Effects of Tanreqing Injection on ICU Mortality among ICU Patients Receiving Mechanical Ventilation: Time-Dependent Cox Regression Analysis of A Large Registry

Objective To assess whether the use of Tanreqing (TRQ) Injection could show improvements in time to extubation, intensive care unit (ICU) mortality, ventilator-associated events (VAEs) and infection-related ventilator associated complication (IVAC) among patients receiving mechanical ventilation (MV). Methods A time-dependent cox-regression analysis was conducted using data from a well-established registry of healthcare-associated infections at ICUs in China. Patients receiving continuous MV for 3 days or more were included. A time-varying exposure definition was used for TRQ Injection, which were recorded on daily basis. The outcomes included time to extubation, ICU mortality, VAEs and IVAC. Time-dependent Cox models were used to compare the clinical outcomes between TRQ Injection and non-use, after controlling for the influence of comorbidities/conditions and other medications with both fixed and time-varying covariates. For the analyses of time to extubation and ICU mortality, Fine-Gray competing risk models were also used to measure competing risks and outcomes of interest. Results Overall, 7,685 patients were included for the analyses of MV duration, and 7,273 patients for the analysis of ICU mortality. Compared to non-use, patients with TRQ Injection had a lower risk of ICU mortality (Hazards ratios (HR) 0.761, 95% CI, 0.581–0.997), and was associated with a higher hazard for time to extubation (HR 1.105, 95% CI, 1.005–1.216), suggesting a beneficial effect on shortened time to extubation. No significant differences were observed between TRQ Injection and non-use regarding VAEs (HR 1.057, 95% CI, 0.912–1.225) and IVAC (HR 1.177, 95% CI, 0.929–1.491). The effect estimates were robust when using alternative statistic models, applying alternative inclusion and exclusion criteria, and handling missing data by alternative approaches. Conclusion Our findings suggested that the use of TRQ Injection might lower mortality and improve time to extubation among patients receiving MV, even after controlling for the factor that the use of TRQ changed over time.