J. Vet. Med. A 50, 190–195 (2003)
Ó 2003 Blackwell Verlag, Berlin
ISSN 0931–184X
Section of Veterinary Anaesthesiology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
Effects of Intravenous Lidocaine on Isoflurane Concentration, Physiological
Parameters, Metabolic Parameters and Stress-related Hormones in Horses
Undergoing Surgery
T. B. Dzikiti1,2, L. J. Hellebrekers1 and P. van Dijk1,3
Addresses of authors: 1Section of Veterinary Anaesthesiology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box
80.153, 3508 TD Utrecht, The Netherlands; 2Department of Clinical Veterinary Studies, Faculty of Veterinary Sciences,
University of Zimbabwe, P.O. Box MP 167, Mt Pleasant, Harare, Zimbabwe; 3Corresponding author: E-mail: [email protected]
With 2 figures and 3 tables
Received for publication: June 14, 2002
Summary
Physiological parameters, metabolic parameters and stressrelated hormones are evaluated in horses anaesthetized with
isoflurane in oxygen combined with lidocaine intravenously.
Two groups of horses anaesthetized with isoflurane (six horses
in each group) were studied: a lidocaine group (IL), which
received intravenous lidocaine and a control group (C), which
received intravenous saline. Horses in both groups were premedicated with detomidine (IV), and anaesthesia was induced
with midazolam-ketamine (IV). The lidocaine group received
intravenous lidocaine as a loading dose of 2.5 mg kg)1 at
15 min after induction of anaesthesia directly followed by a
maintenance dosage of 50 l kg)1 min)1, while the control
group received saline (IV) following the same regime. Endtidal isoflurane and standard physiological parameters were
measured. Blood was sampled for measurement of lidocaine,
stress hormones and metabolic parameters. The end-tidal
isoflurane concentration in the lidocaine group was
0.96 ± 0.06% versus 1.28 ± 0.06% (mean ± SD) in the control group, a significant (P < 0.05) reduction of 25%. No
significant differences were found regarding stress-related
hormones, metabolic and physiological parameters. This study
suggests that the use of lidocaine to decrease the concentration
of isoflurane to obtain a sufficient surgical anaesthesia has no
subsequent effects on physiological and metabolic parameters
or stress-related hormones.
Introduction
Lidocaine has traditionally been used as a local anaesthetic
agent (Hall and Clarke 1991; Harkins et al., 1998) and for the
treatment of premature ventricular contractions (Muir et al.,
1995). Thereafter intravenously administered lidocaine may
contribute to general anaesthesia and analgesia with minimal
negative cardiovascular effects (Wood-Smith et al., 1975).
Lidocaine is known to reduce the requirement for inhalation
anaesthetics in humans (DeClive-Lowe et al., 1958; Philips
et al., 1960), dogs (Himes et al., 1977) and horses (Doherty
and Frazier, 1998) when used in this way.
The anaesthetic effect of isoflurane is accompanied by a
dose-related depression of the cardiovascular and respiratory
function (Steffey and Howland, 1980; Thurmon et al., 1996)
and little analgesic effect (Paddleford, 1991). By combining
isoflurane with lidocaine, potentially less isoflurane will be
U.S. Copyright Clearance Center Code Statement:
needed, and therefore the negative effects of isoflurane on the
cardiopulmonary system may be reduced.
Although no work has been reported on the effects of
lidocaine on required isoflurane concentration in horses
undergoing surgery, there is no evidence to suggest that the
concentration of isoflurane would be effected differently by an
infusion of lidocaine than halothane as was described by
Doherty and Frazier (1998). The purpose of our study was to
determine the effect of intravenous lidocaine infusion on
required isoflurane concentration in horses (ASA class I or II)
anaesthetized for elective surgery. Another objective was to
determine plasma concentrations of cortisol, insulin, nonesterified fatty acids (NEFA) to assess stress response during
isoflurane/lidocaine anaesthesia. Plasma lactate dehydrogenase
(LDH), creatinine kinase (CK) and aspartate aminotransferase
(ASAT) were measured to evaluate influence on procedure
related muscle damage.
Materials and Methods
The study was approved by the Research Board and Clinical
Committee of the Department of Equine Sciences of the
Veterinary Faculty of Utrecht University.
