Article

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Authors: Joo-Hyun Lee1, Yeong-Jin Choo2, Yong-Hun Lee3, Jin-Ho Rhim4, Soo-Han Lee5, Byung-Moon Choi3, Sung-Tae Oh6, Kyu-Taek Choi3, Gyu-Jeong Noh3,7
1 Department of Anesthesiology and Pain Medicine, Danwon Hospital, Ansan, Korea
2 University of Ulsan College of Medicine, Seoul, Korea
3 Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
4 Department of Anesthesiology and Pain Medicine, Chung Hospital, Seongnam, Korea
5 New Drug Development Center, Osong Medical Innovation Foundation, Chungcheongbuk-do, Korea
6 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
7 Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to: Soo-Han Lee: vetingod@gmail.com, Kyu-Taek Choi: byungmoonchoi7@gmail.com,
DOI: 10.1038/s41401-018-0179-3
Received: 30 June 2018
Accepted: 26 September 2018
Advance online: 16 October 2018

Abstract

In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer’s lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer’s lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer’s lactate solution. A two-volume model best described the pharmacokinetics of Ringer’s lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance (kr) and central volume of distribution at baseline (Vc0), respectively. The parameter estimates were as follows: kr (mL/min) = 124 + (MAP/70)14.2, Vc0 (mL) = 0.95 + 3440 × (WT/63), Vt0 (mL) = 2730, and kt (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.
Keywords: anesthesiologist; crystalloid solution; fluid shifts; pharmacokinetics; mean arterial pressure; body weight

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