Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia

BMC Veterinary Research

Brad J White²  J Brandon Reinbold²  Brad Robert²  Ronette Gehring²  Butch KuKanich³  Ruby A Mosher²  Johann F Coetzee¹ 

[1] Present address: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, 50014, Ames, IA, USA;Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, 66506-5601, Manhattan, KS, USA;Department of Anatomy and Physiology, Kansas State University, 66506-5601, Manhattan, KS, USA

关键词: Performance;    Accelerometers;    Heart rate;    Cortisol;    Substance P;    Dehorning;    Meloxicam;    Analgesia;   

Others  :  1119734
DOI  :  10.1186/1746-6148-8-153

 received in 2012-05-22, accepted in 2012-08-15,  发布年份 2012

【 摘 要 】

Background

Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 – 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.

Results

Plasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T_½α = 0.22 ± 0.087 h) and a slower elimination phase (mean T_½β = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).

Conclusions

To our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.

【 授权许可】

   
2012 Coetzee et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]USDA: Dairy 2007, Heifer Calf Health and Management Practices on U.S. Dairy Operations. 2007. USDA:APHIS:VS:CEAH. Fort Collins, CO #N550.0110. 2009. Available at http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_ir_CalfHealth.pdf webcite. Accessed 21 May 2012
• [2]American Veterinary Medical Association: AVMA Policy: Castration and Dehorning of Cattle. 2008. Available at:http://www.avma.org/issues/policy/animal_welfare/dehorning_cattle.asp webcite. Accessed 21 May 2012
• [3]European Agency for the Evaluation of Medicinal Products (EMEA) Web site: Committee for Veterinary Medicinal Products: Meloxicam. Maximum Residue Limit (MRL) Summary Report (2). Available athttp://www.emea.europa.eu/pdfs/vet/mrls/057199en.pdf webcite; accessed on 12 November 2009
• [4]Heinrich A, Duffield TF, Lissemore KD, Squires EJ, Millman ST: The impact of meloxicam on postsurgical stress associated with cautery dehorning. J Dairy Sci 2009, 92(2):540-547.
• [5]Stewart M, Stookey JM, Stafford KJ, Tucker CB, Rogers AR, Dowling SK, Verkerk GA, Schaefer AL, Webster JR: Effects of local anesthetic and nonsteroidal anti-inflammatory drug on pain responses of dairy calves to hot-iron dehorning. J Dairy Sci 2009, 92(4):1512-1519.
• [6]Heinrich A, Duffield TF, Lissemore KD, Millman ST: The effect of meloxicam on behavior and pain sensitivity of dairy calves following cautery dehorning with a local anesthetic. J Dairy Sci 2010, 93(6):2450-2457.
• [7]Ingvast-Larsson C, Hogberg M, Mengistu U, Olsen L: Pharmacokinetics of meloxicam in adult goat and its analgesic effect in disbudded kids. J Vet Pharm Ther 2010, 34:64-69.
• [8]Fulwider WK, Grandin T, Rollin BE, Engle TE, Dalsted NL, Lamm WD: Survey of dairy management practices on one hundred thirteen North Central and northeastern United States Dairies. J Dairy Sci 2008, 91(4):1686-1692.
• [9]Hoe FGH, Ruegg PL: Opinions and practices of Wisconsin dairy producers about biosecurity and animal well-being. J Dairy Sci 2006, 89:2297-2308.
• [10]Webb AI, Pablo LS: Local Anesthetics. In Veterinary Pharmacology and Therapeutics. 9th edition. Edited by Riviere JM, Papich MG. Ames, IA, USA: Wiley-Blackwell; 2009:381-397.
• [11]Kissin I: Preemptive analgesia. Anesthesiology 2000, 93:1138-1143.
• [12]Lees P: Analgesic, anti-inflammatory, antipyretic drugs. In Veterinary pharmacology and therapeutics. 9th edition. Edited by Riviere JM, Papich MG. Ames, IA, USA: Wiley-Blackwell; 457-492.
• [13]Coetzee JF, KuKanich B, Mosher R, Allen PS: Pharmacokinetics of intravenous and oral meloxicam in ruminant calves. Vet Ther 2009, 10(4):E1-E8.
• [14]Landoni MF, Cunningham FM, Lees P: Pharmacokinetics and pharmacodynamics of ketoprofen in calves applying PK/PD modeling. J Vet Pharm Therap 1995, 18(5):315-324.
• [15]Coetzee JF, Gehring R, Bettenhausen AC, Lubbers BL, Thomson DU, KuKanich B, Toerber SE, Apley MD: Mitigation of plasma cortisol response in bulls following intravenous sodium salicylate administration prior to castration. J Vet Pharm Therap 2007, 30(4):305-313.
• [16]Anderson KL, Neff-Davis CALE, Davis VD: Bass: Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations. Amer J Vet Res 1990, 51(9):1464-1467.
• [17]Toutain PN, Reymond V, Laroute P, Garcia M, Popot Y, Gonnaire A, Hirsch R: Narbe. Pharmacokinetics of meloxicam in plasma and urine of horses. Am J Vet Res 2004, 65:1542-1547.
• [18]Jeunesse EC, Bargues IA, Toutain CE, Lacroix MZ, Letellier IM, Giraudel JM, Toutain PL: Paw inflammation model in dog. J Pharmacol Exp Ther 2011, 338:548-558.
• [19]Sutherland MA, Mellor DJ, Stafford KJ, Gregory NG, Ward RN, Bruce RA: Cortisol responses to dehorning of calves given a 5-h local anaesthetic regimen plus phenylbutazone, ketoprofen, or adrenocorticotropic hormone prior to dehorning. Res Vet Sci 2002, 2002(73):115-123.
• [20]Sylvester SP, Mellor DJ, Stafford KJ, Bruce RA, Ward RN: Acute cortisol responses of calves to scoop dehorning using local anaesthesia and/or cautery of the wound. Aust Vet J 1998, 76(2):118-122.
• [21]Schwartzkopf-Genswein KS, Booth-McLean ME, McAllister TA, Mears GJ: Physiological and behavioural changes in Holstein calves during and after dehorning or castration. Can J Anim Sci 2005, 85:131-138.
• [22]American Veterinary Medical Association: Welfare implications of the dehorning and disbudding of cattle. 2010. Available at:http://www.avma.org/reference/backgrounders/dehorning_cattle_bgnd.pdf webcite. Accessed 21 May 2012
• [23]McMeekan CM, Stafford KJ, Mellor DJ, Bruce RA, Ward RN, Gregory N: Effects of a local anaesthetic and a non-steroidal anti-inflammatory analgesic on the behavioural responses of calves to dehorning. NZ Vet J 1999, 47:92-96.
• [24]Coetzee JF: A review of pain assessment techniques and pharmacological approaches to pain relief after bovine castration in the United States. Invited Review. Appl Anim Behav Sci 2011, 135(4):192-213.
• [25]Coetzee JF, Lubbers BL, Toerber SE, Gehring R, Thomson DU, White BJ, Apley MD: Plasma concentrations of substance P and cortisol in beef calves after castration or simulated castration. Am J Vet Res 2008, 69(6):751-762.
• [26]Hopster H, Blokhuis HJ: Validation of a heart-rate monitor for measuring a stress response in dairy cows. Can J Anim Sci 1994, 74:465-474.
• [27]Lefcourt AM, Kahl S, Akers RM: Correlation of indices of stress with intensity of electrical shock in cows. J Dairy Sci 1986, 69:833-842.
• [28]Lay DC, Friend TH, Randel RD, Bower CL, Grissom KK, Jenkins OC: Behavioural and physiological effects of freeze or hot-iron branding on crossbred cattle. J Anim Sci 1992, 70:330-336.
• [29]Grondahl-Nielsen C, Simonsen HB, Damkjer Lund J, Hesselholt M: Behavioural, endocrine and cardiac responses in young calves undergoing dehorning without and with the use of sedation and analgesia. Vet J 1999, 1999(158):14-20.
• [30]Theurer ME, White BJ, Coetzee JF, Edwards LN, Mosher RA, Cull CA: Assessment of behavioral changes associated with oral meloxicam administration at time of dehorning in calves using a remote triangulation device and accelerometers. BMC Vet Res 2012, 8:48. BioMed Central Full Text
• [31]Weary DM, Huzzey JM, von Keyserlingk MAG: Board-Invited Review: Using behavior to predict and identify ill health in animals. J Anim Sci 2009, 87(2):770-777.
• [32]Stanton AL, Kelton DF, Leblanc SJ, Millman ST, Wormuth J, Dingwell RT, Leslie KE: The effect of treatment with long-acting antibiotic at postweaning movement on respiratory disease and on growth in commercial dairy calves. J Dairy Sci 2010, 93(2):574-581.
• [33]Hanzlicek GA, White BJ, Mosier D, Renter DG, Anderson DE: Serial evaluation of physiologic, pathological, and behavioral changes related to disease progression of experimentally induced Mannheimia haemolytica pneumonia in postweaned calves. Am J Vet Res 2010, 71:359-369.
• [34]Ito K, Weary DM, von Keyerslingk MAG: Lying behavior: Assessing within- and between- herd variation in free-stall-housed dairy cows. J Dairy Sci 2009, 92:4412-4420.
• [35]Ito K, von Keyserlingk MAG, LeBlanc SJ, Weary DM: Lying behavior as an indicator of lameness in dairy cows. J Dairy Sci 2010, 93:3553-3560.
• [36]White BJ, Coetzee JF, Renter DG, Babcock AH, Thomson DU, Andresen D: Evaluation of two-dimensional accelerometers to monitor beef cattle behavior post-castration. Amer J Vet Res 2008, 69(8):1005-1012.
• [37]Ting ST, Earley B, Crowe MA: Effect of repeated ketoprofen administration during surgical castration of bulls on cortisol, immunological function, feed intake, growth, and behavior. J Anim Sci 2003, 81:1253-1264.
• [38]Faulkner PM, Weary DM: Reducing pain after dehorning in dairy calves. J Dairy Sci 2000, 83:2037-2041.
• [39]Baldridge SL, Coetzee JF, Dritz SS, Reinbold JB, Gehring R, Havel J, Kukanich B: Pharmacokinetics and physiologic effects of intramuscularly administered xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein calves following castration and dehorning. Am J Vet Res 2011, 72(10):1305-1317.
• [40]Friton GM, Cajal C, Ramirez-Romero R: Long-term effects of meloxicam in the treatment of respiratory disease in fattening cattle. Vet Rec 2005, 156:809-811.
• [41]Garry FB: Disorders of reticuloruminal motor function. In Large Animal Internal Medicine. 3rd edition. Edited by Smith BP. St Louis, MO, USA: Mosby; :723-724.
• [42]Mellor DJ, Stafford KJ, Todd SE, Lowe TE, Gregory NG, Bruce RA, Ward RN: A comparison of catecholamine and cortisol responses of young lambs and calves to painful husbandry procedures. Aust Vet J 2002, 80(4):228-233.
• [43]Leek BF: Review: reticuloruminal motility–a pharmacological target with a difference? Vet Q 2001, 23(1):26-31.
• [44]Robert B, White BJ, Renter DG, Larson RL: Evaluation of three dimensional accelerometers as a method to categorize and classify behavior patterns in cattle. Comput Electron Agric 2009, 67:80-84.
• [45]Kotschwar JL, Coetzee JF, Anderson DE, Gehring R, KuKanich B: Analgesic Efficacy of Sodium Salicylate in an Amphotericin B Induced Bovine Synovitis-Arthritis Model. J Dairy Sci 2000, 92(8):3731-3743.
• [46]Coetzee JF, Mosher RA, Kohake LE, Cull CA, Kelly LL, Mueting SL, KuKanich B: Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves. Vet J 2011, 190(1):98-102.
• [47]Gibaldi M, Perrier D: Pharmacokinetics. 2nd edition. New York, USA: Marcel Dekker Inc; 1982.
• [48]Sall J, Creighton L, Lehman A: JMP Start Statistics. 3rd edition. Belmont, California: Thomson Brooks/Cole; 2004:363.