A comparative study of neurologically-equivalent propofol anaesthetic combinations in the dog

A comparative study of neurologically-equivalent propofol anaesthetic combinations in the dog Antonello Bufalari, Lena E. Nilsson, Charles E. Short, and Claudia Giannoni College of Veterinary Medicine, Institute of Special Pathology and Clinical Surgery 4 San Costanzo, 06100 Peruga, Italy (Bufalari and Giannoni); Stromsholm Referral Animal Hospital, S-730 40 Kolback, Sweden (Nilsson); Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 USA (Short). These studies were completed at the College of Veterinary Medicine, Cornell University Ithaca, New York 14853 USA. SUMMARY Propofol, administered as the sole anaesthetic agent, was evaluated when given alone and to dogs premedicated with acepromazine or medetomidine. Both preanaesthetic agents reduced the dose of propofol required for induction of anaesthesia. Medetomidine significantly reduced the dose of propofol required for the maintenance of anaesthesia for a 30-minute period. An equivalent depth of anaesthesia was established in each protocol as judged by lack of response to mechanical noxious stimuli and total amplitude reduction of brain wave activity. Differences in physiological responses between propofol and acepromazine / propofol were not significant. The dogs in the medetomidine/propofol group had a significantly higher blood pressure and longer duration of anaesthesia and recovery. Oxygen saturation was maintained above 90% by the administration of supplemental oxygen. The study demonstrated the comparative responses to a biologically equivalent depth of anaesthesia, as confirmed by brain wave analysis, using three different techniques using propofol. INTRODUCTION Propofol anaesthesia in dogs is described by several investigators (Funkquist et al. 1991, Morgan et al. 1989, Smith et al. 1993, Vainio 1991, Watkins et al. 1987, Weaver et al. 1990) to include smooth induction of anaesthesia, minimal changes in cardiovascular function (Robertson et al. 1992), respiratory depression and rapid, unexcited recoveries. Propofol has been used in premedicated and nonpremedicated dogs and cats. Variable anaesthetic responses have been observed with these combinations since premedication can alter central nervous system (CNS), cardiopulmonary, or metabolic processes (Blue and Short 1987). Concurrent medications which alter heart rate, blood pressure or cardiac output may influence the responses to propofol (Clacys et al. 1988). Propofol dosage requirements may likewise be influenced by premedication (Weaver et al., 1990). It is anticipated that all premedications which depress the CNS will likewise reduce propofol dose requirements. Potent sedatives and anal- 19 gesics may potentiate the duration of anaesthesia and slow the return of responses to painful stimuli (Vainio 1991). Premedication agents which shift the carbon dioxide response curve or reduce ventilatory volume may potentiate the risk of respiratory depression during induction or maintenance of anaesthesia with propofol. The objectives of this study were (a) to determine if the outward subjective signs of propofol anaesthesia, which may be altered by pre-anaesthetic agents, can be confirmed by compressed spectral analysis (CSA) of the electroencephalogram (EEG) for more objective evaluation, (b) to reconfirm the equivalent dosage of propofol as a sole anaesthetic compared to the requirements following acepromazine or medetomidine premedication (c) to reconfirm a dose related effect in maintaining anaesthesia for a 30 minute period with propofol would provide stable cardiovascular and pulmonary effects in the dog, and (d) to confirm that any changes in cardiopulmonary function are unlikely to alter CNS changes mediated by propofol anaesthesia. MATERIALS AND METHODS Eighteen clinically-healthy purpose bred mongrel dogs were used in this study. There were 9 females and 9 males, weighing 15.2-29.5 kg, between the ages of 15-20 months. Animals were randomly divided into 3 groups. Each group consisted of 6 dogs with equal distribution of males and females. Atropine (atropine sulphate, Anpro Pharmaceuticals) was used for premedication in all 3 groups for the prevention of bradycardia. Group A received propofol (Rapinovet, Coopers Animal Health; DiprivanB, Stuart Pharmaceuticals) 6.6 mg/kgivfor inductionfollowedby 1.1 mg/kgivformaintenance as required to maintain anaesthesia for 30 minutes. Group B received acepromazine (PromAceB, Aveco Company Inc) 0.1 mg/ kg im followed in 15 minutes by 4.4 mg/ kg iv propofol for induction of anaesthesia with 1.1 mg/kg iv boluses for 30 minutes. Group C received 10 pg/ kg im medetomidine (DomitorB, Orion Corporation) followed by a 2.2 mg/kg iv propofol for induction of anaesthesia and 1.1 mg/kg iv boluses to maintain anaesthesia for 30 minutes.

