Clinical Utility of Arterial-Venous Blood Gas Differences in Neonatal Sepsis Diagnosis

Hu Li, Hu Zhenhong, Chen Yali, Gao Fangjian, Nie Lili, Qiu Jianwu*

1Department of Neonatology, YueBei People's Hospital Affiliated to Shantou University Medical College, (Shaoguan, Guangdong, 512026, China)

△Correspondence author: Qiu Jianwu, Email: qiujianwu@yeah.net

Abstract

Objective: To explore the application value of arterial-venous blood gas differences in neonatal sepsis and provide a new objective indicator for early diagnosis.

Methods: This study selected neonates with sepsis admitted to the neonatal department of Yuebei People's Hospital from January 2022 to June 2024 as the observation group (n=22). During the same period, neonates with simple jaundice without infectious factors were chosen as the control group (n=23). By comparing multiple indicators of arterial-venous blood gas analysis between the two groups—including partial pressure of oxygen (PO2), oxygen saturation (SO2), pH value, partial pressure of carbon dioxide (PCO2), oxygen content (CaO2), and lactate (Lac)—and calculating the differences in arterial-venous blood oxygen partial pressure (A-V PO2), arterial-venous blood oxygen saturation (A-V SO2), arterial-venous blood pH (A-V pH), arterial-venous blood carbon dioxide partial pressure (A-V PCO2), arterial-venous blood oxygen content (A-VCaO2), and arterial-venous blood lactate, the clinical significance of these differences in early diagnosis of neonatal sepsis was explored.

Results: In the comparison of arterial-venous blood gas differences, the lactate difference was significantly higher in the observation group than in the control group, and A-VCaO2 was significantly lower in the observation group than in the control group, with statistically significant differences between the two groups (P<0.05). There were no statistically significant differences between the observation group and the control group in terms of A-V PO2, A-V SO2, A-V pH, and A-V PCO2 (P>0.05).

Conclusion: The arterial-venous blood gas differences of A-VCaO2 and lactate are of significant importance as reference values in the early diagnosis of neonatal sepsis.

Keywords: Neonatal Sepsis; Arterial blood gas; Venous blood gas; Arterial-Venous Blood Gas Difference; Lactate

Introduction

Neonatal septicemia, also known as neonatal sepsis, is typically caused by bacteria, viruses, fungi, or other pathogens and leads to a potentially life-threatening systemic response in newborns [1]. Due to the distinct physiological and pathological characteristics of neonates compared to adults, the clinical manifestations of sepsis are often insidious and nonspecific, with rapid disease progression that can easily lead to multiple organ failure and become life-threatening. Therefore, early diagnosis and timely treatment are crucial for improving prognosis in neonatal sepsis. Global statistics indicate that approximately 4 million newborns die within 28 days of birth each year, with about one-third of these deaths attributable to sepsis [2].

The pathophysiological process of sepsis is often accompanied by severe tissue hypoxia, and oxygenation impairment is a critical factor contributing to disease deterioration [3]. Early fluid resuscitation and timely oxygen supply monitoring have been proven to be key measures for improving outcomes in sepsis patients. However, traditional oxygen dynamics monitoring indicators—such as pH value, arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SaO2), venous oxygen saturation (SvO2), and lactate (Lac) in arterial blood gas analysis—have certain limitations in assessing the oxygen supply-demand status and tissue damage in sepsis patients due to influences from various factors including tissue perfusion, hemoglobin content, tissue oxygen supply, and oxygen consumption [4]. In recent years, increasing attention has been focused on the application of arterial-venous blood gas differences (such as the difference between arterial and venous oxygen partial pressure, and the difference between arterial and venous carbon dioxide partial pressure) in sepsis, particularly in evaluating tissue oxygenation status, guiding fluid resuscitation, and monitoring sepsis progression. These indicators provide new objective evidence for clinical assessment by reflecting the balance of oxygen utilization and metabolism in the body [5-7].

Although domestic and international studies have explored the application of arterial-venous blood gas differences in sepsis, research on this method in neonatal sepsis is currently lacking. This study aims to evaluate the clinical utility of these differences in neonatal sepsis by analyzing and comparing the arterial-venous blood gas differences in neonates with sepsis admitted to our hospital from January 2022 to June 2024. It is hoped that this research will provide more objective and effective indicators for early diagnosis, treatment monitoring, and prognosis assessment of sepsis.

