Metabolic and Muscle Profile in ICU Survivors

Official title

Characterisation of the Inflammatory, Metabolic, and Mitochondrial Profiles in the Context of Post-Intensive Care Muscle Dysfunction

Overview

More and more patients survive a critical illness requiring admission to the intensive care unit, but they may be left with sequelae that are independent of the initial pathology. From a physical standpoint, the most visible complication is intensive care unit-acquired muscle weakness. A major factor in the development and persistence of muscle dysfunction appears to be the inflammatory response and the neuroendocrine stress response triggered by the initial critical insult. Persistence of inflammation beyond ICU discharge has been demonstrated in several studies. In response to inflammation, there is also increased oxidative stress associated with mitochondrial dysfunction. The objectives of the present study are therefore: to determine whether the broad inflammatory and metabolic profile of patients who have survived an ICU stay can predict the trajectory of muscle performance over the three months following ICU discharge; to compare this profile and muscle performance with those of non-critically ill surgical patients who have undergone a standardized inflammatory stress of lower intensity than that associated with critical illness; to investigate mitochondrial function in skeletal striated muscle after ICU stay, in light of the inflammatory and metabolic profile; to assess whether abnormalities in mitochondrial function also affect tissues other than skeletal muscle, in particular circulating blood mononuclear cells.

Interventions

• Diagnostic test Inflammation markers
  measurement of CRP, cytokines, MPO, oxidative stress during the first 7 days after ICU admission, between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test Blood nucleosomes
  measurement of blood nucleosomes between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test Erythrocyte membrane fatty acid content
  assessment of Erythrocyte membrane fatty acid content between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test measurement of myokines
  measurement of myokines between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test Resting energy expendure
  assessment of REE by indirect caloriometry during the first 7 days after ICU admission, between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test body composition
  assessment of body composition by BIA during the first 7 days after ICU admission, between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)
• Diagnostic test Omics
  Blood metabolic, lipidomic, proteomic study during the first 7 days after ICU admission (or the day after surgery)
• Diagnostic test Monocyte profile
  Blood leukocyte and monocyte profiles and transcriptomic analysis between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)

Primary outcome measures

• Quadriceps strength [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or the day after the surgery and 3 months after the surgery in surgical patients]
• Handgrip strength [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or the day after the surgery and 3 months after the surgery in surgical patients]
• Muscle mass [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or the day after the surgery and 3 months after the surgery in surgical patients]
• Muscle mass [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or the day after the surgery and 3 months after the surgery in surgical patients]
• Muscle mitochondrial function [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or perioperatively and 3 months after the surgery in surgical patients]
• Muscle function [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge in the critically ill patients, or perioperatively and 3 months after the surgery in surgical patients]
• Physical function [Time frame: between 1 and 7 days after ICU discharge and 3 months after ICU discharge (or the day after surgery and 3 months after hospital discharge)]

Eligibility criteria

Inclusion criteria

• Critical illness:
• anticipated ICU stay >= 7 days
• Major abdominal surgery
• elective surgery

Exclusion criteria

• Active malignancy
• Inherited metabolic disorder
• Known muscle disease
• Pregnancy
• Patient refusal
• Patient unable to express informed consent (dementia, confusion)
• Known coagulation disorder (cirrhosis, genetic coagulopathy) or thrombocytopenia < 100,000/mm³ on the day of biopsy, anemia with hemoglobin < 9 g/dL on the day of biopsy, or treatment with anticoagulant agents (contraindication to muscle biopsies only)
• Pacemaker or other implanted electronic device (contraindication to bioelectrical impedance analysis only)
• Oxygen therapy (contraindication to indirect calorimetry during spontaneous ventilation)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Belgium · 1 center

• CHU Sart Tilman — Liège

Identifiers

NCT: NCT07329530 · IM3SI

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