British Journal of Anaesthesia 1998; 81: 748–753
Comparison of the effects of halothane, isoflurane and methoxyflurane
on the electroencephalogram of the horse
C. B. JOHNSON AND P. M. TAYLOR
Keywords: anaesthetic volatile, halothane; anaesthetic
volatile, isoflurane; anaesthetic volatile, methoxyflurane;
monitoring, electroencephalography; horse
trations have been graded.1 The progressive changes
in frequency spectra were then colour-coded to produce a colour index of depth of anaesthesia. Graded
changes in power spectra with increasing arterial
halothane concentrations have also been found in
infants undergoing facial surgery.2 Despite these
changes, the EEG recorded before the start of
surgery could not be used to predict movement in
response to surgical stimulation.3 This confirmed
similar results in the rat.4
The effects of 0.5%, 1% and 1.5% halothane and
0.5%, 1%, 1.5% and 2% isoflurane were compared
as part of a balanced anaesthetic technique on the
EEG.5 It was found that most of the change in EEG
variables with isoflurane occurred at concentrations
less than MAC. In contrast, halothane produced progressive EEG changes with increasing PE Hal at values
greater than MAC. The values found for isoflurane
from MAC onwards were similar to each other in
magnitude and to those found with halothane at 1.5%.
In the horse, the EEG effects of isoflurane,
halothane, methoxyflurane and enflurane have been
compared.6 A gradual change from control high
frequency–low amplitude patterns to high amplitude
slow waves was found with halothane and
methoxyflurane. In contrast, enflurane and isoflurane
anaesthesia were characterized by slow wave activity
throughout with periods of burst suppression, occurring with increased concentrations. These effects
were not fully described in terms of quantitative
EEG variables. The effects of halothane in anaesthetized horses without surgery have been demonstrated quantitatively after induction of anaesthesia
using xylazine–ketamine7 and thiopental.8 Both
studies found progressive changes in derived EEG
variables with increasing PE Hal. The EEG effects of
halothane have been compared with those of isoflurane in horses undergoing orthopaedic surgery.9
Similar EEG values were found in both groups, however, more changes were seen in response to surgery
with halothane than with isoflurane.
In humans, the middle latency auditory evoked
potential (MLAEP) has been found to change in a
dose-related manner with inhalation anaesthetic
agents.10–12 Although most of the depression in the
MLAEP occurs at sub-MAC anaesthetic concentrations, graded changes have been described for concentrations of up to 2 MAC of halothane and
In humans, the effects of inhalation agents on the
EEG have been studied under various conditions. In
surgical patients, frequency spectra obtained under
adequate and increased end-tidal isoflurane concen-
C. B. JOHNSON, BVSC, PHD, DVA, Dip ECVA, MRCVS, Department of
Clinical Veterinary Science, University of Bristol, Langford House,
Langford, Bristol BS18 7DU. P. M. TAYLOR, MA Vet MB, PHD, DVA,
Dip ECVA, MRCVS, Department of Clinical Veterinary Medicine,
University of Cambridge, Madingley Rd, Cambridge CB3 0ES.
Accepted for publication: June 2, 1998.
Summary
We have investigated in eight ponies the effects
of three different end-tidal concentrations of
halothane, isoflurane and methoxyflurane on
median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential
(DD) of the middle latency auditory evoked
potential (MLAEP). The three concentrations of
each agent were chosen to represent approximately the minimum alveolar concentration
(MAC), 1.25 MAC and 1.5 MAC for each agent.
