Vol. 57 (4) 2002
Adetunji, A., Ajadi, R.A, Adewoye, C.O. and Oyemakinde, B.O
Department of Veterinary Surgery and Reproduction University of
Ibadan, Ibadan, Nigeria.
Changes in heart rate (HR), respiratory rate (RR) and rectal temperature (RT), as well as the quality of anaesthesia and unusual reactions produced by propofol were evaluated in 5 mongrel dogs premedicated with an intramuscular injection of xylazine (2mg/kg) and atropine (0.04 mg/kg). Propofol anaesthesia was induced with an intravenous loading dose of 5mg/kg and maintained either by repeat bolus injections (RBI) of 2.5mg/kg as needed or a continuous infusion rate (CIR) of 0.17mg/kg/min.
With both RBI and CIR techniques, HR increased above pre-induction levels in the first 30 min only, while RR and RT progressively decreased during anaesthesia. Duration of analgesia was 88.4
± 2.6 min with RBI and 87.8 ± 3.5 min with CIR. Duration of recumbency was 122.6 ± 2.2 min with
RBI and 118.2 ± 3.5 min with CIR. Standing times were 6.0 ± 1.8 min and 4.0 ± 1.3 min with RBI and
CIR, respectively. Recovery times with RBI and CIR were respectively 18.6 ± 2.3 min and 17.0 ±
1.7min. Apnoea, cyanosis, retching, vomiting, paddling and opistothonus all appeared infrequently.
It was concluded that administration of propofol by either RBI or CIR provided rapid anaesthetic induction and recovery with very infrequent occurrence of unusual reactions in local dogs premedicated with xylazine.

Veterinary practices located outside the major cities and training institutions that do not have anaesthetic machines employ a total intravenous anaesthesia (TIVA) to carry out even major surgical procedures on animal patients (1). The veterinarian acting as the surgeon-anesthetist usually induces anaesthesia and then delegates its monitoring to a veterinary attendant who invariably has no formal training in anaesthesia. Furthermore, those practices frequently admit and discharge surgical patients on the same day for reasons of limited in-patient facilities, financial constraints or convenience
(personal observation). Under this clinical setting, the ideal technique would provide a reliable, rapid and smooth induction of anaesthesia, adequate hypnosis and analgesia for surgical interventions and minimal suppression of vital organ functions. In addition, recovery would be rapid, uncomplicated and complete so the animal is ready for discharge in a “home - fit” condition to the owner within minutes of the completion of the procedure necessitating the anaesthetic.
In spite of their drawbacks, barbiturates (thiopentone and pentobarbitone) remain the most widely used agents for TIVA in Nigerian dogs premedicated with xylazine. For example, thiopentone is ultrashort-acting and, when administered in a large dose or repeat doses to prolong anaesthesia, it is cumulative leading to prolonged recoveries (2). Although pentobarbitone induces dose-dependent degree and duration of anaesthesia, its major disadvantages include respiratory depression, with a wide variation in response to fixed doses and prolonged recoveries (3). The need for a continued search for a more satisfactory intravenous anaesthetic for use in the environment of this study thus becomes obvious.
Propofol (Diprivan, ICI), an alkyl phenol hypnotic, has been investigated as an intravenous anaesthetic in dogs and cats in the United Kingdom (1, 4, 5, 6, 7). The drug was reported to be a shortacting, rapidly metabolized agent, characterized by a virtual lack of any cumulative effect and by rapid recovery after its administration in bolus doses or by continuous infusion. These favourable reports prompted us to investigate its behaviour in mongrel dogs.
The purpose of the study was to evaluate the quality of anaesthesia and adverse side effects, as well as changes in heart rate (HR), respiratory rate (RR) and rectal temperature (RT), induced by administration of intravenous bolus and continuous infusion of propofol in healthy local dogs premedicated with xylazine.
Dogs
Five adult mongrel dogs of either sex (2 intact males, 3 non-pregnant, non-lactating bitches) were studied. The dogs had a mean (± SEM) body weight of 10.4 (±1.2) kg. They were housed in standard kennels and fed cereal-based diet and fish twice daily. Fresh water was freely available in the kennels. The dogs were conditioned for the experiments for 2 weeks and just before the experiments

