Evaluation of different constant rate infusions of dexmedetomidine in cats undergoing elective surgery

Abstract

Objectives

The objective of the study was to evaluate the effects of three constant rate infusions (CRIs) of dexmedetomidine (DEX; 1, 2 and 3 µg/kg/h) on cardiovascular, respiratory and analgesic outcomes in cats undergoing elective ovariectomy, aiming to identify an infusion rate that optimally balances analgesic benefits with minimal side effects.

Methods

In a randomised, controlled, blinded study, 73 healthy female cats were assigned to one of four groups: DEX1 (1 µg/kg/h), DEX2 (2 µg/kg/h), DEX3 (3 µg/kg/h) or a control group receiving saline solution (CTRL). Anaesthesia was maintained with isoflurane, and physiological variables, including heart rate (HR), blood pressure (BP), respiratory rate (RR) and end-tidal CO₂, were measured at baseline and specific time points during surgery. Intraoperative analgesia was assessed based on rescue analgesia requirements, and recovery quality was evaluated postoperatively.

Results

DEX CRI reduced isoflurane requirements only in DEX3 at T30 compared with the other groups at the same time point. Blood pressure was higher in DEX3 at T15 and T30 compared with the other groups at the same times, while no differences were observed for HR across all groups at any time of the study. The percentage of cases that required rescue analgesia was significantly lower in the DEX3 group (33%) compared with the CTRL (80%), DEX1 (80%) and DEX2 (86%) groups, which were similar. Recovery quality was similar across the groups, with fewer signs of agitation and dysphoria in DEX2 and DEX3, though DEX3 showed a slightly prolonged recovery.

Conclusions and relevance

This study supports the use of DEX CRI in cats as a valuable and safe option for balanced anaesthesia. Among the doses tested, 3 µg/kg/h provided the most clinically evident intraoperative analgesic and isoflurane-sparing effects with an improved quality of recovery. High blood pressure was observed, which may be considered critical in the clinical setting. Further research is needed to explore rate adjustments for more extensive procedures.

Keywords

Anaesthesia dexmedetomidine constant rate infusion

Introduction

Alpha (α)₂-adrenoceptor agonists reduce sympathetic tone, with attenuation of the neuroendocrine and haemodynamic responses to anaesthesia and surgery playing a central role in balanced approaches to anaesthesia and perioperative pain management in small and large animals.^1–3

Dexmedetomidine (DEX) is the dextrorotatory isomer of medetomidine. It is the most potent and selective α₂-agonist currently available in veterinary and human medicine.^4–6 It has the highest affinity for α₂-adrenergic receptors compared with other similar compounds, such as xylazine and medetomidine, and is widely used as a pre-anaesthetic in cats. It induces dose-dependent sedation, muscle relaxation and analgesia, while also reducing the need for general anaesthetics. Its cardiovascular effects include decreased heart rate (HR) and cardiac output (CO), along with increased systemic vascular resistance (SVR).^7–10

The constant rate infusion (CRI) of α₂-agonists is a well-known technique in balanced anaesthesia, enhancing the synergistic effects of different drugs while reducing their dosages and side effects. Ideally, an adequate drug should minimise the required dose of general anaesthetics, improve pain management and recovery quality,^11–13 and limit negative cardiovascular and respiratory effects.

The advantages of DEX CRI, including maintenance of a constant plasma concentration, prolongation of clinical effects and reduction of the total dose of drug, have been studied in both dogs^14,15 and cats.^11,12

Cats seem to be particularly sensitive to the cardiovascular effects of anaesthetic inhalant agents, such as isoflurane, that cause dose-dependent cardiopulmonary depression, including decreased cardiac index, mean arterial pressure and vascular resistance and that is mainly attributable to myocardial depression.^16,17

In this scenario, studies in dogs demonstrate that the use of a low dose of α₂-receptor agonists, particularly DEX, may provide a valid option for balanced anaesthetic protocols with minimal cardiovascular effects.^14,15