During halothane anaesthesia, F95 decreased
progressively
as
halothane
concentration
increased, from mean 13.9 (SD 2.6) at 0.8% to
11.9 (1.1) at 1.2%. DD was lower during anaesthesia with the highest concentration (21 (6.5))
compared with the lowest (27.6 (11.4)). There
were no significant changes in F50. During
isoflurane anaesthesia, there was a small, but
significant increase in F95 between the intermediate and highest concentrations (10.2 (1.5) to
10.8 (1.6)). There were no changes in F50 and
DD. Values of F95, F50 and DD at all isoflurane
concentrations
were
similar
to
those
of
halothane at the highest concentration. During
methoxyflurane
anaesthesia,
F95
and
F50
decreased progressively as methoxyflurane concentration was increased, from 21.3 (0.7) and
6.5 (1), respectively, at 0.26%, to 20.1 (0.6) and
5.6 (0.8), respectively, at 0.39%. DD was lower
during anaesthesia with the highest concentration of methoxyflurane (25.7 (7.8)) compared
with the lowest (39.7 (20.6)). Values of F95, F50
and DD at all methoxyflurane concentrations
were higher than those seen with halothane at
the lowest concentration. The different relative
positions of the dose–response curves for EEG
and MLAEP changes compared with antinociception (MAC) changes suggest differences in
the mechanisms of action of these three agents.
These differences may explain the incomplete
adherence to the Meyer–Overton rule. (Br. J.
Anaesth. 1998; 81: 748–753).
Effects of halothane, isoflurane and methoxyflurane on the EEG of the horse
Table 1 End-tidal concentrations of inhalation agents used at the
three steady states studied
Approximate
MAC multiple
Halothane
Isoflurane
Methoxyflurane
1
1.25
1.5
0.8%
1.0%
1.2%
1.2%
1.5%
1.8%
0.26%
0.32%
0.39%
enflurane.10 12 In contrast, depression of the MLAEP
with isoflurane appears to be complete by 1 MAC.11
There are no data available on the effects of anaesthesia on the equine MLAEP.
The aim of this study was to compare the quantitative effects of isoflurane, halothane and methoxyflurane on the equine EEG at concentrations greater
than MAC, without surgical stimulation. This would
provide a direct comparison of the effects of each
agent on three different measures of CNS function
and also provide comparative information allowing
the EEG effects of the three agents to be compared
with each other. Halothane and isoflurane were
chosen as they are the two main agents used in clinical equine anaesthesia. Methoxyflurane was used as
it is analgesic at sub-MAC concentrations13 and so
may have quantitatively different effects from the
other two agents.
Materials and methods
We studied eight pony geldings, aged 5–10 yr (mean
7 yr), weighing 270–325 kg (mean 305 kg). The
ponies all had the right carotid artery raised surgically to a subcutaneous position. The study was carried out in accordance with the Animals (Scientific
Procedures) Act, 1986 (Home Office Licence
80/666).
After placement of a 14-gauge cannula in the left
jugular vein, anaesthesia was induced on three occasions by i.v. injection of thiopental 3 g. Additional
thiopental was given as required in 0.5- or 1-g increments to allow tracheal intubation, resulting in a
mean dose of 12 (SD 2) mg kg91. The ponies were
placed in the left lateral recumbent position.
Anaesthesia was maintained by inhalation of
halothane, isoflurane or methoxyflurane from a circle
breathing system (JD Medical). A 20-gauge cannula
was placed in the raised carotid artery. The order in
which each pony was given each anaesthetic agent
was not randomized, but at least 2 weeks were left
between subsequent anaesthetics in each animal.
PE′CO2 was monitored using an infrared monitor
(Supermon 7210, Kontron Instruments) and endtidal halothane ( PE Hal ), isoflurane ( PE Iso ) and
methoxyflurane ( PE Meth ) concentrations were monitored using a Piezo-electric anaesthetic agent monitor (Agent Monitor 7860, Kontron Instruments). As
the agent monitor was not able to measure
methoxyflurane concentration directly, it was set to
measure halothane and the sensitivity to methoxyflurane measured before and immediately after each
experiment using a calibrated methoxyflurane vaporizer set to deliver 1% methoxyflurane. The vaporizer
was calibrated at a range of flows and settings using a
Hillgram–Watt refractometer before the start of the
study. Gas samples were obtained from the level of
749
the end of the tracheal tube adjacent to the breathing
system. Respiration was controlled by IPPV using
the ventilator incorporated in the large animal circle
system (modified Bird 7). Peak inspiratory pressure
was set at 20–25 cm H2O.