Methods

1.1 Study Subjects

Neonates with sepsis hospitalized in the neonatal department of Yuebei People's Hospital from January 2022 to June 2024 were selected for this study. Inclusion criteria: neonates clinically diagnosed with neonatal sepsis according to the diagnostic criteria in the 5th edition of Practical Neonatology [8]. Exclusion criteria: neonates with congenital heart disease and other congenital defects. Elimination criteria: neonates who did not have arterial and venous blood samples drawn simultaneously within the specified time or whose samples were unqualified. Neonates with simple jaundice hospitalized in the neonatal department during the same period, with infectious factors excluded, served as the control group. This study was approved by the Ethics Committee of Yuebei People's Hospital (approval number: KY-2021-241), and informed consent was obtained from all parents.

1.2 Research Methods

After a definitive clinical diagnosis was made, all subjects had 0.5 ml of peripheral arterial blood and 0.5 ml of venous blood samples collected simultaneously within a 3-minute interval. Blood gas analysis and internal environment testing were performed within 5 minutes using the GEM Premier 4000 automated blood gas analyzer. Operations were performed by neonatologists according to the instrument manual, and testing reagents and quality control reagents were all instrument-compatible products. Arterial (A) and venous (V) blood gas analysis parameters—including partial pressure of oxygen (PO2), oxygen saturation (SO2), pH value, partial pressure of carbon dioxide (PCO2), oxygen content (CaO2), and lactate—were recorded for both groups. The differences between arterial (A) and venous (V) blood gas analysis parameters were calculated, including arterial-venous oxygen partial pressure difference (A-V PO2), arterial-venous oxygen saturation difference (A-V SO2), arterial-venous blood pH difference (A-V pH), arterial-venous carbon dioxide partial pressure difference (A-V PCO2), arterial-venous oxygen content difference (A-VCaO2), and lactate difference. These differences were compared between the two groups to analyze their clinical significance and statistical relevance.

1.3 Statistical Methods

SPSS 22.0 statistical software was used for data analysis. Normally distributed continuous data were expressed as mean ± standard deviation and analyzed using independent samples t-test. Non-normally distributed continuous data were expressed as median (25th percentile, 75th percentile) and analyzed using non-parametric rank-sum test. Categorical data were expressed as counts and percentages and analyzed using chi-square test (X2 test). P<0.05 was considered statistically significant.

Results

2.1 General Data

This study included 22 neonates in the observation group and 23 neonates in the control group who met the inclusion criteria. In the observation group, there were 15 males and 7 females, with a mean age of 5 days and a mean birth weight of 2822.73±716.93 grams. In the control group, there were 7 males and 14 females, with a mean age of 2 days and a mean birth weight of 3120.43±448.64 grams. No significant differences were observed between the two groups in terms of gender, age, or birth weight, indicating good comparability (P＞0.05). The basic characteristics of the two groups are detailed in Table 1 [TABLE:1].

2.2 Comparison of Arterial-Venous Blood Gas Differences

No statistically significant differences were observed between the observation group and the control group in terms of A-V PO2, A-V SO2, A-V pH, and A-V PCO2 (P＞0.05). However, the lactate difference in the observation group was significantly higher than that in the control group, with a statistically significant difference between the two groups (P<0.05). Additionally, the difference in A-V CaO2 between the observation group and the control group was significant, with a statistically significant difference between the two groups (P<0.05). Details are provided in Table 2 [TABLE:2].

Discussion

Neonatal sepsis is a leading cause of infant mortality worldwide, affecting multiple organ systems with nonspecific and varied manifestations that can rapidly deteriorate and lead to severe consequences [9-11]. The definition of sepsis is based not only on microbial culture results but also on comprehensive assessment of laboratory tests and clinical symptoms. The early symptoms and clinical manifestations of neonatal sepsis can differ from those of adult sepsis, complicating diagnosis and treatment [12,13]. The key lies in timely identification and management to reduce potential threats to neonatal health and decrease mortality and complication risks.