Furthermore, a clinical study by our group suggested that 1 µg/kg/h of DEX CRI proved to be safe and effective in mechanically ventilated dogs under isoflurane anaesthesia and was associated with improved oxygenation and respiratory system mechanics with a stabilising haemodynamic effect.¹⁸

Pharmacokinetic modelling suggests that cats receiving a DEX loading dose of 0.2 µg/kg followed by a targeted infusion of approximately 0.15 µg/kg/h demonstrated a reduction of 20% in the minimum alveolar concentration (MAC) of isoflurane with minimal cardiovascular side effects. The dose was predicted to correspond to a plasma concentration of approximately 0.4 ng/ml.^19,20 DEX decreased the isoflurane requirements in a plasma concentration-dependent manner.²⁰ At plasma concentrations that produced a reduction in MAC, DEX administration resulted in a lower CO and higher SVR compared with an equipotent concentration of isoflurane alone.^19,20

A subsequent clinical study in cats suggested that a loading low dose of DEX (0.5 µg/kg IV) followed by a CRI of 0.5 µg/kg/h reduces the total requirement of isoflurane, with minimal effects on the cardiovascular system.²¹

In this clinical study, we compared the effects of three different CRIs of DEX (1 µg/kg/h, 2 µg/kg/h and 3 µg/kg/h) in a protocol of anaesthesia management in healthy female cats undergoing elective ovariectomy. The aim was to identify the optimal infusion rate that balances positive clinical effects while minimising cardiovascular and respiratory depression.

The main hypothesis of the study was that DEX dose-dependently reduces isoflurane requirements. The secondary hypothesis was that it would have a dose-dependent effect on the quality of anaesthesia, recovery and intraoperative analgesia while optimising cardiorespiratory effects.

Materials and methods

This prospective, randomised, controlled, blinded, clinical study was approved by the ethical committee for clinical studies of the Department of Emergency and Organs Transplantation of the University of Bari (reference number 02/2019). This article is reported in accordance with the Consolidated Standard of Reporting Trials (CONSORT) Statement for the reporting of randomised controlled trials (Figure 1).²²

Figure 1

Flow chart of the cats included in the study, performed in accordance with CONSORT guidelines. CTRL = control group; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h

Subjects

Owned female cats considered healthy (American Society of Anesthesiologists status of 1), based on physical examination, complete blood count and serum biochemistry analysis, were included in the study.^23,24 The exclusion criteria included pregnancy, cardiovascular or respiratory disease, difficulty in handling and the need for medications outside the standard protocol.

Anaesthesia and monitoring

Cats were fasted 12 h before the induction of anaesthesia and had free access to water. Premedication was performed with dexmedetomidine (5 µg/kg, Dexdomitor; Vetoquinol), alfaxalone (1 mg/kg, Alfaxan Multidose; Zoetis) and buprenorphine (10 µg/kg, buprefelican; Dechra) mixed in the same syringe and administrated, with minimal restraint in a quiet environment, into the femoral biceps muscle. At 20 mins after premedication, a cephalic vein was aseptically prepared and cannulated with a catheter (22–24 G; Nipro) for the administration of drugs and fluids.

Anaesthesia was induced with intravenous (IV) alfaxalone administered to effect until the loss of palpebral reflex and jaw tone were obtained. Lidocaine (0.2 ml of a 1% solution, Lidocaina 2%; Ecuphar Italia) was sprayed on the larynx and orotracheal intubation was performed 1 min later with an appropriately sized endotracheal cuffed tube (3–4 mm ID). All cats were turned in dorsal recumbency and connected to a non-rebreathing Bain system. General anaesthesia was maintained with isoflurane in pure oxygen at a flow rate of 300 ml/kg/min, with a minimum flow rate of 1 l/min. All cats received a subcutaneous injection of robenacoxib (1 mg/kg, Onsior; Elanco) and amoxicillin/clavulanic acid (20 mg/kg, Synulox; Zoetis) preoperatively. Lactated Ringer’s solution (RL; Fresenius Kabi) was administered intravenously during the procedure at a rate of 5 ml/kg/h. Spontaneous breathing was maintained throughout the study. A warming unit (Bair Hugger Warmer Series 505) was placed under the surgical drape to provide heating support.

