---
title: "Early Post-Insertion PaO2 and Upper-Body Venous Thrombosis Risk in Critically Ill Adults"
id: "plos-one-17-association-between-early-post-insertion-arterial-oxygen-tension-and-documented"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-17-association-between-early-post-insertion-arterial-oxygen-tension-and-documented"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359719"
published_at: "2026-10-05T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Early Post-Insertion PaO2 and Upper-Body Venous Thrombosis Risk in Critically Ill Adults
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-17-association-between-early-post-insertion-arterial-oxygen-tension-and-documented
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359719)
- **Published At:** 2026-10-05T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This retrospective cohort study used MIMIC‑IV v2.2 (2008–2019) data to test whether the first arterial **PaO2** measured within 24 hours after placement of an eligible upper‑body invasive venous catheter was associated with documented acute upper‑body deep or central venous **thrombosis** during the same hospitalization. - Eligibility required adults (≥18 years), ICU stay ≥24 hours, at least one qualifying upper‑body catheter episode overlapping the ICU stay, and an arterial PaO2 measured after catheter insertion and while the catheter remained in situ. - The final cohort comprised 11,277 hospital admissions from 10,789 unique patients; 195 admissions (1.73%) met the primary thrombotic outcome based on ICD‑9/10 diagnosis codes. - The exposure was the first PaO2 meeting timing criteria (≤24 hours after insertion); PaO2 was analyzed continuously (OR per 10 mmHg) and categorically (≤80, 81–100, >100 mmHg). A PaO2/FiO2 ratio was examined in a sensitivity analysis. - The primary outcome used a prespecified list of ICD codes for acute deep or central upper‑body venous thrombosis; imaging‑adjudicated outcomes were unavailable and diagnosis timestamps were not reliable, so temporal causality could not be confirmed. - Multivariable logistic regression models sequentially adjusted for demographics, labs (hemoglobin, platelets, lactate), catheter characteristics (type, laterality, number), timing, FiO2, respiratory support, and non‑respiratory SOFA. Multiple imputation handled missing covariates and cluster‑robust SEs accounted for repeated admissions. - In unadjusted analysis higher PaO2 associated with lower odds of the outcome (OR per 10 mmHg 0.970; 95% CI 0.952–0.987), but this association attenuated after multivariable adjustment; the fully adjusted model showed no association (OR per 10 mmHg 1.008; 95% CI 0.989–1.027; P = 0.430). - Most secondary and sensitivity analyses corroborated the primary null finding, though a 60‑minute sensitivity analysis produced adjustment‑dependent estimates. - Authors conclude a single early post‑insertion **PaO2** measurement was not independently associated with documented upper‑body venous thrombosis in this cohort, and do not support PaO2‑based thrombosis risk stratification or oxygen‑therapy modification for thrombosis prevention. - Limitations include reliance on diagnosis codes without imaging confirmation, lack of precise thrombosis onset timing relative to PaO2 measurement, single early oxygen measurement (no repeated measures), and potential residual confounding by factors linked to oxygenation, catheter selection, and illness severity. - Authors recommend future studies using repeated oxygenation measures and accurately timed, imaging‑confirmed thrombotic outcomes to better evaluate any causal relationship.