Animals
The horses used for this study were randomly drawn from
patients (ASA class I or II) referred to the Department of
Equine Sciences of Utrecht University for elective surgery
lasting at least 90 min. Six Dutch Warmblood geldings (group
IL) aged 3–21 years (mean 8 years) and weighing 550–697 kg
(mean 603 kg) were anaesthetized with the combination
isoflurane/oxygen and lidocaine IV. Six Dutch Warmblood
horses (three geldings and three mares) aged 2–13 years (mean
8 years) and weighing 550–697 kg (mean 605 kg) anaesthetized
with isoflurane/oxygen were used as a control group (group C).
Study design
All horses had food but not water which was withheld for 6 h
before pre-medication. Pre-medication in both groups was
with detomidine (DomosedanÒ; Orion Corporation, Espoo,
Finland) (0.01 mg kg)1) intravenously. Once sedation had
developed an 8 cm 12-G polytetrafluoroethylene catheter
0931–184X/2003/5004–0190 $15.00/0
www.blackwell.de/synergy
END-TIDAL Isoflurane Concentrations
191
(Intraflon 2Ò; Vygon Nederland BV, Veenendaal, The
Netherlands) was placed percutaneously into the left jugular
vein by which midazolam (Midazolam 5 mg ml)1; Apotheek
Diergeneeskunde, University of Utrecht, the Netherlands)
(0.06 mg kg)1) and ketamine (NarketanÒ 100 mg ml)1; Chassot AG, Belp, Berne, Switzerland) (2.2 mg kg)1) were administered to induce anaesthesia. When recumbent, the horses
were orotracheally intubated and anaesthesia was maintained
with isoflurane (IsofloÒ; Schering-Plough, Essex Tierarznei,
Munchen, Germany) in oxygen (4 l min)1). Isoflurane was
delivered by an out-of-circuit isoflurane vaporizer (Isoflurane
Vapour 19.3Ò; Dräger, Lübeck, Germany). Ringer’s solution
(6 ml kg)1 h)1) was administered intravenously throughout
the procedure. ECG and pulse-oximetry (Pulse oximeter,
Nellcor; Hewlett Packard, Bad Homburg, Germany) were
recorded continuously during anaesthesia. An arterial catheter
was placed percutaneously into the facial artery or lateral
metatarsal artery for measurement of arterial blood pressure
and blood sampling. Systolic, diastolic and mean blood
pressures were monitored continuously using a multichannel
recorder (Multichannel recorder; Hewlett Packard). Inspiratory and expiratory concentrations of isoflurane, carbon
dioxide and oxygen as well as respiratory frequency were
measured continuously using a methane-insensitive infrared
gas analyser (Infra-red anaesthetic gas analyser; Bruel &
Kjaer, Naerum, Denmark). Ventilation was controlled to
maintain PaCO2 between 38 and 42 mmHg. As soon as a
surgical level of anaesthesia was achieved a loading dose of
lidocaine (Lidocaine HCL 2%Ò; Eurovet, Bladel, the Netherlands) (2.5 mg kg)1) to group IL and an equal volume of saline
to group C was administered intravenously over 10 min. A
maintenance dose of lidocaine 50 l kg)1 min)1 (IL) or an
equal volume of normal saline (C) was then administered
during 75 min using an automatic infusion pump (Graseby
3400 Anaesthesia Pump; Graseby Medical Ltd, Watford
Hertz, UK). The dosages of lidocaine were adopted from
Doherty and Frazier (1998). Meanwhile, the end-tidal isoflurane concentration in both groups was reduced as much as
possible depending on the required level of anaesthesia.
Adequacy of anaesthesia was judged by normal clinical signs
and monitored parameters. Arterial and venous blood was
sampled for measurement of pH, PaO2, PaCO2 and blood
concentrations of lidocaine, cortisol, insulin, LDH, CK, ASAT
and NEFA according to the schedule presented in Table 1.
The horses from both groups were followed to the recovery
box to observe, monitor, and record behaviour and length of
the recovery phase.
Blood samples for measurement of LDH, CK and ASAT
were immediately analysed in the laboratory using a colorimetric technique. The samples for cortisol, insulin and NEFA
were immediately centrifuged and plasma was stored at )20°C
until the assays were performed. Insulin and cortisol were
measured by a solid-phase radioimmunoassay using a CoatA-Count kit [Coat-A-CountÒ Insulin and Coat-A-CountÒ
Cortisol; Diagnostic products CorporationÒ, (DPC) Los
Angeles, USA]. NEFA were measured by colorimetry using
a Randox kit (Randox kit; Randox Laboratories Ltd,
Ardmore, UK).