After applying monitoring devices and achieving an adequate level of anaesthesia, a CRI of DEX or saline solution was started 10 mins after intubation, based on study group allocation, using a syringe pump (Vial Program 2 IEC Pump IV Infusion; Fresenius Kabi).

The heart rate (beats/min), end-tidal carbon dioxide partial pressure (EtCO₂; mmHg), respiratory rate (RR; breaths/min) tidal volume (TV; ml) and intrathoracic-oesophageal temperature (T; °C) were continuously monitored (S5 multiparametric anaesthesia monitor; Datex Ohmeda). Haemoglobin oxygen saturation (SpO₂ %) was also continuously monitored (Set Rainbow Pulse Oximeter Rad-87 SpO₂ Cable; Masimo) throughout the procedure. Blood pressure (BP; mmHg) was measured with an ultrasonic Doppler flow detector (Ultrasonic Doppler Flow Detectors; Parks Medical Electronics) with a probe placed on the digital palmar artery.

Surgery consisted of an elective ovariectomy that was performed with a standard middle line laparotomic approach and always executed by the same surgeon (LL).

At the end of the procedure, all anaesthetic drugs were discontinued and the cats were extubated once the swallowing reflex returned and they had recovered from the general anaesthesia. All animals received heating and fluid support until they could move spontaneously and their rectal body temperature reached at least 37°C.

The times of isoflurane discontinuation, extubation, first head movements, sternal recumbency, standing and quality of recovery were recorded for all cats.

Study protocol and randomisation

Cats were randomly allocated to four groups that received different CRIs during anaesthesia: DEX1 group = 1 µg/kg/h of DEX; DEX2 group = 2 µg/kg/h of DEX; DEX3 group = 3 µg/kg/h of DEX; and CTRL group = CRI of 0.9% of saline solution. For the allocation of the cats, a computer-generated list of blocked randomisation numbers was used with an allocation sequence of 1:1:1:1. In total, 15 animals were assigned to each group based on the sample size estimation (see below).

To prepare the DEX CRI solution, a separate operator (CA; not involved in anaesthesia management) diluted the total dose required for a 2 h infusion, calculated based on the cat’s body weight (BW), in a total volume of 10 ml of saline. For the CTRL group, 10 ml of normal saline was prepared. The infusion rate was standardised at 5 ml/h in all cases to ensure the anaesthesiologist remained unaware of the treatment protocol.

After stabilising the depth of anaesthesia and applying the monitoring equipment, baseline (BASE) measurements were recorded, including HR, BP, RR, EtCO₂, T, TV, anaesthetic depth, end-tidal isoflurane concentration (ETiso, %), FiO₂ and SpO₂ at room air (SpAT, %). The SpAT was determined by measuring SpO₂ at an FiO₂ of 0.21. To achieve this, the fresh gas flow of the anaesthesia machine was switched from oxygen to medical air for at least 2 mins, reducing high FiO₂ interference in SpO₂ determination.²⁵ The SpO₂ value was recorded once the oximeter displayed an expired FiO₂ of 0.21 with a good plethysmographic signal (perfusion index [PI] >1%).²⁶ If the SpO₂ values dropped below 85%, FiO₂ was immediately increased. Soon after the BASE measurements, a CRI of DEX or saline solution was administered for 30 mins. Physiological measurements were repeated at 15 mins (T15) and 30 mins (T30) after the infusion began and 15 mins after discontinuation (Tpost). Surgery began 10 mins after the infusion started. After Tpost, isoflurane was discontinued, and the animals were recovered from the anaesthesia.