The boluses (1.1 mg/kg) of propofol were administered at a constant rate with an infusion pump (Bard infusion OR, Bard Medsystems Division) programmed to deliver a 300 pg/ kg/minute infusion. Routine metabolic and haematological profiles were determined on each dog before inclusion in the trial. Monitoring the Cardiovascular System The electrocardiogram (ECG) was monitored using a Datascope 870 and recorded on a Datascope 721A (Datascope, Inc). Heart rates and blood pressures (systolic, diastolic, and mean) responses were monitored using a noninvasive pressure monitor (Dinamap 1846 SX/ P, Critikon Corporation). The cuff was placed on a rear leg above the metatarsal artery. Monitoring the Respiratory System Respiratory rates and end-tidal carbon dioxide levels were recorded using a HP 4721 Oa capnometer (Hewlett- Packard Inc) connected to the endotracheal tube during anaesthesia and to a face mask during recovery. Oxygen saturation was measured by a pulse oximeter (501+, Criticare Systems). The probe was placed on the lateral surface of the tongue of each dog after anaesthesia was induced. All dogs received oxygen, for a variable time duration, whenever the oxygen saturation fell below 90%. Monitoring the Central Nervous System The depth of anaesthesia was determined by observing the reactions of the dogs to the application of a cross clamp on the tail. Objective evaluations were recorded using a CSA Computer assisted EEG recorder (Biologic Traveler Ltd.). Five platinum electrodes were used, one reference and one active, placed subcutaneously in contact with the skull over each cerebral hemisphere with the fifth placed over the central fissures between the eyes as a ground (Short 1991, Short ef az., 1992). Ten 2 second epochs of brain wave activity were recorded and averaged for each data point. Experimental Protocol Preliminary data for all parameters except EEG and oxygen saturation were recorded before any medication. Respiratory rate, end-tidal carbon dioxide, pulse rate, blood pressure (systolic, mean and diastolic) and temperature were recorded. Pre-anaesthetic recordings (predrugs) were followed by recordings 3 minutes after atropine injection (3 minutes post-atropine), and 2 minutes before propofol induction (2 minutes pre-propofol). Propofol was administered 20 minutes after atropine. The initial values for oxygen saturation and EEG measurements were recorded 2 minutes post-propofol induction and continued at 5 minute intervals as long as the dogs would tolerate it. Control awake values for EEG were not recorded. Anaesthetic Assessment The stage of anaesthesia was subjectively assessed by evaluating palpebral reflexes as: (1) reflex absent; (2) faint 20 reflex; (3) weakened reflex; and (4) normal reflex and by evaluating the response to tail clamping. The tail clamping evaluation was performed by placing non-crushing intestinal forceps, engaged to the first serration on the lock, for no more than 3 seconds. Response to the tail clamp within the first 30 minutes was considered as an indication for supplemental propofol administration. The return of a normal reflex (spontaneous movement or positive response to the tail clamp), was considered to be the end of anaesthesia. Raising the head (stage l), sternal recumbency (stage 2), and voluntary standing were measured. Any adverse or unusual responses observed were recorded. Statistical Analysis Analysis of variance (ANOVA) with replication was calculated for each parameter in all groups. A P value <0.05 was judged statistically significant. The protocol was approved by the University Animal Use committee and conducted utilizing good laboratory standards in compliance with the Food and Drug Administration. RESULTS No significant abnormalities were seen in the metabolic and haematology profiles. In all groups, induction of anaesthesia was rapid and smooth and without excitatory effects such as hypertonus, myoclonia, or involuntary movements. Endotracheal intubation was very easy and without complications in 15 of the 18 dogs. Three dogs in group C became recumbent but required additional propofol(l.1 mg/kg) for intubation. During the 30-minute period of general anaesthesia, dogs in all groups