- Email: [email protected]
Cerebral state monitoring in Beagle dogs sedated with medetomidine
Veterinary Anaesthesia and Analgesia, 2006, 33, 237–240
doi:10.1111/j.1467-2995.2005.00263.x
BRIEF COMMUNICATION
Cerebral state monitoring in Beagle dogs sedated with medetomidine Peter JA Bollen
PhD
& Henrik Saxtorph
DVM
Biomedical Laboratory, University of Southern Denmark, Odense, Denmark
Correspondence: Peter Bollen, Biomedical Laboratory, University of Southern Denmark, Winsloewparken 23, DK-5000 Odense C, Denmark. E-mail: [email protected]
Abstract Objective To provide experience of monitoring the level of hypnosis with the Cerebral State Monitor (CSM), a device extracting a single numerical variable between 0 and 100 from the electroencephalogram in dogs sedated with medetomidine during dental scale removal. Study design Prospective observational study. Animals Nine female Beagle dogs weighing 13.3 ± 1.3 kg. Methods Cerebral state index (CSI) and burst suppression ratio (BSR) were recorded from sub-dermal needle electrodes in dogs sedated after subcutaneous injection of 114 ± 11 lg kg)1 medetomidine. Ten minutes after injection CSI monitoring began, and after 5 minutes, dental scale removal with an ultrasonic probe was started. After approximately 30 minutes, the effects of medetomidine were antagonized with atipamezole. Results The CSI had a median value of 43 (range 40–56) in undisturbed sedated dogs. During dental scale removal, CSI increased to a median value of 99 (range 92–100). The BSR in undisturbed sedated dogs ranged from 2 to 15, but fell to zero during dental scale removal. Conclusions Stimulation during dental scale removal might be expected to reduce the level of sedation and hypnosis in dogs to which medetomidine had been administered. The concurrent
increase in CSI and decrease in BSR suggested that a higher CSI was associated with arousal from sedation and a reduction in the depth of hypnosis. More studies are needed to validate CSI in order to better understand the functioning of this monitor. Clinical relevance The CSM shows promise for monitoring the degree of sedation and hypnosis during anaesthesia, and after adequate validation, could contribute to the refinement of anaesthetic techniques in animals. Keywords anaesthetic depth, burst suppression, cerebral state, medetomidine.
Introduction Monitoring anaesthetic depth, i.e. the level of hypnosis and consciousness is particularly challenging in animals. However, two methods are currently popular. The bispectral index (BIS) is a variable derived from the passively recorded electroencephalogram (EEG). Auditory evoked potentials (AEP) represent the EEG response to an auditory stimulus, returning the latency and amplitude of wave forms. Monitors using the AEP can also return a numerical variable. Both approaches have been evaluated in animals. Depth of anaesthesia monitoring using BIS has been reported in cats (March & Muir 2003; Lamont et al. 2004), dogs (Muir et al. 2003; Greene et al. 2003, 2002), pigs (MartinCancho et al. 2003), goats (Antognini et al. 2000) and horses (Haga & Dolvik 2002) while the use of AEPs has been reported in dogs (Murrell et al. 2004; Pypendop et al. 1999), mini-pigs (Andrews et al. 237
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
1990) and rats (Antunes et al. 2003a,b; Haberham et al. 2000; Jensen et al. 1998). Generally, these studies reveal that considerable variation in BIS or AEP indices exists between individual animals. Recently, a new EEG-based monitor has become commercially available. The cerebral state monitor (CSM) is a compact battery-powered device, which has a wireless connection to a computer for data collection and analyses. The device is compact and so can readily be attached to the collar of conscious dogs. The CSM collects the EEG and electromyogram (EMG) and from the former calculates the cerebral state index (CSI) and the burst suppression ratio (BSR). The CSI is a numerical value based on analyses of the frequency of the EEG signal using a fuzzy logic classifier, whereas BSR is calculated as the percentage of an isoelectric EEG signal present during a 30-second period (Danmeter 2004). EEG burst suppression consists of transient sequences of highvoltage slow waves intermingled with sharp waves, alternating with periods of depressed background activity, and is encountered during the deep anaesthesia (Schaul 1998). In experimental studies, the BSR has been