Blood samples collected for lidocaine analysis were stored
at )80°C. The samples were centrifuged and the plasma
was analysed by a fluorescence polarization immunoassay
technique using a TDx/TDxFLx kit (TDxÒ/TDxFLx
Lidocaine assay; Abbot Laboratories, Abbot Park, IL
60064, USA).
Statistical analysis
Statistical analysis was performed using the SPSSÓ 8.0
statistical package (SPSS Inc. Ó Chicago, IL, USA). Differences between the means of group IL and group C with regards
to end-tidal isoflurane concentration, HR, MAP, arterial
blood pH, end-tidal CO2 concentration, PaCO2, PaO2, NEFA
levels, cortisol levels, insulin levels, muscle enzymes at different
time points were analysed using the independent t-test with
variances assumed unequal. A paired t-test was used to
compare time point means for all the parameters to baseline
means. Pearson’s correlation test was used to compare the
decrease in required isoflurane concentration and plasma
lidocaine levels. Data are presented as mean ± SD. Differences were considered to be significant when P < 0.05.
Table 1. Schedule for blood sampling for different parameters
Time
Baseline
T0
T15
T30
T45
T60
T75
T90
T105
Tend
Tend + 30 min
Tend + 60 min
Tend +3 h
Tend + 24 h
Parameter
Type of blood
Anticoagulant
Lidocaine
Venous
Lithium/heparin
Cortisol/Insulin
Venous
EDTA/K3
Muscle enzymes
Venous
Lithium/heparin
NEFA
Venous
NaF/EDTA/K3
pH/blood
Arterial
Heparin
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Baseline ¼ before sedation, T0 ¼ time just after induction, Tend ¼ end of anaesthesia, NEFA ¼ non-esterified fatty acids, K3 ¼ Potassium,
NaF ¼ Sodium fluoride, *point at which blood sample was collected.
T. B. Dzikiti et al.
192
Results
The averaged end-tidal isoflurane concentration in group IL
during lidocaine infusion was 0.96 ± 0.06 and 1.28 ± 0.06%
(mean ± SD) during saline infusion in group C, accounting to
a decrease of 25%. The difference between these two values is
significant (P < 0.05). Plasma lidocaine concentration ranged
from 0.03 to 4.23 lg ml)1 (Fig. 2). There was a strong
correlation (P < 0.05, r ¼ 0.766) between the decrease in
end-tidal concentration of isoflurane and plasma lidocaine
concentration. No significant differences were observed
between group IL and group C with regards to mean arterial
pressure, end-tidal carbon dioxide, pH, PaO2, PaCO2, cortisol,
NEFA, LDH, CK and ASAT. No significant differences were
observed between group IL and group C with regard to insulin
concentration, except at baseline reading, at 90 min of
anaesthesia and at 30 min after end of anaesthesia. A detailed
outline of the results is illustrated in Tables 2 and 3, Figs 1
and 2.
In group C, times to sternal recumbency and standing after
termination of general anaesthesia were 11 ± 7 min and
15 ± 8 min, respectively. In group IL, times to sternal
recumbency and standing after termination of general anaesthesia were 19 ± 9 and 27 ± 13 min, respectively. The
difference in mean values of these times between the two
groups was not statistically significant. Three of the horses in
group C showed excitement during recovery from anaesthesia,
while all the horses in group IL had incident-free recoveries.
The mean pre-operative temperature for both groups was
37°C, while the mean post-operative temperature for both
groups was 36.7°C, and differences never exceeded 0.7°C.
Discussion
The significant reduction (25%) of required isoflurane concentration using 2.14–4.23 lg ml)1 plasma lidocaine concentration compares well with results obtained on the effects of
intravenous lidocaine on halothane requirements in ponies
(Doherty and Frazier, 1998) in which halothane MAC was
reduced by 20–70% in a lidocaine dose-dependent manner.
Further studies are required to determine whether the dosedependency observed in halothane studies also occurs with the
lidocaine–isoflurane combination in horses. Studies in dogs
have shown that intravenously administered lidocaine reduces
halothane requirements by not more than 29% (Himes et al.,
1977; Sasada and Smith 1997). It remains to be seen whether
this ceiling effect also occurs with the lidocaine–isoflurane
combination in horses.
