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

Published online by Cambridge University Press:  02 June 2005

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

Summary

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.

Keywords

ANAESTHETICS, LOCAL, bupivacaine, lidocaine, ropivacaineCELL MOVEMENT, chemotaxisENDOCYTOSIS, phagocytosisFREE RADICALS, superoxideIMMUNE SYSTEM, leukocytesIMMUNOLOGICAL AND BIOLOGICAL FACTORS, calciumREACTIVE OXYGEN SPECIES, peroxides, hydrogen peroxide, hydroxyl radical
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 2 , February 2003 , pp. 104 - 110
Copyright
2003 European Society of Anaesthesiology

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References

Minakami S, Kakinuma K, Takeshige K. Leukocytes and Biological Defence. Tokyo, Japan: Kodansha, 1990.
Swank DW, Moore SB. Roles of the neutrophil and other mediators in adult respiratory distress syndrome. Mayo Clin Proc 1989; 64: 1118–1132.Google Scholar
Irita K, Fujita I, Takeshige K, Minakami S, Yoshitake J. Cinchocaine and amethocaine inhibit activation and activity of superoxide production in human neutrophils. Br J Anaesth 1986; 58: 639–645.Google Scholar
Sasagawa S. Inhibitory effects of local anesthetics on migration, extracellular release of lysosomal enzyme, and superoxide anion production in human polymorphonuclear leukocytes. Immunopharmacol Immunotoxicol 1991; 13: 607–622.Google Scholar
Hattori M, Dohi S, Nozaki M, Niwa M, Shimonaka H. The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients. Anesth Analg 1997; 84: 405–412.Google Scholar
Cederholm I, Briheim G, Rutberg H, Dahlgren C. Effects of five amino-amide local anaesthetic agents on human polymorphonuclear leukocytes measured by chemiluminescence. Acta Anaesthesiol Scand 1994; 38: 704–710.Google Scholar
Hyvonen PM, Kowolik MJ. Dose-dependent suppression of the neutrophil respiratory burst by lidocaine. Acta Anaesthesiol Scand 1998; 42: 565–569.Google Scholar
Gasparoni A, De-Amici D, Ciardelli L, et al. Effect of lidocaine on neutrophil chemotaxis in newborn infants. J Clin Immunol 1998; 18: 210–213.Google Scholar
Hammer R, Dahlgren C, Stendahl O. Inhibition of human leukocyte metabolism and random mobility by local anaesthesia. Acta Anaesthesiol Scand 1985; 29: 520–523.Google Scholar
Mikawa K, Akamatsu H, Nishina K, et al. Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils. Acta Anaesthesiol Scand 1997; 41: 524–528.Google Scholar
Vitola JV, Forman MB, Holsinger JP, Atkinson JB, Murray JJ. Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine. Am Heart J 1997; 133: 315–322.Google Scholar
Lesnefsky EJ, VanBenthuysen KM, McMurtry IF, Shikes RH, Johnston RB Jr, Horwitz LD. Lidocaine reduces canine infarct size and decreases release of a lipid peroxidation product. J Cardiovasc Pharmacol 1989; 13: 895–901.Google Scholar
Peck SL, Johnston RB, Jr, Horwitz LD. Reduced neutrophil superoxide anion release after prolonged infusions of lidocaine. J Pharmacol Exp Ther 1985; 235: 418–422.Google Scholar
Takao Y, Mikawa K, Nishina K, Maekawa N, Obara H. Lidocaine attenuates hyperoxic lung injury in rabbits. Acta Anaesthesiol Scand 1996; 40: 318–325.Google Scholar
Mikawa K, Maekawa N, Nishina K, Takao Y, Yaku H, Obara H. Effect of lidocaine pretreatment on endotoxin-induced lung injury in rabbits. Anesthesiology 1994; 81: 689–699.Google Scholar