applied as a measure of anaesthetic depth (Vijn & Sneyd 1998). The CSI has also been evaluated in humans (Rodriguez et al. 2004; Anderson et al. 2005) although published information is limited. Preliminary results from comparative studies with CSI indicate that the index is comparable with BIS, and can differentiate between the two lowest scales of an observer’s assessment of alertness and sedation (OAAS), indicating the two deepest levels of sedation. The purpose of the present study was to gain experiences with CSI in dogs scheduled for dental scale removal during medetomidine sedation. Materials and methods The current study, which involved cerebral state monitoring during a commonplace clinical procedure, was performed in accordance with Danish and European animal welfare regulations. Nine female Beagle dogs (n ¼ 9), weighing 11.5– 15.5 kg (mean 13.3 kg; SD 1.3 kg) housed at the Biomedical Laboratory under standard conditions, were scheduled for dental scale removal. For this purpose, they were sedated with medetomidine (Domitor, 1 mg mL)1; Orion Pharma, FIN-20360 Turku, Finland). All dogs were injected subcutaneously with 1.5 mL Domitor, i.e. a mean dose of 114 lg kg)1 medetomidine (SD 11 lg kg)1) was given. Once sedation was present, the cerebral state 238
was monitored with the CSM (Danmeter; DK-5000 Odense C, Denmark). Three sterile stainless steel subdermal needle electrodes (Medtronic; DK-2740, Skovlunde, Denmark) were placed on the midline of the skull. The electrodes were positioned in accordance with standard electroencephalographic practice in dogs, described by Pellegrino & Sica (2004). The central occipital electrode (Oz) was taken as negative and the central frontopolar electrode (Fp) as positive; the central vertex electrode (Cz) was taken as reference. Precise placement of the electrodes was not critical for correct monitor functioning. The CSM recorded the EEG with a high common mode rejection ratio and calculated CSI by analyses of the EEG frequency using a fuzzy logic classifier. The BSR was calculated as the percentage of an isoelectric EEG signal present during a 30-second data collection period (Danmeter 2004). The CSI was calculated every second, as an average of the values collected over the preceding 10 seconds. The facial EMG was recorded simultaneously using the CSM electrodes. Electrode impedance was maintained at 1 kX or less (in order to obtain acceptable recordings) and was measured automatically every minute at 0.01 lA. Data were recorded on a portable computer via a wireless connection. From the lowest and highest recorded CSI values, the median, upper and lower quartiles and range were calculated. CSI monitoring began 10 minutes after sedation was present. The animals were left undisturbed during the first 5 minutes of monitoring after which dental scale removal using an ultrasonic probe (Suprasson P5 Booster; Satelec, F-33708 Merignac Cedex, France) was begun. Monitoring continued throughout the procedure. The degree of dental scale formation was moderate and similar in all dogs. The procedure was performed by the same person, and lasted for approximately 15 minutes. After approximately 30 minutes, the effects of medetomidine were reversed using 1.5 mL of atipamezole (Antisedan, 5 mg mL)1; Orion, Turku, Finland) i.e. 5.6 mg kg)1 was injected subcutaneously (SD 0.5 mg kg)1). Results All dogs were immobile and profoundly sedated 10 minutes after medetomidine injection. However, dogs reacted by lifting their heads when placed on the examination table where they remained in lateral recumbency without restraint; their jaws could be opened easily. A clear reaction to the noise and vibration of the ultrasonic probe was observed Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240
100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0
100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0
BSR %
CSI
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
CSI undisturbed BSR undisturbed CSI dental scale BSR dental scale removal removal
Figure 1 Cerebral state index and BSR of undisturbed Beagle dogs (n ¼ 9) sedated with medetomidine, and during dental scale removal. An increase in CSI was observed when dental scale removal was started, whereas a simultaneous decrease in BSR was observed. The horizontal line indicates the location of the median, the box represents the upper–lower quartile interval and the vertical line represents the range.
