Download cardiopulmonary, biochemical, and haematological changes after

Bull Vet Inst Pulawy 52, 453-456, 2008
CARDIOPULMONARY, BIOCHEMICAL,
AND HAEMATOLOGICAL CHANGES
AFTER DETOMIDINE-MIDAZOLAM-KETAMINE
ANAESTHESIA IN CALVES
NUH KILIÇ
Department of Surgery, University of Adnan Menderes, Bati Kampüsü, 09016 Aydın, Turkey
[email protected]
Received for publication May 16, 2008
Abstract
The aim of the study was to investigate the suitability
of detomidine-midazolam-ketamine combination for umbilical
surgery in calves. Fifteen calves subjected to umbilical surgery
received detomidine (100 pg/kg b.w.), midazolam (0.5 mg/kg
b.w.), and ketamine (10 mg/kg b.w.) intravenously (iv), as a
mixture of the drugs. Rectal temperature, and heart, pulse, and
respiratory rate were recorded before drug administration and
at 5, 10, 15, 30, and 45 min after anaesthesia. Haematological
and biochemical parameters were detected before drug
administration, 15, 30, 45, and 60 min after drug injection and
24 h after anaesthesia. The combination of the compounds
resulted in anaesthesia lasting about 45 min and a satisfactory
immobilisation for umbilical surgery, although some
hypoxaemia and respiratory acidosis occurred. The body
temperature of the calves decreased significantly (P<0.05)
during the anaesthesia from 38.5°C to 37.9°C. Haemoglobin,
PCV, and RBC decreased significantly (P<0.05) for a short
time. The values for plasma glucose, creatinine, and ALT
increased significantly (P<0.05). However, they returned to the
baseline at 24 h. Muscle relaxation was good and no
complications were encountered.
Key words: calves, surgery, detomidine,
ketamine, midazolam.
General anaesthesia is required in calves for
complex surgical or diagnostic procedures. Inhalation
anaesthesia requires specific equipment and may only be
possible under hospital conditions. It is rarely feasible
for the use in the field. The adverse effects of
atmospheric pollution and low-level personnel exposure
to volatile anaesthetics must also be considered.
α2-agonists are effective sedatives in calves;
xylazine is currently used to provide sedation and
immobilisation, including recumbency and light planes
of general anaesthesia (4). However, it causes
hypoxaemia and hypercapnia in calves (21, 24) and may
induce acute pulmonary oedema in sheep (27).Various
injectable anaesthetic techniques can be used for calves
under field conditions. Thiobarbiturates alone or in
combination with guaiphenesin (GGE) can be used for
the induction and maintenance of anaesthesia (25).
Ketamine is commonly used in calves alone or
combined with xylazine (23, 29, 30), or medetomidine
(22). The combination of medetomidine and ketamine
produced satisfactory immobilisation for umbilical
surgery, although some hypoxaemia and respiratory
acidosis occurred. Muscle relaxation was good and no
complications were encountered. Tiletamine, another
cyclohexanone
derivative,
and
zolazepam
(a
benzodiazepine) may also be used. This combination has
been investigated for the use with and without xylazine
(11, 26). Propofol, a non-barbiturate, non-steroidal
hypnotic agent produces short-time anaesthesia in most
species. Economic and licensing factors limit its use in
farm animals.
Detomidine alone at the dose rate of 100 µg/kg
produced only mild sedation and analgesia in buffalo
calves (17). The addition of diazepam and ketamine to
detomidine produced anaesthesia of a short duration (15
min) and prolonged sedation and analgesia. The
combination of detomidine- diazepam-ketamine may be
used safely in buffalo calves to induce a transitory
anaesthesia or chemical immobilisation for clinical
examination (17).
The purpose of the present study was to
investigate the suitability of detomidine-midazolameketamine combination for umbilical surgery in calves.
Material and Methods
The study was approved by the University of
Adnan Menderes Institutional Animal Care and Use
Committee.