There was a significant increase in heart rate over time
compared with baseline values in group C and a steady heart
rate in group IL. This suggests that intravenous lidocaine
could have a stabilizing effect on heart rate. A significant
increase in blood pressure from 45 min until end of anaesthesia
compared with baseline values was observed in group IL only
(Table 2). The increase in mean arterial blood pressure
Table 2. Data and independent t-test statistical analysis P-values of the parameters measured during period of anaesthesia in the control group
and group IL
Time
Parameter
ET ISO (vol %)
Control group
Lidocaine group
P-value
Heart rate (bpm)
Control group
Lidocaine group
P-value
MAP (mmHg)
Control group
Lidocaine group
P-value
ET CO2 (% vol)
Control group
Lidocaine group
P-value
pCO2 (mmHg)
Control group
Lidocaine group
P-value
pO2 (mmHg)
Control group
Lidocaine group
P-value
pH
Control group
Lidocaine group
P-value
Baseline
29 ± 3
32 ± 5
NS
0 min
15 min
30 min
45 min
60 min
75 min
1.3 ± 0.2
1.3 ± 0.2
NS
1.3 ± 0.1
1.1 ± 0.1
0.004
1.3 ± 0.1
1.0 ± 0.1*
0
1.2 ± 0.1
0.9 ± 0.1*
0
1.3 ± 0.1
0.9 ± 0.1*
0
1.3 ± 0.1
0.9 ± 0.1*
0
32 ± 5*
31 ± 4
NS
33 ± 3*
32 ± 4
NS
35 ± 4*
31 ± 5
NS
36 ± 4*
31 ± 5
NS
36 ± 5*
29 ± 6
NS
40 ± 3*
31 ± 5
0.022
64 ± 16
75 ± 9
NS
69 ± 12
70 ± 13
NS
72 ± 9
77 ± 16
NS
72 ± 11
87 ± 20*
NS
79 ± 14
94 ± 19*
NS
86 ± 20
99 ± 20*
NS
5.5 ± 0.9
5.7 ± 1.1
NS
4.9 ± 0.3
5.6 ± 1.1
NS
5.4 ± 0.3
5.2 ± 0.9
NS
5.0 ± 0.3
5.5 ± 1.1
NS
5.1 ± 0.3
5.4 ± 0.9
NS
4.7 ± 0.5
5.3 ± 0.8
NS
45 ± 5.5
51 ± 7.3
NS
49 ± 2.3
51 ± 8.5
NS
47 ± 5.2
49 ± 7.4
NS
341 ± 104
223 ± 139
NS
237 ± 84
244 ± 176
NS
210 ± 103
207 ± 156
NS
7.4 ± 0.03
7.4 ± 0.05
NS
7.4 ± 0.02
7.4 ± 0.05
NS
7.4 ± 0.02
7.4 ± 0.04
NS
*Significantly different from time0 min (immediately after induction) value or baseline (before pre-medication) for heart rate, NS ¼ non-significant
difference between control group and lidocaine group, ET ISO ¼ end-tidal isoflurane concentration, MAP ¼ mean arterial pressure, ET
CO2 ¼ end-tidal carbon dioxide concentration, pO2 ¼ arterial blood oxygen partial pressure, pCO2 ¼ arterial carbon dioxide partial pressure.
Values are expressed as mean ± SD.