During anaesthesia, ECG and arterial pressure
(AP) were monitored using the Supermon. The ECG
was recorded using transdermal stainless steel needle
electrodes with standard lead configuration. AP was
recorded using a disposable pressure transducer
(TXX-R, Ohmeda) connected to the carotid artery
cannula. ECG and AP were recorded on a chart
recorder (Lectromed two channel recorder).
Exhaled anaesthetic concentrations were maintained at the required setting for each epoch of data
collection by alteration of the vaporizer setting. PE′CO2
was maintained at 5.3–5.9 kPa by alteration of ventilatory frequency. Experimental studies were started
60 min after induction of anaesthesia.
On each occasion three 15-min data epochs were
recorded at equivalent PE Hal , PE Iso in terms of multiples of the MAC of each agent. Concentrations of
each agent used together with their multiple of MAC
are shown in table 1. MAC values of 0.88, 1.31 and
0.3 were used for halothane,14 isoflurane14 and
methoxyflurane (Steffey, personal communication),
respectively. The end-tidal concentration was
adjusted for each epoch using the vaporizer and was
held at a steady state for 10 min before data collection. Data were always collected in the order 1 MAC,
followed by 1.25 MAC, followed by 1.5 MAC. An
arterial blood sample was obtained anaerobically via
the cannula in the carotid artery for analysis of blood
pH, PO2 and PCO2 immediately before the start and
after the end of each data epoch. The average of the
two values was calculated and taken as the value
during that data epoch.
Throughout the experiments, the EEG was
recorded using a dedicated preamplifier with an
inbuilt auditory stimulus generator (Alert, Medelec).
Three transcutaneous stainless steel needle electrodes were positioned in a similar manner to that
used in conscious ponies.15 The active (non-inverting) electrode was placed in the midline over the
suture of the parietal bones 2–3 cm rostral to the
convergence of the temporalis muscles. The reference
(inverting) electrode was placed over the bony
prominence of the right zygomatic arch. The ground
electrode was placed 5–6 cm caudal to the poll,
5–6 cm to the right of the midline. This positioning of
electrodes gave reliable EEG recordings and a well
defined MLAEP. Electrodes were positioned as soon
as practicable after induction of anaesthesia and were
not moved or disconnected for the duration of the
study. Data were recorded to a personal computer
(450L, Dell) via a digital signal processing card
(DSP with sub-board and 64k RAM, Loughborough
Sound Instruments). Data recording software was
used which was developed specifically for this hardware combination (Auditory Evoked Response
Program, Chris Jordan, Northwick Park Hospital).
EEG data were recorded with a sample rate of
1 kHz and a passband of 0.5–400 Hz. Data were
divided into 2-s epochs and artefact rejection was
performed manually off-line by inspection of the raw
data. Any epochs containing artefact were rejected
before further processing. Data blocks containing
750
British Journal of Anaesthesia
Table 2 Arterial pH, PCO2, PO2 and mean arterial pressure (AP) for each agent concentration during EEG recording (mean (SD)). *P:0.05
denote values significantly different from each other
Agent
Concentration
pH
PCO2
PO2
Mean AP
Halothane
0.8%
1.0%
1.2%
1.2%
1.5%
1.8%
0.26%
0.32%
0.39%
7.325 (0.081)
7.329 (0.104)
7.297 (0.138)
7.387 (0.029)
7.39 (0.037)*
7.405 (0.036)*
7.382 (0.02)
7.375 (0.021)
7.382 (0.034)
6.1 (1)
6.1 (1.2)
6.7 (1.9)
5.3 (0.2)
5.4 (0.4)*
5.1 (0.5)*
5.9 (0.6)
5.9 (0.5)
5.7 (0.6)
36.1 (14.1)
39.2 (15.8)
32.2 (16.8)
42.6 (12.5)
46.6 (16.4)
46.8 (18.5)
48.9 (7.3)
48.3 (7.3)
45.6 (8.4)
10.9 (1.3)
11.7 (1.3)
11.8 (1.5)
10.3 (1.2)
10.5 (1.3)
10.5 (1.1)
16.1 (1.9)*
12.8 (2.6)
12.1 (19)*
Isoflurane
Methoxyflurane
overscale or underscale values were rejected as were
blocks containing burst suppression, specific muscular
activity such as nystagmus or other identifiable EMG.
