European Journal of Anaesthesiology

Original Article

Effects of ropivacaine on human neutrophil function: comparison with bupivacaine and lidocaine

K. Mikawa a1c1, H. Akamatsu a2, K. Nishina a1, M. Shiga a1, H. Obara a1 and Y. Niwa a3
a1 Kobe University Graduate School of Medicine, Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe, Japan
a2 Fujita Health University School of Medicine, Department of Dermatology, Aichi, Japan
a3 Niwa Institute for Immunology, Kochi, Japan

Article author query
mikawa k   [PubMed][Google Scholar] 
akamatsu h   [PubMed][Google Scholar] 
nishina k   [PubMed][Google Scholar] 
shiga m   [PubMed][Google Scholar] 
obara h   [PubMed][Google Scholar] 
niwa y   [PubMed][Google Scholar] 


Background and objective: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers.

Methods: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma.

Results: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 μg mL−1) and lidocaine (20, 200 μg mL−1) impaired neutrophil production of O2, H2O2 and OH (P < 0.05) at similar rates (by 7–10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+]i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did.

Conclusions: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

(Accepted February 2002)

Key Words: ANAESTHETICS, LOCAL, bupivacaine, lidocaine, ropivacaine; CELL MOVEMENT, chemotaxis; ENDOCYTOSIS, phagocytosis; FREE RADICALS, superoxide; IMMUNE SYSTEM, leukocytes; IMMUNOLOGICAL AND BIOLOGICAL FACTORS, calcium; REACTIVE OXYGEN SPECIES, peroxides, hydrogen peroxide, hydroxyl radical.

c1 Correspondence to: Katsuya Mikawa, Department of Anesthesia and Perioperative Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7, Chuo-ku, Kobe 650-0017, Japan. E-mail:; Tel: +81 78 382 6172; Fax: +81 78 382 6189