The measurement of pH, partial pressure of oxygen (pO2), and partial pressure of carbon dioxide (pCO2) in arterial blood has been used for decades to assess metabolic disorders and respiratory status [1]. However, arterial blood sampling is invasive, can be painful, and carries the risk of complications [2]. There has been growing interest in using venous blood samples as a surrogate for arterial blood samples. Obtaining venous blood samples is easier, less invasive, and less painful than obtaining arterial blood samples. Venous blood gas (VBG) testing is a valuable tool for assessing acid-base homeostasis and is commonly used in diabetic ketoacidosis [3]. Estimating arterial pCO2 is challenging, considering the variable contribution of CO2 by individual organs and perfusion areas. Previous studies demonstrated some utility of VBG testing in heterogenus populations [4,5]. Although a good correlation between arterial and venous pCO2 has been well established [6], the reliance on venous blood samples in the clinical management of critically ill patients remains controversial. A meta-analysis [7] of five studies involving patients with chronic obstructive pulmonary disease showed an average difference between arterial and peripheral venous pH and pCO2 of 0.028 and − 5.9 mmHg, respectively. The authors concluded that there was a good agreement on pH; however, the utility of pCO2 in individual cases was limited.

Some researchers have also examined the utility of a central VBG, i.e., a VBG of a mixed central venous sample. A meta-analysis revealed a reasonable correlation regarding pH and pCO2 in hemodynamically stable patients [8]. However, in shock states, the agreement was too poor to be clinically helpful. Central venous pCO2 was found to be within 11 mmHg of the arterial pCO2 in the majority of ventilated trauma patients during initial resuscitation in another study; however, the sample size was small [9].

Some methodological and anatomical considerations are relevant to the challenges in using VBG in clinical practice as well as in designing studies. Depending on the acuity of the situation, the blood gas levels and pH can change within minutes. The mixed venous blood pCO2 is mostly a function of pulmonary CO2 clearance (typically the area of clinical interest) but also of CO2 production [10]. CO2 production is generally a minor factor affecting arterial blood CO2 levels in individuals with an intact and unincumbered ventilatory system. Therefore, the pCO2 is generally determined entirely by alveolar ventilation. The exact venous source is not irrelevant when peripheral venous samples are used. O2 extraction and CO2 production in body areas may vary depending on muscle mass (upper vs. lower extremities) or the proximity of a highly metabolic organ (e.g., the brain in the case of the external jugular vein). The available studies are inconsistent with respect to the site of venous access.

We postulated that there is a small and predictable difference in the pCO2 and pH between the arterial and venous sides of a perfusion area characterized by a low metabolic rate, such as the upper extremity, at rest and that the predictability of this difference is of clinical value in the critically ill population.