## Clinical Analysis & Structured Key Points
Association between early post-insertion arterial oxygen tension and documented acute upper-body deep or central venous thrombosis in critically ill adults: A retrospective MIMIC-IV cohort study | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Abnormal oxygenation may influence thrombosis, but evidence in catheterized critically ill patients remains limited. We examined whether the first arterial partial pressure of oxygen (PaO 2 ) measured within 24 hours after qualifying invasive venous catheter insertion was associated with documented acute upper-body deep or central venous thrombosis during hospitalization. This retrospective observational cohort study used the Medical Information Mart for Intensive Care IV database, version 2.2 (MIMIC-IV v2.2) (2008–2019). Adult intensive care unit admissions were included when a qualifying invasive venous catheter was present and an arterial PaO 2 measurement was obtained after insertion, within 24 hours, and while the catheter remained in situ. PaO 2 was analyzed continuously and categorically (≤80, 81–100, and >100 mmHg). Logistic regression models sequentially adjusted for patient characteristics, laboratory measurements, catheter characteristics, measurement timing, inspired oxygen concentration, respiratory support, and non-respiratory organ dysfunction. Multiple imputation addressed missing covariate data, and patient-clustered robust standard errors accounted for repeated admissions. The cohort included 11,277 hospital admissions from 10,789 patients; 195 admissions (1.73%) had the primary outcome. In the unadjusted model, higher PaO 2 was associated with lower odds of the outcome (odds ratio [OR] per 10-mmHg increase, 0.970; 95% confidence interval [CI], 0.952–0.987), but this association attenuated after adjustment. In the fully adjusted model, PaO 2 was not associated with the outcome (OR, 1.008; 95% CI, 0.989–1.027; P = 0.430). Most secondary analyses supported the primary result, although the 60-minute sensitivity analysis yielded adjustment-dependent estimates. In the complete cohort, a single early post-insertion PaO 2 measurement was not independently associated with documented acute upper-body deep or central venous thrombosis. These findings do not support PaO 2 -based thrombosis risk stratification or modification of oxygen therapy for thrombosis prevention. Future studies should incorporate repeated oxygenation measurements and accurately timed, imaging-confirmed thrombotic outcomes. Citation: Cui Q, Fang A, Zhang H, Meng Q, Zhou S, Peng Y, et al. (2026) Association between early post-insertion arterial oxygen tension and documented acute upper-body deep or central venous thrombosis in critically ill adults: A retrospective MIMIC-IV cohort study. PLoS One 21(10): e0359719. https://doi.org/10.1371/journal.pone.0359719 Editor: Giovanni Giordano, Sapienza University of Rome: Universita degli Studi di Roma La Sapienza, ITALY Received: May 22, 2025; Accepted: September 17, 2026; Published: October 5, 2026 Copyright: © 2026 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The data used in this study were obtained from the Medical Information Mart for Intensive Care IV database, version 2.2 (MIMIC-IV v2.2), hosted by PhysioNet ( https://doi.org/10.13026/6mm1-ek67) . MIMIC-IV is a third-party, credentialed-access database. Interested researchers can obtain access to the same source data through the standard PhysioNet credentialing process, including becoming credentialed PhysioNet users, completing the required CITI “Data or Specimens Only Research” training, and signing the applicable PhysioNet Credentialed Health Data Use Agreement. The authors are not permitted to publicly redistribute the patient-level MIMIC-IV data or the derived patient-level analytic dataset. Researchers who independently obtain authorized access to MIMIC-IV version 2.2 can reconstruct the analytic dataset and replicate the reported analyses using the eligibility criteria, exposure and outcome definitions, covariate definitions, data-processing procedures, and statistical methods described in the Methods and Supporting Information . The authors had no special access privileges to the data, and no additional proprietary or author-only patient-level data were used in this study. Funding: This work was supported by a Scientific Research Project of the Shenzhen Society of Health Economics (grant number: not applicable), awarded to Weixiang Luo; the Shenzhen Basic Research Program (Natural Science Foundation) (grant number: JCYJ20240813103813018), awarded to Qing Cui, Anshuai Fang, and Yueming Peng; the Shenzhen Clinical Research Center for Respiratory Disease (grant number: LCYSSQ20220823091203007), for which no individual author was named as the award recipient; and the Shenzhen Key Laboratory of Respiratory Diseases (grant number: SYSPG20241211173920041), for which no individual author was named as the award recipient. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors declare that they have no competing interests in this section. Introduction Central venous access devices are widely used in critically ill patients for the administration of vasoactive medications, fluids, parenteral nutrition, renal replacement therapy, and other supportive treatments. However, upper-extremity deep or central venous thrombosis is an important complication of vascular access and may lead to catheter dysfunction, treatment interruption, recurrent venous thromboembolism, pulmonary embolism, and post-thrombotic morbidity [ 1 – 4 ]. Reported thrombosis rates vary substantially according to the population studied, catheter type, outcome definition, follow-up duration, and whether systematic imaging surveillance is performed. Peripherally inserted central catheters (PICCs) have been associated with a higher occurrence of venous thromboembolism than conventional central venous catheters in several observational syntheses, particularly in critically ill populations, although findings have not been uniform across study designs [ 2 , 3 ]. Thrombotic susceptibility in the ICU is also influenced by patient and treatment characteristics, including malignancy, sepsis, invasive mechanical ventilation, vasoactive medication use, immobility, and the presence of central venous catheters [ 5 ]. In addition, catheter diameter, the catheter-to-vein relationship, tip position, insertion technique, and other device-related factors may modify thrombotic risk [ 6 ]. Abnormal oxygenation may also be relevant to thrombosis, but the direction and magnitude of the relationship remain uncertain. Recurrent hypoxia–reoxygenation, as observed in obstructive sleep apnea, has been linked to oxidative stress, systemic inflammation, endothelial dysfunction, altered blood viscosity, and increased expression of procoagulant mediators, providing a potential connection between oxygen disturbance and the components of Virchow’s triad [ 7 ]. However, a systematic review of environmental hypoxia in healthy adults found only small and heterogeneous changes in coagulation, platelet activity, and fibrinolysis and did not establish hypoxia as an independent cause of hypercoagulability [ 8 ]. Disease-specific clinical studies have reported lower arterial partial pressure of oxygen (PaO 2 ) among patients with venous thromboembolism or pulmonary embolism in chronic obstructive pulmonary disease [ 9 , 10 ]. These findings may nevertheless reflect respiratory failure, inflammation, immobility, invasive ventilation, or the effects of pulmonary embolism on gas exchange rather than an isolated effect of low PaO 2 . At the opposite end of the oxygen spectrum, exposure to higher inspired oxygen concentrations may increase oxidative stress and reduce antioxidant activity [ 11 ]. Trials of higher versus lower oxygenation targets in mechanically ventilated ICU patients have also used heterogeneous and overlapping target ranges, leaving uncertainty regarding the clinical effects of different oxygen exposures [ 12 ]. Consistent with this uncertainty, large randomized trials comparing lower or conservative oxygenation strategies with higher or usual oxygenation strategies have not demonstrated a consistent clinical advantage of one strategy across critically ill populations [ 13 – 15 ]. Thus, physiological or clinical observations arising from intermittent hypoxia, environmental hypoxia, chronic lung disease, or administered oxygen strategies cannot be directly extrapolated to a single arterial PaO 2 measurement obtained during routine critical care. In critically ill patients, PaO 2 is influenced by inspired oxygen concentration, ventilatory support, pulmonary gas exchange, perfusion, disease severity, and the timing of arterial blood-gas sampling. Many of these factors are also related to the indication for vascular access, catheter selection, and thrombotic risk. Consequently, an apparent association between PaO 2 and thrombosis may be confounded by the clinical and device-related circumstances surrounding oxygen measurement and catheter placement. Direct evidence examining whether an early arterial PaO 2 measurement is associated with upper-body venous thrombosis among catheterized ICU patients, after accounting for these factors, remains limited. We therefore conducted a retrospective observational cohort study using the Medical Information Mart for Intensive Care IV database to examine the association between the first arterial PaO 2 measured within 24 hours after qualifying catheter insertion and documented acute upper-body deep or central venous thrombosis during hospitalization. PaO 2 was evaluated as both a continuous and categorical exposure, potential nonlinear associations were assessed, and the robustness of the findings was examined after adjustment for catheter characteristics, measurement timing, respiratory support, inspired oxygen concentration, and illness severity. Materials and methods Study design and objective This retrospective observational cohort study used deidentified electronic health record data from the Medical Information Mart for Intensive Care IV database and was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. The study aimed to evaluate whether arterial partial pressure of oxygen (PaO 2 ) measured during the first 24 hours after qualifying invasive venous catheter insertion was associated with documented acute upper-body deep or central venous thrombosis during the corresponding hospitalization in critically ill adults. We further examined whether this association remained after adjustment for patient characteristics, catheter-related factors, the timing of PaO 2 measurement, inspired oxygen concentration, respiratory support, and illness severity. The hospital admission was used as the primary unit of analysis. When more than one ICU stay within the same hospital admission met the eligibility criteria, only the earliest eligible ICU stay was retained. A patient could contribute more than one eligible hospital admission. This study evaluated admission-level associations and was not designed as a time-to-event analysis. Because thrombosis diagnoses lacked reliable onset timestamps, temporal precedence of the selected PaO 2 measurement could not be confirmed for every admission. Data source Data were obtained from the Medical Information Mart for Intensive Care IV database, version 2.2 (MIMIC-IV v2.2), a deidentified electronic health record database containing clinical information from patients treated at Beth Israel Deaconess Medical Center in Boston, Massachusetts, between 2008 and 2019 [ 16 ]. The database includes hospital- and ICU-level information on demographics, hospital and ICU encounters, laboratory measurements, bedside observations, procedures, respiratory support, medications, and diagnosis codes. Access to MIMIC-IV is restricted to credentialed researchers who complete the required human-subjects research training and sign the PhysioNet data use agreement. The authors accessed the database through the standard credentialing process and had no special access privileges. Ethics statement The collection and sharing of the MIMIC-IV research resource were reviewed by the Institutional Review Board of Beth Israel Deaconess Medical Center, which approved the data-sharing initiative and granted a waiver of individual informed consent [ 16 ]. The present study was a secondary analysis of deidentified data accessed under the PhysioNet Credentialed Health Data Use Agreement. The investigators had no direct contact with participants and no access to identifiable information. No additional institutional ethics approval was obtained for this analysis because the study used only an existing deidentified database and involved no participant recruitment, intervention, or collection of identifiable information. No additional individual informed consent was obtained. Study population We screened invasive venous catheter records linked to ICU stays in MIMIC-IV. ICU stays were eligible if patients were aged 18 years or older at hospital admission, remained in the ICU for at least 24 hours, had at least one qualifying central venous catheter episode overlapping the ICU stay, and had at least one eligible arterial PaO 2 measurement obtained after catheter insertion and within 24 hours of catheter placement while at least one qualifying catheter remained in situ. Catheters documented in lower-body locations were excluded because the study outcomes were restricted to upper-body deep or central venous thrombosis. Catheters documented in upper-body locations were retained. Otherwise eligible catheter records were not excluded solely because their anatomical location was incompletely documented. The initial extraction included 30,003 invasive venous catheter records corresponding to 18,056 ICU stays among 15,916 patients. After application of the eligibility criteria, 11,474 ICU stays remained. A further 197 ICU stays were excluded because an earlier eligible ICU stay occurred during the same hospital admission. The final cohort comprised 11,277 hospital admissions from 10,789 unique patients. The cohort-selection process is shown in Fig 1 . Download: PNG larger image TIFF original image Fig 1. Flowchart of cohort selection. ICU, intensive care unit; PaO 2 , arterial partial pressure of oxygen. The hospital admission was used as the unit of analysis. When more than one eligible ICU stay occurred during the same hospital admission, only the earliest eligible ICU stay was retained. A patient could contribute more than one