Epidural co-administration of neostigmine and lidocaine or xylazine enhances systemic sedation but not perineal analgesia in adult dairy cows
The aim of this study was to evaluate the behavioural, clinical and analgesic effects of epidural neostigmine in adult dairy cattle. Five healthy, adult Holstein-Friesian dairy cows received five different treatments in a cross-over design with one-week washout period as follows: 2% lidocaine alone (0.22 mg/kg), neostigmine alone (10 μg/kg), neostigmine-lidocaine (10 μg/kg and 0.11 mg/kg), neostigmine-xylazine (10 μg/kg and 0.05 mg/kg) and 0.09% saline alone (6 ml). Analgesia of the perineal region was assessed using the superficial and deep muscle pin-prick techniques. The onset and duration of analgesia and the degree of analgesia, sedation and ataxia were assessed before drug administration (T0) and thereafter at T15, T30, T60, T120 and T180. In addition, cows were monitored for any behavioural or clinical abnormalities over the course of the entire study. Signs of agitation, increased salivation and increased frequency of defecation were observed in cows administered neostigmine epidurally alone or in combination with lidocaine or xylazine. The epidural administration of neostigmine alone did not result in any analgesic effects in any of the cows. Analgesia appeared significantly faster (P ≤ 0.05) in the lidocaine group compared to the neostigmine-lidocaine and neostigmine-xylazine groups. The duration of analgesia produced by neostigmine-xylazine was significantly longer (P ≤ 0.05) than that produced by lidocaine alone or neostigmine-lidocaine. Neostigmine produced a significant degree of sedation (P ≤ 0.05) when administered epidurally alone or in combination with lidocaine or xylazine. The epidural administration of neostigmine alone did not result in any signs of ataxia, while the epidural administration of lidocaine alone, neostigmine-lidocaine and neostigmine-xylazine resulted in variable degrees of ataxia. There were no significant changes in any of the clinical parameters. In conclusion, neostigmine can be co-administered epidurally with lidocaine or xylazine for routine standing surgical procedures in adult dairy cows to enhance sedation but not analgesia.
Alkan M, Kaya K (2014): Postoperative analgesic effect of epidural neostigmine following caesarean section. Hippokratia 18, 44–49.
Atiba Ayman, Ghazy Alaa, Gomaa Naglaa, Kamal Tarek, Shukry Mustafa (2015): Evaluation of Analgesic Effect of Caudal Epidural Tramadol, Tramadol-Lidocaine, and Lidocaine in Water Buffalo Calves (
Bubalus bubalis ). Veterinary Medicine International, 2015, 1-6
https://doi.org/10.1155/2015/575101
Chung CJ, Kim JS, Park HS, Chin YJ (1998): The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean section analgesia. Anesthesia and Analgesia 87, 341–346.
De Rossi R, Bucker Gisele V, Varela Juliana V (2003): Perineal analgesic actions of epidural clonidine in cattle. Veterinary Anaesthesia and Analgesia, 30, 63-70
https://doi.org/10.1046/j.1467-2995.2003.00089.x
DeRossi Rafael, Ruzzon Rafael H. S., Verde-Selva Alexandre B., Bertoni Rodrigo A. (2010): Evaluation of segmental dorsolumbar epidural analgesia with ketamine hydrochloride administered by use of nonstyletted multiple-port catheters via the caudal approach in cattle. American Journal of Veterinary Research, 71, 17-23
https://doi.org/10.2460/ajvr.71.1.17
DeRossi Rafael, Maciel Felipe B., Módolo Tiago J. C., Pagliosa Ronaldo C. (2012): Efficacy of concurrent epidural administration of neostigmine and lidocaine for perineal analgesia in geldings. American Journal of Veterinary Research, 73, 1356-1362
https://doi.org/10.2460/ajvr.73.9.1356
Derossi R., Módolo T. J. C., Maciel F. B., Pagliosa R. C. (2013): Efficacy of epidural lidocaine combined with tramadol or neostigmine on perineal analgesia in the horse. Equine Veterinary Journal, 45, 497-502
https://doi.org/10.1111/j.2042-3306.2012.00654.x
Dzikiti TB, Stegmann GF, Hellebrekers LJ, Auer REJ, Dzikiti LN (2009): Sedative and cardiopulmonary effects of acepromazine, midazolam, butorphanol, acepromazinebutorphanol and midazolam-butorphanol on propofol anaesthesia in goats. Journal of South African Association 80, 10–16.
