European Journal of Cardiovascular Medicine

Accurate measurement of cardiac output is essential for the management of patients with acute and chronic cardiac illness, particularly in the cardiac intensive care unit.1 The direct Fick method, based on oxygen consumption and arteriovenous oxygen difference is the gold standard for cardiac output measurement.1,2 However, it is invasive and technical complexity make it difficult for routine application.3 Consequently, indirect Fick methods and non- invasive techniques using pulse oximetry and estimated oxygen consumption have emerged as easier alternatives.

Oxygen consumption–based equations such as LaFarge, Bergstra, and Krovetz–Goldbloom allow indirect estimation of cardiac output; however, these models were derived from heterogeneous populations, and their validity in critically ill adult cardiac patients remains uncertain.1,4,5 Venous oxygen saturation is another readily available parameter that reflects the balance between systemic oxygen delivery and consumption and may provide both hemodynamic and prognostic information.5 This study aimed to evaluate the correlation between invasive indirect Fick-derived cardiac output and non-invasive estimation methods, and to assess the in-hospital prognostic value of venous oxygen saturation.

The present study was a cross-sectional observational study of 385 patients who presented at tertiary cardiac care centre from June 2021 to May 2022. The study was approved by the ethics committee of the hospital. Demographic and clinical information were derived from all patients. The informed consent was obtained for all patients to participate in the study

All patients between 18-80 years of age or older who presented at tertiary care cardiology centre not meeting any of exclusion criteria included in the study. Patients were excluded if

1. They were younger than 18 or older than 80 years of age;
2. Patient having any detectable shunt lesion
3. Had a serious tachyarrhythmia or bradyarrhythmia at the time of sample collection
4. Serious septic shock, severe anaemia, thyrotoxicosis, A-V fistula v. Brain-dead

Protocol:

The patient’s present and previous cardiac history were assessed. The patient’s weight and height recorded. Body surface area was calculated based on Du Bois Formula i.e.

BSA = (W 0.425 x H 0.725) x 0.007184.

Baseline vital parameters recorded: Heart Rate, SBP, DBP, SpO2. Systemic examination was done and based on history and examination. Baseline Killip and NYHA class were noted. ECG and Echocardiography were done for all patients. Non-invasive RA pressure was estimated according to IVC diameter and its respiratory collapsibility on echocardiography.

Cardiac output, Cardiac index, and Systemic vascular resistance were calculated both invasively and non-invasively obtained data simultaneously. Cardiac output was measured using FICK'S PRINCIPLE.

VO2 was calculated based on LaFarge, Krovet-Goldbloom and Bergstra Formulas.

• Arterial O2 content was measured with below mentioned formula CaO2 = (1.39 x Hb x SpO2) + (0.00314 x PaO2)
• Mixed venous O2 content was measured with below mentioned formula CvO2 = (1.39 x Hb xSvO2) + 0.00314 x PvO2
• According to Fick’s equation cardiac output was calculated as - CO = VO2/ (CaO2-CvO2)

CI = CO/BSA

SVR = 80*(MAP – RA /CO) dynes/sec/cm⁻⁵

• LaFarge Formula for VO2 (ml/min) = 1 – (X × logeage) + (0.378 × Heart Rate) × BSA

(Men: X = 11.49; Women: X = 17.04);

• Bergstra formula for VO2 (ml/min) = 3 × BSA + X – (10.5 × logeage) + 4.8 (Men: X = 10; Women = 0).
• Krovetz-Goldbloom formula for
  • VO2(ml/min)/BSA = (1.39 x height + 84 x weight - 35.6)/BSA Where BSA is calculated with DuBois Formula i.e.
  • BSA [m²] = Weight [kg]⁴²⁵ × height (cm)^0.725 × 0.007184(9)

Statistical Analysis:

All statistical studies were carried out using the SPSS program v20. Quantitative variables were expressed as the mean ± standard deviation and qualitative variables were expressed as number (%). A comparison of parametric values between the two groups was performed using the independent sample t-test. Categorical variables were compared using the chi-square test. Logistic regression was used to predict the variables for venous saturation during ICU stay. A nominal Statistical significance was indicated by a two-tailed P-value ≤0.05 for all analyses carried out in this investigation.