in all dogs when the procedure began. Similarly, the tongue trembled in all cases when the probe was applied and increased jaw tone was noticed. Occasionally, some of the animals snapped their jaws together or jerked their legs. In undisturbed dogs, the CSI range was 40–56, with a median of 43, a lower quartile of 41 and upper quartile of 45. During dental scale removal, CSI increased to a median of 99, with a lower quartile of 98 and upper quartile of 100 (range 92– 100). The range of burst suppression in undisturbed dogs was 2–15%, with a median of 8%, lower quartile of 6 and upper quartile of 12%. No BSR was observed during dental scale removal (Fig. 1). All dogs recovered uneventfully from the effects of medetomidine after atipamezole was given. Discussion Medetomidine is a sedative-hypnotic agent, which produces a calming effect and a decrease in locomotor activity. After given low doses, animals remain conscious, but, in contrast to tranquilizer-sedatives such as acepromazine, higher doses induce a sleep-like state and loss of consciousness (Lees 1991). Medetomidine is a potent a2 agonist and its sedative and analgesic effects are dose dependent. However, its adverse cardiovascular effects appear to ‘plateau’ at high doses, although these can produce potent coronary artery vasoconstriction (Murrell & Hellebrekers Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240
2005). A mean medetomidine dose of 114 lg kg)1, as administered in the current study, produced profound sedation in all dogs, i.e. they remained in lateral recumbency without restraint, and their jaws could be opened easily. The clinical signs of sedation were associated with low CSI values, i.e. 40–56. Preliminary human studies have indicated that CSI and BIS are comparable (Rodriguez et al. 2004; Anderson et al. 2005). In human subjects, BIS values of over 90 represent consciousness, values of 84–91 are associated with an impairment of implicit memory, values of 67–79 are associated with an absence of reaction to verbal commands in 50% of subjects and values <50 are, on statistical grounds, extremely unlikely to be associated with awareness (Chan & Gin 2000). In comparison, in human subjects, CSI values of 100 indicate wakefulness, 80–100 represent sedation, 60–80 indicate light anaesthesia, 40–60 are present during surgical anaesthesia and values <40 indicate deep anaesthesia (Danmeter 2004). Claims that CSI and BIS indices are comparable provide grounds for comparing the results of the present study with BIS values in animals reported elsewhere. Several studies reported BIS values lower than 60 in animals during general anaesthesia, indicating a sufficient level of hypnosis or unconsciousness (Greene et al. 2002; Martin-Cancho et al. 2003; Greene et al. 2003; Antognini et al. 2000; Haga & Dolvik 2002). However, in cats consistently low BIS values were observed (Lamont et al. 2004). Combining isoflurane with medetomidine (8 lg kg)1) reduced mean BIS values from 52 to 31 at 1.5 MAC multiple and from 31 to 9 at 2.0 MAC multiple respectively in dogs, demonstrating a MAC reducing effect of medetomidine (Greene et al. 2003). A similar synergism of medetomidine was observed when combined with thiopental. Dogs sedated with 150 lg kg)1 medetomidine needed only 4.4 mg kg)1 thiopental to achieve a similar level of anaesthesia assessed with AEP and reflex testing, than dogs anaesthetized with 50 lg kg)1 acepromazine and 15.5 mg kg)1 thiopental (Pypendop et al. 1999). The effect of medetomidine alone on BIS or AEP has not been reported. In the present study, low CSI values were seen in undisturbed dogs sedated with medetomidine. However, dogs were easily aroused when dental scale removal began, presumably because of the noise and vibrations caused by the ultrasonic probe. This was associated with concurrent increases of CSI and decreases in the BSR, suggesting that higher values of CSI are associated with awakening from sedation 239