Appropriate doses of detomidine (Domosedan;
Orion Corporation Farmos, Finland), ketamine
(Alfamyne; Egevet, Turkey), and midazolame
454
(Demizolam; Dem, Turkey) were mixed in a syringe and
the mixture was used to induce anaesthesia in 15
Holstein calves (7 males and 8 females), weighing 40120 kg and 5 to 90 d of age, with umbilical problems
(hernia, abscess, omphalophlebitis, urachitis). They were
not fed in the morning of the procedure day. All the
calves were given intravenously 100 pg/kg b.w. of
detomidine, 10 mg/kg b.w. of ketamine, and 0.5 mg/kg
of midazolame. The calves were operated on dorsal
recumbency. Lidocaine (Carbocain; Astra, Sweden) in a
dose of 20 mg/mL was used subcutaneously at the
incision site as a local anaesthetic.
The following variables were measured before
and 5, 10, 15, 30, and 45 min after drug injection: heart
rate (HR, beats/per min), respiratory rate (RR,
breaths/per min), rectal temperature (CT), sodium
(Na+), potassium (K+), ionised calcium (iCa++), arterial
pH (pHa), arterial oxygen tension (paO2), arterial carbon
dioxide tension (paCO2), bicarbonate concentration
(HCO3), and base excess (BE). Respiratory rate was
determined by a direct observation. Arterial blood
samples were collected into heparinised syringes for the
measurement of electrolytes and blood gas values. Air
was removed from the blood gas syringe, and the sample
was immediately analysed using an automated blood gas
analyser (Model ITC Irma Tripoint, Blood analysis
System, ITC, USA), which corrected the reported values
for body temperature to 41°C. The values of total
protein, ALT, AST, creatinine, urea, and glucose were
determined by Microlab 200 (Merck) using
commercially available kits (Biomedical Systems,
Spain). The analyses were carried out according to the
manufacturer’s instructions. To determine the number of
erythrocytes (RBC) and leukocytes (WBC), packed cell
volume (PCV), and haemoglobin (Hb) concentration,
blood was collected into heparinised tubes at baseline
and 15, 30, 45, and 60 min after induction of anaesthesia
with detomidine/midazolam/ketamine and 24 h after the
anaesthesia and analysed by a automatic cell counter
(Abacus Junior Vet, Interpet, Turkey). The animals were
observed continuously during the recovery period until
they were standing.
The data were analysed with 'Statgraphics'
statistical graphics programme using paired and
unpaired Student's t-tests. Minimum statistical
significance was taken as P<0.05.
Results
The calves showed the first signs of sedation
(sunken head and reduced awareness) 0.7±0.3 min after
the administration of the combination of the drugs. They
lay down, usually first to sternal recumbency, 1.1 ± 0.8
min after the injection and were deeply sedated in lateral
recumbency after 1.7 ± 0.57 min. The combination of
detomidine, midazolam, and ketamine resulted in the
anaesthesia lasting about 45 min. Heart and respiratory
rates, pa02, paC02, pH, and electrolytes before and after
administration of medetomidine are shown in Table 1.
There was a statistically significant decrease
(P<0.05) in the mean heart rate, arterial pH, and pa02
and an increase (P<0.05) in paC02 within 5 min of the
injection. Respiratory rate increased significantly
(P<0.05) with time, whereas base excess had a slight
tendency to decrease. The body temperature decreased
significantly (P<0.05) during the anaesthesia from 38.5
±0.3oC to 37.9±0.4. The blood sodium, kalium, and
ionised calcium decreased with time during the whole
period of anaesthesia.
Table 1
Heart rate, respiratory rate, rectal temperature, blood gas values and electrolytes (Na+, K+, and iCa++) in calves
before (baseline) and after intravenous administration of detomidine (0.1 mg/kg),
midazolam (0.5 mg/kg) and ketamine (10 mg/kg)
Time (min)
0 (baseline)
5
10
15
30
45
HR (beats/min)
RR (breaths/min)
T(C)
pH (units)
paCO2 (mmHg)
paO2 (mmHg)
HCO3 (mEq/L)
87±13.6
22.7±12.2
38.5±0.3
7.43±0.01
48±5
93±5.1
29.8±2.3
72.5±6.2 a
37.5±11.5 a
38.4±0.3
7.38±0.01 a
54.5±3.3 a
78.5±3.7 a
29.5±2.8,
77.7±7.7
36.2±12.2 a
38.3±0.2
7.35±0.03 a
55±0.3 a
72.6±6.3 a
29.4±3.0
78.0±11.1
43.1±10.5 a
38.3±0.5
7.33±0.01 a
58±2.3 a
71.7±11.8 a
28.8±1.7
78.9±6.3
44.8±12.2 a
38±0.3
7.31±0.01 a
61±0.24 a
67.72±7.30 a
27.7±2.8
73.1±5.2 a
44.1±13.3 a
37.9±0.4a
7.30±0.02 a
64±0.01 a
66.8±6.2 a.