Baseline characteristics of the study population were mentioned in table 1. The mean age of the population was 59.06 ± 12.37. 358 (92.99%) patients were male and 125 (32.47%) patients were female. 33.2% patients had diabetes, 54.5% patients had hypertension and 35.8% patients were smoker.

Table 2 presents the comparison of invasive and non-invasive cardiac output and cardiac index by different formula. Cardiac output and cardiac index by Lafarge method was significantly (p <0.0001) under estimated and Bergestra formula was significantly (p <0.0001) overestimated compared to ficks method.

Cardiac output calculated using the invasive indirect Fick method demonstrated a significant positive correlation with non-invasive cardiac output estimation (r=0.71, <0.0001).

Oxygen consumption estimated using all three equations showed statistically significant correlations with Fick-derived cardiac output (Table 3). The LaFarge equation showed a moderate positive correlation with Fick-derived cardiac output (r = 0.55, R² = 0.30; 95% CI 0.43–0.64; p < 0.0001), explaining approximately 30% of the variance in invasive measurements. The Bergstra equation demonstrated a moderate inverse correlation with Fick- derived cardiac output (r = −0.43, R² = 0.33; 95% CI −0.53 to −0.30; p < 0.0001), indicating that higher Bergstra-derived estimates were associated with lower invasive Fick-derived values. Among the three methods, the Krovetz–Goldbloom equation exhibited the strongest correlation with invasive indirect Fick-derived cardiac output (r = 0.58, R² = 0.34; 95% CI 0.46–0.67; p < 0.0001), accounting for the highest proportion of explained variance and demonstrating the best linear agreement with the reference standard (Figure 1).

Venous oxygen saturation showed a strong positive correlation with cardiac index (r = 0.68, p <0.0001), indicating a close relationship between global oxygen delivery and cardiac performance. Lower venous oxygen saturation values were associated with reduced cardiac output and adverse hemodynamic profiles.

Multivariable logistic regression analysis identified several invasive hemodynamic and metabolic parameters independently associated with reduced venous oxygen saturation during ICU stay (Table 4). Elevated venous lactate levels were significantly associated with lower

venous saturation (OR = 1.12; 95% CI 1.06–1.18; p < 0.0001), while higher serum bicarbonate levels were inversely associated (OR = 0.79; 95% CI 0.74–0.84; p < 0.0001).

Markers of cardiac performance showed strong associations, with both cardiac output (OR = 0.37; 95% CI 0.27–0.49; p < 0.0001) and cardiac index (OR = 0.26; 95% CI 0.17–0.40; p < 0.0001) independently predicting reduced venous oxygen saturation. Systemic vascular resistance was also significantly associated (OR = 1.00; 95% CI 1.00–1.001; p = 0.02).

Reduced arterial oxygen saturation (SpO₂) demonstrated a strong association with venous desaturation (OR = 0.12; 95% CI 0.01–0.56; p < 0.0001). Impaired renal function, reflected by lower estimated glomerular filtration rate (eGFR), was independently associated with reduced venous oxygen saturation (OR = 0.98; 95% CI 0.97–0.99; p < 0.0001). Higher BNP levels were also associated with venous desaturation (OR = 1.00; 95% CI 1.00–1.002; p = 0.001).

Receiver operating characteristic curve analysis demonstrated that venous oxygen saturation had moderate discriminative ability for predicting in-hospital mortality with 88.6% Sensitivity and 43.1% Specificity and AUC= 0.673, p <0.0001 (figure 2). A venous oxygen saturation threshold of <66% was associated with a higher risk of adverse in-hospital outcomes, supporting its role as a clinically relevant prognostic marker in hospitalized cardiac patients.

