Interleukin-6 as a predictor of early weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome

  1. Kazuya Sakai
  2. Mototsugu Nishii
  3. Ryo Saji
  4. Reo Matsumura
  5. Fumihiro Ogawa
  6. Ichiro Takeuchi

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Abstract

Background

Therapeutic effects of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) have been reported. However, predictive indicators of early weaning from MV post-treatment have not yet been defined, making treating established ARDS challenging. Interleukin (IL)-6 has been associated with the pathogenesis of ARDS.

Objective

Our aim was to clarify clinical utility of IL-6 level in ventilated patients with established ARDS.

Methods

Clinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated ARDS. Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation.

Results

Fifty-two patients were treated with dexamethasone (steroid group), while the remaining 67 patients were not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5±0.6 vs. 16.1±1.0 days, P = 0.0005, respectively) along with significantly decreased levels of IL-6 and CRP. Even when restricted to the steroid group, among variables post-MV, IL-6 level on day 7 was most closely correlated with duration of MV use (Spearman’s rank correlation coefficient [ρ] = 0.73, P < 0.0001), followed by CRP level on day 7 and the percentage change in IL-6 or CRP levels between day 1 and day 7. Moreover, among these variables, IL-6 levels on day 7 showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Consistently, the rate of MV weaning increased significantly earlier in patients with low IL-6 (≤ 20.6 pg/mL) than in those with high IL-6 (> 20.6 pg/mL) (log-rank test P < 0.0001).

Conclusions

In invasively ventilated patients with established ARDS due to SARS-CoV-2, plasma IL-6 levels served as a predictor of early withdrawal from MV after dexamethasone administration.

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  1. ScreenIT

    SciScore for 10.1101/2022.04.04.22273418: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: S1): (1) patients not requiring invasive MV; (2) those with missing data, including clinical, laboratory, and outcome data; (3) those without consent for participation.
    IRB: Management of ventilated patients with ARDS: Management of ARDS and weaning from MV were performed according to the guideline for the management of ARDS in Japan.24 Ethical considerations: This study was approved by the Institutional Ethics Board of the YCUH (No. B210100010).
    Field Sample Permit: Medical record numbers were used for data collection and no personal identifiers were collected or used in the research report.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several limitations of this study. The data set of this study was a backward-looking study, so there were some missing values. Second, this study was conducted at a single institution, resulting in a biased patient population. Third, our sample size is too small to evaluate optimal cutoffs of variables and to determine clinical utility of IL-6 in the treatment of ARDS and its superiority over other markers. Fourth, the cause of ARDS was limited to SARS-CoV-2 infection. Fifth, steroid therapy was not standardized in our study population. Thus, the applicability of IL-6 in clinical practice needs to be prospectively studied in large cohorts of strictly steroid-treated patients with ARDS derived from various etiologies.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.04.04.22273418v1 on medRxiv