ELDOR J., HOFFMAN B., DAVIDSON J. T. (1987): Prolonged bradycardia and hypotension after neostigmine administration in a patient receiving atenolol. Anaesthesia, 42, 1294-1297
https://doi.org/10.1111/j.1365-2044.1987.tb05277.x
Ghazy Alaa, Atiba Ayman, Shukry Mustafa, Kamal Tarek (2015): Comparison of Lidocaine and Lidocaine-Neostigmine for Epidural Analgesia in Water Buffalo Calves (Bubalus Bubalis). Alexandria Journal of Veterinary Sciences, 46, 177-
https://doi.org/10.5455/ajvs.198171
Grant G. J., Piskoun B., Bansinath M. (2002): Intrathecal administration of liposomal neostigmine prolongs analgesia in mice. Acta Anaesthesiologica Scandinavica, 46, 90-94
https://doi.org/10.1034/j.1399-6576.2002.460116.x
Harjai M, Chandra G, Bhatia VK, Singh D, Bhaskar P (2010): A comparative study of two different doses of epidural neostigmine coadministered with lignocaine for post operative analgesia and sedation. Journal of Anaesthesiology and Clinical Pharmacology 26, 461–464.
Ho KM, Ismail H, Lee KC, Branch R (2005): Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis. Anaesthesiology and Intensive Care 33, 41–53.
Ismail ZB, Al-Zghoul A, Al-Zoubi I (2017): Clinical, behavioral, hematological and serum biochemical effects of neostigmine in normal dairy cows following subcutaneous and intramuscular administration of single dose. Research Opinions in Animal and Veterinary Science 7, 49–53.
Lauretti GabrielaRocha (2015): The evolution of spinal/epidural neostigmine in clinical application: Thoughts after two decades. Saudi Journal of Anaesthesia, 9, 71-
https://doi.org/10.4103/1658-354X.146319
Liu Spencer S., Hodgson Peter S., Moore James M., Trautman Walter J., Burkhead Daniel L. (1999): Dose-Response Effects of Spinal Neostigmine Added to Bupivacaine Spinal Anesthesia in Volunteers. Anesthesiology, 90, 710-717
https://doi.org/10.1097/00000542-199903000-00012
Marucio Rodrigo L., Monteiro Eduardo R., Moroz Ludmila R., Fantoni Denise T. (2014): Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in dogs undergoing orthopedic surgery of the pelvic limbs. American Journal of Veterinary Research, 75, 956-963
https://doi.org/10.2460/ajvr.75.11.956
Miranda Hugo F, Sierralta Fernando, Pinardi Gianni (2002): Neostigmine interactions with non steroidal anti-inflammatory drugs. British Journal of Pharmacology, 135, 1591-1597
https://doi.org/10.1038/sj.bjp.0704599
Nagy HebaI.A., El Zayyat NashwaSami, El Dahab HeshamAbo (2014): The effect of addition of neostigmine to epidural levobupivacaine/fentanyl mixture on return of intestinal motility in postoperative ICU. Ain-Shams Journal of Anaesthesiology, 7, 412-
https://doi.org/10.4103/1687-7934.139582
Saifzadeh S, Mehrdad D, Bahram PD, Naghadeh D (2007): Caudal extradural analgesia with lidocaine, xylazine, and a combination of lidocaine and xylazine in the Iranian river buffalo (Bubalus bubalis). Bulletin of Veterinary Institute of Pulawy 51, 285–288.
Singh P., Pratap K., Kinjavdekar P., Aithal H. P., Singh G. R., Pathak R. (2006): Xylazine, Ketamine and their Combination for Lumbar Epidural Analgesia in Water Buffalo Calves (Bubalus bubalis). Journal of Veterinary Medicine Series A, 53, 423-431
https://doi.org/10.1111/j.1439-0442.2006.00849.x
Singh Virendra, Amarpal , Kinjavdekar Prakash, Aithal Hari P (2009): Effect of bupivacaine on epidural analgesia produced by xylazine or medetomidine in buffaloes (Bubalus bubalis). Veterinary Anaesthesia and Analgesia, 36, 77-85
https://doi.org/10.1111/j.1467-2995.2008.00429.x
