Relationship between hemoglobin levels and vancomycin clearance in patients with sepsis

  • Masayuki Chuma
  • Makoto MakishimaEmail author
  • Toru Imai
  • Naohiro Tochikura
  • Shinichiro Suzuki
  • Tsukasa Kuwana
  • Nami Sawada
  • So Iwabuchi
  • Masao Sekimoto
  • Takahiro Nakayama
  • Takako Sakaue
  • Norikazu Kikuchi
  • Yoshikazu Yoshida
  • Kosaku Kinoshita
Pharmacokinetics and Disposition



It is important to accurately estimate accurate vancomycin (VCM) clearance (CLvcm) for appropriate VCM dosing in the treatment of patients with sepsis. However, the pathophysiology of sepsis can make CLvcm prediction less accurate. Clearance of hydrophilic antibiotics is disturbed by organ dysfunction, and hemoglobin levels are negatively correlated with sequential organ function assessment scores. We investigated whether hemoglobin levels are associated with CLvcm in sepsis patients.


We performed a retrospective cohort study of patients treated with VCM in the Emergency and Critical Care Center of Nihon University Itabashi Hospital between 2005 and 2015. We enrolled 72 patients after exclusion of patients who received renal replacement therapy or surgery, had a change in hemoglobin levels more than 2 g/dL or received an erythrocyte infusion during the interval between initial VCM administration and measurement of initial trough levels, had a serum baseline creatinine level of ≥ 2 mg/dL, or were under 18 years old.


Enrolled patients consisted of 13 non-sepsis patients and 59 sepsis patients. In sepsis patients, although CLvcm was correlated with CrCl in HGB ≥ 9 group as well as in non-sepsis patients, its correlation was not observed in HGB < 9 group. Hemoglobin levels were correlated with CLvcm in sepsis patients but not in non-sepsis patient. Multiple linear regression analysis also indicated that lower CLvcm was associated with lower hemoglobin and CrCl.


Lower hemoglobin levels influence a relationship between CLvcm and CrCl in sepsis patients. We propose that VCM dosing should be adjusted for hemoglobin levels in sepsis patients.


Sepsis Hemoglobin Vancomycin clearance Therapeutic drug monitoring 



The authors thank Dr. Kazutaka Oda of Kumamoto University Hospital and Ms. Mizuho Asada of Medical Hospital, Tokyo Medical and Dental University for the helpful advice on the pharmacokinetic analysis and Dr. Andrew I. Shulman for the editorial assistance. This study was presented in part at the 66th meeting of the West Japan Branch of the Japanese Society of Chemotherapy on November 17, 2018, at Kagoshima, Japan, and Masayuki Chuma received the 13th Incentive Award in the Category of Clinical Research Conferred by the Director of the West Japan Branch of the Japanese Society of Chemotherapy. This work was supported by funds from Nihon University School of Medicine.

Authors’ contribution

All authors contributed to the study design: M.C., S.S., T.K., N.S., S.I., T.S, N.K., and Y.Y. were involved in the data acquisition and analysis; M.C. and M.M. interpreted the data; M.C., M.M., T.I, N.T., T.K., N.S., M.S., T.N., N.K., Y.Y., and K.K. contributed to the drafting of the manuscript; and all authors approved the manuscript for submission.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2019_2661_MOESM1_ESM.pdf (42 kb)
ESM 1 (PDF 41 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Masayuki Chuma
    • 1
    • 2
  • Makoto Makishima
    • 3
    Email author
  • Toru Imai
    • 1
  • Naohiro Tochikura
    • 1
  • Shinichiro Suzuki
    • 1
  • Tsukasa Kuwana
    • 4
  • Nami Sawada
    • 4
  • So Iwabuchi
    • 1
  • Masao Sekimoto
    • 1
  • Takahiro Nakayama
    • 1
  • Takako Sakaue
    • 1
  • Norikazu Kikuchi
    • 5
  • Yoshikazu Yoshida
    • 1
  • Kosaku Kinoshita
    • 4
  1. 1.Department of PharmacyNihon University Itabashi HospitalTokyoJapan
  2. 2.Clinical Trial Center for Developmental TherapeuticsTokushima University HospitalTokushimaJapan
  3. 3.Division of Biochemistry, Department of Biomedical SciencesNihon University School of MedicineTokyoJapan
  4. 4.Division of Emergency and Critical Care Medicine, Department of Acute MedicineNihon University School of MedicineTokyoJapan
  5. 5.Department of PharmacyNihon University HospitalTokyoJapan

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