received additional propofol (1.1 mg/kg iv). The first signs of arousal were tail movements and head lifting. Sternal recumbency and recovery were achieved without excitement or complication. Duration of Anaesthesia and Recovery Times Propofol anaesthesia was maintained for 30 minutes. Similar anaesthetic time, extubation, head lift, and sternal recumbency were observed in groups A and 8. All dogs in group C required more time to lift the head than the slowest in groups A and B (Fig. 1). The mean time from end of propofol anaesthesia until sternal recumbency was 8 min 30 sec for group A; 12 min and 2 sec for group B; 30 min and 52 sec for group C. The total recovery time for group B was not significantly slower than for group A. The mean time between starting anaesthetic induction and cessation of propofol administration and the dogs return to the unaided standing position was 43 min in group A (range 3747 min) and 49 min in group B (range 37-59 min). The mean time for recovery in group C was 72 min (range 47-105 min). Cardiovascular System Responses Atropine administration influenced the pulse rate in all groups, heart rate peaking at the time of induction of anaesthesia. The pulse rate then declined during anaes-

~~~~ DURATION OF ANESTHESIA AND RECOVERY TIME Mean Blood Pressure Trend During Propofol Anesthesia 11500 11000 10500 10000 0 55 00 -~ 04500' - 0 4000-035W1 0 30 00 0 25 00, 0 20 w 015001 L 1000. 00500' 00000~ Anntk.?. E.,"b.M Y.d,I *l.,"d I.OS".r* Figure 1: Group A Propofol 6.6 mg/kg iv induction with 1.1 mg/kg maintenance doses as needed. Group B Acepromazine 0.1 mg/kg preanaesthetic. Propofol 4.4 mglkg iv induction with 1.1 mglkg maintenance doses as needed. Group C Medetomidine 10 pglkg preanaesthetic. Propofo12.2 mglkg iv induction with 1.I mglkg maintenance doses as needed. All g~oups received atropine sulfate 0.02 mglkg im 20 minutes prior propofol. Duration of anaesthesia and recovery times. Anaesthesia was maintained by additional 1.1 mglkg infusion doses at a rate constant for all 3 groups indicated by response (+) to cross-clamp of tail for 30 minutes of anaesthesia. Anaesthesia times indicate total anaesthesia time. No dqferences are seen in groups A and B. Anaesthesia lasted approximately 5 minutes longer post-propofol in group C. Extubation was necessary much sooner in groups A and B (>10 minutes) than group C. Dogs in groups A and B were capable of lifting head much sooner (>26 minutes) than in group C. Sternal recumbency was observed much earlier in groups A and B (>25 minutes) than in group C. Total recovery (standing without falling) was significantly faster in groups A and B (>23 minutes) than group C. Acepromazine influences the initial dose requirements of propofol(33% reduction) but not significantly the duration of anaesthesia or initial recovery. Medetomidine with its potent sedativelanalgesic properties increases nnaesthesia time nnd all recovery patterns. thesia as the effect of the atropine diminished and was observed in the range of 96-111 beats/minute at 30 minutes post-propofol for all 3 groups (Fig. 2). There was no significant difference in blood pressure in groups A and B. Blood pressure in group C was elevated for the entire anaesthetic period (Fig. 3). A decrease in the blood pressure in groups A and B, after induction, was observed. The combination of atropine and medetomidine mediated a rise in mean blood pressure up to 158.7 mmhg 60 I 10 1 "p'e 11 *'121. 5'' 1; 15 20 25 10 35 1" 45 511 55 M mod # = post Atropine '* = post Propufol Time (mm.) * = prepropufol 4 = Pmpofollnductmt Figure 3: Mean blood pressures arc illustrated. Systolic, mcan, a17d diastolic blood pressures showed similar trends. Propofol mediates a slight decrease in blood pressure. Higher concentrations of acepromazine than those iised in a group B are known to reduce blood pressure. Groups A and B were characteristd by these hypotensive trends even though reduction was riot significarit. Medetomidine (preanaesthetic in group C) mediates an increase in blood prcssure. In spite ofthe influence of propofol, the administration of ~nedetoinidine 10 minutes prior to propofol mediates an overriding hypertensi7~e trcwd iu this study. Differences