Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Danone Global Research & Innovation Center | INDUSTRY |
| Wageningen University and Research | OTHER |
| TKI Agri & Food | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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:
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:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort | Adult patients with an expected ICU length of stay of ≥72 hours, or who receive (non-) invasive mechanical ventilation (IMV or NIV) within 48 hours after ICU admission with an expected ventilatory support duration of at least 48 hours. |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3-months post-ICU admission |
| Handgrip strength | Assessed with Jamar dynamometer, measured in kilograms (kg). | 3-months post-ICU admission |
| Leg strength and endurance | Assessed by the 30-second chair stand test (30sCST) | 3-months post-ICU admission |
| Muscle size | Assessed by muscle ultrasound of the quadriceps muscles | 3-months post-ICU admission |
| Muscle size | Assessed by calf circumference, measured in cm | 3-months post-ICU admission |
| Body composition | Assessed by bio-electrical impedance analysis (BIA) | 3-months post-ICU admission |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
The study population will consist of 200 adult patients admitted to the ICU of Gelderse Vallei Hospital, Ede, with an expected ICU length of stay of ≥72 hours, or who receive invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV) within 48 hours after ICU admission and are expected to receive this ventilatory support (IMV or NIV) for ≥48 hours.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Arthur HR van Zanten, MD, PhD | Contact | +31318435964 | zantena@zgv.nl | |
| Noortje MP Overwater, MSc | Contact | +31318434119 | noverwater@zgv.nl |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gelderse Vallei Hospital | Recruiting | Ede | Gelderland | 6716 RP | Netherlands |
Deidentified data will be shared upon reasonable request.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Plasma, serum, whole blood, feces
| Handgrip strength | Assessed with Jamar dynamometer, measured in kilograms (kg) | 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 | 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 | 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 | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 2 times during cohort (3-, and 12-months post-ICU admission) |
| Lipid metabolism | Plasma triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol levels | 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 | 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 | 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 | 3 times during cohort (at ICU admission, 3-, and 12-months post-ICU admission) |
| Protein metabolism | Plasma amino acid levels | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 3-, and 12-months post-ICU admission) |
| ID | Term |
|---|---|
| C000657744 | postintensive care syndrome |
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided