- Email: [email protected]
Therapeutic Review: Ropivacaine
Therapeutic Review
Therapeutic Review: Ropivacaine Anderson F. da Cunha, DVM, Dip. ACVA
R
opivacaine (Naropin, APP Pharmaceuticals, Inc., Schaumburg, IL USA), an aminoamide derivative local anesthetic drug that is structurally related to mepivacaine and bupivacaine, has been developed to replace bupivacaine.1,2 The use of bupivacaine has been linked with significant ventricular arrhythmias, decreased myocardial contractility,2,3 convulsions, and cardiac arrests during accidental intravenous injections in dogs,4 rats,5 and humans.6 Ropivacaine is associated with minimum cardiovascular side effects when compared with bupivacaine. In the avian literature, there is unsubstantiated information that birds are more sensitive to local anesthetics than common mammalian species;7 however, that information has never been confirmed. Nevertheless, it is accurate to state that bupivacaine was associated with neurological side effects when administered intraarticularly in chickens.7 Therefore, alternative, less toxic, local anesthetic drugs such as ropivacaine may be useful to provide surgical local analgesia without cardiovascular toxicity in exotic animal species. In clinical studies ropivacaine appears to be suitable for both epidural and regional anesthesia.1 Ropivacaine is slightly less potent,8 and has similar duration,9 higher clearance rate, and shorter elimination half-life when compared with bupivacaine.10 Ropivacaine’s higher clearance rate and shorter halflife offers more benefit over bupivacaine in regards to systemic toxicity.1 In addition, it has been suggested that ropivacaine causes less vasodilation than bupivacaine in humans,11 less cardiovascular and central nervous system (CNS) toxic effects, and less motor impairment than bupivacaine when equieffective doses were administered through the epidural route in dogs.1,4 Moreover, the duration and quality of the local block in dogs were superior and the pain after injection was less evident when compared with lidocaine and bupivacaine.12 Ropivacaine (7.5 mg/kg) has been used for brachial plexus blockade in healthy chickens.13 In that study, after ropivacaine administration, a 15-minutes onset and subsequent duration time of 115 minutes with an intense effect were observed.13 The authors
318
did not detect any signs of cardiovascular or CNS toxicity after the ropivacaine blockage and suggested that ropivacaine was ideal for the brachial plexus blockage in chickens for surgical procedures in the wing.13 In most cases, systemic toxicity of local anesthetics is the result of an accidental intravenous injection.14 After ropivacaine administration, if adverse effects involving the cardiovascular system or CNS are observed, a “lipid rescue” can be performed. In two separate investigations using dogs15 and rats, an intentional overdose of bupivacaine was administered, which was followed by cardiac arrest. During cardiopulmonary resuscitation, a 4 mL/kg bolus of 20% lipid infusion followed by continuous infusion at 0.5 mL/kg/min for 10 minutes was associated with a substantial improvement in the hemodynamic parameters and an increased survival rate.15 Because ropivacaine and bupivacaine have similar physiochemical properties, the described lipid rescue technique has the potential to be useful after a possible ropivacaine overdose. Bupivacaine has been reported to be significantly more lethal than ropivacaine.4 Nevertheless, after using similar convulsant baseline doses of ropivacaine and bupivacaine (4.9 mg/kg and 4.3 mg/kg, respectively), twice the convulsant dosage of bupivacaine (9.8 mg/kg) and ropivacaine (8.6 mg/kg) was administered to dogs for a study evaluating the potential side effects on these animals.4 Once the dogs began to have seizures, an early treatment was performed with thiamylal and oxygen.4 No significant Louisiana State University, School of Veterinary Medicine, Department of Veterinary Clinical Sciences, Baton Rouge, LA USA. Address correspondence to: Anderson F. da Cunha, DVM, Dip. ACVA, Louisiana State University, School of Veterinary Medicine, Skip Bertman Dr, Baton Rouge, LA. E-mail: [email protected]. Published by Elsevier Inc. 1557-5063/11/2004-$0.00 doi:10.1053/j.jepm.2011.07.010
Journal of Exotic Pet Medicine, Vol 20, No 4 (October), 2011: pp 318 –319
319 difference in clinical response was observed between the ropivacaine and bupivacaine study groups.4 Although there is little clinical information regarding the use of ropivacaine in companion exotic animals, it has the promise of being an effective local anesthetic. More studies involving ropivacaine’s use in companion exotic animals are required to develop therapeutic dose levels and determine its effects on these species. Only then can we realize its full potential as a treatment option in exotic pet medicine.
6. 7.
8. 9.
References 1.
2.
3.
4.
5.
Goodman LS, Gilman A, Brunton LL: Goodman & Gilman’s Manual of Pharmacology and Therapeutics. New York, NY, McGraw-Hill Medical Publishing, 2008 Knudsen K, Beckman Suurkula M, Blomberg S, et al: Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 78:507-514, 1997 Szentandrassy N, Szabo A, Almassy J, et al: Effects of articaine and ropivacaine on calcium handling and contractility in canine ventricular myocardium. Eur J Anaesthesiol 27:153-161, 2010 Feldman HS, Arthur GR, Pitkanen M, et al: Treatment of acute systemic toxicity after the rapid intravenous-injection of ropivacaine and bupivacaine in the conscious dog. Anesth Analg 73:373-384, 1991 Dony P, Dewinde V, Vanderick B, et al: The comparative toxicity of ropivacaine and bupivacaine at equi-
10. 11.
12.
13. 14. 15.
potent doses in rats. Anesth Analg 91:1489-1492, 2000 Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285-287, 1979 Hocking PM, Gentle MJ, Bernard R, et al: Evaluation of a protocol for determining the effectiveness of pretreatment with local analgesics for reducing experimentally induced articular pain in domestic fowl. Res Vet Sci 63:263-267, 1997 Scott DB, Lee A, Fagan D, et al: Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69:563-569, 1989 Lee A, Fagan D, Lamont M, et al: Disposition kinetics of ropivacaine in humans. Anesth Analg 69:736-738, 1989 McClure JH: Ropivacaine. Br J Anaesth 76:300-307, 1996 Akerman B, Hellberg IB, Trossvik C: Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 32:571-578, 1988 Feldman HS, Covino BG: Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 67:1047-1052, 1988 Cardozo LB, Almeida RM, Fiuza LC, et al: Brachial plexus blockade in chickens with 0.75% ropivacaine. Vet Anaesth Analg 36:396-400, 2009 Zink W, Graf BM: The toxicity of local anesthetics: the place of ropivacaine and levobupivacaine. Curr Opin Anaesthesiol 21:645-650, 2008 Weinberg G, Ripper R, Feinstein DL, et al: Lipid emulsion infusion rescues dogs from bupivacaineinduced cardiac toxicity. Reg Anesth Pain Med 28: 198-202, 2003
Therapeutic Review: Ropivacaine Anderson F. da Cunha, DVM, Dip. ACVA
R
opivacaine (Naropin, APP Pharmaceuticals, Inc., Schaumburg, IL USA), an aminoamide derivative local anesthetic drug that is structurally related to mepivacaine and bupivacaine, has been developed to replace bupivacaine.1,2 The use of bupivacaine has been linked with significant ventricular arrhythmias, decreased myocardial contractility,2,3 convulsions, and cardiac arrests during accidental intravenous injections in dogs,4 rats,5 and humans.6 Ropivacaine is associated with minimum cardiovascular side effects when compared with bupivacaine. In the avian literature, there is unsubstantiated information that birds are more sensitive to local anesthetics than common mammalian species;7 however, that information has never been confirmed. Nevertheless, it is accurate to state that bupivacaine was associated with neurological side effects when administered intraarticularly in chickens.7 Therefore, alternative, less toxic, local anesthetic drugs such as ropivacaine may be useful to provide surgical local analgesia without cardiovascular toxicity in exotic animal species. In clinical studies ropivacaine appears to be suitable for both epidural and regional anesthesia.1 Ropivacaine is slightly less potent,8 and has similar duration,9 higher clearance rate, and shorter elimination half-life when compared with bupivacaine.10 Ropivacaine’s higher clearance rate and shorter halflife offers more benefit over bupivacaine in regards to systemic toxicity.1 In addition, it has been suggested that ropivacaine causes less vasodilation than bupivacaine in humans,11 less cardiovascular and central nervous system (CNS) toxic effects, and less motor impairment than bupivacaine when equieffective doses were administered through the epidural route in dogs.1,4 Moreover, the duration and quality of the local block in dogs were superior and the pain after injection was less evident when compared with lidocaine and bupivacaine.12 Ropivacaine (7.5 mg/kg) has been used for brachial plexus blockade in healthy chickens.13 In that study, after ropivacaine administration, a 15-minutes onset and subsequent duration time of 115 minutes with an intense effect were observed.13 The authors
318
