A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice

Wesley M. Burnside, Paul A. Flecknell, Angus I Cameron, Aurélie A Thomas

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models.

There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 %) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 %). No statistical differences were detected in regards to administration route (P <= 0.94).

This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.
LanguageEnglish
Article number48
Number of pages9
JournalBMC Veterinary Research
Volume9
DOIs
Publication statusPublished - 13 Mar 2013

Fingerprint

Medetomidine
dexmedetomidine
Dexmedetomidine
medetomidine
enantiomers
Ketamine
ketamine
reflexes
mice
Righting Reflex
anesthesia
depth of anesthesia
Reflex
Anesthesia
General Anesthesia
Tail
Foot
heart rate
Linear Models
tail

Keywords

  • Alpha-2 agonists
  • Dexmedetomidine
  • drug administration route
  • general anaesthesia
  • hypoxaemia
  • ketamine
  • mouse
  • medetomidine
  • subcutaneous injection
  • supplemental oxygen

Cite this

Burnside, Wesley M. ; Flecknell, Paul A. ; Cameron, Angus I ; Thomas, Aurélie A. / A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice. In: BMC Veterinary Research. 2013 ; Vol. 9.
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abstract = "Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models. There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 {\%}) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 {\%}). No statistical differences were detected in regards to administration route (P <= 0.94). This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.",
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A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice. / Burnside, Wesley M.; Flecknell, Paul A.; Cameron, Angus I; Thomas, Aurélie A.

In: BMC Veterinary Research, Vol. 9, 48, 13.03.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice

AU - Burnside, Wesley M.

AU - Flecknell, Paul A.

AU - Cameron, Angus I

AU - Thomas, Aurélie A

PY - 2013/3/13

Y1 - 2013/3/13

N2 - Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models. There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 %) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 %). No statistical differences were detected in regards to administration route (P <= 0.94). This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.

AB - Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with >= 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models. There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P <= 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 +/- 6.7 %) in all treatment groups and were most severe after 89 minutes lapsed (66.7 +/- 7.5 %). No statistical differences were detected in regards to administration route (P <= 0.94). This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.

KW - Alpha-2 agonists

KW - Dexmedetomidine

KW - drug administration route

KW - general anaesthesia

KW - hypoxaemia

KW - ketamine

KW - mouse

KW - medetomidine

KW - subcutaneous injection

KW - supplemental oxygen

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U2 - 10.1186/1746-6148-9-48

DO - 10.1186/1746-6148-9-48

M3 - Article

VL - 9

JO - BMC Veterinary Research

T2 - BMC Veterinary Research

JF - BMC Veterinary Research

SN - 1746-6148

M1 - 48

ER -