0.4 ± 0.25
0.2 ± 0.1
NS
0.2 ± 0.11
0.2 ± 0.2
NS
216 ± 94*
255 ± 90*
NS
0.3 ± 0.14
0.3 ± 0.21
NS
245 ± 68
250 ± 80*
NS
26.9 ± 23*
8.1 ± 6
NS
End + 60 min
0.2 ± 0.08
0.22 ± 0.10
NS
203 ± 62
207 ± 73
NS
27.1 ± 16*
17.5 ± 8*
NS
End + 3 h
178 ± 54
184 ± 89
NS
0.2 ± 0.07
0.2 ± 0.1
NS
188 ± 112
228 ± 140
NS
11.8 ± 7
4.0 ± 2.6
0.038
End + 30 min
159 ± 38
186 ± 79
NS
0.4 ± 0.17
0.2 ± 0.1
NS
237 ± 29
307 ± 40*
NS
5.5 ± 5
2.3 ± 1*
NS
End
351 ± 226*
250 ± 164
NS
0.4 ± 0.08
0.2 ± 0.1
NS
122 ± 93
138 ± 74
NS
2.2 ± 0*
1.6 ± 0*
0.049
90 min
81 ± 27
113 ± 33
NS
0.3 ± 0.10
0.3 ± 0.1
NS
0.3 ± 0.07
0.3 ± 0.2
NS
113 ± 55
91 ± 33*
NS
5.0 ± 3*
2.2 ± 0*
NS
60 min
631 ± 225
527 ± 119
NS
114 ± 57
144 ± 73
NS
112 ± 43
140 ± 38
NS
3.5 ± 1*
2.5 ± 1*
NS
30 min
512 ± 183
503 ± 128
NS
4.2 ± 3*
2.8 ± 1
NS
0 min
9.4 ± 3
5.7 ± 3
0.049
Baseline
201 ± 70
236 ± 99
NS
214 ± 139*
261 ± 142
NS
651 ± 233*
535 ± 158
NS
0.2 ± 0.11
0.1 ± 0.05
NS
172 ± 67
161 ± 34
NS
29.9 ± 22*
19.9 ± 1*
NS
End + 24 h
*Significantly different from baseline (before pre-medication) value, NS ¼ non-significant difference between control group and lidocaine group, End ¼ termination of anaesthesia, NEFA ¼ nonesterified fatty acids, LDH ¼ lactate dehydrogenase, CK ¼ creatinine kinase, ASAT ¼ aspartate amino-transferase.
Values are expressed as mean ± SD.
Insulin (lIU ml)1)
Control group
Lidocaine group
P-value
Cortisol (nmol ml)1 )
Control group
Lidocaine group
P-value
NEFA (mmol l)1)
Control group
Lidocaine group
P-value
LDH (U l)1)
Control group
Lidocaine group
P-value
CK (IU l)1)
Control group
Lidocaine group
P-value
ASAT
Control group
Lidocaine group
P-value
Parameter
Time
Table 3. Data and independent t-test statistical analysis P-values of stress indicators in the group C and group IL
END-TIDAL Isoflurane Concentrations
193
194
Fig. 1. Line graph showing end-tidal isoflurane concentration (vol %)
trend in the control group (ETISO-C) and lidocaine group (ETISO-L);
P < 0.05 at 95% significance level after 15 min.
Fig. 2. Line graph showing end-tidal isoflurane concentration and
plasma lidocaine concentration trend in the group IL.
observed in lidocaine-treated horses could be due to an
increase in systemic resistance caused by lidocaine (Sasada
et al., 1997).
Toxic concentrations of lidocaine may result in paleness,
restlessness, convulsions, respiratory failure and severe cardiovascular depression (Sasada et al., 1997). To prevent these
effects, Doherty and Frazier (1998) suggested that the lidocaine loading dose for purposes of supplementing inhalation
anaesthesia should be given over a period of about 15 min and
the end-tidal anaesthetic concentration be reduced appropriately prior to lidocaine administration. In our study, the
loading dose of lidocaine was administered over 10 min. No
negative effects on the cardiovascular system, respiratory
system or nervous system were observed during the period of
anaesthesia or period of recovery from anaesthesia in lidocaine-treated horses in this study.
Seventy per cent of administered lidocaine is metabolized in
the liver by N-dealkylation and hydrolysis (Wood-Smith
et al.,1975). The metabolites of lidocaine metabolism in the
horse include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine and glycinexylidine (Harkins et al., 1998).
Some of these metabolites have been shown to share some of
the pharmacological effects of lidocaine in guinea-pigs (Burney
et al., 1974), dogs (Smith and Duce, 1971) and in rats (Blumer
et al., 1973). The contribution of some of these metabolites to
the reduction in isoflurane requirement is not known. Plasma
concentrations of these metabolites in the horse could not be
T. B. Dzikiti et al.
measured at the time of our study because no reliable
technique was available. It is therefore impossible to draw
any conclusions about the contribution of these metabolites to
an analgesic effect, if any. In this study, plasma lidocaine
concentration had almost returned to baseline levels within 3 h
of termination of intravenous lidocaine infusion (Fig. 2). This
observation agrees with an earlier observation (Doherty and
Frazier, 1998) in which an elimination half-life of lidocaine of
120 min was observed. In the current study, two plasma
lidocaine concentration peaks were observed (Fig. 2). The first
plasma lidocaine concentration peak observed after 30 min of
anaesthesia was from the bolus injection, while the second
peak was observed at 90 min of anaesthesia. The pharmacokinetics and pharmacodynamics of lidocaine cannot be determined properly in this study, as a steady state of plasma
lidocaine concentration was not achieved within the time the
horses were in anaesthesia. Suggestions have been made to
maintain the intravenous lidocaine for periods longer than the
half-life of lidocaine (Doherty and Frazier, 1998) and to collect
samples more frequently in order to be able to obtain
quantitative information on the pharmacokinetics and pharmacodynamics of lidocaine in horses.