Assessment of the anaesthetic depth and isoflurane administration

After intubation, the vaporiser setting in all cats was adjusted to 1%. Thereafter, the isoflurane dosage was adjusted based on the monitored depth of anaesthesia. Adequate depth of anaesthesia was defined by the presence of the following clinical signs: absence of the palpebral reflex; ventral rotation of the eyeball; minimal to absent jaw (muscles) tone; and no movement in response to surgical stimulation. The anaesthesia was considered too light if one or more of the following clinical signs were observed: presence of palpebral reflex; moderate jaw tone; and movement in response to surgical stimulation. In such cases, the vaporiser setting was increased by 0.3%. Anaesthesia was considered too deep if the eyeball returned to a central position with concurrent absence of the palpebral reflex and jaw tone. In this case, the vaporiser setting was decreased by 0.3%. The depth of anaesthesia and isoflurane adjustments were assessed every 5 mins. If a cat required IV injectable anaesthetic (propofol) due to inadequate depth of anaesthesia, it was excluded from the study.

Intraoperative analgesia

Immediately before the skin incision, HR, BP and RR were recorded and considered as PAIN-BASELINE values. A rapid increase of one or more of these parameters by more than 20% during surgery was considered an indication for rescue analgesia. In such cases, fentanyl (2 µg/kg IV, Fentadon; Eurovet Animal Health BV) was administered. The total number of boluses of fentanyl administered during surgery were recorded for each case.

Postoperative monitoring

After discontinuing isoflurane, the times (in minutes) to extubation, first head movement, sternal recumbency and standing position were recorded. After extubation, all cats were transferred to a quiet ward area, placed in a heated cage and observed for 60 mins. A blinded operator (CV) assessed quality of recovery, starting 5 mins after extubation (T5) and then every 15 mins for the next 60 mins (T15, T30, T45, T60) using a validated scale comprising 18 parameters across six categories. Most parameters were scored 1–5 except for body shape (scored 1–4) and body position (scored 1–3) based on the criteria in Table 1.²⁷ The occurrence of agitation and/or dysphoria (eg, vocalisation, paddling and/or uncoordinated movements) was also recorded during recovery.

Table 1

Scoring system used to assess the quality of recovery from anaesthesia in the cats included in the study²⁶

Recovery score
Parameter	1	2	3	4	5
Movement
Paddling	None	1 leg	2 legs	3 legs	4 legs
Pawing at head	None	1–2 times lightly	1–2 times purposefully	>1–2 times	>1–2 times vigorously
Jerky sudden movements	None	Stands or walks with a little shakiness	Stands or walks with obvious shakiness	Stands and falls down	Cannot stand properly
Pacing in cage	None	1 circle	2 circles	3 circles	4 circles
Settled vs unsettled	Sits quietly content	Sits quietly, moves without getting up occasionally	Moves without getting up	Gets up and sits down	Moves around constantly
Banging into walls	None	Head press gently (1–2 times)	Head press (>1–2 times) or banging into walls (1–2 times)	Bangs into walls (>1–2 times)	Bangs into walls vigorously
Sensitivity to touch
Surgical site	No response	Looks	Twitches	Avoids	Walks away or purposefully avoids
Head	No response	Looks	Twitches	Avoids	Walks away or purposefully avoids
Shoulders	No response	Looks	Twitches	Avoids	Walks away or purposefully avoids
Sacrum	No response	Looks	Twitches	Avoids	Walks away or purposefully avoids
Position
Body position	Standing	Sitting	Lying	–	–
Position in cage	Head points to the cage door or walks towards it	Head close to the cage door but no response	Looks away or at the middle of the cage	Back of cage, does not back away	Back of cage and backs away
Body shape	Normal	Curled	Rigid	Extended	–
Sensitivity to sound
Calling name	No response	Looks	Startle	Jumps	Moves away or tries to
Loud noises in room	No response	Looks	Startle	Jumps	Moves away or tries to
Sensitivity to light	No response	Looks	Looks away	Avoids	Moves away
Other
Sneezing	None	Once	2–3 times	4–5 times	>5 times
Vocalisation	None	Seldom (1–2 times)	Occasional	Frequent	Very frequent

