This is a good paper- Vti C role in the nervous system appears well studied. Different results to
paper with rabbit anaesthesia which is interesting.
My verdict: accepted with minor changes.
Effects of vitamin C on ketamine-diazepam anesthesia in dogs
Marjani M. 1, Selk Ghaffari M. 1, Bahonar A.R.2,Yazdanpanah Abdolmaleki A1.
1-Department of Clinical sciences, Faculty of Veterinary Medicine, Islamic Azad
University-Karaj Branch. Karaj- Iran.
2- Department of Epidemiology, Faculty of Veterinary Medicine, University of Tehran.
Tehran- Iran.
Corresponding author:
Dr. M. Selk Ghaffari
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Effects of vitamin C on ketamine-diazepam anesthesia in dogs
ABSTRACT
The effect of pre-anesthetic administration of vitamin C on general anesthesia with
ketamine-diazepam was evaluated in dogs. A total of 20 dogs were divided into four
groups of five. In this study; heart rate, respiratory rate, duration of anesthesia, body
temperature, blood glucose, and calcium were evaluated before and following induction
of anesthesia. Group one received only 4 ml of sterile intravenous saline. Dogs in group
two anesthetized by intravenous ketamine-diazepam. Two treatment groups; group three
and four were premedicated with 100 mg and 500 mg vitamin C respectively, 30 minutes
before induction of general anesthesia by intravenous ketamine-diazpam combination. In
comparison to group two, significant increase was observed in body temperature of dogs
in group three and four. There was a significant increase in blood glucose level in both
treatment groups (group three and four). The mean ± SD duration of anesthesia was
significantly longer in group two (41.8 ± 2.8 minutes) than group three (22.6 ± 2.5
minutes) and group four (23.2 ± 2.03 minutes). In conclusion, it seems that the
premeditation of vitamin C may be useful in animals suffering from pre-surgical
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hypothermia, hypoglycemia, and in dogs who are suspected to be in a risk with prolonged
anesthesia.
Key words: vitamin C, ketamine, diazepam, anesthesia, dog
Introduction
Ketamine is a dissociative anesthetic drug which is used in clinical practice since 1970
(Lim, 2003). The combination of diazepam-ketamine is a very popular anesthetic
technique for producing short-term anesthesia in dogs (Madison, 2000). Vitamin C plays
important roles in mammalian central nervous system (Tsai et al., 2005). Vitamin C is an
antioxidant vitamin that the brain accumulates from the blood supply and maintains at a
relatively high concentration under widely varying conditions. Although neurons are
known to use this vitamin in many different chemical and enzymatic reactions, only
recently has sufficient evidence emerged to suggest a role for ascorbate in interneuronal
communication (Rebec and Pierce 1994). There are few published studies about the
effects of Vitamin C on general anesthesia in animal models such as rabbits (Elsa and
Ubandawaki 2005). However, these effects have not been extensively investigated in
dogs. The present study concentrates on effects of pre-anesthetic administration of
vitamin C on ketamine- diazepam anesthesia in dogs.
Materials and methods
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A total of 20 mixed breed dogs of both sexes, one year old, approximately weighting 20
to 27 Kg were used for this study. All dogs were healthy and free from clinically
important cardiovascular and respiratory diseases. Dogs were divided into four equal
groups of five. Prior to experimental period baseline values of heart rate, respiratory rate,
rectal temperature and blood levels of glucose and calcium was measured.
Group one received only 4 ml of sterile intravenous saline. Dogs in group two
anesthetized by intravenous ketamine 10mg/kg and diazepam 0.5 mg/kg. The members of
group three were pre-medicated with intravenous vitamin C (100 mg), 30 minutes before
induction of anesthesia by ketamine 10mg/kg and diazepam 0.5 mg/kg combination. The
dogs of group four were received intravenous vitamin C (500 mg), 30 minutes before
induction of the same anesthesia protocol.
Values of cardiorespiratory rate, body
temperature, blood glucose, and calcium concentration were recorded after induction of
anesthesia in all groups. The duration of anesthesia was also evaluated in dogs of group
two, three, and four.
Statistical analysis
Data were analyzed using SPSS 12 software. The differences of values between before
and after anesthesia in each group were tested by paired samples t-test. The level of
significance was 0.05.
Results
Data is summarized in table 1. The heart rates were significantly increased in groups two,
three and four. Body temperature showed significant decrease in group two. In
comparison to group two, significant increase in body temperature? was observed in all
members of group three and group four. The mean of calcium concentration in group two
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was decreased but in treatment groups was increased (p<0.05). There was a significant
increase in blood glucose level in both treatment groups. The mean ± SD duration of
anesthesia was significantly longer in group two (41.8 ± 2.8 minutes) than group three
(22.6 ± 2.5 minutes) and group four (23.2 ± 2.03 minutes).
