Aim: Thymosin alpha 1 (Tα1) is a promising treatment for the improvement of sepsis patients. Until now, its function in reducing acute organ damage of sepsis patients is still unclear. The aim of this study was to determine whether Tα1 can alleviate organ dysfunction in sepsis patients. Methods: This study retrospectively enrolled sepsis patients from a multicenter randomized controlled trial [efficacy of Tα1 for severe sepsis (ETASS)]. The sequential organ failure assessment (SOFA) score on day 0 (initial), day 3, and day 7 was collected. Absolute SOFAday07 was defined as initial SOFA score minus SOFA score on day 7 (initial SOFA–SOFA day7). Delta SOFA score (ΔSOFAday07) was provided by the formula: (initial SOFA–SOFA day7) × 100/initial SOFA, and it was expressed as a percentage. After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Tα1 group and placebo group. The primary outcome was evaluated with a comparison of ΔSOFAday07 decline between patients treated with or without Tα1 therapy. Results: Among 288 enrolled patients, 149 patients received both Tα1 and standard therapy (Tα1 group), and 139 patients received both placebo and standard therapy (placebo group). Compared with the placebo group, the Tα1 group had significantly lower Absolute SOFAday07 [95% confidence interval (CI) 0.8 (0–1.7), P = 0.049]. Among 111 pairs of patients matched by propensity score, the Tα1 group still had lower Absolute SOFAday07 [95% CI 1.0 (0.1–1.9), P = 0.029]. Meanwhile, Tα1 treatment could significantly improve ΔSOFAday07. When the amplitude of ΔSOFAday07 was graded, one third of patients in the Tα1 group had an increase of more than 60%, compared with 22% in the placebo group. Subgroup analysis found that the ΔSOFAday07 improved significantly after Tα1 therapy in sepsis patients with no immunoparalysis at baseline, no complications, and early intervention. Conclusions: For sepsis patients, Tα1 treatment can alleviate organ dysfunction, and ΔSOFAday07 can be used as an indicator of its therapeutic effect (ClinicalTrials.gov identifier: NCT00711620).

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Objectives To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. Methods Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations. Non-linear mixed-effects models were developed using Phoenix NLME software. Results A two-compartment population PK model was used to describe polymyxin B PK. Population estimates of the volumes of central compartment distribution (V) and peripheral compartment distribution (V2), central compartment clearance (CL) and intercompartmental clearance (Q) were 7.857 L, 12.668 L, 1.672 L/h and 7.009 L/h. Continuous renal replacement therapy (CRRT) significantly affected CL, and body weight significantly affected CL and Q. The AUC0-12h of polymyxin B in patients with CRRT was significantly lower than in patients without CRRT. CL and Q increased with increasing body weight. A limited sampling strategy was suggested using a two-sample scheme with plasma at 0.5h and 8h after the end of infusion (C0.5 and C8) for therapeutic drug monitoring in the clinic. Conclusions A dosing regimen should be based on body weight and the application of CRRT. A two-sample strategy for therapeutic drug monitoring could facilitate individualized treatment with polymyxin B in critically ill patients.

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