ofc and A-B were highly significant (p 4.01). (Standard error calculated but not shown for clarity). (SD k 42.6) before general anaesthesia was induced. In group C, all blood pressure measurements peaked around 10-15 minutes post-propofol and then slowly declined. Respirato y System Responses There was little difference in the oxygen saturation between groups (Fig. 4A), while respiratory rates were higher in group A (Fig. 4B). Respiratory rates were more stable in groups B and C. End-tidal carbon dioxide was similar during the anaesthetic period in all groups, and did move outside normal ranges (Fig. 4C). Clinically significant decreases in respiratory rate were not Respiratory Rite lrend During Propofol Anesthesia Heat Rile Responses During Pmpofol Anesthesia 10 10 ~ --f croup c 0. " I prr," I. A *I.- i.. 10 15 M 23 30 35 (0 45 FO 55 bo mrd # i past Atropine '* = past Propoful Time (mm) = pre Pmpofol 4 = Propofnl Induction 20 I 1 OF 3. I.'*'.,:. I0 1 10 IS 30 ;5 ID 4s 50 55 1 me* U = post Atropine I' = post Prupufol Ttmr (rn~n) * = pre prnpofol t = Propofol Inductwn Figure 2: Cardiovascular responses: pulse rate trend. Atropine sulphate (0.02 mglkg im) 20 minutes prior to propofol had a pulse rate influence in all groups. Propofol is associated with an increase in pulse rate. The initial increase was most obviously influenced by medetomidine which is known to mediate a reduction in heart rate due to vasoconstriction and hypertension. (Standard error calculated but not shown for clarity). 21 Figure 4A: Respiratory responses: rate; oxygen saturation, end-tidal carbon dioxide. Respiratory rates were stable in groups B and C and variable in group A. This reflects the relative ease in adjusting propofol supplcniental doses zohrn preanaesthetics were used. oxygen saturation was more depressed zuhen preanaesthetics were used. Ninety percent oxygen saturation was used as a basis for oxygen administration. Following initial reduction in oxy'qen, supplt~metital oxygen administration maintained all groups at similar levels of oxy,yc~~ saturation. Carbon dioxide trends reflect the effect of preanaesthetics end propofol. All carbon dioxide values are within acceptable levcls and do not reflecf carbon dioxide retention levels of concern. (Standard error calculated but not shown for clarity).

~...~ ~- 4 Saturation During hopofol Anesthesia Compressed Spemal Analysis of Brain Wave AItivily during Propofol Anesthesia Ka 91.. pus' Prupufd Time (rnm ] Control due\ undertermined 3% pulse eximeter probe was placed on the tongue 2'' 5- I" li 2" 25 30 5 a (5 50 55 60 Figure 4B: Respiratory responses: rate; oxygen saturation, end-tidal carbon dioxide. Respiratory rates were stable in groups B and C and variable in group A. This reflects the relative ease in adjusting propofol supplemental doses when preanaesthetics were used. Oxygen saturation was more depressed when preanaesthetics were used. Ninety percent oxygen saturation was used as a basis for oxygen administration. Following initial reduction in oxygen, supplcmental oxygen administration maintained all groups at similar levels of oxygen saturation. Carbon dioxide trends reflect the effect of preanaesthetics and propofol. All carbon dioxide values are within acceptable levels and do not reflect carbon dioxide retention levels of concern. u 16 C 4 Response Trend 24pm 91 r'r. 5- I0 25 10 IS 4a 15 ; 55 60 rnd # = port Atropine '* = post I'ropofol Trmr (mm) * = pw Propofol f = Propofol Induction Figure 4C: Respiratory responses: rate; oxygen saturation, end-tidal carbon dioxide. Respiratory rates were stable in groups B and C and variable in group A. This reflects the relative ease in adjusting propofol supplemental doses when preanaesthetics were used. Oxygen saturation was more depressed when preanaesthetics were used. Ninety percent oxygen saturation was usedas a basis for oxygen administration. Following initial reduction in oxygen, supplemental oxygen administration maintained all groups at similar levels of oxygen saturation. Carbon dioxide trends ref7ect the effect of preanaesthetics and propofol. All carbon dioxide values are within acceptable levels and do not reflect carbon dioxide retention levels