Critical Illness； Intensive Care Unit Patients
Conditions
Keywords
Exhaled carbon monoxide；, Group-based trajectory modeling, Prognosis, Inflammation, ICU outcomes
Brief summary
This is a single-center, prospective, observational study in adult intensive care unit (ICU) patients. The study will measure exhaled carbon monoxide (eCO) once daily for up to 7 days after ICU admission using a red blood cell lifespan breath analyzer, which simultaneously estimates erythrocyte lifespan. eCO is a gas produced endogenously during heme degradation and may reflect hemolysis, oxidative stress, and inflammation in critically ill patients. The purpose of this study is to describe how eCO changes over time in ICU patients and to determine whether different eCO patterns are associated with clinical outcomes. The primary outcome is all-cause mortality within 28 days after enrollment. Secondary outcomes include 90-day mortality, acute kidney injury, organ dysfunction assessed by SOFA score, transfusion requirement, changes in anemia-related indices, ICU length of stay, and duration of invasive mechanical ventilation. Participation does not change routine clinical care; study procedures involve breath sampling and collection of clinical data from the medical record.
Detailed description
Background: Endogenous carbon monoxide is generated in the human body and may increase during critical illness due to hemolysis, oxidative stress, and inflammation. Whether longitudinal patterns of exhaled carbon monoxide (eCO) provide prognostic information in critically ill patients remains unclear. Design and setting: This is a single-center, prospective, observational cohort study conducted in an adult intensive care unit (ICU). The study is designed to characterize longitudinal eCO patterns and evaluate their clinical significance in critically ill patients without altering routine clinical management. Study procedures and data collection: eCO will be measured once daily from Day 0 (baseline, within 24 hours of ICU admission/enrollment) through Day 7 when feasible, using a standardized breath analysis device. For patients receiving mechanical ventilation, breath sampling will be performed according to a standardized protocol for ventilated patients. In addition to serial eCO measurements, demographic characteristics, admission diagnosis, comorbidities, severity-of-illness scores, key treatments, and laboratory variables relevant to hemolysis, inflammation, organ function, anemia, and iron metabolism will be collected from the electronic medical record and protocol-defined assessments, as applicable. Analytic approach: Group-based trajectory modeling (GBTM) will be used to identify distinct eCO trajectory groups from repeated measurements. Associations between eCO trajectories and prespecified clinical outcomes will be evaluated using Kaplan-Meier methods and multivariable Cox proportional hazards models with adjustment for clinically relevant covariates. Additional exploratory analyses will assess relationships between eCO trajectories and laboratory biomarker patterns, including anemia-related, iron metabolism-related, and inflammatory indices. Machine learning methods (e.g., XGBoost with SHAP-based interpretation) may also be used in exploratory analyses to develop risk prediction models incorporating eCO and other clinical variables. Study conduct: No intervention is assigned as part of the study, and all treatment decisions remain at the discretion of the treating clinicians.
Interventions
None listed
Sponsors
Shanghai Zhongshan Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Admitted to the intensive care unit (ICU) at the study site 3. Expected ICU length of stay ≥ 48 hours 4. Able to complete exhaled carbon monoxide (eCO) measurement (spontaneously breathing or mechanically ventilated) 5. Written informed consent provided by the patient or a legally authorized representative
Exclusion criteria
1. Carbon monoxide poisoning 2. Active smoking within 24 hours prior to ICU admission 3. Unable to perform breath sampling (e.g., massive airway bleeding, severe airway obstruction, extracorporeal membrane oxygenation) 4. Ineffective sampling due to poor mask seal or special ventilation modes 5. Pregnant or breastfeeding 6. Known hereditary hemoglobinopathies (e.g., sickle cell disease, thalassemia) 7. Patient or family refusal 8. Other conditions deemed unsuitable by investigators
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-day all-cause mortality | From enrollment (Day 0) up to Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90-day all-cause mortality | From enrollment up to Day 90 | — |
| Acute kidney injury (AKI) (KDIGO) | From enrollment through ICU discharge (up to 28 days) | Incidence and staging of acute kidney injury defined by KDIGO 2012 criteria (serum creatinine increase ≥0.3 mg/dL within 48 hours, or ≥1.5 times baseline within 7 days, or urine output \<0.5 mL/kg/h for ≥6 hours) during ICU hospitalization. |
| Organ dysfunction assessed by SOFA score | Daily from Day 0 (baseline) through Day 7 | Daily Sequential Organ Failure Assessment (SOFA) score, a composite organ dysfunction scale ranging from 0 to 24, encompassing respiratory, coagulation, liver, cardiovascular, neurological, and renal subsystems. Each of the 6 organ system components is scored from 0 to 4, with higher scores indicating worse organ dysfunction and greater illness severity. Scores will be assessed daily from Day 0 (baseline) through Day 7. |
| Red blood cell transfusion requirement | Up to 28 days after ICU admission/enrollment | Whether red blood cell transfusion was administered (yes/no), number of transfusion episodes, and total units transfused within 28 days after ICU admission. |
| ICU length of stay | From ICU admission to ICU discharge (up to 90 days) | Total duration of invasive mechanical ventilation during the ICU stay. |
| Duration of invasive mechanical ventilation | From enrollment to liberation from invasive mechanical ventilation or ICU discharge (up to 28 days) | Total duration of invasive mechanical ventilation during the ICU stay. |
| Complete blood count-related panel | Up to 28 days after enrollment | Longitudinal changes in complete blood count-related indices, including hemoglobin, reticulocyte count, and red cell distribution width (RDW), and their associations with eCO trajectories. |
| Changes in iron metabolism related indices | Baseline and up to 28 days after enrollment | Longitudinal changes in iron metabolism- and erythropoietin-related indices, including serum iron, ferritin, transferrin saturation, soluble transferrin receptor, and erythropoietin (EPO), and their associations with eCO trajectories. |
Contacts
CONTACTFei Leng, MD.
CONTACTHongyu He
PRINCIPAL_INVESTIGATORMing Zhong
Fudan University
Outcome results
None listed