Stress response is non-specific, consisting of activation of the
sympathoadrenal and corticomedullary systems. These
responses include secretion of catecholamines (epinephrine
and norepinephrine), adrenocorticotrophic hormone (ACTH),
cortisol, glucagon, cAMP, vasopressin, growth hormone, renin
and a non-concomitant decrease in insulin (Benson et al.,
2000). The results obtained for the levels of cortisol, NEFA
and muscle enzymes in this study show no significance
difference between the mean values of group C and group
IL. This suggests that there is no difference with regard to
stress levels between the two groups. There are two factors that
could have influenced plasma insulin concentration in this
study. First detomidine, which is known to decrease plasma
insulin concentration (Brown et al., 1985) and secondly, stress
response, which is characterized by production of catabolic
hormones, such as cortisol, which have an anti-insulin effect.
In our study, first there was a decrease in plasma insulin levels
in both groups, and then there was an increase in plasma
insulin concentration from the end of anaesthesia up to 24 h
post-operatively. The decrease in plasma insulin concentration
first noticed in both groups could have been due to the
detomidine effect, while the increase later noticed after end of
anaesthesia could be due to the reduced stress response postsurgery and the reduced detomidine effect. NEFA have
become increasingly popular in evaluating stress response
(Carrol et al., 1997). Low concentrations during anaesthesia
have been documented in horses and are believed to be
associated with less sympathetic tone and perhaps decreased
fear and apprehension (Carrol et al., 1997). In the current
study, no significant differences in NEFA concentration were
found between group C and group IL. Horses may have
increased ASAT and LDH values as a result of surgical
trauma, hepatic injury or post-anaesthetic myopathy (Stockham, 1995). CK has a high specificity for muscle damage. The
fact that no differences were found between the control group
and the lidocaine group suggests that intravenous lidocaine
has no significant impact with regards to muscle enzyme
concentration. When compared with baseline values, a significant increase in LDH after 24 h from end of anaesthesia was
observed in group C. A significant increase in CK after 3 and
END-TIDAL Isoflurane Concentrations
24 h from end of anaesthesia when compared with baseline
values was also observed in group C. The results obtained on
stress response factors indicate that generally there is very little
difference with regard to stress when isoflurane–lidocaine
anaesthetized horses are compared with isoflurane-anaeshetized horses.
The results of this study have shown that intravenously
administered lidocaine at dosages already indicated reduces
the amount of isoflurane used by 25%. Use of less isoflurane
will reduce the occurrence of unwanted side-effects. Long-term
exposure to volatile anaesthetics poses a significant health risk
to personnel (Joubert, 1999). With use of less isoflurane, there
is less exposure, and therefore reduced health risk to personnel.
Volatile anaesthetics destroy the ozone layer and are classified
as greenhouse gases. (Joubert, 1999). Supplementing isoflurane
anaesthesia with intravenous lidocaine might reduce the rate of
emission of isoflurane and its by-products (chloroflourocarbons, CFCs) to the ozone layer (Joubert, 1999).
We therefore conclude that, intravenous administration of
lidocaine at 2.5 mg kg)1 and 50 l kg)1 min)1, loading and
maintenance dosages, respectively, results to a 25% reduction
in isoflurane requirement, without negative effects on the
cardiovascular system. Further studies are required to determine the effects of intravenous lidocaine administration in
endotoxaemic horses and to determine the pharmacokinetics
of the metabolites of lidocaine.
Acknowledgements
We would like to thank all staff members of the Department of
Equine Sciences, Faculty of Veterinary Medicine, Utrecht
University for their support, Dr Cas Kruitwagen of the Centre
for Biostatistics, Utrecht University for statistical analysis of
data and Prof. Dr J. Fink-Gremmels for analysing lidocaine
data.
References
Benson, G. J., T. L. Grubb, C. Neff-Davis, W. A. Olson, J. C.
