Serum concentration of ketamine and antinociceptive effects of ketamine and ketamine-lidocaine infusions in conscious dogs.
BACKGROUND
Central sensitization is a potential severe consequence of invasive surgical procedures. It results in postoperative and potentially chronic pain enhancement. It results in postoperative pain enhancement; clinically manifested as hyperalgesia and allodynia. N-methyl-D-aspartate (NMDA) receptor plays a crucial role in the mechanism of central sensitisation. Ketamine is most commonly used NMDA-antagonist in human and veterinary practice. However, the antinociceptive serum concentration of ketamine is not yet properly established in dogs. Six dogs were used in a crossover design, with one week washout period. Treatments consisted of: 1) 0.5 mg/kg ketamine followed by continuous rate infusion (CRI) of 30 μg/kg/min; 2) 0.5 mg/kg ketamine followed by CRI of 30 μg/kg/min and lidocaine (2 mg/kg followed by CRI of 100 μg/kg/min); and 3) 0.5 mg/kg ketamine followed by CRI of 50 μg/kg/min. The infusion was administered up to 120 min. Nociceptive thresholds and ketamine serum concentrations were measured before drug administration, and at 5, 10, 20, 40, 60, 90, 120, 140 and 160 min after the start of infusion.


RESULTS
Maximum concentration recorded was 435.34 ± 26.18 ng/mL, 582.34 ± 227.46 ng/mL and 733.77 ± 133.6 ng/mL for K30, KL30 and K50, respectively. The concentration at 120 min was 250.87 ± 39.87, 221.73 ± 91.03 and 343.67 ± 63.21 ng/mL at 120 min in K30, KL30 and K50, respectively. All the three infusion regimes maintained serum concentrations above 200 ng/mL. The thresholds returned towards baseline values within 20 min, after cessation of infusion.


CONCLUSIONS
Serum concentration to produce mechanical antinociceptive effects in dogs is between 100 and 200 ng/mL. All the three infusion regimes in this study provided antinociceptive effects throughout the infusions. In this study, we found that the serum concentration of ketamine to produce mechanical antinociceptive effects in dogs is above 200 ng/mL. All three infusion regimes provided antinociceptive effects throughout the infusions without causing harmful effects. Further studies are recommended in a clinical setting.
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.|Department of Surgery and Obstetrics, Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University Tandojam, Sindh, 70060, Pakistan.
Ubedullah
U
Kaka
Material Synthesis and characterization laboratory, Institute of Advanced technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Bullo
B
Saifullah
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Adamu Abdul
AA
Abubakar
Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.|Institutes of Tropical Agriculture, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Yong Meng
YM
Goh
Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.|Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Sharida
S
Fakurazi
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.|Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University Tandojam, Sindh, 70060, Pakistan.
Asmatullah
A
Kaka
Department of Animal Sciences, Faculty of Agriculture, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.|Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University Tandojam, Sindh, 70060, Pakistan.
Atique Ahmed
AA
Behan
Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Mahdi
M
Ebrahimi
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. chen@upm.edu.my.
Hui Cheng
HC
Chen
D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D007649:Ketamine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000662:veterinary*; D010147:Pain Measurement / Q000187:drug effects / Q000662:veterinary
D000700:Analgesics; D000779:Anesthetics, Local; D007649:Ketamine; D008012:Lidocaine
Dog; Ketamine; Lidocaine; NMDA receptor; Nociceptive mechanical thresholds