Persistent critical illness in acute hypoxic respiratory failure: A retrospective cohort study

Michael Kalinoski, Leah Bolden, Qi Wang, R. Adams Dudley, Nathan Mesfin, Nicholas E. Ingraham

Abstract

Persistent critical illness (PerCI) describes patients with prolonged intensive care unit (ICU) dependence after their acute phase of illness and affects 5–20% of the general ICU population.

Introduction

Persistent critical illness (PerCI) describes patients who survive the initial phase of critical illness but remain ICU-dependent because their recovery is delayed or fails entirely [1]. PerCI is thought to be the pathophysiological consequence of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), causing chronic inflammation and delayed clinical progression [2]. 

Materials and methods

We included adult patients (≥ 18 years of age) admitted to an ICU who required invasive mechanical ventilation within 72 hours of admission between January 2011 and December 2022. Our 12-hospital health system comprises both academic (n = 2) and community (n = 10) hospitals, with ICUs serving a mix of medical, surgical, cardiac, and mixed ICU patient populations.

Results

Among 10,626 eligible patients, 3,107 (29.2%) met criteria for PerCI (Fig 1). The mean age was 60.9 years (SD 15.9), 58.0% were male, and 81.5% were non-Hispanic White. The majority were admitted from the emergency department (59.1%) and under surgical services (54.8%).

Discussion

Nearly one in three mechanically ventilated patients with AHRF developed PerCI in our cohort, which is 5–10 times higher than reported in general ICU populations using the same 10-day threshold [1,10,12]. 

Conclusion

PerCI affected 30% of mechanically ventilated AHRF patients, exceeding rates in general ICU populations. PerCI was associated with a threefold increase in post-onset mortality risk and eight identifiable clinical factors were associated with PerCI across two complementary analytic models. 

Citation: Kalinoski M, Bolden L, Wang Q, Dudley RA, Mesfin N, Ingraham NE (2026) Persistent critical illness in acute hypoxic respiratory failure: A retrospective cohort study. PLoS One 21(9): e0358431. https://doi.org/10.1371/journal.pone.0358431
Editor: Marcelo Arruda Nakazone, Faculdade de Medicina de São José do Rio Preto, BRAZIL

Received: March 28, 2026; Accepted: August 31, 2026; Published: September 16, 2026

Copyright: © 2026 Kalinoski 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: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by the National Institute of Health National Heart, Lung, and Blood Institute grant number K23HL166783. Grant recipient was NI. 
https://www.nih.gov/about-nih/nih-almanac/national-heart-lung-blood-institute-nhlbi. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.