of concern. observed in any of the 3 groups of dogs except for one dog in group A which became apnoeic. This occured after induction of anaesthesia was completed and resolved within 6 minutes, during which time manual ippv was performed. Oxygen saturation was first measured at 2 minutes post-anaesthesia induction, and all 3 groups were initially below 90% saturation: group A 87.7% (f 9.9), group B 85% (* 3.7), and group C 83.3% (k 6.8). Central Nervous System The activity of the central nervous system was evaluated both subjectively and objectively in order to maintain equipotent levels of propofol with and without medications influencing the CNS. Total amplitude of the 22 Figure 5: EEG Total amplitude (pv)lspectral edge (Hz). Equivalent doses qf preanaestheticlpropofol administration was achieved with nonsignificant differences in brain wave activity during 30 minutes ofstable anaesthesia. EEG response trends (total amplitude) were similar in recovery with the exception of time delays for medetomidine preanaesthesia. Spectral edge responses were predictable with the highest SE (were high frequency B activity) in propofol group A. Group B showed a lower SE95% due to cerebral influence of the tranquilizer acetylpromazine and group C showed the lowest SE95% characteristic of the influence of the potent a,-adrenergic agonist mcdetomidinc. It is concluded the equipotent dose Combinations of propofol wifhlwithoict preanaesthetics was accomplished. EEG was similar in all groups during 30 minutes of anaesthesia until significant increase at the time of head lift (Fig. 5). Increases in total amplitude were significant in recovery compared to the anaesthetised state. There was a secondary drop in EEG activity during sternal recumbency when the dogs showed external relaxation and sedation before standing (Fig. 5). Spectral edge frequencies were highest for propofol alone, lower during acepromazine/ propofol and lowest following medetomidinel propofol (Fig. 5). Body Temperature During anaesthesia, all dogs showed a reduction in temperature of an average of 1.3 OC. DISCUSSION Bradycardia has not been reported with propofol in previous trials but is a frequent finding following a2- adrenergic agonist administration in the dog. Maintaining the heart rate by the administration of atropine sulphate has been shown to make it possible to record more accurate blood pressure values with indirect measuring techniques. Atropine was therefore administered at 0.02 mg/ kg im 20 minutes before induction of anaesthesia with propofol anaesthesia in all dogs in each treatment group to avoid bias of data. Acepromazine has been used in combination with propofol induction in several studies (Morgan and Legge, 1989, Smith et al., 1993, Watkins et al., 1987, Weaver et al., 1990). It has also been investigated as a premedicant before halothane anaesthesia in a comparative study with xylazine, pethidine (meperidine), and medetomidine (Raiha et al. 1989). As a result, its use as a premedication agent in the dog has been well established. Acepromazine is known to reduce the dose requirements for injectable anaesthetic induction agents. Acepromazine reduces the sensitivity of the myocardium to arrhythmia and can cause vasodilatation and associated hypotension. Medeto-

~~~ ~~~~~~~~~ ~ midine is an a2-adrenoceptor agonist with sedative and analgesic properties in dogs and cats. It has been used in combination with thiopentone sodium and halothane (Bergstrom 1988, Young et al., 1990), ketamine, and ketamine/ halothane (Short 1991). Studies have been completed confirming its use in combination with propofol by infusion (Vainio 1991), or bolus administration (Short 1992). Medetomidine pen alone mediates an increase in systemic blood pressure, a decrease in heart rate, a significant reduction in cerebral activity, and muscle relaxation (Short 1991). Anticholinergic premedication (Vainio et al., 1989a) has been advocated in order to to reduce the incidence of bradycardia. Medetomidine significantly reduces anaesthetic requirements by up to 90%. In this study, induction of anaesthesia was achieved with 6.6 mg/kg iv propofol in nonmedicated animals, 4.4 mg/ kg iv after 0.1 mg/ kg acepromazine