Serum concentration of ketamine and antinociceptive effects of ketamine and ketamine-lidocaine infusions in conscious dogs

Abstract

BackgroundCentral 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.ResultsMaximum 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.ConclusionSerum 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.

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

“…A study of Bergadano et al (2009) [54], investigating the analgesic effects of a low-dose constant rate infusion of ketamine, showed that ketamine's antinociceptive effects were evident when plasma concentrations ranged between 220-370 ng/mL. Another study investigating antinociceptive effects of different ketamine infusion regimes found that the serum concentration of ketamine to produce mechanical antinociceptive effects is above 200 ng/mL [55]. In the present study, mean Cmax after IN administration was 1694.48 ng/mL and mean plasma concentrations stayed above 200 ng/mL until 2 h after ketamine administration, indicating antinociceptive effects in this time frame.…”

Antinociceptive and analgesic effect of continuous intravenous infusion of maropitant, lidocaine and ketamine alone or in combination in cats undergoing ovariohysterectomy

“…Continuous IV infusion of maropitant, lidocaine, or ketamine alone promoted an antinociceptive effect. In dogs, continuous infusions of ketamine and lidocaine alone or in combination or with other drugs induce antinociceptive effects and decrease analgesic requirements [ 7 , 37 ]. The groups that received combinations did not significantly differ from the group that received only maropitant.…”

Continuous Infusion of Ketamine and Lidocaine Either with or without Maropitant as an Adjuvant Agent for Analgesia in Female Dogs Undergoing Mastectomy

“…A technique used in mastectomy is intermittent bolus administration and continuous infusion of ketamine and lidocaine. This protocol provides a constant concentration of these drugs, faster recovery, and normalization of plasma levels [ 1 , 5 , 6 ].…”