27.2±4.1
BE (mEq/L)
6.6±2.5
4.8±3.7
3.6±2.3 a
1.7±1.8 a
-1.3±3.30 a
-2.8±4.2
Na+(mmol/L)
138±2.3
136±3.3
132±2.1
134±4.3
132±2.3
132±4.3
K+(mmol/L)
iCa++(mmol/L)
4.40±1.3
1.32±0.3
4.2±1.1
1.29±0.2
3.97±0.9
1.26±0.4
4.27±1.2
1.27±0.6
3.8±0.9
1.23±0.3
3.9±1.3
1.20±0.2
Values are reported as mean ± SE.
a
Mean value differs significantly (P<0.05) from baseline value; BE= base excess
a
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Table 2
Haematological and biochemical changes in calves before (baseline) and after administration of detomidine (0.1
mg/kg), midazolam (0.5 mg/kg) and ketamine (10 mg/kg)
Time
ALT
ALP
TP
Ure (mg/dl)
Creatinin (mg/d L)
Glucose (mEq/L)
Hb (g/dL)
PCV
WBC
RBC
0 (baseline)
26.8±3.6
288.5±12.3
6.8±0.8
24.6±1.6
1.23±0.07
64.3±1.9
10.88±0.8
28.8±1.9
16.6±0.2
6.92±0.4
15 min
32.5±3.2
331.1±3.8
6.3±0.8
31.2±2.7
1.45±0.03 a
80.5±2.8 a
10.82±1.1
27.5±2.9
13.3±0.3
6.32±0.3
30 min
40.7±4.2 a
340.3±0.6
6.5±0.8
39.9±0.3 a
1.47±0.03 a
79.4±3.1 a
9.95±0.8
26.6±1.1
12.2±0.8
5.80±0.2
45 min
42.0±1.1 a
360.9±1.5
6.2±0.8
32.0±2.1 a
1.61±0.1 a
81.8±2.7 a
9.76±1.2 a
26.2±2.1 a
12.6±0.5
5.66±0.3 a
60 min
43.89±0.3 a
385±0.2 a
6.0±0.8
36.1±5. 6 a
1.68±0.02 a
83.7±2.28 a
9.82±1.4 a
26.4±2.5 a
11.8±0.4
5.75±0.2 a
24 h
23.1±2.2
300.5±0.2
6.9±0.8
28.5±2.6
1.26±0.01
61.3±3.4
11.2±1.6
30.5±1.9
18.6±0.8
7.01±0.4
Values are reported as mean ± SE.
a
Mean value differs significantly (P<0.05)
The haematological and biochemical variables
are shown in Table 2. The ALT and ALP increased
significantly (P<0.05) with time during the anaesthesia
and returned to the baseline at 24 h. The values of serum
concentrations of creatinine, urea nitrogen, and glucose
showed a significant (P<0.05) increase during postinjection period. Haemoglobin, PCV, and RBC
decreased significantly (P<0.05) for a short time in all
animals after the injection of the compounds. The values
for PCV and Hb; however, it returned to the baseline
and the values for WBC showed a non-significant
increase at 24 h.
