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Clinical effects of constant rate infusions of medetomidine–propofol combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery

Acta Veterinaria Scandinavica201860:71

https://doi.org/10.1186/s13028-018-0426-0

  • Received: 18 July 2018
  • Accepted: 29 October 2018
  • Published:

Abstract

Background

The aim of the present study was to evaluate clinical efficacy of constant rate infusions (CRIs) of medetomidine–propofol combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery. Thirty horses were sedated intravenously (IV) with medetomidine (6.0 μg/kg) and midazolam (0.02 mg/kg) and induced IV with ketamine (1.0 mg/kg) and propofol (1.0 mg/kg). These horses were randomly allocated to three groups and maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10). End-tidal sevoflurane concentration (ETSEVO), cardiovascular parameters, plasma propofol concentration, and recovery time and quality were compared among groups. Data were analyzed by using ANOVA with Tukey’s multiple comparison test, considering P < 0.05 significant.

Results

ETSEVO (%) was 2.4 ± 0.1 in Group M, 1.7 ± 0.2 in Group MP3, and 1.4 ± 0.2 in Group MP6; ETSEVO declined significantly in a propofol-dose-dependent manner. The rates of dobutamine infusion (μg/kg/min) required to keep the mean arterial blood pressure over 70 mmHg were significantly lower in Group MP3 (0.20 ± 0.10) and Group MP6 (0.15 ± 0.06) than in Group M (0.37 ± 0.18). Recovery time and quality did not differ among groups. All horses in Group MP3 required only one attempt to stand, and recovery quality was excellent. Plasma propofol concentrations were stable throughout maintenance of anesthesia in Group MP3, whereas those in Group MP6 increased significantly with increasing duration of maintenance.

Conclusions

CRIs of medetomidine–propofol reduced the sevoflurane requirement for surgical anesthesia as the propofol dose increased, compared with a CRI of medetomidine alone. Additionally, the two propofol protocols provided good maintenance of cardiovascular function. CRIs of medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) resulted in excellent-quality recovery. This protocol could therefore be an especially useful additive to sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.

Keywords

  • Constant rate infusion
  • Medetomidine
  • Propofol
  • Racehorse
  • Sevoflurane

Background

Sevoflurane has the advantages of rapid induction, easy control of anesthetic depth and rapid recovery because of its low blood solubility [13]. However, sevoflurane is known to induce dose-dependent cardiopulmonary depression, which increases the risk of peri-anesthetic mortality and death [46]. Therefore, in equine practice, balanced anesthesia is usually applied to decrease the requirement of inhalant anesthetics and thus limit their cardiovascular depressant effects [7].

The short half-life of medetomidine and its selectivity and potency make it suitable for use as a constant rate infusion (CRI) for balanced anesthesia in horses [811]. In our previous study, we found that medetomidine CRI (3.0 µg/kg/h) reduced the sevoflurane requirement during arthroscopic surgery by approximately 10% in Thoroughbred racehorses, resulting in good maintenance of cardiopulmonary function and an improvement in the quality of recovery from anesthesia [12]. However, the anesthetic sparing effect of medetomidine CRI on sevoflurane was insufficient to fully minimize cardiac depression, and cardiovascular depression during the maintenance period still remained a concern.

Propofol has been described as an intravenous (IV) anesthetic suitable for total intravenous anesthesia (TIVA) lasting > 2 h because of its short half-life and the resultant rapid and good recovery [13, 14]. In a previous report, TIVA with propofol was suggested to be suitable for long-term anesthesia in horses because the degree of cardiovascular depression was less than inhalation anesthesia [15]. Medetomidine–propofol TIVA has been successfully employed with good cardiovascular function and anesthetic recovery in a wide range of surgical procedures in horses [16]. Additionally, the use of propofol with inhalational anesthesia has been reported in horses [17, 18]. Villalba et al. [18] demonstrated that medetomidine–propofol CRI reduced the minimum alveolar concentration (MAC) of isoflurane in experimental horses, improved the stability of arterial blood pressure, and resulted in a good-quality recovery. However, to the best of our knowledge, the sevoflurane requirement during CRIs of medetomidine–propofol and the adequate propofol infusion rate when propofol is combined with inhalational anesthetic agents under surgical procedures have not been investigated in clinical cases. We hypothesized that CRIs of medetomidine–propofol would result in a useful decrease in sevoflurane requirement in relation to the rate of propofol CRI, and that this decrease would be associated with good cardiovascular function and a good-quality recovery.

