An Overview of Venous Blood Gas Analysis

INTRODUCTION

Although arterial blood gas (ABG) analysis is the gold standard to assess acid–base balance and blood oxygenation, the use of venous blood gas (VBG) analysis outside of paired ABG/VBG measurements for hemodynamic assessment has been increasing and gaining popularity. The reasons attributed to this popularity are various. Venous sampling is a less invasive procedure. It is easier to collect, it is subject to far fewer complications than arterial punctures, it does not require specialized training, and it allows for less traumatic repeated collections in patients who are critically ill. VBGs cannot be used to assess oxygenation status but can be used to screen for acid–base status disturbances and to evaluate metabolic function. The parameters assessed in VBG analysis include pH, partial pressure of CO₂ (pCO₂), and calculated bicarbonate (). As with ABGs, VBGs must be collected anaerobically in a blood gas syringe and analyzed promptly.^1,2

Several types of venous specimens can be obtained for VBG analysis. The typical specimen collected from a routine venipuncture is different from the central venous and mixed venous ones. Each specimen type may have different gas concentrations, depending on the collection site. A peripheral venous specimen is collected from an arm vein, whereas a central venous specimen is collected via a central venous catheter (CVC) placed in the jugular or subclavian vein. A mixed venous specimen is collected from the pulmonary artery and provides the most accurate picture of the body’s metabolic processes because it reflects the venous return to the heart from the entire body. It best represents overall tissue oxygen consumption and metabolic state. However, a mixed venous specimen is more difficult to collect because pulmonary artery catheterization is not often performed. Therefore, a central venous specimen is most often used as a substitute. Peripheral venous specimens can also be used to screen for acid–base disorders.²

This systematic literature review examines the current trend of using VBG analysis in clinical assessment and evaluates the concerns related to the collection and interpretation of VBGs.

METHODS

This literature review of journal articles from 2019 to 2025 was obtained from Arkansas State University’s Library OneSearch tool. This tool searches all the library’s databases simultaneously with a single prompt. Relevant databases included in OneSearch include CINAHL Ultimate, ProQuest, Gale, MEDLINE Ultimate, NAHRS, and UpToDate. The nursing and health professions component of this tool alone includes 50 databases. The search term used was “venous blood gases.” The search was refined to only include the full-text versions of scholarly and peer-reviewed journal articles from January 1, 2019, to November 1, 2025. This yielded too many results. OneSearch suggested search term filters, and the “blood gas analysis” filter was selected. These filters operate on resource metadata, enabling refinement by availability, resource type, date, subject, and location. Application of the filter narrowed the results to 211. Systematic review or abstract-only publications were excluded, as were any nonhuman studies, bringing the number to 150. Each article was screened, and these types of articles were excluded: articles that did not discuss the laboratory analysis of VBGs; those that were exclusive to respiratory therapy such as those discussing ventilator management, commentaries, or case reports; those discussing umbilical gases only; veterinary articles or other articles on VBG in nonhuman subjects; articles discussing lactate only; articles not related to hospital settings or emergency departments (EDs); and articles not available in English. This brought the total number of articles to 18. Additionally, 3 articles used in the 2025 American Society for Clinical Laboratory Sciences/Association of Genetic Technologists/Society of American Federal Medical Laboratory Scientists Joint Annual Conference session titled “Pre- and post-analytical factors in blood gas analysis” by Xander van Wijk were included in this review.^3⇓-5

THE ADVANTAGE OF VBG ANALYSIS

VBGs are less painful, easier to obtain, and carry fewer complications than ABGs. A multicenter randomized controlled trial assessed whether switching to venous sampling for blood gas analysis as an alternative to arterial sampling reduced pain. They also assessed how this switch would affect the clinical management of ED patients. The study randomly evaluated 113 patients who were nonhypoxemic, presented to the ED, and required blood gas analysis. The primary outcome was the maximal pain during sampling, and the secondary outcomes were ease of sampling and physician satisfaction with the results provided. They found a significant difference in the perceived pain between the 2 groups, with the mean maximal pain of the arterial group almost twice that of the venous group. They also found that the perceived ease of sampling by the staff was statistically greater in the venous group than in the arterial group. The usefulness of the results provided did not significantly differ between the 2 groups, and the physicians found them equally useful.⁶