Statistical analysis

Sample size calculation was based on previous data,^13,21 with an estimated clinically significant variation in end-tidal isoflurane of 0.3%. A power analysis was conducted for a two-tailed t-test, assuming a power of 0.8 and an α error of 0.05 (Granmo, Version 7.12). The results of this analysis indicated that a minimum of 15 cats per group would be sufficient to detect significant differences in ETiso values among groups. Normal distribution of study variables was assessed using the Shapiro–Wilks test, where a P value <0.05 indicated a rejection of the null hypothesis of normality. The effects of time, treatment and their interaction on physiological variables during the intraoperative and postoperative periods were analysed using linear mixed-effect models fitted by Restricted Maximum Likelihood (REML) and Tukey’s post hoc tests. Cats were used as random factors, while treatment and time were considered fixed factors. Statistical analyses were performed using R software version 1.3.1093 (R Foundation).

Results

A total of 73 cats were enrolled in the study. Of them, four were excluded because a change in the premedication protocol was required because of the difficulty of restraining the animals and two because of the presence of comorbidities (Figure 1). Data regarding age, BW and the dose of alfaxalone required for the induction were similar among groups (Table 2).

Table 2

Data regarding age, body weight (BW) and the dose of alfaxalone for intubation of the cats included in the study according to their group

	CTRL (n = 15)	DEX1 (n = 15)	DEX2 (n = 15)	DEX3 (n = 15)
Age (years)	18 (36–12)	12 (9.5–24)	10 (8–13.5)	12 (12–19.5)
BW (kg)	3.2 (3.4–3.1)	3 (2.8–3.6)	3.5 (3.1–4)	3.4 (3–3.7)
Alfaxalone (mg/kg)	2.6 (2–3.5)	3 (2.4–3.1)	2.3 (2.1–3.1)	1.93 (1.4–2.9)

Data are mean (95% confidence interval)

CTRL = control group; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h

The means and 95% CIs of the cardiovascular data recorded during anaesthesia at the different time points are reported in Table 3.

Table 3

Cardiovascular data recorded in the cats at different time points in the study

Parameters	Groups	BASE	T15	T30	Tpost
HR (beats/min)	CTRL	137 (124–151)	143 (132–155)	132 (120–144)	123 (111–135)
	DEX1	129 (119–138)	138 (125–151)	135 (120–150)	133 (118–147)
	DEX2	133 (125–141)	138 (127–148)	135 (126–143)	126 (118–134)
	DEX3	135 (125–145)	129 (117–141)	118 (103–134)	124 (110–138)
BP (mmHg)	CTRL	85 (71–99)	108 (94–121)	110 (93–127)	106 (90–122)
	DEX1	90 (70–110)	104 (87–121)	105 (88–122)	99 (82–116)
	DEX2	98 (88–109)	121 (104–138)	126 (112–141)	122 (98–146)
	DEX3	102 (87–116)	140 (121–159)	148 (131–165)	109 (87–131)

Data are mean (95% confidence interval)

Cardiovascular data were recorded at 15 mins (T15) and 30 mins (T30) after the infusion began and 15 mins after discontinuation (Tpost)

BP = blood pressure; CTRL = control group; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h; HR = heart rate

Doppler BP was significantly higher at T15 (P = 0.003) and T30 (P <0.001) in the DEX3 group compared with the other groups at the same time points (Figure 2). HR was similar at different times within and among the groups (Table 3).

