Clinical use of dexmedetomidine as premedicant in cats undergoing propofol–sevoflurane anaesthesia

Abstract

The purpose of this report was to evaluate the cardiorespiratory effects and efficacy of dexmedetomidine as a premedicant agent in cats undergoing ovariohysterectomy anaesthetized with propofol–sevoflurane. Cats were randomly divided into two groups of eight animals each. Dexmedetomidine (0.01 mg/kg) or 0.9% saline was administered intravenously (D and S, respectively). After 5 min, propofol was administered intravenously and anaesthesia was maintained with sevoflurane. Heart and respiratory rates, arterial blood pressure, oxygen saturation, rectal temperature and the amount of propofol needed for induction were measured. Premedication with dexmedetomidine reduced the requirement of propofol (6.7±3.8 mg/kg), but induced bradycardia, compared with the administration of saline (15.1±5.1 mg/kg). Recovery quality was significantly better in D but no significant difference in time to return of swallowing reflex was observed between groups (D=2.5±0.5 min;S=3.2±1.8 min). In conclusion, dexmedetomidine is a safe and effective agent for premedication in cats undergoing propofol–sevoflurane anaesthesia with minimal adverse effects.

Introduction

α₂-Agonists have widespread use as preanaesthetic medication in cats (Ansah et al 1998). Dexmedetomidine shows the highest affinity for α₂-adrenergic receptors compared with other similar compounds such as xylazine and medetomidine and has gained interest in veterinary anaesthesiology over medetomidine (Kuusela et al 2000). Cardiovascular changes associated with dexmedetomidine administration in dogs include bradycardia, reduction of cardiac output and increased systemic vascular resistance, well-recognized adverse effects of α₂-adrenoceptors agonists (Virtanen 1989, Kitahara et al 2002).

Propofol is a short-acting hypnotic agent that is usually injected as a single bolus for induction to allow intubation and initiation of inhalant anaesthesia, a popular technique in small animals (Short and Bufalari 1999). Administration of a single dose of propofol transiently decreasedarterial pressure, accompanied by a stable heart rate (Cullen and Reynoldson 1993).

Sevoflurane is a volatile anaesthetic agent similar to isoflurane (Hikasa et al 1997) and it has gained popularity as an inhalation anaesthetic agent for veterinary use, especially in feline patients (Tzannes et al 2000). Although sevoflurane preserves heart rate, it causes dose-dependent cardiopulmonary depression including decreased cardiac index, mean arterial pressure and vascular resistance (Hikasa et al 1997, Mutoh et al 1997).

The aims of our study were to evaluate the anaesthetic effects and cardiorespiratory variables of intravenous (IV) dexmedetomidine in cats undergoing ovariohysterectomy during anaesthesia with propofol–sevoflurane.

Materials and methods

Sixteen adult female cats, weighing from 2.0 to 4.5 kg (mean 3.3±1.0 kg) were used. Cats were housed in individual cages prior to surgery. All cats were considered to be healthy on the basis of a physical examination, serum biochemical analysis and complete blood count. This project was approved by the local institutional care and use committee. Written approval was obtained from cat owners prior to inclusion in this study. Food was withheld for 12 h before anaesthetic induction. The cats were randomly divided into two groups of eight animals each. Dexmedetomidine (0.01 mg/kg) (Precedex, Abbott) or 0.25 ml of 0.9% saline was administered IV in groups D or S, respectively. After 5 min, propofol was administered IV in small increments (1.0 mg/kg) over 1 min until the trachea could be intubated. Five minutes after endotracheal intubation, anaesthesia was maintained with sevoflurane (Sevorane, Abbott) carried in oxygen at flow of 200 ml/kg/min, delivered using a Bain breathing circuit. During anaesthetic maintenance, cats breathed spontaneously and the vapourizer setting was kept at 3.4%, which represents 1.3 MAC (MAC, minimal alveolar concentration) in cats (Doi et al 1983). Ten minutes after starting administration of sevoflurane, ovariohysterectomy was started by a single surgeon in all animals. At the end of surgery, animals were disconnected from anaesthetic circuit.

