Heparin improves the mortality of patients with non-pulmonary sepsis-associated ARDS: A MIMIC-IV database analysis based on propensity score matching

Abstract

Background: Non-pulmonary sepsis often induces Acute Respiratory Distress Syndrome (ARDS). Dysregulated inflammation and coagulation disorders play important roles in the development of non-pulmonary sepsis-associated ARDS (NPS-ARDS). Heparin, with its potential anticoagulant and anti-inflammatory properties, may be used in the treatment of NPS-ARDS.

Methods: This is a retrospective observational study that uses Structured Query Language (SQL) to extract clinical data of NPS-ARDS patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Based on the dosage of heparin, patients were divided into three groups: low-dose heparin treatment group (0-5000u/d), medium-dose heparin treatment group (5000u-10000u/d), and high-dose heparin treatment group (greater than 10000u/d). Propensity score matching (1:1) was used to match similar patients from the NPS-ARDS patients who did not use heparin to each heparin treatment group. The study compares the effects of heparin at different dosages on short-term mortality (7-day, 28-day, and 60-day mortality) and one-year cumulative survival rate in NPS-ARDS patients.

Results: PSM reduced the impact of confounding factors on the results to some extent. Low and medium doses of heparin did not improve patient mortality. However, high-dose heparin improved the short-term mortality of NPS-ARDS patients (7-day mortality: 4.1% vs. 14.3%, P < 0.001; 28-day mortality: 9.4% vs. 22.6%, P < 0.001; 60-day mortality: 13.2% vs. 24.8%, P = 0.001) and one-year cumulative survival rate (Log Rank = 8.349, P = 0.004), but it also prolonged ICU stay (6.7 ± 6.2 days vs. 5.7 ± 4.8 days, P = 0.041) and invasive mechanical ventilation (11.7 ± 6.9 hours/day vs. 5.7 ± 4.8 hours/day, P < 0.001).

Conclusion: In patients with NPS-ARDS, high-dose heparin was associated with significantly improved short- and long-term survival, albeit at the cost of prolonged ICU stay and mechanical ventilation.

Fig 1. Experimental Flowchart.

Divide patients into different heparin groups based on the amount of heparin used. Use PSM (1:1) to match similar patients from the NPS-ARDS patients who did not receive heparin with each heparin group. Compare the effects of different doses of heparin on the prognosis of NPS-ARDS patients.

Fig 2. Flowchart of Patient Selection.

1,515 patients were included in this study, with 818 patients receiving heparin treatment and 697 NPS-ARDS patients who did not receive heparin.

Fig 3. Survival analysis among different dosage heparin groups and the control group.

A: Univariate Survival Curve: The one-year cumulative survival rate in the heparin treatment group was significantly higher than that in the control group (Log Rank = 6.024, P = 0.014); B: Univariate Survival Curve: There was no difference in the one-year cumulative survival rate between the low-dose heparin group and the control group (Log Rank = 0.075, P = 0.784); C: Univariate Survival Curve: The difference in the one-year cumulative survival rate between the medium-dose heparin group and the control group (Log Rank = 2.169, P = 0.141); D: Univariate Survival Curve: The high-dose heparin group demonstrated superior one-year cumulative survival compared to controls (Log Rank = 8.349, P = 0.004).