Comparison of empirical high-dose and low-dose of meropenem in critically ill patients with sepsis and septic shock A randomized controlled study protocol

Background: Sepsis and septic shock syndrome are the main problems in modern medicine. Current treatment guidelines for the sepsis recommend an appropriate and timely antibiotic treatment. Meropenem has activity against a wide variety of Gramnegative and Gram-positive bacteria. At present, there are few studies on the application of high-does meropenem in the patients with sepsis and septic shock. We therefore carry out the randomized controlled research to compare the low-dose and high-dose meropenem in the critically ill sepsis and septic shock patients, and to assess the safety of the two regimens. Method: This is a prospective, single-center, and randomized research authorized through the local research ethics committee of Zhejiang Chinese Medical University (No.32198276). Sixty-four participants with a diagnosis of sepsis and septic shock are analyzed. Patients who meet the following conditions will be included: (1) patients older than 18 years old, (2) patients diagnosed with the sepsis and septic shock, and (3) patients (or their relatives) who have signed a consent. Patients with the following conditions will be excluded (1) patients with infective endocarditis and central nervous system infection; (2) Within 24 hours after the randomization of patients needing surgery; (3) Within 24 hours after the randomization, patients who received extracorporeal membrane oxygenation (ECMO); (4) Patients with known meropenem allergy. They are assigned to 2 groups, namely, the standard-does group and high-dose group, in the standard-does group, they receive low-dose meropenem (intravenous injection of 1 g meropenem for more than 30 minutes, followed by intravenous injection of 1 g meropenem for more than three hours every 8 hours), and in the high-dose group, patients receive high-does meropenem (intravenous injection of 2 g meropenem for more than 30 minutes, and then intravenous injection of 2 grams of meropenem for more than three hours every 8 hours). The main outcomes are the modified Acute Physiology and Chronic Health Evaluation II (APACHE II) and scores of Sequential Organ Failure Assessment (SOFA). And the secondary outcomes are the 14-day mortality and 28-day mortality, the rate of microbiological cure and clinical cure, ventilator-free days, vasopressor-free days, hospital-free days and the ICU-free days, as well as safety in the two regimen groups. All analysis in our work is carried out via utilizing the software of IBM SPSS Statistics for Windows, version 20. Results: Figure 1 reveal the primary outcomes and the secondary outcomes. Conclusion: This protocol can provide a reliable evidence for the safety and effectiveness of the high-dose meropenem in the critically ill sepsis and septic shock patients.