7. — View Citation

Lu Z, Ge H, Xu L, Guo F, Zhang G, Wu Y. Alterations in diaphragmatic function assessed by ultrasonography in mechanically ventilated patients with sepsis. J Clin Ultrasound. 2019 May;47(4):206-211. doi: 10.1002/jcu.22690. Epub 2019 Jan 22. — View Citation

Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Namendys-Silva SA, Martin-Loeches I, Leone M, Lupu MN, Vincent JL; ICON Investigators. Sepsis in Intensive Care Unit Patients: Worldwide Data From the Intensive Care over Nations Audit. Open Forum Infect Dis. 2018 Nov 19;5(12):ofy313. doi: 10.1093/ofid/ofy313. eCollection 2018 Dec. — View Citation

Solverson KJ, Grant C, Doig CJ. Assessment and predictors of physical functioning post-hospital discharge in survivors of critical illness. Ann Intensive Care. 2016 Dec;6(1):92. doi: 10.1186/s13613-016-0187-8. Epub 2016 Sep 20. — View Citation

Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diaphragm thickening function	This outcome corresponds to the difference in mean ultrasound diaphragm thickening fraction between ICU discharge and 3 months after hospital discharge.	Month 3
Secondary	Function of thickening the diaphragm during inspiratory efforts	This outcome corresponds to the difference in mean between the two groups in the fraction of diaphragm thickening, on ultrasound, within the first 72 hours of admission and on discharge from the intensive care unit.	Month 1
Secondary	Evolution of diaphragm mobility during inspiratory efforts	This outcome corresponds to the difference in diaphragmatic excursion means within the first 72 hours of admission, at discharge from intensive care and 3 months after hospital discharge.	Month 3
Secondary	Evolution of intercostal, transversus abdominis and oblique abdominal muscle function	This outcome corresponds to the comparison of thickness of intercostal, transverse and oblique abdominal muscles within the first 72 hours of admission, on discharge from intensive care and 3 months after hospital discharge.	Month 3
Secondary	Evolution of the cross-sectional area of the rectus femoris on ultrasound	This outcome corresponds to the comparison of the cross-sectional area of the rectus femoris within the first 72 hours of admission, on discharge from the intensive care unit and 3 months after hospital discharge.	Month 3
Secondary	Evolution of the structure of the various muscle groups assessed by ultrasound	This outcome corresponds to the comparison of gray levels on image captures of different muscle groups using Image J software®.	Month 3
Secondary	Global measurement of dyspnea	This outcome corresponds to theVAS-Dyspnea comparison (numerical scale from 0 to 10) within the first 72 hours of admission to intensive care, at discharge from intensive care, at discharge from hospital and 3 months after discharge from hospital.	Month 3
Secondary	Functional impact of dyspnea	This outcome corresponds to london chest activity of daily living scale at hospital discharge (estimate of previous condition) and 3 months after discharge. london chest activity of daily living	Month 3
Secondary	Short Form-36 Questionnaire of Quality of life	This outcome corresponds to the Short Form-36 comparison at hospital discharge (estimate of previous condition) and 3 months after discharge.	Month 3
Secondary	Relationship between diaphragm function and dyspnea, and quality of life	This outcome corresponds to the correlation between diaphragm thickening fraction and LCADL scale, SF-36 quality-of-life questionnaire physical score.	Month 3