Discussion
According to Blaze et al. (2) after
administration of medetomidine and ketamine to the
calves, paCO2 increased and heart rate, paO2, and pH
decreased,
as
has
been
reported
during
xylazine/ketamine narcosis. Five minutes after the first
medetomidine/ketamine injection, all the calves were
acidotic. The lowest individual arterial pH measured in
this study was 7.3, which was no lower than the lowest
pH recorded by the mentioned authors. The combination
of detomidine, midazolam, and ketamine resulted in
anaesthesia lasting about 45 min. The duration of
anaesthesia induced by xylazine/ketamine (0.2 mg/kg
b.w. and 5 mg/kg b.w. or 10 mg/kg b.w., respectively)
was approximately 23 min in calves older than 10 weeks
of age (29).
In our experience, the duration of the sedation
and analgesia induced by detomidine/midazolam/
ketamine is enough for students to perform umbilical
herniotomy. In the present study, local analgesic
solution was used only in the subcutaneous tissues to
reduce
the
need
for
another
dose
of
detomidine/midazolam/ketamine while the skin was
sutured, and only for calves operated in dorsal
recumbency. The calves did not react when the muscular
layers or peritoneum were manipulated. The potency of
detomidine made it possible to reduce the dose of
ketamine to 0.5 mg/kg b.w., which is only 10% of the
dose used in combination with xylazine (2, 29).
Rectal temperature decreased in this study. A
decrease in RT was recorded following systemic
administration of α2-adrenoceptor agonists (16), which
was attributed to the depression of the hypothalamic
thermoregulatory centre (12). The decrease in RT was
also probably the result of a reduced basal metabolic rate
(BMR) and muscle activity, and depression of
thermoregulatory centre (18). Hypothermia was also
observed after administration of medetomidine in goats
(13).
Haemoglobin, PCV, and RBC decreased for a
short time in all the groups after the administration of
detomidine, midazolam, and ketamine. However, the
values for PCV and Hb returned to the base line and the
values for WBC showed a non-significant increase at 24
h. Pooling of circulating blood cells in the spleen and
other reservoirs secondary to decreased sympathetic
activity could be the reason for a decrease in Hb, PCV,
and WBC (8, 17). The decrease in PCV and Hb during
the period of anaesthesia or sedation might be attributed
to the shifting of fluid from extravascular compartment
to intravascular compartment in order to maintain
normal cardiac output in the animals (28).
The values for plasma glucose increased in
animals of all the groups. Hyperglycaemic effects of α2adrenoceptor agonists are well known. There have been
many investigations into the hyperglycaemic effects of
xylazine (5, 6) and medetomidine (3). The
hyperglycaemic effect might be to the result of α2adrenergic receptor inhibition of insulin release by the
stimulation of α2-adrenoreceptors in the pancreatic β
cells (1) and to an increased glucose production in the
liver (6).
A significant increase in plasma creatinine was
recorded in all the groups. The values returned to
baseline in 24 h in all animals. The increase in plasma
creatinine might be attributed to the temporary
inhibitory effect of these drugs on the renal blood flow,
which in turn might have caused a rise in plasma
creatinine values. However, it is difficult to ascribe this
to possible renal damage, because all the reported values
were within normal physiological limits (7). Parenteral
administration of xylazine was also reported to cause a
456
rise in creatinine level in buffaloes (14). Plasma urea
nitrogen showed a significant increase in all the groups
during post-injection period. This might be attributed to
a temporary inhibitory effect of the drug on the renal
blood flow, which in turn might have caused a rise in
BUN (9). In addition, increased hepatic urea production
from amino acid degradation could account for the
observed increase in BUN values as was recorded by
Eichner et al. (5). Similar changes in BUN were also
reported after administration of detomidine in goats (10)
and after xylazin-diazepam administration in horses (8).
However, no change in BUN was observed after
xylazine injection in goats (10).
The ALT and ALP increased during the
anaesthesia. As the values returned to the preadministration level, the possibility of pathological
changes in the liver could therefore, be ruled out. It
corroborates with the findings of Koichev et al. (9) after
detomidine administration in cattle and sheep. Changes
in plasma electrolytes (Na+, K+, and Ca++) were only
transient, and the values returned to near normal level
after 24 h.
The combination of detomidine, midazolam,
and ketamine produced satisfactory immobilisation and
anaesthesia for umbilical surgery in calves, although
some hypoxaemia and respiratory acidosis occurred.
Muscle relaxation was good and no complications were
encountered.
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