eligible hospital admission. https://doi.org/10.1371/journal.pone.0359719.g001 Exposure assessment The primary exposure was arterial PaO 2 measured after placement of a qualifying central venous catheter. For each eligible ICU stay, catheter episodes were reconstructed using the documented insertion and removal times. The beginning of the qualifying catheter episode was defined as the index time. An arterial PaO 2 measurement was eligible if it was obtained: At or after the index catheter insertion time; Within 24 hours after catheter insertion; During the corresponding ICU stay; and While at least one qualifying catheter remained active. The first arterial PaO 2 measurement satisfying all four criteria was selected as the exposure value. The interval between catheter insertion and the selected PaO 2 measurement was calculated in minutes. For an additional post hoc descriptive analysis, the interval from ICU admission to the selected PaO 2 measurement was also calculated in minutes. PaO 2 was analyzed in two prespecified forms: As a continuous variable, with odds ratios reported per 10-mmHg increase; and As a categorical variable divided into ≤80 mmHg, 81–100 mmHg, and >100 mmHg, with ≤80 mmHg used as the reference group. In a secondary sensitivity analysis, the ratio of PaO 2 to the fraction of inspired oxygen was analyzed as an alternative oxygenation exposure. Outcome definitions The primary outcome was documented acute upper-body deep or central venous thrombosis during the hospital admission. The outcome was identified using a prespecified list of International Classification of Diseases, Ninth and Tenth Revision diagnosis codes recorded in the MIMIC-IV diagnoses_icd table. The primary outcome definition included acute thrombosis involving deep veins of the upper extremity, axillary veins, subclavian veins, or internal jugular veins. Superficial venous thrombosis and thrombosis identified only by anatomically unspecified upper-extremity codes were not included in the primary outcome. Two additional outcome definitions were evaluated in sensitivity analyses: A broader secondary outcome that included other documented upper-body venous thrombosis diagnoses, including superficial or less anatomically specific venous thrombosis; and A strict outcome restricted to primary-outcome diagnoses with laterality potentially compatible with the qualifying catheter: a right-sided diagnosis with a right-sided catheter, a left-sided diagnosis with a left-sided catheter, or a bilateral diagnosis. Diagnoses with unspecified laterality did not satisfy the strict definition. The complete ICD-9-CM and ICD-10-CM code list and the rules used to construct the primary, broader, and strict outcome definitions are provided in Supplementary Table S10 in S1 File . No chart-adjudicated or imaging-adjudicated reference standard was available; therefore, the sensitivity and specificity of the coding algorithm could not be estimated. Because the diagnosis codes were assigned at the hospitalization level and lacked reliable timestamps, the exact onset time of thrombosis could not be determined. Accordingly, it could not be confirmed that the selected PaO 2 measurement preceded thrombus formation in every admission. The available data also could not establish that the coded thrombosis was caused by the qualifying catheter. Therefore, the outcome was described as a documented hospitalization-level thrombotic outcome rather than confirmed catheter-related thrombosis. Covariates We collected demographic characteristics, comorbidity burden, laboratory measurements, catheter-related characteristics, measurement timing, respiratory variables, and indicators of illness severity as potential confounding factors. These variables included age at hospital admission, sex, race or ethnicity, Charlson Comorbidity Index, hemoglobin, platelet count, baseline lactate, catheter type, catheter laterality, the number of active catheters, the interval between catheter insertion and PaO 2 measurement, FiO 2 at the time of PaO 2 measurement, respiratory-support status, and the non-respiratory component of the first-day SOFA score. Race or ethnicity was used in descriptive analyses and an additional sensitivity analysis but was not included in the primary fully adjusted model. Hemoglobin and platelet count were obtained from the most recent complete blood count recorded within the 24 hours preceding the selected PaO 2 measurement. Lactate was preferentially obtained from the same arterial blood gas record as PaO 2 ; when unavailable in the same record, the most recent lactate measurement within the preceding 24 hours was used. Hemoglobin, platelet count, and lactate were analyzed as continuous variables. Statistical analysis Continuous variables were summarized as medians with interqua
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