Despite being young, healthy, and physically fit, some intensive care unit (ICU) patients experience significantly worse functional recovery after critical illness than older patients with multiple comorbidities although a poor precondition seems to be associated with worse ICU outcomes. This paradox highlights a fundamental gap in our understanding of the determinants of long-term recovery. While nonmodifiable factors such as age and pre-existing disease explain part of the variation, they cannot fully account for the wide heterogeneity in outcomes. Metabolic disturbances during critical illness, such as hypercatabolism, impaired muscle metabolism, nutritional deficits, systemic inflammation, and disruption of gut health, are likely to influence recovery trajectories, yet remain poorly characterized. Because these processes represent potentially modifiable targets, combining their evaluation with nonmodifiable patient characteristics is essential for unraveling the complex, multifactorial mechanisms underlying post-intensive care syndrome (PICS). This explorative, prospective, observational study aims to investigate the associations between metabolic signatures during the acute phase of critical illness and PICS outcomes throughout the recovery trajectory of ICU survivors, with a primary focus on physical functioning. In addition, the study explores the longitudinal course of metabolic parameters from ICU admission up to 12 months post-discharge, and whether these signatures can help identify distinct recovery phenotypes. Participants will be followed for 12 months, with study assessments at ICU admission, ICU discharge, and at 3-, 6-, and 12-months post-ICU admission.
Yearly, more than 70.000 patients are admitted to the intensive care unit (ICU) in the Netherlands. Although survival rates from critical illness have improved over the last decades, still patients suffer from profound weakness and functional impairments, collectively referred to as post-intensive care syndrome (PICS). PICS encompasses a cluster of long-lasting physical, cognitive, and mental health problems that have a severe impact on patients' quality of life. Studies investigating strategies to improve recovery after critical illness have shown limited effectiveness. This might be due to heterogeneous recovery trajectories observed among ICU survivors. Research has focussed on the associations between non-modifiable factors (e.g., age, sex and disease severity) and PICS outcomes. However, comprehensive assessment of potentially modifiable metabolic signatures (such as hypercatabolism, muscle metabolism, nutritional status, inflammatory response, and gut health) is lacking. These modifiable factors might be of interest as these likely shape the recovery trajectory of critical illness survivors. This approach, by combining the assessment of nonmodifiable factors together with potentially modifiable factors, is essential for understandiing the complex, multifactorial, pathophysiological mechanisms underlying PICS. The TOPICS study aims to explore the associations between modifiable factors during critical illness (such as hypercatabolism, muscle metabolism, nutritional status, inflammatory response, and gut health), and physical and psychological functioning in ICU survivors. The main questions it aims to answer are: 1. What are the associations between metabolic signatures during the acute phase of critical illness and physical functioning 3-months post-ICU admission? 2. What are the associations between metabolic signatures during the acute phase of critical illness and physical functioning across different time points in the recovery phase? 3. What are the associations between metabolic signatures during the acute phase of critical illness and psychological functioning (cognitive functioning and mental health status) across different time points during the recovery phase? 4. What is the trajectory of PICS outcomes, quality of life and metabolic parameters during one year following ICU admission? 5. Can distinct patient phenotypes with different recovery trajectories be identified based on metabolic and physical functioning outcomes? The study is a monocentre, longitudinal, explorative, prospective, observational study. Study measurements will be performed upon ICU admission, and in the recovery period (ICU discharge, 3-, 6-, and 12-months post-ICU admission). Study procedures include: 1. Completion of questionnaires on health-related quality of life, cognitive functioning, mental health status, and sleep quality. 2. Assessment of physical functioning. 3. Collection of blood samples. 4. Collection of fecal samples. 5. Assessment of dietary intake. The study population will consist of 200 adult patients admitted to the ICU of Gelderse Vallei Hospital, Ede, who receive (non-) invasive mechanical ventilation (IMV or NIV) within 48 hours after ICU admission and are expected to receive ventilatory support for at least 48 hours.
Study Type
OBSERVATIONAL
Enrollment
200
Gelderse Vallei Hospital
Ede, Gelderland, Netherlands
RECRUITINGSubjective physical functioning
Assessed by the Physical Component Score (PCS) of the Short Form-36 (SF-36) questionnaire, ranging from 0 to 100. Scores above or below the average of 50 indicate better or worse physical health compared to the general population, respectively.
