Comparison of lactate clearance between high-dose and conventional-dose of meropenem in sepsis and septic shock patients at emergency department; post-hoc analysis of a randomized controlled trial

Abstract

In sepsis and septic shock, patients often face hemodynamic instability, resulting in fluid leakage, heightened capillary permeability, increased distribution volume, and compromised antimicrobial concentrations. Lactate clearance is a well-established marker of illness severity, particularly in the context of sepsis, where it serves as a reliable predictor of mortality. It is notably useful in the determination of resuscitation endpoints. This study aimed to compare lactate clearance within 6 hours between two meropenem dose groups. We conducted a secondary analysis of a randomized controlled trial involving participants aged 18 or older, diagnosed with sepsis and septic shock as per sepsis-3 criteria, and receiving meropenem in an emergency department (ED) setting. The study occurred between December 1, 2017, and August 31, 2018. Of 43 patients, 21 (48.84%) were in the high-dose meropenem group and 22 (51.16%) in the conventional-dose group. Remarkably, a significantly higher proportion of patients in the high-dose group achieved lactate clearance greater than 10% within 6 hours compared to the conventional-dose group (95.2% vs. 63.6%, P=0.01). Lactate clearance greater than 10% at 3 days was 85.7% and 86.4% in the high-dose and conventional-dose groups, respectively (P=0.95). For 30-day mortality, there were 14.3% and 22.7% in the high-dose and conventional-dose groups, respectively (P=0.47). High-dose patients had 18.0 hospital-free days (range 0 to 24) versus 10.0 days (range 0 to 17.0) in the conventional-dose group (P=0.17). In summary, this study highlights a higher rate of sepsis and septic shock patients in the high-dose group achieving lactate clearance within 6 hours. This suggests potential benefits linked to the high-dose meropenem regimen for this specific group of patients.