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

View Article: PubMed Central - PubMed

ABSTRACT

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.

Conclusion: 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.

No MeSH data available.


Comparison (Mean ± SD) between serum concentration of K30, KL30 and K50 in 6 dogs during and after CRI. K30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min, KL30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min and lidocaine 2 mg/kg loading dose followed by 100 μg/kg/min, K50 = Ketamine 0.5 mg/kg loading dose followed by 50 μg/kg/min CRI. At each time point, groups with similar alphabet are not different (P < 0.05)
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Fig1: Comparison (Mean ± SD) between serum concentration of K30, KL30 and K50 in 6 dogs during and after CRI. K30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min, KL30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min and lidocaine 2 mg/kg loading dose followed by 100 μg/kg/min, K50 = Ketamine 0.5 mg/kg loading dose followed by 50 μg/kg/min CRI. At each time point, groups with similar alphabet are not different (P < 0.05)

Mentions: The serum concentrations (Mean ± SD) of K30, KL30 and K50 across time points are illustrated in Fig. 1. Maximum concentration was observed at 1 min for K30 (435.34 ± 26.18 ng/mL), KL30 (582.34 ± 227.46 ng/mL), and K50 (733.77 ± 133.6 ng/mL), which remained stable for 20 min, and declined gradually reaching around 250.87 ± 39.87, 221.73 ± 91.03 and 343.67 ± 63.21 ng/mL at 120th min in K30, KL30 and K50, respectively. The serum concentration decreased rapidly to less than 100 ng/mL within 20 min following the end of infusions in all three treatments. Between 1 and 40 min, serum concentration of K50 was higher than K30, while concentration of KL30 lied in between K50 and K30. By 60th min, the three groups were not statistically different.Fig. 1


Serum concentration of ketamine and antinociceptive effects of ketamine and ketamine-lidocaine infusions in conscious dogs
Comparison (Mean ± SD) between serum concentration of K30, KL30 and K50 in 6 dogs during and after CRI. K30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min, KL30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min and lidocaine 2 mg/kg loading dose followed by 100 μg/kg/min, K50 = Ketamine 0.5 mg/kg loading dose followed by 50 μg/kg/min CRI. At each time point, groups with similar alphabet are not different (P < 0.05)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5016942&req=5

Fig1: Comparison (Mean ± SD) between serum concentration of K30, KL30 and K50 in 6 dogs during and after CRI. K30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min, KL30 = Ketamine 0.5 mg/kg loading dose followed by 30 μg/kg/min and lidocaine 2 mg/kg loading dose followed by 100 μg/kg/min, K50 = Ketamine 0.5 mg/kg loading dose followed by 50 μg/kg/min CRI. At each time point, groups with similar alphabet are not different (P < 0.05)
Mentions: The serum concentrations (Mean ± SD) of K30, KL30 and K50 across time points are illustrated in Fig. 1. Maximum concentration was observed at 1 min for K30 (435.34 ± 26.18 ng/mL), KL30 (582.34 ± 227.46 ng/mL), and K50 (733.77 ± 133.6 ng/mL), which remained stable for 20 min, and declined gradually reaching around 250.87 ± 39.87, 221.73 ± 91.03 and 343.67 ± 63.21 ng/mL at 120th min in K30, KL30 and K50, respectively. The serum concentration decreased rapidly to less than 100 ng/mL within 20 min following the end of infusions in all three treatments. Between 1 and 40 min, serum concentration of K50 was higher than K30, while concentration of KL30 lied in between K50 and K30. By 60th min, the three groups were not statistically different.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

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&nbsp;mg/kg ketamine followed by continuous rate infusion (CRI) of 30&nbsp;&mu;g/kg/min; 2) 0.5&nbsp;mg/kg ketamine followed by CRI of 30&nbsp;&mu;g/kg/min and lidocaine (2&nbsp;mg/kg followed by CRI of 100&nbsp;&mu;g/kg/min); and 3) 0.5&nbsp;mg/kg ketamine followed by CRI of 50&nbsp;&mu;g/kg/min. The infusion was administered up to 120&nbsp;min. Nociceptive thresholds and ketamine serum concentrations were measured before drug administration, and at 5, 10, 20, 40, 60, 90, 120, 140 and 160&nbsp;min after the start of infusion.

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

Conclusion: Serum concentration to produce mechanical antinociceptive effects in dogs is between 100 and 200&nbsp;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&nbsp;ng/mL. All three infusion regimes provided antinociceptive effects throughout the infusions without causing harmful effects. Further studies are recommended in a clinical setting.

No MeSH data available.