The anticipation of pain can cause patients to either hyperventilate or hold their breath (hypoventilate) in the moments before arterial puncture. A prospective observational study enrolled 30 patients who were undergoing elective surgery under anesthesia. Following anesthesia and before surgery, the ventilator settings were altered to mimic hyper- or hypoventilation. Arterial and venous specimens were obtained at baseline and at timed intervals from indwelling arterial and peripheral venous catheters. Arterial pH and pCO₂ changed rapidly within the first 15 to 30 seconds post-hyperventilation or post-hypoventilation and plateaued at 60 seconds. Peripheral venous values remained relatively constant until the 60-second mark and changed minimally thereafter. Mean arterial changes were significantly different at the 30-second mark when compared with baseline in response to both hyper- and hypoventilation. The study concluded that a peripheral VBG may provide a more reliable description of acid–base status, as it is not subject to the same gas fluctuations as an ABG.⁷

TRADITIONAL USE OF VBGs: ABG/VBG PAIRED ANALYSES

VBGs have been used clinically in the intensive care unit (ICU) for decades in the setting of a paired analysis with ABGs. A VBG analysis on a central venous specimen is paired with an ABG analysis to calculate the venous-to-arterial carbon dioxide pressure difference (Δpv-aCO₂). When paired with the central venous oxygen saturation (sO₂), these parameters offer insight into the hemodynamic status, cardiac output, and tissue perfusion of patients who were critically ill. The reference interval for Δpv-aCO₂ is 2 to 6 mm Hg, with elevated readings indicating decreased tissue perfusion or ischemic hypoxia.²

Another calculation based on paired ABG and VBG analyses is cardiac output, which can be calculated using the Fick principle. This requires the measured volume of oxygen consumption (VO₂) and blood gas analyses from arterial and pulmonary artery (mixed venous) specimens, with a central venous specimen often substituted for the mixed venous one. The formula for cardiac output is the measured VO₂ divided by the difference between arterial and venous oxygen content (Figure 1). Oxygen content is calculated with hemoglobin and sO₂ values using the formula shown in Figure 2. It is best to use the functional sO₂ measured by CO-oximetry because the estimated sO₂ (derived from the partial pressure of oxygen [pO₂]) can exceed the measured sO₂, especially at lower sO₂s. This is because of the shape of the oxygen–hemoglobin dissociation curve. At approximately 50% sO₂, a small difference in the pO₂ can elicit a large difference in sO₂ and skew the calculation.³

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Figure 1.

Fick’s principle formula.

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Figure 2.

Oxygen content calculation.

NEWER VBG APPLICATIONS IN VARIOUS CLINICAL CONDITIONS AND SETTINGS

Can VBGs be used as an alternative to ABG in the ED and in the critical care unit? A cross-sectional study in a tertiary care hospital investigated the agreement between 113 ABG and VBG paired analyses in a clinically diverse population who presented to their ED. The study found excellent, acceptably narrow limits of agreement in the arterial and venous pH, base excess, and levels. The pO₂ showed poor agreement, as expected. The pCO₂ also showed acceptably narrow limits of agreement, but the zero bias was outside of the limits. The study concluded that VBG analysis for pH, , and base excess can be a reliable substitute for ABG analysis.⁸

Is a central VBG (cVBG) analysis in a patient who is critically ill reliable? A prospective observational study compared 292 sets of cVBG/ABG values from 82 patients admitted to the medical ICU. They found clinically acceptable agreement between cVBG and ABG values in patients who were mechanically ventilated, with a central venous sO₂ of at least 70%. They concluded that cVBG analysis may be a substitute for ABG analysis in patients who are mechanically ventilated once tissue perfusion is restored.⁹

Are VBGs from a midline catheter sample as reliable as those from a CVC? A prospective observational study evaluated the use of VBGs from a midline catheter, which is a type of peripheral venous access. The study evaluated 40 ICU patients and found good agreement for pH and pCO₂ between the midline catheter and the CVC specimens. The correlation among the midline catheter, CVC, and arterial specimens for pH, pCO₂, lactates, and electrolytes was found to be moderate to strong. They concluded that in patients who are stabilized and critically ill, midline catheters are a reliable alternative to CVC and arterial lines to monitor acid–base disturbances, CO₂ levels, and electrolytes.¹⁰