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
and a reduction in the depth of hypnosis. All dogs stayed immobilized throughout the procedure. After the adequate validation, CSI may be able to contribute to the refinement of anaesthetic techniques for animals by indicating changes in the level of sedation and hypnosis. However, further validation of CSI is necessary for better understanding of the monitor’s function. Acknowledgements Line Bjoerndal Gravesen (Biomedical Laboratory) is acknowledged for technical assistance and Danmeter A/S (DK-5000 Odense C, Denmark) for placing CSM and data collection software at our disposal. References Anderson RE, Barr G, Jakobsson JG (2005) Cerebral state index during anaesthetic induction: a comparative study with propofol or nitrous oxide. Acta Anaesthesiol Scand 49, 750–753. Andrews RJ, Knight RT, Kirby RP (1990) Evoked potential mapping of auditory and somatosensory cortices in the miniature swine. Neurosci Lett 114, 27–31. Antognini JF, Wang XW, Carstens E (2000) Isoflurane anaesthetic depth in goats monitored using the bispectral index of the elecroencephalogram. Vet Res Commun 24, 361–370. Antunes LM, Roughan JV, Flecknell PA (2003a) Effects of different propofol infusion rates on EEG activity and AEP responses in rats. J Vet Pharmacol Ther 26, 369–376. Antunes LM, Golledge HDR, Roughan JV et al. (2003b) Comparison of electroencephalogram activity and auditory evoked responses during isoflurane and halothane anaesthesia in the rat. Vet Anaesth Analg 30, 15–23. Chan MTV, Gin T (2000) What does the bispectral EEG monitor? (editorial). Eur J Anaesthesiol 17, 146–148. Danmeter AS (2004) Cerebral State Monitor User Manual (2nd UK edition). Greene SA, Tranquilli WJ, Benson GJ et al. (2003) Effect of medetomidine administration on bispectral index measurements in dogs during anesthesia with isoflurane. Am J Vet Res 64, 316–320. Greene SA, Benson GJ, Tranquilli WJ et al. (2002) Relationship of canine bispectral index to multiples of sevoflurane minimal alveolar concentration, using patch or subdermal electrodes. Comp Med 52, 424–428. Haberham ZL, van den Brom WE, Venker-van Hagen AJ et al. (2000) The rat vertex-middle latency auditoryevoked potential as indicator of anaesthetic depth: a comparison with evoked-reflex testing. Brain Res 873, 287–290. Haga HA, Dolvik NI (2002) Evaluation of the bispectral index as an indicator of degree of central nervous system 240
depression in isoflurane-anesthetized horses. Am J Vet Res 63, 438–442. Jensen EW, Nygaard M, Henneberg SW (1998) On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats. Med Eng Physics 20, 722–728. Lamont LA, Greene SA, Grimm KA et al. (2004) Relationship of bispectral index to minimum alveolar concentration multiples of sevoflurane in cats. Am J Vet Res 65, 93–98. Lees P (1991) Sedatives, Anticonvulsants, Central Muscle Relexants, Analgesics, Antipyretics and Anti-Inflammatory Agents. In: Veterinary applied pharmacology and therapeutics. Brander CG, Pugh DM, Bywater RJ, Jenkins WL (eds). Bailliere Tindall, London, pp. 328–354. March PA, Muir WW (2003) Use of the bispectral index as a monitor of anesthetic depth in cats anesthetized with isoflurane. Am J Vet Res 64, 1534–1541. Martin-Cancho MF, Lima JR, Luis L et al. (2003) Bispectral index, spectral edge frequency 95% and median frequency recorded for various concentrations of isoflurane and sevoflurane in pigs. Am J Vet Res 64, 866–873. Muir