Thurmon, D. C. Linder, W. J. Tranquilli, and O. Vanio, 2000:
Perioperative stress response in the dog: effect of pre-emptive
administration of medetomidine. Vet. Surg. 29, 85–91.
Blumer, J., J. M. Amstrong, and A. J. Atkinson, 1973: The convulsant
potency of lidocaine and its N-dealkylated metabolites. J. Pharmacol. Exp. Ther. 186, 31–36.
Brown, M. J., A. D. Struthers, L. DiSilvio, T. Yeo, M. Ghatei, and
J.M. Burrin, 1985: Metabolic and haemodynamic effects of alpha2adrenoceptor stimulation and antagonism in man. Clin. Sci. 68
(Suppl. 10), 137–139.
195
Burney, R. G., C. A. DiFazio, M. J. Peach, and M. J. Silvester, 1974:
Antiarrythmic effects of lidocaine metabolites. Am. Heart J. 88,
765–769.
Carrol, C. L., N. S. Matthews, S. M. Hartsfield, M. R. Slater, T. H.
Champney, and S. W. Erickson, 1997: The effect of detomidine and
its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behaviour in awake ponies. Vet.
Surg. 26, 69–77.
DeClive-Lowe, S. G., J. Desmond, and J. North, 1958: Intravenous
lignocaine anaesthesia. Anaesthesia 13, 138–146.
Doherty, T. J., and D. L. Frazier, 1998: Effect of intravenous lidocaine
on halothane minimum alveolar concentration in ponies. Equine.
Vet. J. 30, 300–303.
Hall, L. W., and K. W. Clarke, 1991: Veterinary Anaesthesia, 9th edn,
pp. 175–176. Bailliere Tindall, London.
Harkins, J. D., G. D. Mundy, W. E. Woods, A. Lehner, W.
Karpiesiuk, W. A. Rees, L. Dirikolu, S. Bass, J. Boyles, and T.
Tobin, 1998: Lidocaine in the horse: its pharmacological effects and
their relationship to analytical findings. J. Vet. Pharmacol. Ther. 21,
462–476.
Himes, R. S., C. A. DiFazio, and R. G. Burney, 1977: Effects of
lidocaine on the anesthetic requirements for nitrous oxide and
halothane. Anesthesiology 47, 437–440.
Joubert, K. E., 1999: The hidden dangers of anaesthetic machines.
Tydskr. S. Afr. Vet. Ver. 70, 140–141.
Muir, W. W., R. T. Skarda, and R. M. Bednarski, 1995: Handbook of
Veterinary Anaesthesia, 2nd edn, p. 416. Mosby, USA.
Paddleford, R. R., 1991: Manual of Small Animal Anaesthesia, 2nd
edn, pp. 138, 183 and 312. W.B. Saunders Company, New York.
Philips, O. C., W. B. Lyons, L. C. Harris, A. T. Nelson, T. D. Graff,
and T. M. Frazier, 1960: Intravenous lidocaine as an adjunct to
general anesthesia: a clinical evaluation. Anesth. Analg. 39, 317–
322.
Sasada, M. P., and S. P. Smith, 1997: Drugs in Anaesthesia and
Intensive Care, 2nd edn, pp. 208–211 and 216–218. Oxford University Press, New York.
Smith, E. R., and B. R. Duce, 1971: The acute antiarrythmic and toxic
effects in mice and dogs of 2-ethlyl-amino-2161 acetoxylidine (L-86),
a metabolite of lidocaine. Expt. Ther. 179, 580–585.
Steffey, E. P., and D. Howland Jr, 1980: Comparison of circulatory
and respiratory effects of isoflurane and halothane anaesthesia in
horses. Am. J. Vet. Res. 41, 821–825.
Stockham, S. L., 1995: The Veterinary Clinics of North America, Vol.
11, pp. 391–414. W.B. Saunders Company, Philadelphia, USA.
Thurmon, J. C., W. J. Tranquilli, and G. J. Benson, 1996: Lumb and
JonesÕ Veterinary Anaesthesia, 3rd edn, pp. 607 and 297–329.
Williams and Wilkins, Baltimore, Maryland, USA.
Wood-Smith, F. G., M. D. Vickers, and H. C. Stewart, 1975: Drugs in
Anaesthetic Practice, 4th edn, pp. 238–239. Butterworths, London
and Boston.