Table 1: Baseline Characteristics of the Population

  Table 2: Comparison Of Invasive And Non-Invasive Estimation Of Cardiac Output And Cardiac Index

Table: 3 Correlations with Fick-derived cardiac output

Table 4: Predictors of Venous Saturation with Various Invasive Parameters

In this study correlation of cardiac output measured by invasive Fick’s method with other non- invasive method like Lafarge formula, Bergestra formula and Krovet- goldbloom formula. We used the formula for invasive and non-invasive estimation of cardiac output and cardiac index. The cardiac output measured by the Krovetz–Goldbloom formula showed the strongest correlation and highest explained variance, while the Bergstra equation exhibited a significant inverse relationship with invasive Fick-derived cardiac output. Additionally, venous oxygen saturation emerged as a robust surrogate of cardiac index and an independent in-hospital prognostic marker.

The indirect Fick method remains the reference standard for cardiac output measurement, but its routine use is limited by invasiveness and logistical constraints. Consequently, non-invasive estimation strategies have gained interest, particularly in critically ill patients where serial hemodynamic assessment is required.3 Previous studies have shown variable agreement between estimated and invasively measured cardiac output, largely dependent on the accuracy of oxygen consumption (VO₂) estimation models and patient population characteristics.1,6,7

In our observation, the Krovetz–Goldbloom equation demonstrated the best performance, explaining approximately one-third of the variance in invasive cardiac output measurements. This finding is consistent with prior observations that Krovetz–Goldbloom–derived VO₂ estimates perform better in adult populations, as the equation incorporates broader physiological assumptions and was validated across wider age ranges compared with pediatric- derived models.8,9 The superior performance of this method suggests greater suitability for adult cardiac ICU patients, in whom metabolic demand and oxygen extraction are highly variable.1,3

The Bergstra equation showed a moderate but significant inverse correlation with invasive Fick-derived cardiac output. This inverse relationship is clinically practicable and probably reflects the constraints of the Bergstra version, which is more often used in pediatric populations and is predicated predominantly on body surface area based VO₂ estimation.10 In critically ill adult patients, oxygen consumption is influenced by anemia, fever, neurohormonal activation, catecholamine therapy, and altered peripheral oxygen extraction. 11 Under these conditions, fixed or body size based VO₂ assumptions may overestimate oxygen consumption in low-output states, leading to systematic underestimation of calculated cardiac output and an apparent inverse association with invasive measurements.

Importantly, we also observed a strong correlation between venous oxygen saturation and cardiac index, with a venous saturation threshold of <66% identifying patients at increased risk of adverse in-hospital outcomes. This finding aligns with prior studies demonstrating that reduced mixed or central venous oxygen saturation reflects impaired global oxygen delivery and reduced cardiac output in heart failure and shock states.12-14 Even after adjustment for hemoglobin concentration and arterial oxygen saturation, venous oxygen saturation remained independently associated with cardiac output, underscoring its utility as a readily available bedside marker of hemodynamic compromise.

Collectively, our findings support the clinical utility of non-invasive cardiac output estimation in selected settings, particularly when using equations better suited to adult physiology. Furthermore, venous oxygen saturation provides complementary prognostic information and may serve as a practical surrogate for cardiac output assessment in hospitalized cardiac patients when invasive measurements are not feasible.

In our study it was found that cardiac output measured by standard Ficks’-derived method when compared to other non-invasive methods such La farge, Bergestra and krovet-goldbloom formula was found to have significant underestimation of vo2 by Lafarge and krovet- goldbloom formula while overestimation by Bergestra formula. There is significant correlation in venous saturation with various non-invasive and invasive parameters done on routine basis in patients admitted to cardiac ICCU. This venous saturation levels can help as a simple earliest tool to determine prognosis and guiding intensive management of patients.

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