Blood gas analysis (BGA) is a frequently performed point-of-care test intended to assess acid-base balance, ventilation status, and O₂ delivery in patients with critical or acute illnesses. This analysis enables rapid evaluation of respiratory function, oxygenation, electrolyte levels, and metabolic conditions, making it indispensable in emergency rooms, intensive care units (ICUs), and operating rooms, as well as for managing patients with respiratory and metabolic disorders. In particular, BGA is vital for assessing critically ill patients and determining appropriate treatment strategies, emphasizing the necessity of rapid and accurate analysis. The most preferable sample for BGA is arterial blood, collected anaerobically through arterial puncture or via an indwelling arterial catheter, making arterial sampling the gold standard method. This distinguishes BGA from general blood tests, which typically utilize venous blood obtained via peripheral venipuncture. Occasionally, capillary blood is used, primarily for neonates and infants. Although venous blood is helpful for assessing acid-base balance, it cannot be used to accurately evaluate oxygenation status, thereby limiting its usefulness in BGA.

Arterial blood gas analysis (ABGA) involves drawing blood from an artery, most commonly the radial artery, due to its easy accessibility and lower risk of complications. Prior to using the radial artery, verifying adequate collateral circulation through the Allen test is essential. Alternative sites include the brachial and femoral arteries, although the brachial artery poses a risk of nerve injury, and the femoral artery carries greater risks of bleeding and infection, usually restricting its use to emergency scenarios. Possible complications of ABGA include pain, bleeding, hematoma formation, arterial spasm, thrombosis, infection, and damage to adjacent tissues or nerves. Such complications can be minimized by employing proper techniques and careful handling [1,2]. Given the critical need for expertise to ensure patient safety and comfort, only trained medical professionals are authorized to perform arterial blood collection.

Venous blood gas analysis (VBGA) is less invasive and simpler than ABGA, enhancing patient comfort and reducing complications such as bleeding, hematoma, and arterial spasm. It also enables repeated sampling, a significant advantage for continuous patient monitoring. Critically ill ICU patients frequently have arterial catheters placed primarily for continuous blood pressure monitoring, facilitating easier and more comfortable arterial blood sampling for BGA, although arterial catheter insertion remains an invasive procedure requiring technical expertise [3]. However, many critically ill patients needing frequent blood gas analyses have central venous catheters (CVCs), enabling safe venous blood collection and reducing the need for repeated venipuncture. Using venous blood for BGA enhances convenience for healthcare providers and offers a safer, more comfortable option for patients. Table 1 presents a comparison of the key differences between ABGA and VBGA. VBGA provides notable advantages, including ease of sampling, reduced invasiveness, and suitability for repeated testing. Venous samples can be collected via peripheral venipuncture or a CVC, decreasing pain and complications such as bleeding, hematoma, or ischemia compared to arterial puncture. Additionally, VBGA facilitates rapid patient assessment and treatment monitoring in emergency rooms and ICUs, increasing patient comfort and clinical workflow efficiency.

VBGA is valuable for assessing acid-base status to a certain degree, but it cannot deliver accurate oxygenation data provided by ABGA. Consequently, ABGA is indispensable for evaluating respiratory status and O₂ delivery, while VBGA serves effectively as a supplementary tool. Most clinical BGA research has historically focused on arterial blood, and established reference ranges are extensively validated using arterial samples. Although these arterial values are well-established among clinicians, there is increasing interest in exploring the potential of venous blood as an alternative in specific circumstances, driven mainly by practical challenges related to arterial sampling.

Since the partial pressures of gases are measured directly, the three primary parameters evaluated in BGA are pH, partial pressure of carbon dioxide (pCO₂), and partial pressure of oxygen (pO₂). The bicarbonate (HCO₃^–) concentration, on the other hand, is calculated indirectly from these measurements. Together, pH, pCO₂, and HCO₃^– are essential for assessing the patient's acid-base status. The differences between arterial and venous blood result from the physiological exchange of O₂ and CO₂ occurring within the capillary beds of tissues and alveoli. This two-step gas exchange process is vital for blood's fundamental role: delivering O₂ from the lungs to peripheral cells and transporting CO₂ from cells back to the lungs for removal. Proper functioning of this exchange process is critical for maintaining adequate metabolic activity and respiration.

