Acta vet. scand. 1988, 29, 109-116.

From the Department of Surgery, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden. Cardiovascular and Pulmonary Effects of a New Sedative/ Analgesic (Medetomidine) as a Preanaesthetic Drug in the Dog

By Karin Bergstr(Jm

Bergstrom, K.: Cardiovascular and pulmonary effects of a new sedative/analgesic (Medetomidine) as a preanaesthetic drug in the dog. Acta vet. scand. 1988, 29, 109-116. - Cardiovascular and pulmonary effects of a new sedative/analgesic (medetomidine) as a preanaesthetic drug in the dog. A study was carried out to in• vestigate the possible usefulness of medetomidine (Farmos Group, Turku, Fin• land) for premedication prior to general anaesthesia with thiopental sodium and halothane. The main emphasis was laid on the circulatory and respiratory effects of medetomidine. Dogs treated with xylazine (2 mg/kg) or placebo (physiological saline solution) served as controls. Medetomidine caused a decrease in blood pres• sure, heart rate and respiratory rate at all dose levels tested. These decreases were essentially dose -dependent, but there were great individual variations. It is concluded that the drug can be useful for premedication at the lowest dose le• vel tested (10 µ/kg). The sedative effect, however, is so strong that an even lower dose might be sufficient for the present purpose.

anaesthesia; sedation; analgesia; thiopental.

Introduction This unfortunate situation demands good The use of different sedatives as preanaes• knowledge of the sedative and its effects on thetic drugs in animals is today worldwide the circulation and respiration. and has been adopted from human medi• The usefulness of medetomidine, an alpha• cine. Within the latter discipline one of the adrenoreceptor agonist (Savo/a et al. 1986), most important reasons for such premedica• as a sedative/analgesic for diagnostic and tion is to moderate the patient's anxiety therapeutic procedures that do not require about the general anaesthesia and the follo• general anaesthesia is currently being stu• wing operation. This aspect is in most cases died by other investigators. of no current interest in veterinary medicine In the present study medetomidine was te• and it is therefore important to consider the sted as a preanaesthetic drug in the dog. need for premedication prior to a general Dogs treated with physiological saline solu• anaesthesia in each individual case. tion (placebo) or xylazine served as controls. One specific situation in veterinary medicine Xylazine is known as a sedative in the dog is when deep sedation has been produced for and its cardiopulmonary effects have been an examination (e.g. an X-ray) and the re• studied (Klide et al. 1975). Xylazine is also sults indicate a need for general anaesthesia. used as a preanaesthetic drug and the

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Cardiovascular and pulmonary effects ofmedetomidine 111

Recordings at 15 min intervals were conti• Depth of the general anaesthesia (reflexes nued during the first hour of the post-anaes• and response to pain stimuli - see above). thetic period, and then 2, 3, 6 and 20 h after Colour of mucous membranes, capillary re• termination of the general anaesthesia. Fi• fill time, pulse quality and type of respira• nally, the dogs once again underwent a rou• tion. tine clinical examination, as prior to the test. The investigator tried to keep the anaesthe• Results sia deep enough for surgical procedures by Blood pressure following it in a conventional way with the Interindividual variations of the mean arte• help of the reflex pattern. rial blood pressure occurred in the groups re• After the one-hour general anaesthesia, ad• ceiving sedatives without prior atropine in• ministration of the inhalation anaesthetic jection. In fact the dog with the lowest mean was ceased and the dogs were allowed to re• blood pressure value (after the sedation and cover, breathing air. during the general anaesthesia) belonged to the group piemedicated with medetomidine Variables recorded 10 µg/kg (Fig. 1). In a few dogs the blood Objective recordings: ECG and blood pressure was recorded continuously during pressure (systolic, mean and diastolic) were the first 10 min of the sedation period. This recorded on an ink-jet recorder (Mingograf check, however, did not give any further in• 34, Siemens-Elema, Solna, Sweden). Lead formation. II, CR was used to measure the heart rate In the sedated dogs premedicated with atro• and a pressure transducer (EMT 311, Sie• pine (10 min prior to the injection of the se• mens-Elema) recorded the blood pressure dative), the blood pressure rose markedly via the artery catheter. The blood pressure during the sedation period. The increase was mentioned in the results is the mean blood most pronounced in the groups receiving pressure. medetomidine 10 and 60 µg/kg. The mean The respiratory rate was calculated by obser• values in these groups reached 175 and 210 ving respiratory chest expansion. mmHg, respectively. Blood gas-analysis was performed on arte• Fifteen minutes after the thiopental injec• rial blood samples drawn through the artery tion, the blood pressure in these atropine catheter. All blood samples were collected groups had dropped to the initial level (125- anaerobically into heparinized 2 ml plastic 150 mm Hg) or were even lower. During the syringes. The samples were analysed within 5 course of the general anaesthesia the pressu• min after collection, using a standard elec• re decreased slightly further. trode technique (ABL 3 Radiometer, Copen• The placebo dogs treated with atropine be• hagen, Denmark). Blood-gas values were haved differently. The blood pressure did corrected according to the rectal temperatu• not change considerably during the course of re. the test. Note! The dogs in the xylazine group were Subjective recordings: Response to not tested with atropine. pain stimuli (pin prick sensation, reaction to pinch in the coronary border). Heart rate Degree of sedation (e.g. response to sound, The heart rate and the blood pressure recor• ability to stand, calmness). dings showed an essentially similar pattern,