Figure 2

Mean and SD of Doppler blood pressure measurements collected before (BASE) and at 15 mins (T15) and 30 mins (T30) after the start of the infusion. Tpost indicates the time at 15 mins after the end of the infusion. *P <0.05 compared with the other groups of the study. CTRL = saline solution infusion; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h

The means and 95% CIs of the respiratory variables recorded during the study are reported in Table 4. No differences were found within and among the groups at the different times for RR, TV, SpAT and EtCO₂.

Table 4

Respiratory variables recorded in the cats at different time points in the study

Parameters	Groups	BASE	T15	T30	Tpost
RR (breaths/min)	CTRL	19 (18–21)	20 (16–23)	18 (16–20)	17 (15–20)
	DEX1	19 (15–22)	22 (18–26)	20 (15–25)	19 (16–22)
	DEX2	20 (17–23)	24 (19–29)	19 (15–24)	20 (17–23)
	DEX3	21 (17–24)	23 (18–27	24 (20–28)	21 (18–24)
TV (ml)	CTRL	33 (22–43)	33 (25–41)	32 (21–42)	29 (21–37)
	DEX1	30 (22–38)	32 (22–42)	31 (22–39)	29 (19–38)
	DEX2	22 (17–26)	25 (19–31)	23 (18–27)	21 (18–24)
	DEX3	225 (21–29)	25 (22–28)	22 (19–25)	25 (21–29)
SpAT (%)	CTRL	97 (96–98)	97 (95–98)	98 (97–99)	97 (96–98)
	DEX1	95 (93–96)	97 (95–98)	97 (95–98)	95 (94–97)
	DEX2	97 (96–97)	97 (96–97)	97 (96–98)	98 (97–99)
	DEX3	96 (94–96)	96 (95–97)	96 (95–97)	96 (95–97)
EtCO₂ (mmHg)	CTRL	37 (32–41)	35 (32–38)	34 (31–36)	34 (31–37)
	DEX1	36 (33–39)	34 (31–38)	33 (30–36)	34 (32–37)
	DEX2	36 (34–38)	35 (33–37)	34 (31–37)	37 (33–41)
	DEX3	36 (33–38)	35 (32–38)	36 (33–38)	35 (32–38)

Data are mean (95% confidence interval)

Respiratory data were recorded at 15 mins (T15) and 30 mins (T30) after the infusion began and 15 mins after discontinuation (Tpost) CTRL = control group; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h; RR = respiratory rate; TV = tidal volume; SpAT = SpO₂ at room air; EtCO2 = end-tidal carbon dioxide

The mean value of the ETiso (Figure 3) required to maintain an adequate level of anaesthesia was lower (P <0.001) at T30 in the DEX3 group (1.3, 95% CI 1.2–1.5) compared with the CTRL group (1.8, 95% CI 1.5–2.1), DEX1 (1.7, 95% CI 1.5–2) and DEX2 (1.5, 95% CI 1.4–1.7). No differences were found between the groups at the different time points in the study.

Figure 3

Mean and SD of the values of ETiso before (BASE) and at 15 mins (T15) and 30 mins (T30) after the start of the infusion. Tpost indicates the time at 15 mins after the end of the infusion. *P <0.05 compared with the other groups of the study. CTRL = saline solution infusion; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h; ETiso = end-tidal isoflurane

The cases requiring rescue analgesia during surgery were significantly lower in the DEX3 (5/15, 33%) group compared with the other groups (CTRL = 12/15, 80%; DEX1 = 12/15, 80%; DEX2 = 13/15, 86%).

Figure 4 shows the distribution of fentanyl boluses administered to cats across the different study groups. The DEX3 group received a significantly lower number of boluses compared with the other groups.

Figure 4

Box and whisker plots describing the number of fentanyl boluses received during surgery among the different study groups. CTRL = saline solution infusion; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h. *P <0.05 compared with the other groups of the study

Figure 5 shows the mean and SD of the times of extubation, first head movement, sternal recumbency and standing position. Times were similar among the groups except for standing, which was longer in the DEX3 group (73.4 ± 10.6 mins) compared with the other groups (CTRL: 33.4 ± 21.8 mins; DEX1: 33.6 ± 22.3 mins; DEX2: 37.4 ± 20.8 mins).