Baseline values were determined immediately prior to drug administration. Noninvasive oscillometric systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure and arterial haemoglobin oxygen saturation were determined six times using a multiparametric monitor (DX 2010, Dixtall) and the means were calculated for each variable. Heart rate was recorded by a lead II ECG (ECGPC, Tecnologia Eletrônica Brasileira) during anaesthesia and surgery. For this purpose, sterile stainless needles, lubrificated with ligdocaine jelly, were inserted into the subcutaneous and ECG electrodes were attached to them. Respiratory rate was measured by observing chest excursions. Rectal temperature was measured by using a digital thermometer (Digital Clinical thermometer, Omrom). Monitoring of blood pressure was achieved by placing a cuff circumferentially around the left antebrachium of animals, with the cuff width being approximately 40% of the total circumference of the limb. The infrared sensor for oxygen saturation determination was placed on the cat's lips during all measurements. Recordings were made before premedication, before induction, 5 min afterinduction and every 15 min thereafter until the end of anaesthesia.

The duration of anaesthesia was defined as the time from anaesthetic induction until disconnection from the anaesthetic circuit, and the surgery time was defined as the time from the first skin incision until the last suture was placed in the skin. The elapsed time from turning off the vapourizer to return of swallowing reflex was recorded. The endotracheal tube was removed immediately after the return of the pharyngeal reflex. The return of swallowing reflex was assessed by a sudden increase in the respiratory rate or thoracic muscle movements after a gentle movement of the endotracheal tube. Cats received 0.4 mg/kg of butorphanol (IM) (Toburgesic, Fort Dodge) for postoperative analgesia immediately after extubation. The amount of propofol needed for induction was recorded. Quality of anaesthetic induction and recovery was evaluated by incidence of adverse effects (myoclonus, apnoea, emesis, cyanosis and excitation).

Cardiorespiratory variables were examined by means of ANOVA for repeated measures followed by the Tukey test to compare values within and between groups. Time to pharyngeal reflex and the effect of premedication on propofol requirements were compared using a Student's t-test. For all analyses, values of P<0.05 were considered statistically significantly different. Data are given as mean±SD.

Results

There were no significant differences in the mean body weight or baseline values between the two treatment groups. No serious side effects, such as apnoea, myoclonus or emesis were observed during induction. The requirement for propofol was statistically lower in D (6.7±3.8 mg/kg) compared to S (15.1±5.1 mg/kg).

Time to return of swallowing reflex did not differ significantly between D (2.5±0.5 min) and S (3.2±1.8 min). The incidence of adverse effects during recovery, such as nausea and sneezing, was significantly higher in cats treated with saline (n=6) when compared with cats given dexmedetomidine (n=2). There were no significant differences between groups for the duration of anaesthesia (D=92.3±8.7 min; S=88.6±8.3 min) and surgery (D=65.2±9.7 min; S=70.4±6.3 min).

Dexmedetomidine significantly decreased heart rate 5 min after administration in D, and heart rate remained significantly lower than the baseline value thereafter. Heart rate did not change significantly from baseline value throughout anaesthesia in S (Fig 1).

Fig 1.

Mean (±SD) heart rate of cats premedicated at time 0 with dexmedetomidine (D) or saline (S). Anaesthesia was induced at 10 min with propofol to effect and maintained with sevoflurane. ∗Significantly different from baseline value (P<0.05). Mean values between groups with different alphabetic superscripts are significantly different (P<0.05).

Five minutes after induction with propofol, arterial blood pressure decreased significantly in cats given saline, whereas in cats that were given dexmedetomidine, blood pressure remainedstable. Arterial blood pressure decreased significantly in both groups after administration of sevoflurane; however, mean values during anaesthetic maintenance were not significantly different between groups over time (Table 1).

Table 1.

Mean (±SD) systolic (SABP), diastolic (DABP) and mean arterial blood pressure (MABP) of cats premedicated at time 0 with dexmedetomidine (D) or saline (S)

Time (min)
	D	S	D	S	D	S
0	116±5	114±9	83±6	86±1	93±10	93±9
5	110±7	103±5	82±7	80±5	95±5	90±4
10	117±13	95±12∗	86±9	73±24∗	97±12	85±15∗
15	96±12∗	92±16∗	75±14∗	77±19∗	82±11∗	85±10∗
30	93±19∗	98±11∗	72±14∗	70±12∗	88±15∗	84±11∗
45	99±9∗	98±10∗	66±10∗	61±14∗	79±10∗	77±10∗
60	95±8∗	98±10∗	61±13∗	60±15∗	69±9∗	72±16∗
75	93±13∗	92±8∗	67±10∗	77±14∗	73±13∗	85±12∗
90	98±10∗	99±14∗	72±12∗	74±12∗	82±6∗	87±8∗

Anaesthesia was induced at 10 min with propofol to effect and maintained with sevoflurane. ∗Significantly different from baseline value (P<0.05).

