Association Between Pathophysiology and Volume of Distribution Among Patients With Sepsis or Septic Shock Treated With Imipenem: A Prospective Cohort Study

Abstract

Abstract Background This study was performed to explore the apparent volume of distribution (Vd) of imipenem in patients with sepsis or septic shock. Methods A prospective, observational, single-center study was conducted in patients with sepsis or septic shock. The patients were treated with 1 g of imipenem mixed with 200 mL of normal saline infused intravenously over a 3-hour period at 8-hour intervals. The concentration of imipenem was 5 mg/mL, and the rate of infusion was 5.5 mg/min. Blood samples for measuring imipenem serum concentrations with high-performance liquid chromatography were obtained before and at 0, 1, 2, 3, and 5 hours after drug infusion on study days 1 and 3. Pharmacokinetic parameters were calculated according to a noncompartment model. Results A total of 25 adult patients were enrolled in this study, of whom 15 were diagnosed with sepsis and 10 with septic shock. The initial Vd (Vc) of imipenem was significantly lower in the sepsis than that in the septic shock group (mean [standard deviation], 26.5 [7.1] vs 40.7 [11.0] L; P = .001). The Vc of imipenem was significantly related to serum albumin levels (r = −0.517; P = .008) as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (r = 0.606; P = .001). Multivariate linear regression identified serum albumin levels and APACHE II scores on day 1 as independent factors influencing the Vc of imipenem (P < .05). The difference in Vd between the imipenem steady state and the initial state was significantly higher in nonsurvivors than in survivors (mean [standard deviation], 1.7 [21.5] vs −13.1 [11.4] L; P = .046). Conclusions APACHE II scores and serum albumin levels were found in this study to be independent factors that may affect the Vc of imipenem in patients with sepsis or septic shock. Clinical Trials Registration clinicaltrials.gov, NCT03308214.