WW, Wiese AJ, March PA (2003) Effects of morphine, lidocaine, ketamine and morphine-lidocaineketamine drug combinations on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res 64, 1155–1160. Murrell JC, de Groot HN, Venker-van Hagen AJ et al. (2004) Middle-latency auditory-evoked potential in acepromazine-sedated dogs. J Vet Intern Med 18, 196–200. Murrell JC, Hellebrekers LJ (2005) Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Vet Anaesth Analg 32, 117–127. Pellegrino FC, Sica RE (2004) Canine electroencephalographic recording technique: findings in normal and epileptic dogs. Clin Neurophysiol 115, 477–487. Pypendop B, Poncelet L, Verstegen J (1999) Use of midlatency auditory-evoked potentials as indicator of unconsciousness in the dog: characterisation of the effects of acepromazine-thiopentone, medetomidinethiopentone and medetomidine-butorphanol-midazolam combinations. Res Vet Sci 67, 35–39. Rodriguez BE, Jensen EW, Martinez P et al. (2004) Definition of a New Index for Depth of Anaesthesia Using EEG Sub-Parameters Combined by Fuzzy Logics. European Society of Anaesthesiology Annual Meeting, June 5–8, Lisbon, Portugal. Schaul N (1998) The fundamental neural mechanisms of electroencephalography. Electroencephalogr Clin Neurophysiol 106, 101–107. Vijn PC, Sneyd JR (1998) I.V. anaesthesia and EEG burst suppression in rats: bolus injections and closed-loop infusions. Br J Anaesth 81, 415–421. Received 12 February 2005; accepted 7 July 2005.
Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240
doi:10.1111/j.1467-2995.2005.00263.x
BRIEF COMMUNICATION
Cerebral state monitoring in Beagle dogs sedated with medetomidine Peter JA Bollen
PhD
& Henrik Saxtorph
DVM
Biomedical Laboratory, University of Southern Denmark, Odense, Denmark
Correspondence: Peter Bollen, Biomedical Laboratory, University of Southern Denmark, Winsloewparken 23, DK-5000 Odense C, Denmark. E-mail: [email protected]
Abstract Objective To provide experience of monitoring the level of hypnosis with the Cerebral State Monitor (CSM), a device extracting a single numerical variable between 0 and 100 from the electroencephalogram in dogs sedated with medetomidine during dental scale removal. Study design Prospective observational study. Animals Nine female Beagle dogs weighing 13.3 ± 1.3 kg. Methods Cerebral state index (CSI) and burst suppression ratio (BSR) were recorded from sub-dermal needle electrodes in dogs sedated after subcutaneous injection of 114 ± 11 lg kg)1 medetomidine. Ten minutes after injection CSI monitoring began, and after 5 minutes, dental scale removal with an ultrasonic probe was started. After approximately 30 minutes, the effects of medetomidine were antagonized with atipamezole. Results The CSI had a median value of 43 (range 40–56) in undisturbed sedated dogs. During dental scale removal, CSI increased to a median value of 99 (range 92–100). The BSR in undisturbed sedated dogs ranged from 2 to 15, but fell to zero during dental scale removal. Conclusions Stimulation during dental scale removal might be expected to reduce the level of sedation and hypnosis in dogs to which medetomidine had been administered. The concurrent
increase in CSI and decrease in BSR suggested that a higher CSI was associated with arousal from sedation and a reduction in the depth of hypnosis. More studies are needed to validate CSI in order to better understand the functioning of this monitor. Clinical relevance The CSM shows promise for monitoring the degree of sedation and hypnosis during anaesthesia, and after adequate validation, could contribute to the refinement of anaesthetic techniques in animals. Keywords anaesthetic depth, burst suppression, cerebral state, medetomidine.
