Clinical trial NCT06010186: Evolution of Muscle Function, Breathlessness and Quality of Life Following Intra or Extra-Abdominal Sepsis in ICU Patients
Official title: Evolution of Muscle Function, Breathlessness and Quality of Life Following Intra or Extra-Abdominal Sepsis in ICU Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sepsis
Septic Shock
Lead sponsor: Fondation Hôpital Saint-Joseph
Sponsor class: OTHER
First posted: 2023-08-24
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Diaphragm thickening function
timeFrame: Month 3
Secondary outcomes:
measure: Function of thickening the diaphragm during inspiratory efforts
timeFrame: Month 1
measure: Evolution of diaphragm mobility during inspiratory efforts
timeFrame: Month 3
measure: Evolution of intercostal, transversus abdominis and oblique abdominal muscle function
timeFrame: Month 3
measure: Evolution of the cross-sectional area of the rectus femoris on ultrasound
timeFrame: Month 3
measure: Evolution of the structure of the various muscle groups assessed by ultrasound
timeFrame: Month 3
measure: Global measurement of dyspnea
timeFrame: Month 3
measure: Functional impact of dyspnea
timeFrame: Month 3
measure: Short Form-36 Questionnaire of Quality of life
timeFrame: Month 3
measure: Relationship between diaphragm function and dyspnea, and quality of life
timeFrame: Month 3
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Paris Saint-Joseph
Study officials:
affiliation: Hôpital Paris Saint-Joseph
name: Johan WORMSER
role: PRINCIPAL_INVESTIGATOR
References:
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.
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