Venous blood returns to the heart after delivering O₂ and nutrients to tissues. As blood traverses tissues, it accumulates CO₂ and metabolic wastes. Consequently, venous blood contains lower O₂ levels, reduced O₂ saturation, and higher CO₂ concentrations compared to arterial blood, resulting in a slightly lower pH. Recognizing these differences is crucial when selecting an appropriate blood sample for diagnostic evaluation. In contrast, arterial blood becomes oxygenated as it passes through the lungs, absorbing O₂ and releasing CO₂, before traveling to the left side of the heart via pulmonary veins. Previous studies [4-13] exploring the feasibility of venous blood for BGA follow a consistent and straightforward methodology. Accurate comparisons between arterial and venous BGA require anaerobic sampling and timely analysis using identical equipment. Research has consistently demonstrated that central venous pH is slightly lower than arterial pH, with an average arterial-venous (A-V) difference of approximately 0.03 pH units; this difference is clinically acceptable when accounted for in interpretation. Similarly, central venous pCO₂ is higher than arterial pCO₂, with a systematic negative bias of roughly –0.6 kPa (–5.0 mm Hg), making it a viable substitute in most clinical scenarios. Because HCO₃^– is derived from pH and pCO₂, central venous HCO₃^– typically shows slightly higher values than arterial HCO₃^–, and thus can also serve as an appropriate alternative. In contrast, arterial and venous pO₂ values demonstrate no reliable correlation due to variations in tissue O₂ consumption and blood flow dynamics, exhibiting an average A-V difference of approximately 8.33 kPa (63 mm Hg)±7.88 kPa (59 mm Hg). As a consequence, venous pO₂ cannot accurately predict arterial pO₂ levels, necessitating direct ABGA for precise oxygenation assessments. However, pulse oximetry offers a noninvasive method for continuously monitoring arterial O₂ saturation. Except in situations where assessing oxygenation is essential due to respiratory issues, VBGA is preferable for evaluating acid-base status, avoiding the complications associated with arterial sampling. Furthermore, patients requiring frequent BGA also routinely undergo venous blood draws for other diagnostic tests. Utilizing a single venous sample for multiple diagnostic evaluations would enhance efficiency, improve patient safety, and reduce healthcare costs.

Numerous previous studies evaluating the reliability of venous blood have utilized samples obtained through peripheral venipuncture [4,8,14,15]. Peripheral blood collected via venipuncture differs in gas variables from central venous and mixed venous blood. Unlike arterial blood, which maintains stable gas values until it reaches the tissue capillary bed, venous blood gas measurements may vary depending on the collection site. Central venous blood specifically refers to blood samples obtained through a CVC. Besides facilitating blood sampling for diagnostics, CVCs allow continuous central venous pressure monitoring, which is vital for managing hemodynamically unstable patients. Additionally, these catheters provide vascular access for the administration of medications, fluids, and blood transfusions. Typically, a CVC is inserted via the jugular or subclavian vein, and its tip is positioned near the junction of the superior vena cava and the right atrium, thereby collecting venous blood predominantly from the upper body. However, as this blood excludes input from the inferior vena cava, central venous blood does not represent true mixed venous blood. Complete mixing of venous blood occurs only after it circulates to the pulmonary artery. Consequently, only pulmonary artery catheterization enables the collection of fully mixed venous blood. This distinction is crucial for accurately evaluating systemic oxygenation and hemodynamic status. However, pulmonary artery catheters are seldom employed in our ICU. Thus, central venous blood often serves as a substitute for mixed venous blood in clinical practice. While central venous blood cannot fully replace mixed venous blood, it can function as a partial alternative in specific clinical scenarios. Mixed venous blood, obtained directly from the pulmonary artery, reflects a comprehensive mixture of venous return from the entire body, thereby accurately representing overall tissue O₂ consumption and metabolic state. In contrast, central venous blood is drawn from the superior vena cava or other central veins and primarily includes venous return from the upper body, offering only partial metabolic and oxygenation information (Figure 1). Typically, the central venous oxygen saturation (ScvO₂) is approximately 2%–3% lower than that of mixed venous oxygen saturation (SvO₂), and thus it can be used as a supplementary indicator, particularly in patients with conditions such as sepsis or shock [16].

Hemodynamic monitoring supports clinical decision-making, thus playing a crucial role in critical care [17]. A key objective is to provide timely alerts to facilitate decision-making before adverse events occur. Most variables in hemodynamic monitoring reflect macro-circulation parameters, as optimizing macro-hemodynamic conditions is generally assumed to enhance micro-circulation; however, this is often not the case [18]. Over time, BGA has remained superior to lactate, base deficit, and ScvO₂, as it provides essential information on cardiac output, microcirculatory perfusion, and anaerobic metabolic activity. Specifically, the venous-to-arterial CO₂ pressure difference (∆pv-aCO₂) serves as a critical indicator of these physiological processes. Given that these parameters represent fundamental targets for hemodynamic monitoring, BGA holds significant clinical value in assessing a patient's circulatory and metabolic status [19]. The data obtained from BGA more accurately reflect the true microcirculatory flow and metabolic state, indicating impaired O₂ utilization and hemodynamic instability [20,21].