Are VBGs reliable in screening for acid–base disturbances, such as diabetic ketoacidosis (DKA) and renal failure? An observational study of 76 patients with DKA found excellent agreement between arterial and venous pH and acceptably good agreement between arterial and venous pCO₂ and . Peripheral venous pH is slightly more acidotic than arterial pH, depending on metabolic burden. The study concluded that the VBG is a minimally invasive, safer option to assess the pH and in cases of DKA.¹¹ In the case of renal failure, ABGs and VBGs also correlate well. In a cross-sectional study of 101 patients in a tertiary care hospital, arterial and venous specimens were obtained from patients with acute and chronic renal failure undergoing hemodialysis. The study found that venous pH and correlate strongly with arterial values in that patient population.^4,11

Are VBGs reliable in cases of shock or hypotension when peripheral circulation is not ideal? A 1-year cross-sectional study evaluated 250 patients presenting to the ED with hypotension. The study included cases of sepsis (45.6%), hypovolemia (34.4%), cardiogenic shock (18%), and obstructive shock (2%). The study found a strong correlation and agreement between ABG and VBG for pH, pCO₂, , lactate, sodium, potassium, chloride, ionized calcium, serum urea nitrogen, base excess, and arterial/alveolar ratio. They concluded that VBGs could be a reasonable alternative to ABG in patients who are hypotensive.¹² Hypotension can cause hypoperfusion to peripheral areas. Therefore, in another cross-sectional study of patients with shock, 30 paired specimens were obtained to compare the VBG values obtained from peripheral sampling vs CVC sampling. The study revealed an excellent correlation between peripheral venous pCO₂ and central venous pCO₂. Therefore, peripheral venous specimens can be substituted for central venous specimens in patients presenting with shock who do not have a central line already placed. This is helpful in the clinical evaluation of the Δpv-aCO₂, used to assess the adequacy of cardiac output, a critical metric in patients with shock.¹³

COLLECTION AND TRANSPORT CONSIDERATIONS

VBG specimens are easier to collect than arterial specimens, but care must be taken in the collection and transport processes. Similar preanalytical issues can compromise the validity of the ABG and VBG results. Even though VBGs are not used to assess oxygenation, oxygen contamination of the specimen can affect the results. It is tempting to collect a VBG specimen in a lithium heparin–evacuated tube as part of a set of tubes for a patient workup during a routine venipuncture.⁴ However, evacuated tubes contain residual air, enough to falsely affect the results. Blood gas specimens collected in evacuated tubes show falsely increased pH and pO₂ and falsely decreased pCO₂ and caused by the interaction of the gases in the specimen with the residual air in the tube. These shifts exceed the total allowable error, making this type of specimen invalid for blood gas analysis. It is also impossible for specimens collected in evacuated tubes to be tested anaerobically on the blood gas analyzer. Venous specimens in evacuated tubes can be submitted for pH analysis only, but the tubes must be filled at least two-thirds full for an accurate pH measurement. Best practice states that blood gases, arterial or venous, must be collected in a 1- to 3-mL self-filling, heparinized, plastic, disposable syringe, also known as a blood gas syringe. The syringe must be filled to its stated capacity because underfilling can cause variations in the hemoglobin, hematocrit, and lactate results.^1,4,14,15

Oxygen can also contaminate the specimen if a bubble is left in the blood gas syringe. In a VBG, oxygen contamination can falsely decrease the pCO₂ and falsely increase the pH. This contamination is made worse if the specimen is shaken during travel in a pneumatic tube system. Care must be taken to remove any bubbles from the specimen at the time of collection, especially if the specimen is going to be sent through the tube system. Oxygen can also contaminate the specimen if the syringe is put in an ice-water bath. This is typically performed to slow cellular metabolism in the specimen in an attempt to preserve the specimen until analysis. However, icing the specimen contracts the plastic in the syringe, opening up pores that allow exogenous oxygen from the room to enter the specimen. Cellular metabolism is only a concern when leukocytosis or thrombocytosis is present. Therefore, the general recommendation is to keep the specimen at room temperature, with no air contamination, and to analyze it within 30 minutes. However, studies have demonstrated that a VBG specimen collected in a blood gas syringe, stored on ice, is stable for 60 minutes.^3,5,16,17

