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Effects of xylazine–ketamine–diazepam
anesthesia on blood cell counts and plasma
biochemical values in sheep and goats

ARTICLE in COMPARATIVE CLINICAL PATHOLOGY · JANUARY 2010

DOI: 10.1007/s00580-009-0923-7

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Zuhair Bani Ismail Khaleel Jawasreh

Jordan University of Science and Technology Jordan University of Science and Technology
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Comp Clin Pathol (2010) 19:571–574
DOI 10.1007/s00580-009-0923-7

ORIGINAL ARTICLE

Effects of xylazine–ketamine–diazepam anesthesia on blood

cell counts and plasma biochemical values in sheep and goats
Zuhair Bani Ismail & Khaleel Jawasreh &
Ahmad Al-Majali

Received: 4 August 2009 / Accepted: 8 October 2009 / Published online: 21 October 2009
# Springer-Verlag London Limited 2009

Abstract To examine the effects of xylazine, ketamine, a combination of xylazine, ketamine, and diazepam can be
diazepam anesthesia on clinical pathology parameters in used to induce short term anesthesia in sheep and goats with
sheep and goats, seven adult, healthy, non-pregnant Awassi minimum effects on clinical laboratory parameters.
sheep weighing 40–60 kg and seven adult, healthy non-
pregnant Damascus breed goats weighing 35 to 55 kg were Keywords Injectable anesthesia . Xylazine . Ketamine .
used. Anesthesia was induced using 0.1 mg/kg xylazine, Diazepam . Sheep . Goats . Clinical pathology
5 mg/kg ketamine, and 0.25 mg/kg diazepam as a single
intravenous injection. Blood cell counts and plasma biochem-
ical analysis were performed before anesthesia (T0), 2 h after Introduction
recovery, 24 h after recovery, and 5 days later. Hematological
analysis indicated that there was a significant increase in Xylazine (alpha2 adrenergic agonists) is the most commonly
neutrophil percentages (P≤0.05) in sheep and goats at 2 h used anesthetic agent in ruminants. It usually induces a dose-
and 24 h after recovery. There was a mild lymphopenia and a dependent sedative-hypnotic effect, and it can be combined
significant leukocytosis at 24 h after recovery in both species. with other anesthetic agents to obtain surgical anesthesia.
Packed cell volume was significantly increased at 24 h and at The use of xylazine in ruminants is associated with moderate
2 h and 24 h after recovery in sheep and goats, respectively, to severe cardiopulmonary depression, prolonged induction
while total red blood cell count was significantly decreased at and recovery, ineffective in excited animals, and at higher
24 h after recovery in sheep and goats. There were no doses, rumen stasis, apnea and bradycardia (Ewing 1990;
significant changes in hemoglobin, blood urea nitrogen, Riebold 1995; Wallincford et al. 1996).
creatinine, total protein, and albumin concentrations. Glucose Ketamine is an N-methyl-D-aspartate receptor antagonist
was significantly elevated at 2 h after recovery in goats only. (Ersek 2004). It induces a state referred to as dissociative
Aspartate aminotransferase, alkaline phosphatase, and anesthesia. Ketamine has a wide range of effects in animals,
gamma-glutamyl transpeptidase were not significantly including analgesia, anesthesia, elevated blood pressure,
changed at any sampling point. It is therefore concluded that and bronchodilation. Ketamine is primarily used for the
induction and maintenance of general anesthesia, usually in
combination with other sedative drugs such as xylazine or
butorphanol (Lin 1996; Lin and Pugh 2002).
Z. Bani Ismail (*) : A. Al-Majali Diazepam is a benzodiazepine derivative drug. It
Department of Veterinary Clinical Sciences, Faculty of Veterinary
possesses anxiolytic, anticonvulsant, hypnotic, sedative,
Medicine, Jordan University of Science and Technology,
Irbid 22110, Jordan skeletal muscle relaxant, and amnestic properties
e-mail: zuhair72@just.edu.jo (Mandrioli et al. 2008). A combination of diazepam and
ketamine with or without xylazine is frequently used to
K. Jawasreh
induce general anesthesia in small ruminants. Cardiopul-
Livestock and Range Land Research,
National Center for Agriculture Research and Extension, monary side effects of using various anesthetic reagents
Amman, Jordan have been studied in animals (Stegmann 1999; Taylor et al.
572 Comp Clin Pathol (2010) 19:571–574

Table 1 Hematological and

plasma biochemical values Parameter Time of sampling
(mean±SD) in Awassi sheep
following xylazine–ketamine– T0 2h 24 h 5 days
diazepam anesthesia (n=7)
RBC (×106) 9±3 8.9±1.5 8.2±2.1a 8.7±2.9
PCV (%) 28±2 28.4±1.3 33±5a 29±2.5
Hb (g/dl) 10±1.5 10.2±2 9.7±1.4 10.4±1.3
WBC (×103) 7±2.5 7.2±2 8.3±3.5a 7.5±2.8
Neutrophils (%) 40±12 55±13.5a 54±11a 42±12.5
Lymphocytes (%) 49±18 43±9 44±12 48±17
BUN (mg/dl) 15±4 14.2±2.8 14.9±3 15.2±1.8
Creatinine (mg/dl) 0.5±0.3 0.7±0.1 0.5±.2 0.5±0.4
Glucose (mg/dl) 68±9 75±12 70±9 72±13
Total protein (g/dl) 6.2±0.5 6.5±.1 6.3±.4 6±0.8
Albumin (g/dl) 2.3±0.5 2±0.5 2.1±0.9 2±0.2
AST (U/ml) 55±10 49±15 53±17 51±12
ALP (U/ml) 120±32 117±12 123±9 125±15
a
Indicate significant changes GGT (U/ml) 31±12 23±10 29±12 33±14
(P≤0.05)