did not detect any signs of cardiovascular or CNS toxicity after the ropivacaine blockage and suggested that ropivacaine was ideal for the brachial plexus blockage in chickens for surgical procedures in the wing.13 In most cases, systemic toxicity of local anesthetics is the result of an accidental intravenous injection.14 After ropivacaine administration, if adverse effects involving the cardiovascular system or CNS are observed, a “lipid rescue” can be performed. In two separate investigations using dogs15 and rats, an intentional overdose of bupivacaine was administered, which was followed by cardiac arrest. During cardiopulmonary resuscitation, a 4 mL/kg bolus of 20% lipid infusion followed by continuous infusion at 0.5 mL/kg/min for 10 minutes was associated with a substantial improvement in the hemodynamic parameters and an increased survival rate.15 Because ropivacaine and bupivacaine have similar physiochemical properties, the described lipid rescue technique has the potential to be useful after a possible ropivacaine overdose. Bupivacaine has been reported to be significantly more lethal than ropivacaine.4 Nevertheless, after using similar convulsant baseline doses of ropivacaine and bupivacaine (4.9 mg/kg and 4.3 mg/kg, respectively), twice the convulsant dosage of bupivacaine (9.8 mg/kg) and ropivacaine (8.6 mg/kg) was administered to dogs for a study evaluating the potential side effects on these animals.4 Once the dogs began to have seizures, an early treatment was performed with thiamylal and oxygen.4 No significant Louisiana State University, School of Veterinary Medicine, Department of Veterinary Clinical Sciences, Baton Rouge, LA USA. Address correspondence to: Anderson F. da Cunha, DVM, Dip. ACVA, Louisiana State University, School of Veterinary Medicine, Skip Bertman Dr, Baton Rouge, LA. E-mail: [email protected]. Published by Elsevier Inc. 1557-5063/11/2004-$0.00 doi:10.1053/j.jepm.2011.07.010
Journal of Exotic Pet Medicine, Vol 20, No 4 (October), 2011: pp 318 –319
319 difference in clinical response was observed between the ropivacaine and bupivacaine study groups.4 Although there is little clinical information regarding the use of ropivacaine in companion exotic animals, it has the promise of being an effective local anesthetic. More studies involving ropivacaine’s use in companion exotic animals are required to develop therapeutic dose levels and determine its effects on these species. Only then can we realize its full potential as a treatment option in exotic pet medicine.
6. 7.
8. 9.
References 1.
2.
3.
4.
5.
Goodman LS, Gilman A, Brunton LL: Goodman & Gilman’s Manual of Pharmacology and Therapeutics. New York, NY, McGraw-Hill Medical Publishing, 2008 Knudsen K, Beckman Suurkula M, Blomberg S, et al: Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 78:507-514, 1997 Szentandrassy N, Szabo A, Almassy J, et al: Effects of articaine and ropivacaine on calcium handling and contractility in canine ventricular myocardium. Eur J Anaesthesiol 27:153-161, 2010 Feldman HS, Arthur GR, Pitkanen M, et al: Treatment of acute systemic toxicity after the rapid intravenous-injection of ropivacaine and bupivacaine in the conscious dog. Anesth Analg 73:373-384, 1991 Dony P, Dewinde V, Vanderick B, et al: The comparative toxicity of ropivacaine and bupivacaine at equi-
10. 11.
12.
13. 14. 15.
potent doses in rats. Anesth Analg 91:1489-1492, 2000 Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285-287, 1979 Hocking PM, Gentle MJ, Bernard R, et al: Evaluation of a protocol for determining the effectiveness of pretreatment with local analgesics for reducing experimentally induced articular pain in domestic fowl. Res Vet Sci 63:263-267, 1997 Scott DB, Lee A, Fagan D, et al: Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69:563-569, 1989 Lee A, Fagan D, Lamont M, et al: Disposition kinetics of ropivacaine in humans. Anesth Analg 69:736-738, 1989 McClure JH: Ropivacaine. Br J Anaesth 76:300-307, 1996 Akerman B, Hellberg IB, Trossvik C: Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 32:571-578, 1988 Feldman HS, Covino BG: Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 67:1047-1052, 1988 Cardozo LB, Almeida RM, Fiuza LC, et al: Brachial plexus blockade in chickens with 0.75% ropivacaine. Vet Anaesth Analg 36:396-400, 2009 Zink W, Graf BM: The toxicity of local anesthetics: the place of ropivacaine and levobupivacaine. Curr Opin Anaesthesiol 21:645-650, 2008 Weinberg G, Ripper R, Feinstein DL, et al: Lipid emulsion infusion rescues dogs from bupivacaineinduced cardiac toxicity. Reg Anesth Pain Med 28: 198-202, 2003