and an average of 2.75 mg/kg in dogs receiving 10 pg/kg im medetomidine (Table 1). There were 3 dogs in group C that required 3.3 mg/ kg total dose in contrast to the projected 2.2 mg/ kg for induction before intubation (Table 1) could be completed. Maintenance of anaesthesia was achieved by repeated administration of 1.1 mg/ kg doses of propofol as needed to prevent arousal. The stability of the total amplitude in EEG recordings, the lack of difference between groups and absence of a subjective reponse to a pain stimulus suggest that adequate anaesthesia was achieved (Fig. 5). The level of anaesthesia would appear equipotent in each of the treatment groups. The dosage level and frequency of supplemental propofol reflected the CNS effects of premedication. Recoveries from anaesthesia after propofol was discontinued, reflected further the influence of the pre-anaesthetic agent chosen (Fig. 1). Since there were no significant differences in analysis of the EEG recordings from the 3 treatment groups and all had similar subjective levels of anaesthesia, the dosage of propofol was most significantly influenced by medetomidine. Heart rates were influenced by the administration of atropine which offset the tendency of medetomidine to Table 1: Inflpence of Pre-anaesthetic on Propofol Dosage Requirements Duration of Total anaesthesia propofol Number of between (mg/kg/ repeated bolus minute) doses (minutes) Mean group A 0.39 5.8 06:05 Dosage variation within group A (range) 48 04342-08:38 Mean group B 0.33 5.7 07:21 Dosage variation within group B (range) 2-8 03:0517:06 Mean group C 0.19 4.5 10:15 Dosage variation within group C (range) 3-8 03:51-1428 *Duration of anaesthesia - 30 minute maintenance 23 - mediate bradycardia (Fig. 2). Medetomidine induced bradycardia probably reflects a reflex response to hypertension. Since dogs in group C also received atropine, hypertension was prolonged as the atropine prevented the parasympathetic reflex induced bradycardia. In the abscence of atropine, we would have anticipated that the influence of medetomidine on blood pressure would wane within 30 minutes ( Bergstrom, 1988,Vainio et al., 1989a). This difference in our protocol probably accounts for the shorter duration in hypertension noted by Vainio et al. (1989a). Apnoea is the most common adverse effect of propofol (Smith et al. 1993). It can be affected by the total dose or by the speed of administration of propofol. Pre-anaesthetic medication influence dosage requirements as shown in this study. High incidences of apnoea have been reported (Smith et al., 1993). In this study, only one dog developed apnoea. The initial oxygen saturation values indicated that medetomidine/ propofol induced more profound respiratory depression than observed in the other groups, however, administration of oxygen, when oxygen saturation of <90% was observed, corrected the respiratory depression. Adjustments in the administration of propofol with and without premedication made it possible to achieve similar planes of anaesthesia in this study. The apparent levels of total CNS depression achieved were also reflected in similar EEG total amplitude (Fig. 5). The brain wave frequency trends have not been previously reported and are believed to reflect responses mediated by the preanaesthetic agents used (1) propofol alone (highest spectral edge) with more fast frequency activity; (2) propofol/ acepromazine (medium range spectral edge); and (3) propofol/ medetomidine (low range spectral edge frequency with more slow wave activity). Since neurological responses reflected stable and predictable anaesthesia in each group, differences in other parameters such as blood pressure reflect the influence of acepromazine and medetomidine. The dogs in this study were similar in size, breeding, age, and temperament with consistent results. This may explain the difference between this study and that of Fonda (1991) who using a similar anaesthetic protocol (atropine, acetylpromazine, propofol) in dogs of different age, size, and condition obtained different results There were no significant differences in duration of anaesthesia between groups A and B in our study. We found a small difference in