Introduction Monitoring anaesthetic depth, i.e. the level of hypnosis and consciousness is particularly challenging in animals. However, two methods are currently popular. The bispectral index (BIS) is a variable derived from the passively recorded electroencephalogram (EEG). Auditory evoked potentials (AEP) represent the EEG response to an auditory stimulus, returning the latency and amplitude of wave forms. Monitors using the AEP can also return a numerical variable. Both approaches have been evaluated in animals. Depth of anaesthesia monitoring using BIS has been reported in cats (March & Muir 2003; Lamont et al. 2004), dogs (Muir et al. 2003; Greene et al. 2003, 2002), pigs (MartinCancho et al. 2003), goats (Antognini et al. 2000) and horses (Haga & Dolvik 2002) while the use of AEPs has been reported in dogs (Murrell et al. 2004; Pypendop et al. 1999), mini-pigs (Andrews et al. 237
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
1990) and rats (Antunes et al. 2003a,b; Haberham et al. 2000; Jensen et al. 1998). Generally, these studies reveal that considerable variation in BIS or AEP indices exists between individual animals. Recently, a new EEG-based monitor has become commercially available. The cerebral state monitor (CSM) is a compact battery-powered device, which has a wireless connection to a computer for data collection and analyses. The device is compact and so can readily be attached to the collar of conscious dogs. The CSM collects the EEG and electromyogram (EMG) and from the former calculates the cerebral state index (CSI) and the burst suppression ratio (BSR). The CSI is a numerical value based on analyses of the frequency of the EEG signal using a fuzzy logic classifier, whereas BSR is calculated as the percentage of an isoelectric EEG signal present during a 30-second period (Danmeter 2004). EEG burst suppression consists of transient sequences of highvoltage slow waves intermingled with sharp waves, alternating with periods of depressed background activity, and is encountered during the deep anaesthesia (Schaul 1998). In experimental studies, the BSR has been applied as a measure of anaesthetic depth (Vijn & Sneyd 1998). The CSI has also been evaluated in humans (Rodriguez et al. 2004; Anderson et al. 2005) although published information is limited. Preliminary results from comparative studies with CSI indicate that the index is comparable with BIS, and can differentiate between the two lowest scales of an observer’s assessment of alertness and sedation (OAAS), indicating the two deepest levels of sedation. The purpose of the present study was to gain experiences with CSI in dogs scheduled for dental scale removal during medetomidine sedation. Materials and methods The current study, which involved cerebral state monitoring during a commonplace clinical procedure, was performed in accordance with Danish and European animal welfare regulations. Nine female Beagle dogs (n ¼ 9), weighing 11.5– 15.5 kg (mean 13.3 kg; SD 1.3 kg) housed at the Biomedical Laboratory under standard conditions, were scheduled for dental scale removal. For this purpose, they were sedated with medetomidine (Domitor, 1 mg mL)1; Orion Pharma, FIN-20360 Turku, Finland). All dogs were injected subcutaneously with 1.5 mL Domitor, i.e. a mean dose of 114 lg kg)1 medetomidine (SD 11 lg kg)1) was given. Once sedation was present, the cerebral state 238
was monitored with the CSM (Danmeter; DK-5000 Odense C, Denmark). Three sterile stainless steel subdermal needle electrodes (Medtronic; DK-2740, Skovlunde, Denmark) were placed on the midline of the skull. The electrodes were positioned in accordance with standard electroencephalographic practice in dogs, described by Pellegrino & Sica (2004). The central occipital electrode (Oz) was taken as negative and the central frontopolar electrode (Fp) as positive; the central vertex electrode (Cz) was taken as reference. Precise placement of the electrodes was not critical for correct monitor functioning. The CSM recorded the EEG with a high common mode rejection ratio and calculated CSI by analyses of the EEG frequency using a fuzzy logic classifier. The BSR was calculated as the percentage of an isoelectric EEG signal present during a 30-second data collection period (Danmeter 2004). The CSI was calculated every second, as an average of the values collected