Effects of blood loss and fluid volume replacement on serum and tissue gentamicin concentrations during colorectal surgery

Background: The prophylactic administration of antimicrobial agents to surgical patients has become standard practice to minimize the risk for postsurgical infection. During surgery, factors such as renal clearance, fluid administration, and blood loss contribute to drug concentrations achieved in the blood and tissues. The aminoglycoside gentamicin was chosen to investigate these factors because it is used for standard antimicrobial prophylaxis in colorectal surgery. Objective: The aim of this study was to investigate the effects of surgical blood loss and fluid volume replacement on gentamicin concentrations in serum and in 3 tissue types (subcutaneous fat, epiploic fat, and colonic wall) in patients undergoing colorectal surgery. Methods: This uncontrolled, open-label study was conducted at the Aretaieion Hospital (Athens, Greece) between November 2002 and March 2003. Patients selected for this study were scheduled to undergo elective colorectal surgery of ⪖ 2-hour duration with general and epidural anesthesia and to receive gentamicin as major antimicrobial prophylaxis. Blood and tissue samples were obtained concurrently at specific times throughout each procedure. The effect of intraoperative blood loss on gentamicin concentrations and its pharmacokinetic properties was determined. Results: Sixteen patients completed the study (11 men, 5 women; white race, 16 patients [100%]; mean [SD] age, 61 [3] years [range, 39–80 years]). Mean (SEM) serum gentamicin concentration was found to be insufficient; the maximum plasma drug concentration/minimum inhibitory concentration (MIC) ratio was