Respiratory rate decreased significantly after propofol induction in cats premedicated with saline. The mean values for respiratory rate in cats receiving dexmedetomidine were significantly higher than those given saline from 15 to 45 min, after which values for respiratory rate were similar (Fig 2). Haemoglobin saturation slightly decreased after induction in both groups, but this reduction was not significant (Table 2). During the anaesthetic period values for SpO₂ were similar. Rectal temperature progressively decreased in both groups in a similar pattern compared to baseline values (Table 2).

Fig 2.

Mean (±SD) respiratory rate of cats premedicated at time 0 with dexmedetomidine (D) or saline (S). Anaesthesia was induced at 10 min with propofol to effect and maintained with sevoflurane. ∗Significantly different from baseline value (P<0.05). Mean values between groups with different alphabetic superscripts are significantly different (P<0.05).

Table 2.

Mean (±SD) haemoglobin saturation (SpO₂) and rectal temperature (RT) of cats premedicated at time 0 with dexmedetomidine (D) or saline (S)

Time (min)	SpO2(%)		RT (°C)
	D	S	D	S
0	97±1	96±1	38.7±0.3	38.4±0.4
5	94±2	97±1	38.8±0.4	38.4±0.3
10	92±1	91±5	38.5±0.2	38.2±0.4
15	95±4	98±2	38.1±0.4	38.2±0.6
30	97±2	98±1	37.8±0.5	38.0±0.5
45	98±1	99±2	37.3±0.5∗	37.4±0.7∗
60	98±1	98±1	37.1±0.6∗	37.2±0.7∗
75	98±2	98±1	37.0±0.6∗	37.1±0.6∗
90	99±1	99±1	36.8±0.6∗	37.0±0.7∗

Anaesthesia was induced at 10 min with propofol to effect and maintained with sevoflurane. ∗Significantly different from baseline value (P<0.05).

Discussion

The present study shows that dexmedetomidine significantly reduced the mean induction dose of propofol in cats and that it can be used as premedication during anaesthesia with sevoflurane in this species. The anaesthetic sparing effects of dexmedetomidine on propofol requirements and isoflurane concentration have been shown in dogs (Kuusela et al 2001b), but similar studies have not been performed in cats.

Unlike dogs, the laryngeal reflex persists even in medium planes of anaesthesia in cats, which could explain the higher dose of propofol needed for intubation in this species (Short and Bufalari 1999). The higher dose of propofol in cats given saline may have resulted from the slowerinjection rate used in our study, as the speed of injection of propofol is an important factor to achieve an optimal blood concentration of this agent and therefore, produce adequate anaesthesia (Short and Bufalari 1999, Murison 2001). In this study we have demonstrated that administration of dexmedetomidine reduced the anaesthetic requirements of propofol in cats, as previously described in dogs premedicated with xylazine or medetomidine (Cullen and Reynoldson 1993). Dexmedetomidine has been shown to reduce sevoflurane requirements in humans (Fragen and Fitzgerald 1999). We did not evaluate the sparing effect of dexmedetomidine on sevofluraneanaesthesia because we wanted to compare the effects of dexmedetomidine in cats given the same concentration of sevoflurane in a clinical setting.

Better recovery quality in the D could beattributed to the lower dose of propofol administered compared with the saline group, as adverse effects observed in this experiment, such as nausea and sneezing, are often associated with propofol use in cats (Short and Bufalari 1999). Administration of dexmedetomidine in humans reduced the incidence of nausea and vomiting during the postoperative period (Cassinghamet al 2002), and this was also observed in this study. The absence of apnoeic episodes in this study is probably due to the slower administration of propofol during induction as previously described in dogs (Murison 2001).