over the preceding 10 seconds. The facial EMG was recorded simultaneously using the CSM electrodes. Electrode impedance was maintained at 1 kX or less (in order to obtain acceptable recordings) and was measured automatically every minute at 0.01 lA. Data were recorded on a portable computer via a wireless connection. From the lowest and highest recorded CSI values, the median, upper and lower quartiles and range were calculated. CSI monitoring began 10 minutes after sedation was present. The animals were left undisturbed during the first 5 minutes of monitoring after which dental scale removal using an ultrasonic probe (Suprasson P5 Booster; Satelec, F-33708 Merignac Cedex, France) was begun. Monitoring continued throughout the procedure. The degree of dental scale formation was moderate and similar in all dogs. The procedure was performed by the same person, and lasted for approximately 15 minutes. After approximately 30 minutes, the effects of medetomidine were reversed using 1.5 mL of atipamezole (Antisedan, 5 mg mL)1; Orion, Turku, Finland) i.e. 5.6 mg kg)1 was injected subcutaneously (SD 0.5 mg kg)1). Results All dogs were immobile and profoundly sedated 10 minutes after medetomidine injection. However, dogs reacted by lifting their heads when placed on the examination table where they remained in lateral recumbency without restraint; their jaws could be opened easily. A clear reaction to the noise and vibration of the ultrasonic probe was observed Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240
100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0
100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0
BSR %
CSI
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
CSI undisturbed BSR undisturbed CSI dental scale BSR dental scale removal removal
Figure 1 Cerebral state index and BSR of undisturbed Beagle dogs (n ¼ 9) sedated with medetomidine, and during dental scale removal. An increase in CSI was observed when dental scale removal was started, whereas a simultaneous decrease in BSR was observed. The horizontal line indicates the location of the median, the box represents the upper–lower quartile interval and the vertical line represents the range.
in all dogs when the procedure began. Similarly, the tongue trembled in all cases when the probe was applied and increased jaw tone was noticed. Occasionally, some of the animals snapped their jaws together or jerked their legs. In undisturbed dogs, the CSI range was 40–56, with a median of 43, a lower quartile of 41 and upper quartile of 45. During dental scale removal, CSI increased to a median of 99, with a lower quartile of 98 and upper quartile of 100 (range 92– 100). The range of burst suppression in undisturbed dogs was 2–15%, with a median of 8%, lower quartile of 6 and upper quartile of 12%. No BSR was observed during dental scale removal (Fig. 1). All dogs recovered uneventfully from the effects of medetomidine after atipamezole was given. Discussion Medetomidine is a sedative-hypnotic agent, which produces a calming effect and a decrease in locomotor activity. After given low doses, animals remain conscious, but, in contrast to tranquilizer-sedatives such as acepromazine, higher doses induce a sleep-like state and loss of consciousness (Lees 1991). Medetomidine is a potent a2 agonist and its sedative and analgesic effects are dose dependent. However, its adverse cardiovascular effects appear to ‘plateau’ at high doses, although these can produce potent coronary artery vasoconstriction (Murrell & Hellebrekers Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240
2005). A mean medetomidine dose of 114 lg kg)1, as administered in the current study, produced profound sedation in all dogs, i.e. they remained in lateral recumbency without restraint, and their jaws could be opened easily. The clinical signs of sedation were associated with low CSI values, i.e. 40–56. Preliminary human studies have indicated that CSI and BIS are comparable (Rodriguez et al. 2004; Anderson et al. 2005). In human subjects, BIS values of over 90 represent consciousness, values of 84–91 are associated with an impairment of implicit memory, values of 67–79 are associated with an absence of reaction to verbal commands in 50% of subjects and values <50 are, on statistical grounds, extremely unlikely to be associated with awareness (Chan & Gin 