Finucane BT, Sandler AN, McKenna J, et al. A double-blind comparison of ropivacaine 0.5, 0.75, 1.0% and bupivacaine 0.5%, injected epidurally, in patients undergoing abdominal hysterectomy. Can J Anaesth 1996; 43: 442–449.Google Scholar
Welters ID, Menzebach A, Langefeld TW, Menzebach M, Hempelmann G. Inhibitory effects of S-(−) and R-(+) bupivacaine on neutrophil function. Acta Anaesthesiol Scand 2001; 45: 570–575.Google Scholar
Mamiya K, Tomoda MK, Edashige K, Ueda W, Manabe M. Local anesthetics enhance nitric oxide production by human peripheral neutrophils. Physiol Chem Phys Med NMR 1995; 27: 111–119.Google Scholar
Haines KA, Reibman J, Callegari PE, Abramson SB, Philips MR, Weissmann G. Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. J Immunol 1990; 144: 4757–4764.Google Scholar
Miyachi Y, Yoshioka A, Imamura S, Niwa Y. Anti-oxidant effects of gold compounds. Br J Dermatol 1987; 116: 39–46.Google Scholar
Mikawa K, Akamatsu H, Nishina K, et al. The effect of phosphodiesterase III inhibitors on human neutrophil function. Crit Care Med 2000; 28: 1001–1005.Google Scholar
Wulf H, Behnke H, Vogel I, Schroder L. Clinical usefulness, safety, and plasma concentration of ropivacaine 0.5% for inguinal hernia repair in regional anesthesia. Reg Anesth Pain Med 2001; 26: 348–351.Google Scholar
Gin T, Chan K, Kan AF, Gregory MA, Wong YC, Oh TE. Effect of adrenaline on venous plasma concentrations of bupivacaine after interpleural administration. Br J Anaesth 1990; 64: 662–666.Google Scholar
Mather LE, Tucker GT, Murphy TM, Stanton-Hicks DA, Bonica JJ. The effects of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia. II: Pharmacokinetics. Br J Anaesth 1976; 48: 989–994.Google Scholar
Mikawa K, Akamatsu H, Nishina K, Shiga M, Obara H, Niwa Y. Inhibitory effects of pentobarbital and phenobarbital on human neutrophil functions. J Intensive Care Med 2001; 16: 9–87.Google Scholar
Kruger NJ. The Bradford method for protein quantitation. Methods Mol Biol 1994; 32: 9–15.Google Scholar
Lew DP, Andersson T, Hed J, Di-Virgilio F, Pozzan T, Stendahl O. Ca2+-dependent and Ca2+-independent phagocytosis in human neutrophils. Nature 1985; 315: 509–511.Google Scholar
Santoro P, Agosti V, Viggiano D, Palumbo A, Sarno T, Ciccumarra F. Impaired d-myo-inositol 1,4,5-triphosphate generation from cord blood polymorphonuclear leukocytes. Pediatr Res 1995; 38: 564–567.Google Scholar
Thomas JM, Schug SA. Recent advances in the pharmacokinetics of local anaesthetics. Long-acting amide enantiomers and continuous infusions. Clin Pharmacokinet 1999; 36: 67–83.Google Scholar
Kondo Y, Kondo F, Asanuma M, Tanaka K, Ogawa N. Protective effect of orengedoku-to against induction of neuronal death by transient cerebral ischemia in the C57BL/6 mouse. Neurochem Res 2000; 25: 205–209.Google Scholar
Qayumi AK, Janusz MT, Jamieson WR, Lyster DM. Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. J Thorac Cardiovasc Surg 1992; 104: 256–261.Google Scholar
Ryoke K, Osaki T, Hamada T. The study of local anesthetics. I. Gas-chromatographed lidocaine concentration in blood, urine and in the injected tissue. J Jpn Dent Soc Anesthesiol 1980; 8: 182–193.Google Scholar
Eriksson AS, Sinclair R, Cassuto J, Thomsen P. Influence of lidocaine on leukocyte function in the surgical wound. Anesthesiology 1992; 77: 74–78.Google Scholar