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

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.