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Cardiovascular and pulmonary effects ofmedetomidine 113 except in the placebo group (Figs. 2a and Respir•lory rate I min 60 2b). 50 In 2 of the atropine-premedicated groups 40 (medetomidine 60 µg/kg and placebo) the lO 20 heart rate increased during the first 10 min 10 after the atropine injection. In the other 2 groups (medetomidine 10 and 30 µg/kg, re• spectively) the increase occurred within 10 min after administration of the sedative (i.e. 20 min after the atropine injection). Maxi• mum values for all groups were reached 10 min after sedation, with the following mean values: placebo, 263 beats/min; medetomi• dine 10 and 60 µg/kg, 225/min; and medeto• midine 30 µg/kg, 146/min. During the later part of the sedation, the heart rate started to drop in all groups given atropine (including the placebo group), and continued to decrea• se during anaesthesia, though less in the pla• cebo group than in the others (placebo: Figure 3. The respiratory rate in dogs given sedation about 150 beats/min; remaining groups: 80- prior to general anasthesia. Five groups with 5 dogs 120/min). in each. Mean value and standard deviation. O Placebo Post-anaesthetically the curves for the atro• e Rompun pine and non-atropine groups showed the t:;. Medetomidine IO µg/kg same appearance. ..a. Medetomidine 30 µg/kg 0 Medetomidine 60 µg/kg ECG The ECG recordings did not differ between the groups. Nor did they diverge from other temperature in the placebo group regained ECGs in generarl during this form of anaes• the normal level about 1 h after the end of thesia. anaesthesia. In the other groups (including medetomidine 60 µg/kg), a normal tempera• Respiration ture was attained after 3-6 h. During sedation the respiratory frequency decreased and the breathing became deeper Blood-gas analysis (Fig. 3). Pa02 generally decreased slightly (in all The respiratory rate in the atropine groups groups) after administration of thiopental was similar to that in the groups not treated (from about 13 kPa to 8-11 kPa) and then with atropine before sedation. increased markedly during general anaesthe• sia (to 40-50 kPa).

Temperature Normal Pa02 values were reached within the The rectal temperature fell during general first 15 min after the anaesthetic gas had anaesthesia, but less markedly in the placebo been turned off. and medetomidine 60 µg/kg groups. The PaC02 rose temporarily after the induction