1992; McEwen et al. 2000). However, little information is Materials and methods
available on the systemic effects of using xylazine–
ketamine–diazepam combination to induce and maintain Experimental design
general anesthesia in small ruminants. Undesirable systemic
effects due to this combination in various organs can be Seven healthy, adult non-pregnant Awassi sheep weighing
revealed by studying the changes in biochemical and/or 40–60 kg and seven adult, healthy non-pregnant Dam-
hematological parameters (Topal et al. 2003; Steffey et al. ascus breed goats weighing 35 to 55 kg were used.
1993). Thus, the aim of this study was to examine the Animals were kept at the National Center for Agriculture
clinical pathology effects of xylazine–ketamine–diazepam Research and Extension farm at Al-Khanasri region in
anesthesia in Awassi sheep and Demascus breed goats. North Jordan. The study was conducted during April of

Table 2 Hematological and

plasma biochemical values Parameter Time of sampling
(mean±SD) in Damascus goat
following xylazine–ketamine– T0 2h 24 h 5 days
diazepam anesthesia (n=7)
RBC (×106) 11.3±2.5 10.5±3 9.3±2.2a 10.8±1.2
a
PCV (%) 27±2 29.7±1.6 28.5±2.7a 27±0.6
Hb (g/dl) 9±1.3 8.9±1.4 9.2±1.6 9±1.8
WBC (×103) 8±4 8.3±3.5 9.9±3a 8.2±2.9
Neutrophils (%) 37±9 49±12a 47±9a 39±7
Lymphocytes (%) 62±13 59±12 58±9.5 60±15
BUN (mg/dl) 25±6 24±3 25.5±5.6 23±6.5
Creatinine (mg/dl) 0.7±0.8 0.76±0.7 0.6±0.9 0.67±0.8
Glucose (mg/dl) 72±16 78±14a 69±23 71±13
Total protein (g/dl) 7.3±0.6 7.5±0.1 7.4±0.9 7.2±0.5
Albumin (g/dl) 3.0±0.7 2.9±0.3 3.0±0.4 2.8±0.8
AST (U/ml) 41±22 36±28 44±23 49±18
ALP (U/ml) 55±17 53±14 58±20 51±15
a
Indicate significant changes GGT (U/ml) 33±12 29±16 31±11 33±11
(P≤0.05)
Comp Clin Pathol (2010) 19:571–574 573