commenced, they were judged to be in good general health based on findings at complete physical examination.
Drugs
The drugs used for the study included:
(i) Propofol (Diprivan, ICI - Zeneca Pharmaceuticals) supplied as 10mg/ml of white, oil - in - water emulsion in a 20-ml ampoule for intravenous injection. One ampoule of propofol was used per dog to prevent contamination and possible systemic bacterial sepsis since the emulsion readily supports bacterial growth (8, 9).
(ii) Xylazine hydrochloride (Chanazine
®
, Chanelle Pharmaceuticals) supplied as 20 mg/ml of stable, colourless aqueous solution in a 20-ml multidose vial for injection.
(iii) Atropine sulphate (non-proprietary) supplied as 0.6mg/ml of colourless solution in a 1-ml ampoule for injection.
Experimental Design and Procedure
Propofol was administered in two series of experiments involving repeated bolus injections and continuous infusion, respectively, in dogs premedicated with xylazine and atropine. Each dog was subjected to both techniques of drug administration at 1-week interval and anaesthesia was induced and maintained for about 90 min. During each trial, the dog was given intravenous infusion of 5 per cent dextrose saline.
Food but not water was withheld from the dogs for 12h before the trials. The dogs were premedicated with xylazine and atropine mixed in the same syringe at an intramuscular dose rates of
2mg/kg and 0.04mg/kg, respectively. Once the signs of sedation became evident, venous access was gained via the cephalic vein with a 19-gauge winged needle and intravenous administration of 5per cent dextrose saline was started at an infusion rate of 10ml/kg/h. Whenever it was intended to administer propofol by infusion, 15ml of the drug was added to a 500-ml bag of dextrose saline after withdrawing an equal volume of fluid from the bag.
Propofol was administered to each dog at an intravenous dose rate of 5mg/kg over 5 seconds and orotracheal intubation was carried out. The dosage of propofol was chosen based on previous reports of 4-6mg/kg, used with or without preanaesthetic drugs in dogs (1, 6, 10). Propofol anaesthesia was maintained for a period of about 90 min by either repeat bolus injection (RBI) with hand-held syringe at a dose rate of 2.5mg/kg each time as needed or a continuous infusion rate (CIR) of
0.17mg/kg/min by gravity flow. Depth of anaesthesia for each dog was assessed by the degree of muscle relaxation, toe-pinch withdrawal and palpebral reflex.

The following data were recorded: HR, RR, RT and mucous membrane colour after premedication, immediately after anaesthetic induction with propofol, and thereafter at 15, 30, 45, 60,
75 and 90min. The HR in beats/min was determined with the aid of a precordial stethoscope. The RR in breaths/min was counted by visual observation of chest excursion. The RT in degree centigrade was measured using mercury - in - glass clinical thermometer.
The quality of propofol anaesthesia was assessed as follow:
(i) Onset of analgesia: time interval (in min) between the initial bolus injection of propofol to disappearance of the pedal reflex. Pain was assessed by response to pressure applied to the toe web with haemostatic forceps closed to the first ratchet.
(ii) Duration of analgesia: time interval (in min) between the disappearance and return of the pedal reflex.
(iii) Duration of recumbency: time interval (in min) between xylazine-induced recumbency and the dog’s assumption of sternal posture.
(iv) Standing time: time interval (in min) between assumption of sternal posture and the dog’s ability to stand.
(v) Recovery time: time interval (in min) between the last bolus injection or cessation of infusion of propofol and the dog’s ability to stand.
In addition, previously reported unusual reactions linked with the administration of propofol
(10, 11) were also observed. These included: pain on injection, apnoea, cyanosis, excitement, retching and vomiting. Limb withdrawal during propofol injection was considered to be a sign of pain perception. Apnoea was defined as complete cessation of spontaneous breathing effort. Manifestations of excitement included vocalization, violent paddling movements, opistothonus and periodic rigidity of one or more limbs in the course of propofol anaesthesia.
Statistical Analysis
Data are expressed as mean ± SEM of 5 dogs. Means of HR, and RT were compared using analysis of variance (ANOVA) for repeated measure, followed by the least significant difference test as appropriate. Means of the anaesthetic indices were compared using students’ t test for paired data. A value of P<0.05 was considered significant in all cases.