Figure 5

Mean and SD of the times of extubation, first head movement, sternal recumbence and standing position in the cats of the study. *P <0.05 compared with the other groups of the study. CTRL = saline solution infusion; DEX= dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h

The incidence of agitation/dysphoria was significantly lower in the DEX2 (15%) and DEX3 (0%) groups compared with the CTRL (86%) and DEX1 (40%) groups.

The recovery scores were similar among groups at all time points (Figure 6).

Figure 6

Mean and SD of the recovery scores recorded in the cats of the study. CTRL = saline solution infusion; DEX = dexmedetomidine; DEX1 = DEX infusion at 1 µg/kg/h; DEX2 = DEX infusion at 2 µg/kg/h; DEX3 = DEX infusion at 3 µg/kg/h

Discussion

The study results show that DEX infusion (1–3 µg/kg/h) in cats undergoing clinical isoflurane-based anaesthesia provides an isoflurane-sparing effect, with the 3 µg/kg/h dose also offering additional analgesia. In addition, a dose-dependent reduction in agitation/dysphoria during recovery was observed. Respiratory function was not affected by DEX infusion at all doses, while arterial blood pressure increased at 3 µg/kg/h.

Low-dose DEX infusion has been shown to be a useful adjunct to balanced anaesthetic protocols in veterinary species. In cats, Simon et al²¹ demonstrated that a DEX infusion of 0.5 µg/kg/h showed mild intraoperative analgesic effects along with a sparing effect on isoflurane requirements with some moderate cardiovascular and respiratory effects. The present study found analgesic and sparing effects only at 2 and 3 µg/kg/h. In addition, significant haemodynamic effects (hypertension) were seen only at 3 µg/kg/h, and no depressant respiratory effects were seen at any dose tested in our study. In contrast with the present study, Simon et al²¹ used a different sedation protocol including hydromorphone. Moreover, the DEX group received a loading dose, which can explain the different results of our study.

The differentiation between sedation and analgesia is particularly relevant in the context of α₂-agonists, as highlighted in previous studies. Van Oostrom et al²⁸ demonstrated that sedation with DEX in dogs was achieved at lower plasma concentrations compared with those required for analgesia, highlighting the notion that the reduction in rescue analgesia requirements observed in our study may partially reflect sedative effects. This underscores the complexity of isolating analgesic effects from sedative and suggests that more sophisticated methodologies, such as neurophysiological assessments, may be needed to better characterise these effects. Our findings are consistent with this observation, as the DEX3 group showed superior intraoperative haemodynamic stability, evidenced by fewer HR and BP fluctuations during surgical stimuli, but also exhibited cardiovascular effects such as increased arterial BP. These findings align with the pharmacodynamics of DEX, which combines central α₂-agonist-induced analgesia and sedation with peripheral vasoconstriction.¹⁰ Interestingly, while the DEX3 group exhibited higher BP, the HR tended to decrease across all DEX groups, which aligns with its centrally mediated sympatholytic effects. The results of previous studies in other species, such as dogs, where DEX demonstrated a similar cardiovascular profile, promoting stable BP with minimal HR reduction when used in lower doses.^14,15 Carvalho et al²⁹ found that 5 µg/kg of DEX IM followed by a CRI of 1 µg/kg/h was associated with an impairment of CO and late diastolic function, together with a reduction of the HR and increase in systolic pressure.

In contrast, in our study, the DEX1 and DEX2 groups maintained cardiovascular parameters (BP and HR) that were similar to those of the control group, with no significant differences observed at any time point.