Throughout the period of data recording, a broadband binaural click stimulus was presented to the
ponies. This stimulus was generated by the EEG
recording system and was delivered by audio ear
pieces (FEN20, Ross Audio) placed in the external
auditory meatii. On each occasion the ear pieces
were inserted in a similar manner and to a similar
depth. No animals showed signs of auditory canal
pathology or excessive wax build up at any time
during the study. The auditory stimulus had a
pulse width of 0.4 ms and was delivered at a rate of
6.122 Hz.
The raw EEG was analysed using specialized software (Spectral Analysis Program, Chris Jordan
Northwick Park Hospital). Fast Fourier transformation was performed on each 2-s block of data using a
10% raised cosine window function. The resultant
frequency histograms were analysed further to produce a median frequency (F50) and 95% spectral
edge frequency (F95). F50 and F95 were averaged
over 30 consecutive blocks to give a single value for
each minute of recording.
MLAEP was derived by averaging of the EEG signal. The 100 ms of EEG after each click stimulus
were averaged over 512 consecutive artefact-free
sweeps. A 100-Hz low pass filter was applied to
the data before calculation of the second differential
to remove any contribution of higher frequencies to
the calculation. The second differential (DD) of
the area of the MLAEP between 30 and 90 ms after
the stimulus was estimated by the software using the
following function:
y( n ) =x( n+d )+x( n − d ) − 2×x( n )
where x(n):nth sample value, d:sample interval
used in the calculation and y(n):second differential
estimate for sample n.
The second differential estimate was calculated for
each sample point over the period from 30 to 90 ms
post-stimulus. These estimates were summated to
give an index which was scaled so that a typical
human MLAEP would give a value of ⱖ100 in an
awake patient and 10–15 in a deeply anaesthetized
patient.16
In order to standardize the MLAEP data, DD
derived from each waveform were assigned to the
nearest whole number of minutes after the start of
the experiment to the last sweep which was included
in the signal average.
F95, F50 and DD for all data epochs at each agent
concentration were compared using analysis of variance with Dunnett’s post hoc test17 where statistically
significant differences were found. pH, PO2 and PCO2
were compared for all animals in a similar manner.
Results
There were no data after isoflurane anaesthesia for
one pony as this experiment was abandoned because
of repeated violent movements at both 1.2% and
1.5% isoflurane. EEG data from one pony during
halothane anaesthesia were not included as they were
found to be contaminated by high frequency (50 Hz)
artefacts. There were no arterial blood-gas data after
halothane anaesthesia for two of the ponies because
of a malfunction of the blood-gas analyser.
There were no significant differences in pH, PO2,
PCO2 or mean AP recorded during administration of
the three concentrations of halothane. There were
statistically significant reductions in PCO2 and
increases in pH between 1.5% and 1.8% end-tidal
isoflurane. There was a statistically significant
decrease in AP between 0.26% and 0.39% end-tidal
methoxyflurane. All blood-gas data are shown in
table 2.
Values for F95, F50 and DD with halothane are
shown for all animals in table 3. Values for individual
animals are illustrated in figure 1. When all animals
were considered together, there was a progressive
reduction in F95 which was statistically significant
for all three PE Hal . There were no significant changes
in F50 with increasing PE Hal . There was a statistically
significant reduction in DD between 0.8% and
1.2% PE Hal.
Values for F95, F50 and DD with isoflurane are
shown for all animals in table 4. Values for individual
animals are illustrated in figure 2. When all animals
were considered together, there was a significant
increase in F95 between 1.5% and 1.8% PE Iso . There
Table 3 Change in F95, F50 and DD with PE Hal (mean (SD)).
*P:0.05 denotes values significantly different from each other;
†P:0.05 denotes values significantly different from all others in
group
PE Hal
0.8 %
F95
F50
DD
13.9 (2.6)†
3 (0.9)
27.6 (11.4)*
1.0 %
1.2 %
13 (1.6)†
3.1 (0.5)
24.8 (10.1)
11.9 (1.1)†
2.8 (0.5)
21 (6.5)*
Effects of halothane, isoflurane and methoxyflurane on the EEG of the horse
751
Figure 1 F95, F50 and DD values for PE Hal in individual animals
(see table 3 for significant differences between values).