There was no problem in injecting propofol as a bolus for anaesthetic induction despite its milk-like appearance. Following the injection of an induction dose of 5mg/kg, anaesthesia could be maintained by the administration of repeat doses of one-half of the induction dose, every 10 to 17 min as needed. Alternatively, propofol anaesthesia could also be effectively maintained by a fixed infusion rate of 0.17mg/kg/min. With CIR there was decreased frequency of patient handling as well as documentation requirements.
Following the induction of propofol anaesthesia, mean HR tended to increase in the first 30 min above the pre-induction values with both techniques of propofol administration. Conversely, propofol anaesthesia generally produced progressive decreases in RT. Similarly the RR decreases below the pre-induction level following propofol injection but thereafter rose above the post induction level. (Fig 1).
During the predetermined 90-min period of observation, RBI and CIR of propofol produced analgesia for 88.4 ± 2.6min and 87.8 ± 3.5 min, respectively. Duration of recumbency was 122.6 ±
2.2 min with RBI and 118.2 ± 3.5 min with CIR. Standing times were 6.0 ± 1.8 min and 4.0 ± 1.3 min with RBI and CIR, respectively. Recovery times with RBI and CIR were respectively 18.6 ± 2.3 min and 17.0 ± 1.7 min. There were no significant differences (P>0.05) in these indices. (Table 1).
Table 1: Characteristics of propofol anaesthesia produced with repeat bolus injections and continuous infusion in xylazine - premedicated dogs.
Onset of analgesia
Duration of analgesia
Duration of recumbency
Standing time
Repeat Bolus Continuous infusion
1.4 ± 0.2
1.2 ± 0.2
88.4 ± 2.6
122.6 ± 2.2
6.0 ± 1.8
87.8 ± 3.3
4.0 ± 1.3
118.2 ± 3.5
Recovery time
18.6 ± 2.3
17.0 ± 1.7
Adverse side effects of propofol anaesthesia recorded in this study are shown in Table 2.
There was no sign of pain on injection of propofol. At induction, apnoea lasting up to 50 seconds was the most prevalent side-effect, but did not require any form of assisted ventilation. Other side-effects linked with the course of propofol anaesthesia occurred infrequently and included retching, vomiting, cyanosis, paddling (with the repeat bolus only), opistothonus and salivation. Cyanosis was observed after the induction of anaesthesia but before orotracheal intubation. Salivation, retching, vomiting, opistothonus and paddling were recorded in the recovery period. Arrhythmias, vocalization, muscle tremors and limb rigidity were not observed. Several of the dogs had more than one adverse effect.

Table 2: Frequency of unusual reactions linked with the repeat bolus injections and continuous infusion of propofol in xylazine - premedicated dogs.
Pain on Injection
Apnoea
Coughing
Retching
Vomiting
Cyanosis
Arrhythmias
Vocalization
Panting
Muscle twitching
Violent paddling movement
Opistothonus
Limb rigidity
Urination
Repeat Bolus Continuous infusion
-(5) -(5)
+(4)
-(5)
+(2)
+(1)
+(1)
-(5)
+(1)
-(5)
+(1)
+(1)
+(1)
-(5)
-(5)
-(5)
-(5)
-(5)
-(5)
-(5)
+(2)
+(2)
-(5)
+(1)
-(5)
+(1)
-(5)
-(5)
-: Not observed
+: Observed
( ): Number of affected dogs in parenthesis.

Fig. 1 :
Mean heart rates, respiratory rates and rectal temperatures of five xylazine-sedated dogs anaesthetised with a loading dose (5mg/kg) of propofol, followed by either repeated bolus dosing (2.5mg/kg) or continous infusion (0.17mg/kg/min) over a 90min period. At time 0, values were obtained immediately after induction of anasthesia with propofol. At time -15, values were obtained after premedication with xylazine and atropin (2mg/kg and 0.4mg/kg IM, respectively)

Total intravenous anaesthesia has several potential advantages for the practicing veterinarian acting as surgeon-anaesthetist because it is relatively easy to manage, veterinary attendants can be instructed easily in its use, and only comparatively inexpensive apparatus is required for its delivery.
Furthermore, TIVA avoids the pollution of the theatre and environment with traces of inhalational anaesthetic agents. Recovery is primarily determined by the rate of metabolism of the agents employed
(1). In this trial, the intravenous administration of propofol by repeat bolus doses or continuous infusion provided rapid anaesthetic induction and recovery with very low frequency of occurrence of unusual reactions in local dogs premedicated with xylazine.
As a hypnotic, propofol has no reported intrinsic analgesic potency (3), necessitating the concurrent administration of an analgesic agent. In this study, the dogs were premedicated with 2 mg/kg of xylazine to provide a good basis for propofol anaesthesia in terms of stress-free induction and significant analgesic effect. With RBI, the interval between increments provides some indication of its duration of effective anaesthesia. A dosing interval of 10 to17 min employed in this trial is longer than
2.5 to 9.4 min previously reported in dogs premedicated with acepromazine (5). This discrepancy in dosing intervals may relate to the effect of premedication with xylazine. Langley and Heel (12) stated that the rate of propofol infusion would depend on any other adjunct drugs administered and the degree of surgical stimulation, but is usually from 0.15 to 0.4 mg/kg/min. In this trial, the low infusion rate of
0.17 mg/kg/min used may relate both to the effect of xylazine and absence of any surgical stimulation.
In spite of the milk-like appearance of propofol’s emulsion, it is free-flowing and could be injected easily through even a 21-gauge needle. Its aqueous emulsion formulation does not produce histamine release in the dog and no anaphylactoid response. Nonetheless, proper administration of the agent requires a consideration of its pharmacokinetics. In this regard, the rate of administration must be sufficiently rapid to compensate for the rapid redistribution from the brain to other non-nervous tissues
(13). In practical terms, the drug is preferably administered by first injecting a loading (induction) dose to be followed by RBI injection of one-half the induction dose as needed or by CIR infusion at a rate up to 0.4mg/kg/min (5).
Apart from the quality of anaesthesia, the haemodynamic effects of an anaesthetic agent have an important role in determining the outcome during and after anaesthesia. In this study, mean HR increased above the pre-induction level in the first 30 min of propofol administration by both repeat bolus and continuous infusion technique (Figure 1). This finding could not be explained solely by its ability to cause tachycardia since the increased HR did not persist throughout the 90 min observation period. It is probable that premedication with atropine contributed to the increased HR through its vagolytic effect. Propofol also caused a decrease in mean RR (figure 1) possibly by depressing central inspiratory drive and the ventilatory response to arterial carbon dioxide tension (14). The effect of respiratory depression observed in this trial is unknown since blood gas analysis was not carried out.