Heart rate remains stable after a single dose of propofol (Short and Bufalari 1999), but premedication with xylazine or medetomidine caused bradycardia in dogs (Cullen and Reynoldson 1993). In cats, the bradycardic effect of dexmedetomidine on propofol anaesthesia was comparable to effects observed in dogs. Sevoflurane maintains or increases heart rate in dogs (Mutoh et al 1997, Branson et al 2001) and cats (Hikasaet al 1997), which probably contributed to the stable heart rate in cats of S. Bradycardia, as observed in cats premedicated with dexmedetomidine, has been observed in cats and dogs given medetomidine followed by isoflurane (Keeganet al 1995, Golden et al 1998). The bradycardic effect of dexmedetomidine, which is similar to the other α₂-adrenoceptor agonists (Ansah et al 1998, Kuusela et al 2000), is a result of a decrease in central sympathetic drive and an indirect baroreceptor-mediated increase in vagal tone (Virtanen 1989).

In dogs, propofol decreases arterial pressure for at least 30 min after its administration (Cullen and Reynoldson 1993), which could explain the decreased arterial blood pressure after induction in cats given saline. The absence of obvious cardiovascular depression in D after induction may be directly associated with the reducedpropofol requirements in this group. Dose-dependent decreases in arterial blood pressure, cardiac output and systemic vascular resistance are reported for sevoflurane (Mutoh et al 1997). It has been suggested that central hypotensive effects predominate over peripheral vasoconstrictive effects following administration of low doses of α₂-adrenoceptor agonists (Kuusela et al 2001a), but in our study, dexmedetomidine did not produce any changes in arterial blood pressure when compared to the control group. IV α₂-agonists administration caused a transitory increase in blood pressure until 3 min later (Doherty 1988). This short period of hypertension may have not been observed in our study because the time of blood pressure measurement was after 5 min or because a low dose of dexmedetomidine was used. Oscillometric blood pressure technique has been commonly used to measure blood pressure during anaesthesia in feline patients (Bransonet al 1997). In cats, oscillometric technique produced good prediction of direct systolic blood pressure, but it consistently underestimated direct diastolic blood pressure (Branson et al 1997). Although bradycardia may affect the efficacy of oscillometric blood pressure readings, a significant decrease in HR was not observed in cats given dexmedetomidine (Branson et al 1997).

Sustained hypertension induced by medetomidine in combination with IV and inhalant anaesthetic agents has been reported in cats(Dobromylskyj 1996, Golden et al 1998) and dogs (Cullen and Reynoldson 1993, Keegan et al 1995). However, hypertension was not observed in dogs anaesthetized with dexmedetomidine–isoflurane (Kuusela et al 2001b), as observed in this present study with cats, which might suggest that hypertension might be attributable to levomedetomidine, the l-isomer contained in medetomidine.

Depression of respiratory function, expressed as a decrease in tidal volume and respiratory rate, has been reported after propofol administration (Short and Bufalari 1999, Murison 2001), which could be indirectly assessed by the lower haemoglobin saturation in groups after propofol induction. The stability of respiratory rate in cats treated with dexmedetomidine could have resulted from the lower dose of propofol in this group, as previously observed (Kuusela et al 2001b). Sevoflurane, in clinical concentrations, does not change respiratory rate in dogs (Branson et al 2001), but it significantly decreases respiratory rate in cats (Hikasa et al 1997), but this was not observed in this study when cats were given dexmedetomidine compared with saline.

In the present study we did not observevariations in rectal temperature between dexmedetomidine- and saline-treated cats. Cats are more prone to α₂-adrenoceptor agonists-induced hypothermia than dogs (Doherty 1988). Hypothermia can be attributed to the effects of α₂-adrenoceptor agonists by a decrease in heat production related to the decrease in muscular activity, or by a direct effect on noradrenergic hypothalamic mechanisms implicated in thermoregulation (Virtanen 1989).

In conclusion, despite the occurrence of bradycardia, dexmedetomidine is a useful premedicant agent in cats undergoing propofol–sevoflurane anaesthesia, but further study is needed to determine whether it has beneficial effects over other protocols. However, due to the significant decrease in heart rate, dexmedetomidine should be used with caution in cats with cardiovascular compromise.