In healthy individuals, ScvO₂ is typically around 3% lower than SvO₂, which is attributable to the lower O₂ extraction ratio (O₂ER) in the lower body compared to the upper body [16]. However, in shock conditions, this ScvO₂/SvO₂ relationship reverses due to increased O₂ extraction in the lower body. Specifically, in patients with septic shock, ScvO₂ may exceed SvO₂ by up to 8% because of enhanced O₂ER in the lower extremities [16]. Some studies indicate that ScvO₂ can reliably substitute SvO₂ values in clinical assessments [22]. ScvO₂ is directly influenced by the O₂ consumption-to-delivery ratio (VO₂/DO₂), decreasing when O₂ transport is insufficient and increasing when O₂ utilization is reduced [23]. When DO₂ declines, the body compensates by elevating O₂ER. Without timely intervention, however, this compensation eventually fails, causing VO₂ to become dependent on DO₂ [24]. Up to this critical threshold, known as cellular dysoxia, ScvO₂ decreases proportionally to reductions in DO₂. Beyond this point, delayed or insufficient interventions result in severe tissue hypoxia, causing disproportionate shifts toward anaerobic metabolism. Thus, ScvO₂ is a valuable marker of cellular oxygenation. If ScvO₂ is low, enhancing DO₂ initially leads to increased VO₂, yet ScvO₂ remains low despite appropriate intervention. ScvO₂ begins to rise only when VO₂ becomes independent of DO₂, marking entry into the independent zone [25]. However, low ScvO₂ does not always warrant increased DO₂, as this intervention can produce adverse effects. Instead, interventions that lower VO₂—such as sedation, pain management, fever control, and managing agitation or tremors—should be prioritized [26]. Thus, personalized therapeutic strategies are essential. A high ScvO₂ may indicate clinical improvement but can also reflect inappropriately low VO₂, suggesting that elevated ScvO₂ alone does not necessarily exclude the need for therapeutic interventions. Regardless of ScvO₂ values—low, normal, or high—it is most effective when assessed alongside ∆pv-aCO₂ [27]. Although lactate is a commonly used indicator, it does not always accurately represent tissue hypoxia or anaerobic metabolism, as nonhypoxic processes can also elevate lactate levels. Hence, lactate should be considered in conjunction with other parameters [28].

CO₂ measurements offer deeper insights into macro- and micro-hemodynamics than O₂ parameters and respond more rapidly than lactate [29]. As a metabolic byproduct of the Krebs cycle, increased tissue CO₂ during aerobic metabolism suggests heightened oxidative activity or elevated carbohydrate intake [30]. Conversely, elevated CO₂ can also indicate increased anaerobic metabolism [28,31]. ∆pv-aCO₂, which is calculated from central venous and arterial blood gas analyses, represents the difference between venous and arterial partial pressures of CO₂. Its normal range is 2–6 mm Hg [32]. Variations in ∆pv-aCO₂ are primarily influenced by changes in blood flow rather than tissue hypoxia. Elevated ∆pv-aCO₂ typically reflects decreased tissue perfusion, assuming adequate O₂ delivery is maintained [33]. According to Fick's equation applied to CO₂ metabolism, CO₂ elimination depends on the difference between venous CO₂ content (CvCO₂) and arterial CO₂ content (CaCO₂), multiplied by cardiac output (CO): (CvCO₂ – CaCO₂) × CO [34]. Consequently, the primary determinant of ∆pv-aCO₂ variations is CO, with an inverse proportional relationship [34]. Even with low CO, hyperventilation may maintain a normal or reduced ∆pv-aCO₂. Consequently, ∆pv-aCO₂ serves as a practical bedside marker of CO and microcirculatory blood flow. Research indicates that in hypoxic hypoxia, ∆pv-aCO₂ remains below 6 mm Hg [29]. Conversely, ischemic hypoxia, characterized by reduced blood flow without altered arterial O₂ pressure, elevates ∆pv-aCO₂ above 6 mm Hg [29]. Hemodynamic monitoring using BGA has long provided bedside diagnostic capabilities, enabling timely and effective interventions, and will continue to be valuable. No single hemodynamic monitoring method—static or dynamic—is perfect, as measurement interpretation and clinical decision-making remain operator-dependent, each approach presenting distinct advantages and limitations. Unlike sophisticated monitoring devices, blood gas analyzers are broadly available in hospitals, making them highly practical tools for evaluating circulatory status. Thus, utilizing BGA for hemodynamic monitoring effectively informs diagnosis and therapy.

VBGA is an increasingly valuable alternative to ABGA, offering a less invasive, safer, and more practical method for evaluating acid-base balance and ventilation in critically ill patients. While ABGA remains indispensable for precise oxygenation assessment, VBGA reliably measures pH, pCO₂, and HCO₃^–, making it particularly beneficial in emergency and intensive care settings. VBGA’s ease of sampling, reduced complication risk, and suitability for repeated measurements enhance workflow efficiency and patient comfort. As clinical practice continues to evolve, integrating VBGA alongside ABGA will optimize patient management by balancing diagnostic accuracy with clinical practicality, ultimately enhancing patient outcomes.