2008. Animals were fed an adequate diet of hay and grain Tables 1 and 2, respectively. In the hematological analysis,
twice daily, in addition to a limited daily access to there were a significant (P≤0.05) increase in total white
pasture. Animals were routinely administered anthelmen- blood cell count, neutrophil percentage, and PCV value at
tic prophylaxis four times per year. Animals were 24 h after recovery in sheep. Neutrophil percentage was
thoroughly examined for abnormalities in different body also significantly (P≤0.05) elevated at 2 h. In goats, total
systems. Animals with abnormalities were excluded. In white blood cell count, neutrophil percentage, and PCV
addition, whole blood was collected for hematological value were significantly (P≤0.05) elevated at 24 h after
and biochemical analysis before the start of the study. recovery. In addition, neutrophil percentage and PCV value
Only animals that showed normal blood parameters were were significantly (P≤0.05) elevated at 2 h after recovery.
included in the study. In both species, there was a non-significant decrease in
Before induction of anesthesia, animals were kept off lymphocyte percentage at 2 and 24 h after recovery. The
feed and water for 12 h and 2 h, respectively. Anesthesia reported increase in total white blood cells and percentage
was induced using 0.1 mg/kg, 5 mg/kg, and 0.25 mg/kg of neutrophils at 2 and 24 h after recovery is typical of
xylazine, ketamine, and diazepam, respectively, as a single corticosteroid induced stress response (Carrol et al. 1997).
intravenous injection in the same syringe. Whole blood for The increased in PCV value could be due to mild
hematological and plasma biochemical analyses was with- dehydration.
drawn from all animals from the jugular vein. Blood cell In the plasma biochemical analysis, blood urea nitrogen,
counts and plasma biochemical analysis were performed and creatinine were not significantly elevated at any time
before anesthesia (T0) and at 2 h after recovery, 24 h after point. In goats, glucose value was significantly elevated at
recovery, and 5 days later. Hematological analysis was 2 h after recovery and not significantly elevated in sheep.
performed using electronic cell counter (ABC Vet hematol- Mild hyperglycemia has been related to an increase in
ogy analyzer, ABX Diagnostics, France). Plasma was adrenaline and/or corticosteroids secretion (Carrol et al.
collected by centrifugation of blood tubes at 5,000×g for 1997). Total protein values were not significantly elevated
10 min at 4°C, and stored at −20°C until analyzed. Plasma at 2 and 24 h after recovery which may also be explained
was analyzed for TP (Biuret method), albumin (BCG by a mild but not significant hemoconcentration.
method), blood urea nitrogen (Colorimetric method), creat- Liver enzymes including AST, ALP and GGT were not
inine (Kinetic method), glucose (GOD-PAP method), AST significantly affected in sheep and goats following xyla-
(IFCC method), GGT (Kinetic method) and ALP (Kinetic zine–ketamine–diazepam anesthesia. Relative increase in
method) using commercially available kits and reagents AST, ALP and GGT has been reported in sheep, calves, and
according to manufacturers' recommendations. horses following prolonged halothane anesthesia due to the
induction of hepatic microsomal enzymes by halothane
Analysis of data (Steffey et al. 1993; Rajaian et al. 2008). It seems that none
of the used drugs in this study induces such hepatic
Data are presented as mean±SD of means. Non-paired microsomal changes.
Student's t test was used to examine the significance of Results of this study show that xylazine–ketamine–
differences between parameters in sheep and goats. The diazepam anesthesia can be used safely in sheep and goats
difference was considered statistically significant at P≤0.05. after a single intravenous injection. However, studies on the
effect of repeated injections of this combination are needed
in the future.
Results and discussion
Acknowledgements This project was partially sponsored by the
Deanship of Research at Jordan University of Science and Technol-
The average surgical anesthesia induced using a combina-
ogy. The authors would like to thank the National Center for
tion of xylazine, ketamine, and diazepam was 67 and Agriculture Research and Extension, for providing the animals used
60 min in sheep and goats, respectively. Smooth induction in this study and for their technical help.
within approximately 3–5 min was achieved in both
species. Prolonged but smooth recovery however was
observed. In small ruminants, rapid smooth induction and References
gradual recovery while producing sufficient depth of
anesthesia have been reported using this combination Carrol GL, Hartsfield SM, Hambleton R (1997) Anesthetic effects of
(Carrol et al. 1997; Lin and Pugh 2002; Ceylan et al. 2007). tiletamine-zolazepam, alone or in combination with butorphanol,
in goats. JAVMA 211:593–597
Changes in hematological and biochemical values
Ceylan C, Aydilek N, Ipek H (2007) Effects of tiletamine-zolazepam
following xylazine-ketamine-diazepam anesthesia in anesthesia on plasma antioxidative status and some hematolog-
Awassi sheep and Damascus goats are summarized in ical parameters. Acta Vet Hung 55:191–197
574 Comp Clin Pathol (2010) 19:571–574

Ersek R (2004) Dissociative anesthesia for safety's sake: ketamine and Riebold TW (1995) Large animal anesthesia: principles and techni-
diazepam-a 35-year personal experience. Plast Reconstr Surg ques. Iowa State University Press, Ames, Iowa
113:1955–1959 Steffey EP, Giri SN, Dunlop CL, Cullen LK, Hodgson DS, Willits N
Ewing KK (1990) Anesthesia techniques in sheep and goats. Vet Clin (1993) Biochemical and hematological changes following pro-
North Am Food Anim Pract 6:759–778 longed halothane anesthesia in horses. Res Vet Sci 55:338–345
Lin HC (1996) Lumb and Jones' veterinary anesthesia. Williams and Stegmann GF (1999) Observations on some cardiopulmonary effects
Wilkins, Media, Pennsylvania of midazolam, xylazine and a midazolam/ketamine combination
Lin HC, Pugh DG (2002) Sheep and goat medicine. Saunders, Pennsylvania in the goat. JSAVA 70:122–126
Mandrioli R, Mercolini L, Raggi MA (2008) Benzodiazepine Taylor JH, Botha CJ, Swan GE, Műlders MSG, Grobler MJ (1992)
metabolism: an analytical perspective. Curr Drug Metab Tiletamine hydrochloride in combination with zolazepam hydro-
9:827–844 chloride as an anaesthetic agent in sheep. JSAVA 63P:63–65
McEwen MM, Gleed RD, Ludders JW, Stokol T, Del Piero F, Erb HN Topal A, Gul N, Llcol Y, Gorgul OS (2003) Hepatic effects of
(2000) Hepatic effects of halothane and isoflurane anesthesia in halothane, isoflurane or sevoflurane anaesthesia in dogs. JVMA
goats. JAVMA 217:1697–1700 50:530–533
Rajaian H, Nazifi S, Nayeri K, Saberi FA (2008) Effects of 2 h anesthesia Wallincford BD, Lancia RA, Soutiere EC (1996) Antagonism of
with halothane on blood cell counts and serum biochemical values xylazine in white-tailed deer with intramuscular injection of
in sheep and calves. Comp Clin Pathol 17:13–16 yohambine. JWD 32:399–402