Blood gas analysis technology is primarily used to measure gas concentrations in blood (such as oxygen and carbon dioxide), pH values, and other metabolic products. This technique plays a crucial role in medical diagnosis and critical patient management, particularly in the diagnosis and management of neonatal sepsis. Arterial blood gas analysis is one of the key tools for evaluating neonatal sepsis. By measuring critical indicators such as pH value, partial pressure of carbon dioxide (PaCO2), and partial pressure of oxygen (PaO2) in arterial blood, clinicians can assess the adequacy of ventilation and oxygenation, acid-base balance status, and electrolyte levels, thereby evaluating the respiratory and circulatory function of neonates. Given the difficulty and potential risks associated with arterial blood sample collection, numerous studies have explored the possibility of using venous blood samples as an alternative. Venous blood gas analysis is typically used to evaluate the metabolic status and tissue perfusion of neonates. By measuring pH value, lactate level, base excess, and other indicators in venous blood, clinicians can further understand the metabolic status and tissue perfusion of neonates. However, due to physiological differences between venous and arterial circulation, variations in patients' clinical conditions, and inconsistencies in sampling procedures, studies have found significant heterogeneity and variability in the accuracy of using venous blood gas analysis as a substitute for arterial blood gas analysis [14]. The analysis results of arterial and venous blood provide different clinical information, helping physicians comprehensively assess the oxygenation status, ventilation function, acid-base balance, and physiological state of neonates. Understanding these parameters and their clinical applications is of utmost importance for improving neonatal outcomes. In the evaluation of neonatal sepsis, venous blood gas analysis can be used in combination with arterial blood gas analysis to provide a more comprehensive understanding of the neonate's physiological status. In recent years, arterial-venous blood gas differences have emerged as a novel monitoring indicator and have gradually gained attention in the medical community. Research has shown that arterial-venous blood gas differences can more sensitively reveal tissue oxygenation status and metabolic disturbances, demonstrating high predictive value particularly in sepsis patients [15].

Arterial-venous blood gas differences (such as A-V pH, A-V PCO2, A-V PO2, A-V SO2, etc.) can provide critical information about neonatal circulatory and metabolic status, helping physicians determine whether neonates have inadequate tissue perfusion or metabolic disturbances.

In the field of neonatal sepsis research, lactate has been widely recognized as a marker of metabolic disturbance. Lactate production primarily originates from muscles and the liver, while its clearance mainly depends on liver and kidney function. During the pathological process of sepsis, inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) inhibit liver and kidney function, leading to decreased lactate clearance capacity and consequently elevated lactate levels [16]. Elevated lactate levels are typically associated with inadequate tissue perfusion and poor oxygenation. In the early stages of sepsis, the lactate response to infection can be observed even before C-reactive protein (CRP) elevation, making lactate useful for early diagnosis and prognosis assessment of neonatal sepsis [17]. One study noted that in the clinical sepsis group, a lactate value higher than 2 mmol/L in venous blood gas analysis at 6 hours after birth was associated with sepsis occurrence (P=0.041) [16]. When the cutoff value for lactate at 6 hours after birth in the clinical sepsis group was determined to be 3.38 mmol/L, the sensitivity was 57.9% and specificity was 68.5% (P=0.032). Further research has shown that lactate levels are not only associated with sepsis occurrence but also closely related to patient prognosis; persistently elevated lactate levels typically indicate the need for more aggressive intervention and treatment [18]. Lactate difference refers to the concentration difference between venous and arterial blood lactate. Under normal conditions, the arterial-venous lactate difference may not be significant. Animal experiments have shown that arterial blood lactate is slightly higher than venous blood lactate, but the difference is not significant [19]. Adult exercise studies have demonstrated that arterial lactate is significantly higher than venous lactate in the early stages of exercise, but the difference gradually narrows over time [20]. However, in sepsis conditions, the arterial-venous lactate difference may change due to tissue hypoxia and microcirculatory disturbances [19]. In sepsis, microcirculatory disturbances and tissue hypoxia lead to increased lactate production and decreased clearance, which may result in an increased arterial-venous lactate difference. Lactate levels are positively correlated with sepsis severity and poor prognosis, and improving lactate clearance rate can improve outcomes in pediatric sepsis patients [21]. Increased arterial-venous blood lactate difference reflects the degree of lactate accumulation in tissues, indicating worsening tissue perfusion insufficiency and metabolic disturbance. In this study, the lactate difference in arterial-venous blood gas analysis was significantly increased in the observation group compared with the control group, with a statistically significant difference (P<0.05). This suggests that metabolic disturbance is more severe in neonates with sepsis. During neonatal sepsis, microcirculatory disturbances and tissue hypoperfusion lead to increased lactate production, while simultaneously, microcirculatory disturbances reduce lactate clearance, resulting in significantly elevated venous blood lactate and consequently an increased arterial-venous lactate difference. Lactate difference has high application value in the early diagnosis of sepsis. Elevated lactate difference can help clinicians identify neonatal sepsis early, even in the absence of obvious clinical symptoms, thereby enabling early intervention to improve oxygenation status and metabolic disturbance in neonates.