Nonetheless, respiratory depression generally has the potential to induce hypercapnia and respiratory acidosis, which of course should be mild and of no clinical significance in dogs breathing spontaneously. It is also remarkable that mean RT dropped to about 36 o
C within 90 min of propofol anaesthesia (figure 1). During anaesthesia, the factors known to contribute to the development of hypothermia include the anaesthetic agents in use, patient physical status, surface area of the surgical preparation, operative site, anaesthetic depth, length of surgery, infusion of cold fluids and environmental temperature (15). In this study, the progressive drop in RT could only be ascribed to the anaesthetic agents (xylazine, propofol), anaesthetic depth and infusion of cold fluid (dextrose saline).
With concomitant surgical procedure therefore it is reasonable to expect clinical hypothermia to develop in propofol-anaesthestised dogs whose body temperature is left uncontrolled.
In this trial, propofol provided rapid induction of anaesthesia, as well as smooth rapid recovery after its administration by both repeat bolus and continuous infusion techniques (Table 1).
These characteristics clearly relate to the drug’ pharmacokinetics (12). Its high lipid solubility results in rapid blood / brain equilibrium and hence rapid onset of action. The high lipid solubility also results in rapid and extensive redistribution, which contributes to the termination of the drug’s anaesthetic effect.
Propofol is also rapidly cleared by hepatic and, perhaps, extrahepatic metabolism (16). The large volume of distribution, together with rapid elimination, prevents saturation of the redistribution sites, thereby making the hypnotic particularly suitable for infusion anaesthesia (12). Furthermore, the rapid redistribution and metabolism of the drug also explains the rapid, smooth recovery from propofol anaesthesia. The finding that both techniques of propofol administration did not influence the recovery time (Table 1) indicated that the agent has no cumulative effect. In contrast, repeat doses of thiopentone has been shown to have a cumulative effect and prolonged periods of anaesthesia in local dogs (2). In general, propofol would appear to offer some advantages over the barbiturates, including minimal cumulative effects and rapid complete recovery. The only concern for veterinary use of propofol relates to its cost and limited shelf life once the ampoule is opened (7, 9).
Proper anaesthetic management means more than a return of the subject to consciousness; it also includes the quality of anaesthesia provided. A prevalence of up to 58 per cent of pain on injection has been reported from previous studies of propofol in dogs, cats and humans (6, 7, 17). Pain on injection has been related to the free aqueous concentration of propofol in the emulsion (18). It is therefore surprising that sign of pain on injection was not evident in this trial (Table 2). Langley and
Keel (12) have suggested that pain on injection could be minimized by the administration of analgesic drugs before given propofol and by employing a large vein for injection. In this study, Premedication with xylazine, (an 
2
- adrenoreceptor agonist with analgesic property), the injection of propofol through a preplaced winged needle with free-flowing fluids, and the use of the relatively large cephalic vein for propofol administration might have eliminated this adverse effect (18, 19). A transient apnoea frequently followed a loading dose of propofol in this trial (Table 2). This finding is in accord with other studies on propofol in dogs and humans (1, 14). Fortunately, the observed apnoea was transient in nature and hence of no clinical significance. Cyanosis observed in this trial (Table 2) resolved in the dogs after orotracheal intubation even in the absence of artificial ventilation with oxygen. Failure to

record arrhythmias in this study (Table 2) is interesting. Propofol in high doses reportedly predisposes to adrenaline-induced ventricular arrhythmias (20). Inability to record arrhythmias in this study may be attributable to the low dose of propofol employed, the absence of any concomitant surgical procedure that might have produced high circulating concentrations of catecholamines, or other factor. Overall, propofol anaesthesia in local dogs would appear to be linked with very low frequency of occurrence of unusual reactions, which are of no clinical significance.
This work was supported by the Senate Research Grant srg/fVm/94-95/11a of the University of Ibadan, Ibadan, Nigeria.
LINKS TO OTHER ARTICLES IN THIS ISSUE
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