These findings suggest that a lower DEX CRI (DEX1 or DEX2) may offer a safer profile for intraoperative cardiovascular stability in cats. DEX2 did not show significant differences in rescue analgesia requirements or cardiovascular parameters compared with DEX1 and the control group, indicating a comparable effect among these groups. However, we acknowledge that CO and other cardiac functions were not evaluated in our study, so we cannot rule potential effects of our protocols. In addition, other drugs in the protocol may have mitigated some previously reported negative effects.

No significant differences were observed in RR, TV, SpAT or EtCO₂ among the groups at different time points, indicating that DEX had minimal respiratory depressant effects, even at higher infusion rates. This contrasts with the respiratory depression often observed with inhalant anaesthetics like isoflurane,¹⁷ supporting the use of DEX in CRI to reduce the need for inhalants and improve respiratory outcomes. These findings are consistent with prior studies where DEX was shown to decrease isoflurane requirements without exacerbating respiratory depression in cats.^11,21

The ability of DEX to provide dose-dependent analgesia is well documented and supported by its central α₂-adrenoceptor agonist, which reduces the transmission of nociceptive signals.⁹ Based on our results, infusion rates of 1 and 2 µg/kg/h did not provide a significant clinical advantage in terms of analgesia and isoflurane reduction. On the contrary, these effects were achieved only at 3 µg/kg/h, which should be considered the optimal dose among those tested in this study. At 3 µg/kg/h, a tendency to have higher intraoperative blood pressure should also be expected. This is one of the few studies in which the analgesic effect of DEX has been tested in a real clinical scenario, where the use of balanced anaesthetic protocols together with the real surgical stimulation may change the outcome compared with experimental studies. In addition, it should be noted that different protocols and/or different surgical procedures may produce different results, which should be studied in future clinical trials.

The recovery quality was generally acceptable across all groups, but it was more favourable in the DEX2 and DEX3 groups, which showed fewer signs of agitation or dysphoria. On the other hand, the DEX3 group experienced slightly prolonged recovery times, likely related to the residual effects of DEX at higher doses. These findings are consistent with those of previous studies, where DEX administration, either via CRI or epidural injection, was associated with smoother recoveries and minimal postoperative complications in feline patients.^11,21 Both CRI and epidural DEX caused a longer recovery time, attributed to the sedative effects of the drug. According to our results, despite the prolonged recovery, cats displayed fewer behavioural signs of discomfort, such as vocalisation, post-anaesthetic shivering and agitation. The overall quality of recovery was enhanced by DEX’s ability to prevent agitation and shivering, making the process smoother and more comfortable for the animals.

The main limitations of the study were that, despite the power analysis, we cannot exclude that the results may be different in a larger population. In addition, the haemodynamic monitoring was limited to basic clinical parameters, including the use of a non-invasive Doppler BP, and we cannot exclude the effect of the tested drug regimens when using more invasive cardiovascular monitoring. The clinical nature of the study may have included some variables that could influence the translation of the results to different clinical conditions, anaesthetic protocols and surgical procedures. Furthermore, as demonstrated by Van Oostrom et al,²⁸ the differentiation between analgesia and sedation in the context of α₂-agonists may require advanced methodologies, such as evoked potentials, to provide a more precise characterisation of these effects.

Conclusions

This study demonstrates that DEX CRI at 3 µg/kg/h provides the most adequate effect in terms of intraoperative analgesia, isoflurane sparing and quality of recovery among the rates tested. Lower doses did not show a significant advantage over the control for intraoperative analgesia. A dose-dependent effect on reducing the incidence of dysphoria and agitation was also observed between 1 and 3 µg/kg/h. At the highest dose, a slightly prolonged recovery and higher BP can be expected. Future studies should further investigate the effects of DEX CRI on intraoperative analgesia, cardiovascular effects and quality of recovery in cats with different pathological conditions.

Footnotes

Accepted: 5 March 2025

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The study has been supported by a scholarship from the Orion company.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers, tissues and samples) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Caterina Vicenti

Luca Lacitignola

Francesco Staffieri

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