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Relationship between hemoglobin levels and vancomycin clearance in patients with sepsis

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

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.

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Author notes

  1. Masayuki Chuma

    Present address: Clinical Trial Center for Developmental Therapeutics, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima, 770-8503, Japan

Authors and Affiliations

  1. Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, Japan

    Masayuki Chuma, Toru Imai, Naohiro Tochikura, Shinichiro Suzuki, So Iwabuchi, Masao Sekimoto, Takahiro Nakayama, Takako Sakaue & Yoshikazu Yoshida

  2. Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan

    Makoto Makishima

  3. Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Tokyo, Japan

    Tsukasa Kuwana, Nami Sawada & Kosaku Kinoshita

  4. Department of Pharmacy, Nihon University Hospital, Tokyo, Japan

    Norikazu Kikuchi

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  1. Masayuki Chuma
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Contributions

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.

Corresponding author

Correspondence to Makoto Makishima.

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Chuma, M., Makishima, M., Imai, T. et al. Relationship between hemoglobin levels and vancomycin clearance in patients with sepsis. Eur J Clin Pharmacol 75, 929–937 (2019). https://doi.org/10.1007/s00228-019-02661-w

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