Association of the PaO₂/PaCO₂ Ratio With ICU Mortality Independent of Oxygen Saturation and Mean Arterial Pressure: Insights From the MIMIC-II Database
Conditions: Mortality in Intensive Care Units
Sponsor: Tanta University

1. Study Title 
Association of the PaO₂/PaCO₂ Ratio With ICU Mortality Independent of Oxygen 
Saturation and Mean Arterial Pressure: A MIMIC-II Retrospective Cohort Study 
Acronym: RATIO-MIMIC 
 
2. Study Objectives 
Primary Objective: 
 
To determine whether the PaO₂/PaCO₂ ratio is independently associated with 
ICU mortality in critically ill adults, adjusting for oxygen saturation (SpO₂) and 
mean arterial pressure (MAP). 
Secondary Objectives: 
 
To explore the relationship between PaO₂/PaCO₂ ratio categories (e.g., tertiles 
or quartiles) and ICU length of stay. 
 
To perform subgroup analyses by mechanical ventilation status, age, or primary 
ICU diagnosis. 
 
3. Study Design 
 
Type: Observational 
 
Design: Retrospective cohort study 
 
Population: Adult ICU patients (≥18 years) in MIMIC-II database 
 
Sampling Method: Retrospective census of all eligible patients meeting 
inclusion/exclusion criteria 
 
Cohorts/Groups: Single cohort; exposure analyzed as continuous and 
categorical (quartiles or tertiles) 
 
Time Frame: ICU admissions from 2001–2008 (MIMIC-II database) 
 
4. Study Population 
 
Inclusion Criteria: 
1. Adult patients (≥18 years) at ICU admission 
2. First (index) ICU admission during hospitalization 

3. At least one arterial blood gas measurement with PaO₂ and PaCO₂ 
4. Available SpO₂ and MAP during ICU stay 
5. Documented ICU discharge status 
 
Exclusion Criteria: 
1. Age <18 years 
2. Missing or non-numeric PaO₂ or PaCO₂ values 
3. Missing ICU outcome data 
4. Physiologically implausible ABG values 
5. ECMO during ABG measurement (if identifiable) 
6. No SpO₂ or MAP measurements during ICU stay 
7. Repeat ICU admissions beyond index stay 
8. DNR/comfort-care orders prior to ABG measurement (optional for 
sensitivity analyses) 
 
5. Data Collection and Variables 
 
Exposure Variable: PaO₂/PaCO₂ ratio (calculated from ABG measurements) 
 
Outcome Variable: ICU mortality (yes/no) 
 
Covariates for Adjustment: 
o Oxygen saturation (SpO₂) 
o Mean arterial pressure (MAP) 
o Age, sex, ICU type (medical/surgical), comorbidities (if available) 
o Mechanical ventilation status 
 
Time Points: First ABG per ICU stay (primary), or median/peak ABG values for 
sensitivity analysis 
 
6. Statistical Analysis Plan (SAP) 
6.1 Descriptive Analysis 
 
Continuous variables: mean ± SD or median (IQR) 

 
Categorical variables: counts and percentages 
 
Compare baseline characteristics across PaO₂/PaCO₂ quartiles using 
ANOVA/Kruskal-Wallis for continuous variables and chi-square/Fisher’s exact 
test for categorical variables 
6.2 Primary Analysis 
 
Model: Multivariable logistic regression 
 
Dependent Variable: ICU mortality (binary) 
 
Independent Variable: PaO₂/PaCO₂ ratio (continuous or categorical) 
 
Covariates: SpO₂, MAP, age, sex, ICU type, comorbidities 
 
Effect Measures: Adjusted odds ratios (ORs) with 95% confidence intervals 
 
Assessment of Independence: Evaluate whether PaO₂/PaCO₂ remains 
statistically significant after adjustment 
6.3 Secondary Analyses 
 
Subgroup Analyses: Mechanical ventilation status, age categories, ICU type 
 
Sensitivity Analyses: 
o Excluding extreme ABG values 
o Excluding DNR/comfort-care patients 
o Using alternative PaO₂/PaCO₂ calculation methods (first ABG vs. 
median ABG) 
 
Time-to-event Analysis (Optional): Cox proportional hazards for ICU length of 
stay, treating death as event 
6.4 Missing Data Handling 
 
Exclude patients missing primary exposure or outcome 
 
For covariates (SpO₂, MAP, comorbidities): 
o If <5% missing: complete-case analysis 
o If >5% missing: consider multiple imputation 
6.5 Statistical Software 
 
R (version ≥4.0) or STATA (version ≥16) 
 
Two-sided p-value <0.05 considered statistically significant 

 
7. Ethical Considerations 
 
Secondary analysis of de-identified public data (MIMIC-II) 
 
No new patient consent required 
 
Approved by MIT and Beth Israel Deaconess Medical Center Institutional Review 
Boards for public data use 
 
8. Reporting 
 
Follow STROBE guidelines for observational studies 
 
Present baseline tables, regression results, and flowchart of included/excluded 
patients 
 
Include sensitivity and subgroup analyses 
 
Report odds ratios, 95% CI, and p-values