Acta vet. scand. vol. 29 no. I • 1988 114 K. Bergstrom of anaesthesia and the intubation (from In the fourth group (medetomidine 30 about 5 kPa to 5.5-7 kPa). µg/kg), the dogs displayed moderate to pro• In all groups there was a slight decrease in found sedation after 3-5 min. The analgesia base excess during anaesthesia (about 1-2 was moderate. In 3 of the dogs in this group mmol/l). Irregular values were observed du• (1 with atropine, 2 without), the mucous ring the post-anaesthetic period in the membranes appeared a little pale after seda• groups premedicated with xylazine and med• tion, compared with the colour prior to se• etomidine 60 µg/kg. dation. The dogs of the last group (medetomidine 60 Sedation µg/kg) were profoundly sedated within 10 Dogs pretreated with atropine are not descri• min after injection of the drug. One dog, ho• bed separately. wever, was excited for 3-10 min after the in• The degree of sedation differed between the jection, and 2 dogs showed a slight spasm in groups. their limbs from time to time during the se• The placebo dogs were calm, but totally un• dation period. In these dogs the mucous sedated and their response to pain stimuli membranes were also slightly paler than was the same as prior to the injections. prior to sedation. The dogs in this group ex• The dogs of the xylazine group were mode• hibited very little response to painful stimuli. rately to profoundly sedated after 10-20 The profoundly sedated dogs were unable to min, and there was obvious pain depression, stand, and did not react to loud sounds. In though not so strong as in the medetomidine many of the sedated dogs (especially at hig• 30 and 60 µg/kg groups. One of the xylazi• her dose levels) the nictitating membrane co• ne-treated dogs started to wave her bed up vered a considerable part of the eye. The ref• and down about 10 min after the injection, lexes of the moderately to profoundly seda• and did not stop until thiopental was given. ted dogs were obviously reduced. A second dog in this group developed a slight spasm in the limbs 5 min after the in• Induction of anaesthesia jection, and a third dog began to perform In all the sedated groups a lower dose of trot-like movements with the forelimbs 20 thiopental sodium was needed for intuba• min after injection of the sedative Gust prior tion compared with the placebo group (Ta• to induction of the general anaesthesia). ble 1). The third group (medetomidine 10 µg/kg) showed slight sedation 10 min after the in• Post-anaesthetic period jection and moderate sedation after about 20 The interval between the end of inhalation min, except for 1 dog, which became very and the moment of extubation was shortest profoundly sedated - actually more than in the placebo group (mean value 6. 75 min) those receiving 60 µg/kg. The pain depres• and longest in the group receiving medeto• sion in these dogs was slight, except in the midine 30 and 60 µg/kg (18.1 and 17 .5 min, profoundly sedated dog mentioned above respectively). The other 2 groups were inter• (this dog also showed lower values of blood mediate with respect to this interval (8 min pressure, heart rate and respiratory rate than for xylazine and 12.5 min for medetomidine the others). 10 µg/kg).

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116 K. Bergstrom

tion from the cardiovascular effects of the Walter H H: Effects of atropine on xylazine-pento• sedatives. barbital anaesthesia in dogs: Preliminary study. Atropine prior to sedation cannot be recom• J. Amer. vet. Res. 1985, 46, 856-858. mended on the basis of the present experien• ce, as it is not known how the effect of atro• Sammenfattning Effekt pa blodcirkulation och respiration pine, with tachycardia and arterial hyperten• av ett nytt sedativumlanalgetikum (medetomidin) som preane• sion, affects the risks of the anaesthesia. stetikum till hund. UndersOkningens syfte var att faststlilla om medeto• Acknowledgements midin (Farmos group, Turku, Finland) kan anvlin• This study was supported by grants from Farmos das till premedicinering infOr allmlin anestesi med group, Turku, Finland. tiopentalnatrium och halotan. FramfOr allt under• The skilful assistance of Ann-Marie LOfgren and Pia sOktes medetomidinets cirkulatoriska och respirato• Funkquist during the studies is greatly appreciated. riska effekter. Hundar behandlade med xylazin (2 mg/kg) respektive placebo (fysiologisk koksalt!Os• References ning) anvlindes som kontroller. Klide AM, Calderwood H W, Soma LR: Cardiopul• Medetomidin orsakade slinkning av blodtryck, monary Effects of Xylazine in Dogs. Amer. J. hjlirtfrekvens, och andningsfrekvens vid alla dose• vet. Res. 1975, 36, 931-935. ringar som testades. Dessa effekter var principiellt Seldinger S I: Catheter replacement of the needle in dosberoende, men det fanns stora individuella skill• percutaneous arteriography. Acta Radio!. 1953, nader. 39, 368-376. Medetomidin kan anvlindas fOr premedicinering i Savo/a JM, Ruskocho H, Puurunen J, Salonen JS, den lligsta testade doseringen (10 µg/kg). Den sedati• Korki N T: Evidence for medetomidine as a se• va effekten lir emellertid sa stark att en linnu lligre lective and potent agonist at alphai-adrenorecep• dos eventuellt skulle kunna vara tilrlicklig for linda• tors. J. Auton. Pharmac. 1986, 5, 275-284. mfilet.

(Received September 13, 1987).

Reprints may be requested from: Karin Bergstrom, Department of Surgery, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, S-750 07 Uppsala, Sweden.

Acta vet. scand. vol. 29 no. I - 1988