2000). In comparison, in human subjects, CSI values of 100 indicate wakefulness, 80–100 represent sedation, 60–80 indicate light anaesthesia, 40–60 are present during surgical anaesthesia and values <40 indicate deep anaesthesia (Danmeter 2004). Claims that CSI and BIS indices are comparable provide grounds for comparing the results of the present study with BIS values in animals reported elsewhere. Several studies reported BIS values lower than 60 in animals during general anaesthesia, indicating a sufficient level of hypnosis or unconsciousness (Greene et al. 2002; Martin-Cancho et al. 2003; Greene et al. 2003; Antognini et al. 2000; Haga & Dolvik 2002). However, in cats consistently low BIS values were observed (Lamont et al. 2004). Combining isoflurane with medetomidine (8 lg kg)1) reduced mean BIS values from 52 to 31 at 1.5 MAC multiple and from 31 to 9 at 2.0 MAC multiple respectively in dogs, demonstrating a MAC reducing effect of medetomidine (Greene et al. 2003). A similar synergism of medetomidine was observed when combined with thiopental. Dogs sedated with 150 lg kg)1 medetomidine needed only 4.4 mg kg)1 thiopental to achieve a similar level of anaesthesia assessed with AEP and reflex testing, than dogs anaesthetized with 50 lg kg)1 acepromazine and 15.5 mg kg)1 thiopental (Pypendop et al. 1999). The effect of medetomidine alone on BIS or AEP has not been reported. In the present study, low CSI values were seen in undisturbed dogs sedated with medetomidine. However, dogs were easily aroused when dental scale removal began, presumably because of the noise and vibrations caused by the ultrasonic probe. This was associated with concurrent increases of CSI and decreases in the BSR, suggesting that higher values of CSI are associated with awakening from sedation 239
Cerebral state monitoring in dogs PJA Bollen and H Saxtorph
and a reduction in the depth of hypnosis. All dogs stayed immobilized throughout the procedure. After the adequate validation, CSI may be able to contribute to the refinement of anaesthetic techniques for animals by indicating changes in the level of sedation and hypnosis. However, further validation of CSI is necessary for better understanding of the monitor’s function. Acknowledgements Line Bjoerndal Gravesen (Biomedical Laboratory) is acknowledged for technical assistance and Danmeter A/S (DK-5000 Odense C, Denmark) for placing CSM and data collection software at our disposal. References Anderson RE, Barr G, Jakobsson JG (2005) Cerebral state index during anaesthetic induction: a comparative study with propofol or nitrous oxide. Acta Anaesthesiol Scand 49, 750–753. Andrews RJ, Knight RT, Kirby RP (1990) Evoked potential mapping of auditory and somatosensory cortices in the miniature swine. Neurosci Lett 114, 27–31. Antognini JF, Wang XW, Carstens E (2000) Isoflurane anaesthetic depth in goats monitored using the bispectral index of the elecroencephalogram. Vet Res Commun 24, 361–370. Antunes LM, Roughan JV, Flecknell PA (2003a) Effects of different propofol infusion rates on EEG activity and AEP responses in rats. J Vet Pharmacol Ther 26, 369–376. Antunes LM, Golledge HDR, Roughan JV et al. (2003b) Comparison of electroencephalogram activity and auditory evoked responses during isoflurane and halothane anaesthesia in the rat. Vet Anaesth Analg 30, 15–23. Chan MTV, Gin T (2000) What does the bispectral EEG monitor? (editorial). Eur J Anaesthesiol 17, 146–148. Danmeter AS (2004) Cerebral State Monitor User Manual (2nd UK edition). Greene SA, Tranquilli WJ, Benson GJ et al. (2003) Effect of medetomidine administration on bispectral index measurements in dogs during anesthesia with isoflurane. Am J Vet Res 64, 316–320. Greene SA, Benson GJ, Tranquilli WJ et al. (2002) Relationship of canine bispectral index to multiples of sevoflurane minimal alveolar concentration, using patch or subdermal electrodes. Comp Med 52, 424–428. Haberham ZL, van den Brom WE, Venker-van Hagen AJ et al. (2000) The rat vertex-middle latency auditoryevoked potential as indicator of anaesthetic depth: a comparison with evoked-reflex testing. Brain Res 873, 287–290. Haga HA, Dolvik NI (2002) Evaluation of the bispectral index as an indicator of degree of central nervous system 240
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Ó 2006 Association of Veterinary Anaesthetists, 33, 237–240