recovery time between groups A and B, however, there were obvious differences in dosage requirements and recovery time in the dogs premedicated with medetomidine. This could be an advantage if post-surgical analgesia is desired. If not, its effects may be reversed with atipamezole, a specific a2-adrenergic antagonist. However, it should be understood that reversal of medetomidine sedation can result in excitement since recovery from the anaesthetic effect of propofol is rapid. The administration of atipamezole will also reverse the medetomidine mediated bradycardia, which has been recorded to last for 4-6 hours following medetomidine (Vainio et ai., 198913). This study confirmed that propofol at the doses and rate of administration used provided anaesthesia without

~ major complications. Physiologically acceptable responses were maintained in the three propofol protocols. The anaesthetic protocols used provided significantly similar levels of anaesthesia by both objective (EEG) and subjective (clinical signs) evaluation of cerebral activity levels. REFERENCES Bergstrom K (1988). Cardiovascular and pulmonary effects of a new sedative / analgesic (medetomidine) as a preanaesthetic drug in the dog. Acta Veterinaria Scandinavia. 29, 109-116. Blue JT and Short CE (1987). Preanaesthetic evaluation and clinical pathology. In: Principles and Practice of Veterinary Anaesthesia. 1st ed. Short CE, ed. Williams and Wilkins, Baltimore, Maryland, pp. 3-7. Clacys MA, Gepts E and Camu F (1988). Haemodynamic changes during anaesthesia induced and maintained with propofol. British Journal of Anaesthesia. 60, 3-9. Fonda D (1991). Continuous infusion anaesthesia with propofol in dogs: clinically optimized dosages. Proceedings of the 4th International Congress of Veterinary Anaesthesia. 159.161. Funkquist P and Peterson C (1991). Propofol - ett nytt narkosmedel f6r hund och katt. Sv. Vet. Tidn, 93,555-559. Morgan DWJ and Legge K (1989). Clinical evaluation of propofol as an intravenous anaesthetic agent in cats and dogs. Veterina y Record. 122, 31-33. Raiha MP, Raiha JE and Short CE (1989). A comparison of xylazine, acepromazine, meperidine, and medetomidine as preanaesthetics to halothane anaesthesia in dogs. Acta Veterinaria Scandanavia. 85, 97-102. Robertson SA, Johnston S and Beemsterhoer J (1992). Cardiopulmonary anesthetic and post-anesthetic effects of intravenous infusions of propofol in greyhounds and nongreyhounds. American Iournal of Veterinary Research. 53(6), 1027-1032. Short CE (1991). The efftcts of selected a2-adrenoreceptor agonists on cardiovascular and pulmonary functions and brain wave activity in horses and dogs. Veterinary Practice Publishing Company, Santa Barbara, California. Short CE (1992). a2-agents in animals: sedation, analgesia, and anaesthesia. Veterinary Practice Publishing Company, Santa Barbara, California, pp. 52-55. Short CE, Raiha JE, Raiha MI' and Otto K (1992). Comparison of neurologic responses to the use of medetomidine as a sole agent or preanaesthetic in laboratory beagles. Acta Veterinaria Scandanavia. 33, 77-88. Smith J A, Gaynor JS, Bednarski RM and Muir WW (1993). Adverse effects of administration of propofol with various preanaesthetic regimens in dogs. Journal of the American Veterinary Medical Association. 202, 1111-1115. Vainio 0 (1991). Propofol infusion anaesthesia in dogs premedicated with medetomidine. Journal of Veterinary Anaesthesia. 18, 35-37. Vainio 0 and Palmu L (1989)a. Cardiovascular and respiratory effects of medetomidine in dogs and influence of anticholinergics. Acta Veterinaria Scandinavia. 30, 401-408. Vainio 0, Vaha- Vahe T and Palmu L (1989)b. Sedative and analgesic effects of medetomidine in dogs. Journal of Veterinary Dharniacolqy and Therapeutics. 12,224-231. Watkins SB, Hall LW and Clarke KW (1987). Propofol as an intravenous anaesthetic agent in dogs. Veterinary Record. 120,326-329. Weaver BMQ and Raptopoulos D (1990). Induction of anaesthesia in dogs and cats with propofol. Veterinary Record. 126,617-620. Young LE, Brearley JC, Richards DLS, Bartram DH and Jones RS (1990). Medetomidine as a premedicant in dogs and its reversal by atipamezole. Journal of Small Animal Practice. 31,554-559. 24