Background: Arterial blood gas analysis (ABGA) is the reference standard for the diagnosis of respiratory failure (RF) and metabolic disturbance (MD), but peripheral venous blood gas analysis (PVBGA) is increasingly being used for the estimation of carbon dioxide, pH, and other variables in the context of acutely unwell adults presenting to hospitals and emergency departments.

Objectives: The primary objective of this review is to evaluate the performance of PVBGA by comparing it with the reference standard ABGA, which is assumed to be error-free for the diagnosis of (1) respiratory failure, (2) hypercarbia, and (3) metabolic disturbance (the three target conditions) in adults. The secondary objective is to evaluate the performance of the index test to diagnose nine specific subtypes of respiratory failure and metabolic disturbance. The definitions for these additional conditions are determined by changes to one or more of the following: pH (acidity), pO2 (partial pressure of oxygen), pCO2 (partial pressure of carbon dioxide), HCO3 (bicarbonate), as stated in the Methods section of this review (target conditions). We aimed to explore the following covariates: participant demographics (e.g. age, weight, and sex); participant comorbidities (e.g. chronic lung disease, chest wall deformity, and central nervous system disorder such as spinal cord injury); and the indication for blood gas sampling (e.g. shortness of breath, critical illness, resuscitation, trauma, or whilst under general anaesthesia).

Search methods: On 10 July 2024, we searched the electronic databases MEDLINE, EMBASE, CINAHL, and LILACS. We also manually searched 19 respiratory and critical care journals, and we searched ClinicalTrials.gov for ongoing trials.

Selection criteria: We considered consecutive series studies and case-control studies that directly compared the index test PVBGA to the reference standard ABGA for adults over the age of 16 years. The included studies contained data for any one of the target conditions of respiratory failure and metabolic disturbance, as determined by individual changes to pO2 (partial pressure of oxygen), pCO2 (partial pressure of carbon dioxide), pH (acidity), and HCO3 (bicarbonate) concentration. Studies that only provided mean values for summed data were ineligible for inclusion. However, we invited authors of such studies to provide individual patient data for inclusion in this systematic review. There are nine studies awaiting classification.

Data collection and analysis: Two authors independently evaluated the quality of the relevant studies and extracted data from them. We conducted a quality assessment using the QUADAS-2 tool. Our statistical analysis used 2 x 2 tables for the positive and negative results of each test. We estimated a bivariate meta-analysis of sensitivity and specificity.

Main results: We included six studies (919 participants) in our quantitative analysis. All studies were at high risk of bias due to one or more of the following factors: patient selection, since it was unclear if consecutive patients were included or where they were located; index test, with poor reporting of cut-offs; flow and timing domain because the fraction of inspired oxygen was frequently not stated and any difference between the collection of the VBGA and the ABGA could introduce bias. Respiratory failure For the diagnosis of respiratory failure of any type, when using PVBGA, the estimated summary sensitivity (Sn) was 97.6% (95% credible interval (CI) 94.1 to 99.4) and the estimated summary specificity (Sp) was 36.9% (95% CI 17.1 to 60.1) (6 studies, 805 participants of whom 291 (36%) were diagnosed with respiratory failure by ABGA; sensitivity: low-certainty evidence; specificity: very low certainty evidence). Isolated hypercarbia For the diagnosis of isolated hypercarbia (regardless of oxygen level), when using PVBGA, the estimated summary Sn was 97.1% (95% CI 93.3 to 99.2); the estimated summary Sp value was 53.9% (95% CI 39.8 to 66.7) (6 studies with 805 participants, 269 (33%) with ABGA confirmation; low-certainty evidence). Other findings Results for metabolic disturbance and our secondary target conditions are presented in the full review.

Authors’ conclusions: Very limited data suggest PVBGA performs poorly as a diagnostic test for respiratory failure compared to the reference standard of ABGA. The index test PVBGA was highly sensitive for the diagnosis of respiratory failure and isolated hypercarbia, but its specificity was poor for these two primary target conditions. The high sensitivity means PVBGA may have a useful role as a “rule out test” for respiratory failure and isolated hypercarbia; however, the high false-positive rates make the clinical interpretation of a positive test difficult. Moreover, we are uncertain regarding these estimates because we have only low to very low certainty about the evidence. Further studies that use (ABGA) established thresholds for the diagnosis of each target condition are needed.

Byrne AL, Pace NL, Thomas PS, Symons RL, Chatterji R, Bennett M. Peripheral venous blood gas analysis for the diagnosis of respiratory failure, hypercarbia and metabolic disturbance in adults. Cochrane Database Syst Rev. 2025 Jun 25;6:CD010841. doi: 10.1002/14651858.CD010841.pub2. PMID: 40557830.