Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial.

INTRODUCTION: Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens. The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection, and to evaluate the safety of both dosing regimens. METHODS: Patients admitted to the interdisciplinary Intensive Care Unit (ICU) who suffered from severe infections and received meropenem were randomized either in the Infusion group (n = 120) or in the Bolus group (n = 120). Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours. Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours. Clinical and microbiological outcome, safety, meropenem-related length of ICU and hospital stay, meropenem-related length of mechanical ventilation, duration of meropenem treatment, total dose of meropenem, and ICU and in-hospital mortality were assessed. RESULTS: Clinical cure at the end of meropenem therapy was comparable between both groups (83.0% patients in the Infusion vs. 75.0% patients in the Bolus group; P = 0.180). Microbiological success rate was higher in the Infusion group as opposed to the Bolus group (90.6% vs. 78.4%; P = 0.020). Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success (OR = 2.977; 95% CI = 1.050 to 8.443; P = 0.040). Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group (10 (7 to 14) days vs. 12 (7 to 19) days; P = 0.044) as well as shorter duration of meropenem therapy (7 (6 to 8) days vs. 8 (7 to 10) days; P = 0.035) and lower total dose of meropenem (24 (21 to 32) grams vs. 48 (42 to 60) grams; P < 0.0001). No severe adverse events related to meropenem administration in either group were observed. CONCLUSIONS: Continuous infusion of meropenem is safe and, in comparison with higher intermittent dosage, provides equal clinical outcome, generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients.

Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial.

INTRODUCTION: Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery. The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with standard hemodynamic management in multiple-trauma patients. METHODS: This was a randomized controlled trial. Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit (ICU) were randomly assigned to the protocol group with esophageal Doppler monitoring and to the control group. Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler, whereas control patients were managed conventionally. Blood lactate levels and organ dysfunction during ICU stay were evaluated. RESULTS: Eighty patients were randomly assigned to Doppler and 82 patients to control treatment. The Doppler group received more intravenous colloid during the first 12 hours of ICU stay (1,667 +/- 426 ml versus 682 +/- 322 ml; p < 0.0001), and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group (2.92 +/- 0.54 mmol/l versus 3.23 +/- 0.54 mmol/l [p = 0.0003] and 1.99 +/- 0.44 mmol/l versus 2.37 +/- 0.58 mmol/l [p < 0.0001], respectively). No difference in organ dysfunction between the groups was found. Fewer patients in the Doppler group developed infectious complications (15 [18.8%] versus 28 [34.1%]; relative risk = 0.5491; 95% confidence interval = 0.3180 to 0.9482; p = 0.032). ICU stay in the Doppler group was reduced from a median of 8.5 days (interquartile range [IQR] 6 to16) to 7 days (IQR 6 to 11) (p = 0.031), and hospital stay was decreased from a median of 17.5 days (IQR 11 to 29) to 14 days (IQR 8.25 to 21) (p = 0.045). No significant difference in ICU and hospital mortalities between the groups was found. CONCLUSION: Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels, a lower incidence of infectious complications, and a reduced duration of ICU and hospital stays.