Research on blood oxygen content in neonatal sepsis has primarily focused on the effects of sepsis on oxygen delivery (QO2) and tissue oxygenation, as well as how these changes impact neonatal physiological and pathological states. One study showed that metabolic acidosis in neonatal GBS sepsis is associated with tissue ischemia caused by reduced oxygen delivery [22]. By comparing piglets with similar reductions in systemic oxygen delivery, researchers found differences in blood oxygen content reduction between the sepsis and non-sepsis groups, which may be related to sepsis development and tissue oxygenation and metabolic status. Arterial-venous oxygen content difference is an important indicator for assessing tissue oxygenation status, reflecting oxygen utilization in the microcirculation and closely related to tissue oxygenation status and oxygen supply-demand balance in neonates. A narrowed arterial-venous oxygen difference may indicate impaired tissue oxygen utilization, which in sepsis may lead to a reduced arterial-venous oxygen difference. A reduced arterial-venous blood oxygen content difference reflects inadequate oxygen extraction [23]. In this study, the arterial-venous blood oxygen content difference was significantly different between the observation group and the control group (P<0.05), indicating poorer oxygenation status, higher tissue oxygen consumption, and insufficient oxygen supply or abnormal oxygen metabolism in the neonatal sepsis group. When used together with lactate difference, the effect is particularly prominent for early identification of sepsis. Sepsis is often accompanied by microcirculatory disturbances and poor oxygenation, making arterial-venous blood oxygen content difference a valuable indicator for early detection of oxygenation impairment.

A-V PCO2 can accurately reflect carbon dioxide metabolism and excretion and is an important indicator for evaluating tissue oxygen supply-demand status, cardiac output, and tissue microcirculatory status, providing a relatively objective reflection of tissue oxygenation status. Increased A-V PO2 typically indicates more severe tissue hypoxia. A-V SO2 serves as a key parameter for assessing oxygenation status, and its increase often suggests obstacles in oxygen delivery. In this study, changes in A-V PO2, A-V SO2, A-V pH, and A-V PCO2 did not show statistically significant differences, which may be related to the limited sample size and the fact that the study subjects were primarily early-stage sepsis patients. Therefore, future studies with larger sample sizes are needed to further validate these findings.

In the early diagnosis of neonatal sepsis, lactate difference and A-V CaO2 demonstrate significant application potential. These indicators can help clinicians more rapidly and objectively evaluate neonatal oxygenation status and metabolic state, providing strong evidence for treatment decisions in sepsis. Although differences in A-V PO2, A-V SO2, A-V pH, and A-V PCO2 did not show statistical significance, these indicators still provide valuable supplementary information for comprehensive assessment of neonatal oxygenation and acid-base status. Therefore, arterial-venous blood gas differences can serve as an auxiliary diagnostic tool for neonatal sepsis, offering clinicians more objective and accurate guidance. The advancement of blood gas analyzers toward point-of-care use, functional diversification, and micro-sampling has enabled detection not only of blood gas and internal environment parameters but also hemoglobin, carboxyhemoglobin, bilirubin, and multiple other indicators [24,25], greatly facilitating timely detection and diagnosis in neonates. In the future, through expanded sample sizes or combined analysis with more clinical indicators in in-depth studies, it is hoped that further revelations can be made regarding the association between arterial blood gas differences and prognosis in sepsis patients, thereby enhancing clinical diagnosis.

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Author Contributions:

Hu Li: Conceived the research idea and designed the study protocol;
Hu Zhenhong, Gao Fangjian, Nie Lili: Collected experimental data;
Hu Li, Chen Yali: Analyzed data and wrote the manuscript;
Qiu Jianwu: Revised the final version of the manuscript.

Correspondence: (*Corresponding author: Qiu Jianwu, Chief Physician, Master's Supervisor, Email: qiujianwu@yeah.net)