Figure 2 F95, F50 and DD values for PE Iso in individual animals
(see table 4 for significant differences between values).
were no significant differences in F50 or DD. Values
of F95, F50 and DD with isoflurane at all PE Iso were
similar to those seen with halothane at 1.2%.
Values for F95, F50 and DD with methoxyflurane
are shown for all animals in table 5. Values for individual animals are illustrated in figure 3. When all
animals were considered together, there was a significant decrease in F95 and F50 between 0.26% and
0.39% PE Meth. DD at 0.39% was significantly less
than that at 0.26%. Values for F95, F50 and DD seen
with methoxyflurane at all PE Meth were greater than
those seen with halothane at 0.8%.
Burst suppression was a feature of the EEG during
isoflurane anaesthesia. There was an increasing
incidence with increasing PE Iso. Burst suppression
was not seen during halothane or methoxyflurane
anaesthesia.
Discussion
Table 4 Change in F95, F50 and DD with PE Iso (mean (SD)).
*P:0.05 denotes values significantly different from each other
We have shown that the EEG effects of the three
inhalation agents halothane, isoflurane and
methoxyflurane were quantitatively different from
each other compared with the MAC of these agents.
Within the concentration window studied, halothane
produced a progressive reduction in F95, F50 and DD
while the values for isoflurane were all at one extreme
of the halothane curve and the values for methoxyflurane all at the other extreme. As a progressive increase
in the incidence of burst suppression was seen with
increasing PE Iso, the values for isoflurane may represent
maximal depression of F95, F50 and DD.
Data were collected in the order 1 MAC, followed
by 1.25 MAC, followed by 1.5 MAC. In a previous
Table 5 Change in F95, F50 and DD with PE Meth (mean (SD)).
*P:0.05 denotes values significantly different from each other;
†P:0.05 denotes values significantly different from all others in
group
PE Meth
PE Iso
F95
F50
DD
1.2%
1.5%
1.8%
10 (1.7)
2.4 (0.4)
23.3 (6.8)
10.2 (1.5)*
2.4 (0.3)
23.2 (6.8)
10.8 (1.6)*
2.4 (0.5)
22.7 (9.2)
F95
F50
DD
0.26%
0.32%
0.39%
21.3 (0.7)†
6.5 (1)†
39.7 (20.6)*
20.6 (0.9)†
6.1 (1)†
31.7 (18.6)
20.1 (0.6)†
5.6 (0.8)†
25.7 (7.8)*
752
Figure 3 F95, F50 and DD values for PE Meth in individual animals
(see table 5 for significant differences between values).
study investigating the effects of increasing concentrations of halothane on the EEG, the order in which
the different concentrations were given was randomized.8 Both F95 and F50 showed a progressive reduction with increasing halothane concentration, but the
changes with F50 were not as marked as those with
F95. More recently, it was suggested that F50 may
respond to changes in anaesthetic concentration in a
sluggish manner (D. Sapsford, personal communication). Consequently, the order of anaesthetic agent
concentrations in this study was not altered between
animals in an attempt to standardize this possible
source of error. The similarity in the halothane
results between this and the previous study8 suggest
that a sluggish response in F50 did not contribute to
the results in either case.
pH and PCO2 changes seen with isoflurane, and
arterial pressure changes seen with methoxyflurane
were small and all values were within normal limits
for anaesthetized horses.18 It is unlikely that changes
of such a small magnitude would have any direct
effect on the EEG variables studied.
Methoxyflurane has been demonstrated to have
analgesic effects at sub-MAC concentrations.13
In contrast, isoflurane has been shown to have no
analgesic effect when given to human volunteers at
subanaesthetic concentrations.19 These differences
made it desirable to include methoxyflurane in this
British Journal of Anaesthesia
study despite the problems encountered using this
agent in the horse.20 It was not possible to obtain
PE Meth values higher than 0.39% and so this value was
chosen together with a value less than MAC (0.26%)
and an intermediate one (0.32%). These values do
not directly correspond to those of halothane and
isoflurane in terms of multiples of MAC. However,
the quantitative differences between methoxyflurane
and the other agents are too great to be explained by
this alone.