The purpose of this study was to evaluate the clinical effects of CRIs of medetomidine–propofol combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.

Methods

Horses

Thirty Thoroughbred racehorses with chip fractures of the carpal bones were included in this study. Informed consent was obtained from the owner and the trainer before arthroscopic surgery. The surgery was performed on a single leg or both legs by experienced surgeons. All horses were subjected to preanesthetic electrocardiography, blood biochemistry and hematology on the day before surgery. Food, but not water, was withheld for 12 h prior to anesthesia.

Experimental protocol

All horses were premedicated with medetomidine (Dorbene; Vetcare Oy, Salo, Finland) (6.0 μg/kg, IV) and midazolam (Dormicum; Astellas Pharma Inc., Tokyo, Japan) (20 μg/kg, IV) together. Anesthesia was induced by injection of 1% propofol (Propofol 1%; Nichi-Iko Co., Ltd., Toyama, Japan) (1.0 mg/kg, IV) and ketamine (Ketalar; Daiichi-Sankyo Co., Ltd., Tokyo, Japan) (1.0 mg/kg, IV) in three groups. After induction of anesthesia, the horses were intubated endotracheally and positioned in dorsal recumbency. Anesthesia was maintained with sevoflurane (Sevofrane; Maruishi Pharmaceutical Co., Ltd., Osaka, Japan) and oxygen (approximately 5 L/min) to produce a surgical plane of anesthesia. The horses were connected to a circle system and intermittent positive pressure ventilation initiated (MOK 94; Silver Medical Co., Tokyo, Japan) with a peak airway pressure of 25 cmH2O. The ventilator settings were chosen to maintain the arterial carbon dioxide tension (PaCO2) between 45 and 55 mmHg. Lactated Ringer’s solution was administered at a rate of approximately 10 mL/kg/h throughout anesthesia.

Horses were randomly assigned to one of three groups and received either medetomidine infused IV at 3.0 μg/kg/h throughout maintenance (Group M) (10 horses); medetomidine IV at 3.0 μg/kg/h plus propofol IV at 3.0 mg/kg/h (Group MP3) (10 horses); or medetomidine IV at 3.0 μg/kg/h plus propofol IV at 6.0 mg/kg/h (Group MP6) (10 horses).

A base-apex lead electrocardiogram was used to monitor heart rate (HR) and rhythm. A 20-G catheter was placed in the facial artery for measurement of arterial blood pressure and for arterial blood sample collection after connection to the breathing circuit. Respiratory gas was collected continuously, and the end-tidal sevoflurane concentration (ETSEVO) was determined by infrared absorption. The ETSEVO was recorded throughout anesthesia, and HR, systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), and mean arterial blood pressure (MAP) were recorded every 5 min by an anesthesia monitoring system (BP608; Omron Colin Co., Ltd., Tokyo, Japan). Arterial blood samples were collected every 15 min and arterial carbon dioxide partial pressure (PaCO2), arterial oxygen partial pressure (PaO2) and pH were immediately analyzed by a blood-gas analyzer (ABL800 FLEX; Radiometer Co., Ltd., Tokyo, Japan). Hypotension was defined as MAP < 70 mmHg and corrected with dobutamine (Dobutrex; Shionogi & Co., Ltd., Osaka, Japan) infusion. The vaporizer setting of sevoflurane was based on observation of standard clinical signs to achieve a surgical plane of anesthesia. Anesthetic depth was judged to be light, if movement, brisk palpebral response, spontaneous nystagmus or sudden changes in arterial blood pressure and HR were observed.