ANALYSIS AND INTERPRETATION

Once collected, a VBG specimen is analyzed in the same manner as an ABG specimen. It is important to note the specimen type collected to ensure proper interpretation of the results. This can be challenging because reference intervals for VBGs must first be established by the laboratory. A study of 134 VBG specimen results from adult volunteers was conducted by Ress et al¹⁸ to establish reference intervals (Table 1). These were verified against a calculated VBG reference interval established from a meta-analysis of the differences between ABG and VBG (Table 2).¹⁸ Each institution must perform validation studies to use VBG in its patient population and to establish usable reference intervals. To use the study’s VBG reference intervals by transference, the authors suggest the following: (a) performing a subject assessment to compare reference populations, (b) completing a statistical analysis of a small number of reference individuals (eg, n = 20), and (c) evaluating a larger number of reference individuals but fewer than needed for a standard reference interval study (eg, n = 120).¹⁸ It is recommended to have the VBG built in the laboratory information system as a separate test from the ABG so it can have the appropriate reported parameters and reference intervals.

Another VBG interpretation strategy is to use mathematical conversion models to approximate ABG values from VBG results. Shastri et al¹⁹ compared 2 mathematical models using paired arterial and central venous blood specimens. They applied a statistical method and a physiological method to 386 specimen pairs. Mathematical techniques include complex black-box statistical methods that use deep neural networks and include clinical variables and white-box models that use linear regression based on physiological and biochemical processes. Both methods appeared equal in their ability to transform central venous pH and pCO₂ to arterial values. However, the authors warrant caution when using either model in critically ill populations.¹⁹

Jörg et al²⁰ evaluated 3 mathematical models to estimate arterial pCO₂ based on venous pCO₂. These models were proposed by Lemoël et al,²¹ Farkas,²² and Zeserson et al.²³ They evaluated these 3 models with 250 blood gas specimen pairs from the ED. Most patients in the study presented with respiratory distress (84% of the cases). The model by Zeserson et al²³ uses a linear correlation with simple subtraction of a static value, and the models by Lemoël et al²¹ and Farkas²² use an adaptive conversion that factors in venous functional oxygen saturation as an indirect measure of oxygen uptake (shown in Table 3). After evaluation, the Farkas model proved to be the best and most accurate at estimating arterial pCO₂. However, all 3 models were comparable in terms of agreement and precision. Caution must be exercised when evaluating patients in critical care because all models showed a decrease in precision when patients underwent ongoing supplemental oxygen therapy or presented with hypo- or hypercapnia.²⁰

Shastri et al²⁴ evaluated a physiology-based mathematical model to transform peripheral venous blood acid–base values into mathematically arterialized equivalents following acute, transient changes in ventilation. For this model, the pH and pCO₂ agreement was excellent. They concluded that in clinical situations in which patients might hold their breath or hyperventilate while the arterial specimen is being collected, using arterialized venous blood values gives a stable representation of steady-state arterial values.²⁴ Thomsen et al²⁵ compared arterial specimens, arterialized venous specimens, and capillary specimens in ICU and pulmonary ward patients. They included 91 patients with respiratory failure in their analysis and used the v-tac mathematical arterialization method. Overall, arterialized venous and capillary pH and pCO₂ compared well with arterial values and were within the predefined clinically acceptable differences. For pO₂, the arterialized venous or capillary values describe the arterial values with similar precision, albeit they are slightly less precise at higher pO₂ values. They concluded that mathematical arterialization functions well in a range of ICU and pulmonary ward patients.²⁵ Therefore, after validating a mathematical model, physicians can use one that fits their patient population to convert VBG values to arterialized values, taking care to exercise caution in the interpretation when pO₂ values are high.

In conclusion, VBGs can be used as a less invasive tool to assess acid–base balance and to evaluate metabolic function. The ABG is still the gold standard for acid–base status and gas exchange assessment. However, ABGs can be misinterpreted if the patient holds their breath (hypoventilation) or gets anxious and hyperventilates. In such cases, VBGs are more stable and reliable because they are not subject to interference by hypo- or hyperventilation. VBG specimens must be collected in blood gas syringes while minimizing oxygen contamination and analyzed promptly. Although the results so far are promising, more studies are needed on the clinical implications of using VBGs in specific disease states. The VBG pH and values have the strongest correlation to ABGs, and when paired with the pCO₂, they can be useful to screen for acid–base status disturbances and to evaluate metabolic function. Each institution must validate its use and establish reference intervals for the population it serves. Mathematical models to arterialize VBG values can be used by physicians after validation. Therefore, VBGs are a useful test to incorporate in a laboratory’s test menu.