The progressive decrease in F95 and DD with
increasing concentrations of halothane were similar
to previous findings.5 6 8 The lack of change with
isoflurane and methoxyflurane and the progressive
appearance of periods of burst suppression with
isoflurane were also similar.5 6 As the EEG variables
for isoflurane at all three PE Iso were similar to those
for halothane at 1.2%, it is probable that the slope of
the isoflurane dose–response curve for CNS depression occurs at a lower concentration in terms of
multiples of MAC than that for halothane. Similarly,
the EEG variables for methoxyflurane at all three
PE Meth demonstrated less CNS depression than 0.8%
halothane, suggesting that CNS depression occurs at
higher concentrations in terms of multiples of MAC
with methoxyflurane than either isoflurane or
halothane. The difference in the relative positions of
the dose–response curves for CNS depression and
antinociception with halothane and isoflurane would
explain the finding in the horse that the CNS was
more responsive during surgery with halothane
anaesthesia than isoflurane anaesthesia.9
The MAC of an anaesthetic agent is related to the
ability of that agent to prevent response to a noxious
stimulus. This is a measure of the antinociceptive
potential of the anaesthetic agent. The degree of
depression of the EEG variables investigated is
incomplete at 1 MAC of halothane whereas with
isoflurane, depression of these variables is complete
by 1 MAC. The EEG variables did not appear to be
completely depressed at any of the three methoxyflurane concentrations. In terms of multiples of MAC,
there appears to be a spectrum of potency for CNS
depression from methoxyflurane (least potent)
through halothane to isoflurane. This suggests that
methoxyflurane is more antinociceptive than isoflurane as response to a standard nociceptive stimulus is
prevented by a concentration of methoxyflurane
which induces less CNS depression than the
required concentration of isoflurane. Halothane
would appear to have an intermediate antinociceptive effect.
Traditionally, the inhalation agents have been the
anaesthetic agents to which others have been compared. The concept of depth of anaesthesia which led
to the classic signs and stages of anaesthesia21 was
developed from experience with ether and modified
as other inhalation agents appeared. The inhalation
agents are all volatile compounds with low molecular
weight. Because of the Meyer–Overton theory22 23
which links potency to fat solubility, it has been suggested that they have a similar site of action within a
lipophilic biophase. This, together with the concept
of pressure reversal, has led to the belief that general
anaesthesia with the inhalation agents is a result of a
physical effect in the cell membrane rather than a
receptor-mediated effect and as such affects all cells
Effects of halothane, isoflurane and methoxyflurane on the EEG of the horse
in the body. This would lead to a global effect on the
CNS producing a generalized depression of function
rather than specific, pharmacologically localized
effects.24
These data appear to question the usefulness of
comparing effects of anaesthetic agents other than
that of antinociception in terms of multiples of
MAC. If the different effects of inhalation anaesthetic agents occur at different concentrations relative to each other, there must be pharmacologically
localized kinetic or dynamic differences between
them. Effects of inhalation anaesthetic agents at
differing sites or even receptors may explain the
incomplete adherence of these agents to the
Meyer–Overton rule.
Acknowledgements
We thank M. Bloomfield and R. Eastwood for help with the experimental work and J. Bowring for calibration of the methoxyflurane
vaporizer. The Elise Pilkington Trust provided financial support.
C. B. J. was a Horserace Betting Levy Board Scholar.
References
1. Thomsen CE, Christensen KN, Rosenfalck A. Computerised
monitoring of depth of anaesthesia with isoflurane. British
Journal of Anaesthesia 1989; 63: 36–43.
2. Sugiyama K, Joh S, Hirota Y, Kiyomitsu Y, Niwa H, Matsuura
H. Relationship between changes in power spectra of electroencephalograms and arterial halothane concentration in
infants. Acta Anaesthesiologica Scandinavia 1989; 33: 670–675.