Table 1.
Changes in cardiorespiratory parameters, body temperature, blood
glucose and calcium concentration.
Group1
Group 2
Group 3
Group 4
Pre-anesthetic heart rate: Mean (SD)
(n=5)
106 (13.5)
(n=5)
116(7.5)
(n=5)
130(809)
(n=5)
132(8)
Post-anesthetic heart rate: Mean (SD)
106(13.7)
188(10.2)
168(20.6)
204(11.7)
P value
1
0.04
0.04
0.03
Measured parameter
Pre-anesthetic respiratory rate: Mean (SD)
20. 8 (0.66)
Post-anesthetic respiratory rate: Mean (SD) 20.4 (0.4)
P value
0.31
22..2 (3.2)
21. 2 (0.58)
18.4 (1.7)
19.4 (1.4)
24. 8 (2.05)
26 (3.4)
0.17
0.07
0.07
Pre-anesthetic body temperature Mean (SD)
38..98 (0.15)
39.18 (0.09)
38.62 (0.5)
38.85 (0.14)
Post-anesthetic body temperature Mean(SD)
39 (0.16)
38. 3 (0.21)
39. 32 (0.33)
39 (0.14)
----------
0. 0 4
0.0 4
0. 0 3
P value
Pre-anesthetic glucose level: Mean (SD)
111.8 (11.81)
78.7 (9.7)
69.1 (3.1)
79. 98 (2.6)
Post-anesthetic glucose level: Mean (SD)
112 (11.7)
73. 8 (7.1)
72. 8 (4.4)
86.06 (2.5)
0.31
0. 34
0.04
0.04
P value
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Pre-anesthetic calcium level : Mean (SD)
9.3 (0. 34)
10. 58 (0. 27)
10. 5 (0. 26)
9.96 (0.14)
Post-anesthetic calcium level : Mean (SD)
9.26 (0.34)
10. 26 (0.21)
10.72 (0.23)
10. 66 (0.27)
0.15
0. 04
0. 03
0. 04
P value
Discussion
The saline placebo produced no effect in this study. In current investigation, our findings
in regards to increasing of body temperature and shortening of the duration of anesthesia
in dogs of group three and four is probably due to psychostimulant property of vitamin C.
The mechanism behind this finding is closely related to similar physiological properties
of vitamin C and amphetamine in the central nervous system (Elsa and Ubandawaki
2005). Amphetamine has powerful CNS stimulation actions. It lessens the degree of
central depression caused by various drugs, and produces other signs of central nervous
system stimulation. These effects are throught to be due to cortical stimulation and
possibly to stimulation of reticular activating system (Brunton, 2006). Furthermore
vitamin C is found in high concentrations in the striatum and suggests that the
extracellular level of this vitamin plays a critical role in behavioral activation (Rebec,
2001). We found significant increases in heart rate in dogs of groups two, three and four.
These results directly attributed to cardiac effects of ketamine. Ketamine is an analogue
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of phencyclidine which causes an increase in heart rate, cardiac output and arterial blood
pressure (Tilley, 1992). The observed increase in blood glucose level are similar to
results of Elas and Ubandawki 2005 in rabbits, who described that vitamin C appears to
be similar in structure to glucose and many animals convert the intermediate gluconic
acid to vitamin C. Although the increase in calcium levels in groups three and four was
statistically significant, but was a small increase? and is unlikely to be clinically
important. In conclusion, it seems that the premedication of vitamin C may be useful in
animals suffering from pre-surgical hypothermia, hypoglycemia, and in dogs who are
suspected to be in a risk with prolonged anesthesia.
References
Brunton LL: Goodman & Gilman's the Pharmacological Basis of Therapeutics. 11th
edition, McGraw-Hill Companies, 257, 2006.
Elsa, A and Ubandawaki, S Ketamine anesthesia following premedication of rabbits with
vitamin C. J Vet Sci., 6:239-41, 2005.
Lim, DK: Ketamine associated psychedelic effects and dependence. Sing. Med. J. 44,
31-4, 2003.
Madison E, Page SW, Church D: Small Animal Pharmacology. W.B. Saunders,
Philadelphia, 95, 2002.
Rebec GV , Pierce RC: A vitamin as neuromodulator: ascorbate release into the
extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission.
Prog Neurobiol. 43:537-65, 1994.
Rebec GV, Wang Z: Behavioral activation in rats requires endogenous ascorbate release
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Tilley LP: Essentials of Canine and Feline Electrocardiography, Interpretation and
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