Time frame: 3-months post-ICU admission
Handgrip strength
Assessed with Jamar dynamometer, measured in kilograms (kg).
Time frame: 3-months post-ICU admission
Leg strength and endurance
Assessed by the 30-second chair stand test (30sCST)
Time frame: 3-months post-ICU admission
Muscle size
Assessed by muscle ultrasound of the quadriceps muscles
Time frame: 3-months post-ICU admission
Muscle size
Assessed by calf circumference, measured in cm
Time frame: 3-months post-ICU admission
Body composition
Assessed by bio-electrical impedance analysis (BIA)
Time frame: 3-months post-ICU admission
Subjective physical functioning
Assessed by the Physical Component Score (PCS) of the Short Form-36 (SF-36) questionnaire, ranging from 0 to 100. Scores above or below the average of 50 indicate better or worse physical health compared to the general population, respectively.
Time frame: 3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Handgrip strength
Assessed with Jamar dynamometer, measured in kilograms (kg)
Time frame: 3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Leg strength and endurance
Assessed by the 30sCST
Time frame: 3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Muscle size
Assessed by muscle ultrasound of the quadriceps muscles
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Muscle size
Assessed by calf circumference, measured in cm
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Body composition
Assessed by BIA
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)
Cognition
Abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14), ranging from 0 to 56. A higher score indicates more cognitive errors.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Cognition
Montreal Cognitive Assessment (MoCA), ranging from 0 to 30. A higher score indicates better cognition.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Anxiety
Hospital Anxiety and Depression Scale (HADS), ranging from 0 to 42. Questions 1, 3, 5, 7, 9, 11 and 13 measure symptoms of anxiety (range: 0-21). Higher scores indicate worse symptoms of anxiety.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Depression
Hospital Anxiety and Depression Scale (HADS), ranging from 0 to 42. Questions 2, 4, 6, 8, 10, 12 and 14 measure symptoms of depression (range: 0-21). Higher scores indicate worse symptoms of depression.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Post-traumatic stress disorder
Trauma Screening Questionnaire (TSQ), ranging from 0 to 10. A higher score indicates worse symptoms of Post-Traumatic Stress Disorder.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Health-related Quality of Life
Short Form 36 (SF-36), ranging from 0 to 100. A higher score indicates a better Health-related Quality of Life.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Sleep quality
Pittsburgh Sleep Quality Index (PSQI), ranging from 0 to 21. Higher scores indicate worse sleep quality.
Time frame: 4 times during cohort (at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Level of independence
Barthel index, ranging from 0-20. Higher scores indicate higher independence of the participant.
Time frame: 4 times during cohort (ICU admission, 3-, 6- and 12-months post-ICU admission)
Frailty
Rockwood Clinical Frailty Scale (CFS), ranging from 1 to 9. A higher score indicates a more severe degree of frailty.
Time frame: 5 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, 6- and 12-months post-ICU admission)
Dietary intake
24-hour recall, combined with a dietary food record.
Time frame: 2 times during cohort (3-, and 12-months post-ICU admission)
Lipid metabolism
Plasma triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Glucose metabolism
Plasma glucose levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Glucose metabolism
Plasma insulin levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Glucose metabolism
Blood HbA1c levels
Time frame: 3 times during cohort (at ICU admission, 3-, and 12-months post-ICU admission)
Protein metabolism
Plasma amino acid levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Thyroid hormones
Plasma thyroid hormone levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Markers for kidney function
Plasma kidney function markers
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Markers for liver function
Plasma liver function markers
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Markers for muscle metabolism
Plasma muscle metabolism markers
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Micronutrient levels
Blood micronutrient levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Systemic inflammation markers
Plasma systemic inflammation marker levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Neuro-inflammation markers
Plasma neuro-inflammation marker levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Intestinal inflammation markers
Fecal intestinal inflammation marker levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Microbiota composition
Microbiota composition in feces (e.g., abundance, diversity and function)
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Intestinal fermentation markers
Fecal fermentation marker levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Intestinal integrity markers
Serum and plasma intestinal integrity marker levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA)
Plasma and fecal SCFA and BCFA concentrations
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Tryptophan metabolism
Plasma tryptophan metabolite levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Haematological health
Mean corpuscular volume
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Haematological health
Haemoglobin levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Haematological health
Haematocrit levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Haematological health
Leucocyte levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
Haematological health
Thrombocyte levels
Time frame: 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission)
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