3. Dwyer RC, Rampil IJ, Eger EI, Bennett HL. The electroencephalogram does not predict depth of isoflurane anesthesia.
Anesthesiology 1994; 81: 403–409.
4. Rampil IJ, Laster MJ. No correlation between quantitative
electroencephalographic measurements and movement
response to noxious stimuli during isoflurane anesthesia in
rats. Anesthesiology 1992; 77: 920–925.
5. Lloyd-Thomas AR, Cole PV, Prior PF. Quantitative EEG and
BAE potentials: comparison of isoflurane with halothane
using the cerebral function monitor. British Journal of
Anaesthesia 1990; 65: 306–312.
6. Auer JA, Amend JF, Garner HE, Hutcheson DP, Salem CA.
Electroencephalographic responses during volatile anaesthesia in domestic ponies: a comparative study of isoflurane,
methoxyflurane and halothane. Electroencephalographic
Responses 1979; 3: 130–134.
7. Otto K, Short CE. Electroencephalographic power spectrum
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
753
analysis as a monitor of anaesthetic depth in horses. Veterinary
Surgery 1991; 5: 362–371.
Johnson CB, Young SS, Taylor PM. Analysis of the frequency
spectrum of the equine electroencephalogram during
halothane anaesthesia. Research in Veterinary Science 1994; 56:
373–378.
Ekström PM, Short CE, Geimer TR. Electroencephalography
of detomidine–ketamine–halothane and detomidine–ketamine–isoflurane anaesthetized horses during orthopaedic
surgery: a comparison. Veterinary Surgery 1993; 22: 414–418.
Thornton C, Heneghan CPH, James MFM, Jones JG. The
effects of halothane and enflurane with controlled ventilation
on the auditory evoked potentials. British Journal of
Anaesthesia 1984; 56: 315–323.
Schwender D. Wachheit während narkose. Wissenschaftliche
Verlagsabteilung Abbott GmbH, Wiesbaden, 1992.
Newton DEF, Thornton C, Jordan C. The auditory evoked
response as a monitor of anaesthetic depth. In: Sebel PS,
Bonke B, Winograd E, eds. Memory and Awareness in
Anesthesia. New Jersey: Prentice Hall, 1993; 274–280.
Siker ES, Wolfson B, Ciccarelli HE, Telan RA. Effect of subanesthetic concentrations of halothane and methoxyflurane
on pain threshold in conscious volunteers. Anesthesiology
1967; 28: 337–342.
Steffey EP, Howland D, Giri S, Eger EI. Enflurane, halothane
and isoflurane potency in horses. American Journal of
Veterinary Research 1977; 38: 1037–1039.
Mayhew IG, Washbourne JR. A method of assessing auditory
and brainstem function in horses. British Veterinary Journal
1990; 146: 509–518.
Jordan C. Auditory Evoked Response Program AVG manual,
1994.
Dunnett CW. New tables for multiple comparisons with a
control. Biometrics 1964; 20: 482–491.
Muir WW, Hubbell JAE, Skarda R. Handbook of Veterinary
Anaesthesia. St Louis: Mosby, 1989.
Roth D, Petersen-Felix S, Bak P, Arendt-Nielsen L, Fischer
M, Bjerring P, Zbinden AM. Analgesic effect in humans of
subanaesthetic isoflurane concentrations evaluated by evoked
potentials. British Journal of Anaesthesia 1996; 76: 38–42.
Steffey EP. Inhalation anaesthetics and gases. In: Muir WW,
Hubbell JAE, eds. Equine Anaesthesia. St Louis: Mosby, 1991;
352–379.
Guedel AE. Inhalation Anesthesia. New York: Macmillan,
1937.
Meyer HH. Zur theorie der Alkoholnarkose. I. MITT. Welche
eigenschaft der Anesthetica bedingt ihre Narkotische
wirkung? Archives of Experimental Pathological Pharmacology
1899; 42: 109–118.
Overton E. Studien uber die narkose. Jena: Verlag von Gustav
Fischer, 1901.
Miller KW, Paton WDM, Smith EB. Site of action of general
anaesthetics. Nature (London) 1965; 206: 574–577.