Immediately after end of sevoflurane anesthesia, horses in all three groups were transported to the recovery room. They were allowed to recover without assistance and were given no additional sedatives. Oxygen was supplied via the endotracheal tube using a demand valve at one to two breaths per minute until spontaneous ventilation resumed. Extubation was performed once spontaneous ventilation resumed but prior to swallowing. The recovery phases were continuously monitored by use of a wide-angle high-resolution camera located at 3 m high on the wall of the recovery room. On the basis of these images, the quality of recovery was subjectively assessed by experienced anesthetists who were unaware of drug given using a scoring of 1–5 (1: poor; 2: marginal; 3: fair; 4: good; 5: excellent) [19]. The number of attempts to stand and the times taken from the end of anesthesia to the appearance of spontaneous respiration, extubation, first movement, sternal recumbency, first attempt to stand, and standing were recorded.

Plasma propofol analysis

Blood samples were collected from all horses in Groups MP3 and MP6 after induction of anesthesia; 15, 30, and 45 min after connection to the breathing circuit; and immediately after standing. All blood samples were immediately placed on ice, and then the plasma was separated from the blood and frozen at − 20 °C. Propofol in plasma was extracted by liquid–liquid extraction using methyl tert-butyl ether. The extracted substance was analyzed by using liquid chromatography–tandem mass spectrometry with a Shimadzu Prominence HPLC system (Shimadzu Co., Tokyo, Japan) and AB Sciex QTRAP 4000 mass spectrometer (AB Sciex, Framingham, MA, USA).

Statistical analysis

Data on age, body weight, mean ETSEVO, mean dobutamine infusion rate, blood gases, duration of anesthesia, and recovery times were tested for statistically significant differences between groups by using one-way analysis of variance (ANOVA). If significant differences were found, a Tukey multiple comparison test was conducted. Data on repeatedly measured variables (cardiovascular parameters in the three groups and plasma propofol concentrations in Groups MP3 and MP6) were tested for significant differences among and within groups by using repeated measures ANOVA. If significant differences were found, a post hoc analysis (pair-wise Tukey multiple comparison test) was conducted. Values are given as means ± deviation (SD). Data on the number of attempts to stand and recovery scores were tested for significant differences among groups by using Kruskal–Wallis one-way ANOVA with a Dunn’s post hoc test. Statistical significance was set at P < 0.05.

Results

No abnormalities were found in any horses in the results of preanesthetic blood examination and electrocardiography. The horses in all three groups recovered uneventfully, without post-operative complications. The mean ± SD age and body weight were 2.7 ± 0.5 years and 445 ± 32 kg in Group M, 3.1 ± 0.9 years and 450 ± 17 kg in Group MP3, and 3.2 ± 0.6 years and 463 ± 26 kg in Group MP6. There were no significant differences in age and body weight among the three groups. Durations of anesthesia in Group M, Group MP3, and Group MP6 were 59 ± 9 min, 65 ± 17 min, and 70 ± 20 min; these values did not differ significantly. The ETSEVO values during the maintenance period are shown in Fig. 1. The ETSEVO values (%) were 2.4 ± 0.1 in Group M, 1.7 ± 0.2 in Group MP3, and 1.4 ± 0.2 in Group MP6. The ETSEVO values in Group MP3 and Group MP6 were significantly lower than those in Group M (P < 0.001 and P < 0.001, respectively). In addition, a significant difference in ETSEVO was found between Group MP3 and Group MP6 (P = 0.003). The HR, SAP, DAP, and MAP values during maintenance anesthesia in the three groups are shown in Table 1. There were no significant differences among the groups. The MAP values were maintained over 70 mmHg throughout the maintenance period in all groups. However, the mean dobutamine infusion rates required to maintain the MAP over 70 mmHg in Group MP6 (0.15 ± 0.06 μg/kg/min) and Group MP3 (0.20 ± 0.10 μg/kg/min) were significantly lower than those required in Group M (0.37 ± 0.18 μg/kg/min) (P < 0.001 and P = 0.007, respectively). The mean values of PaCO2 were 49 ± 2 mmHg in Group M, 52 ± 4 mmHg in Group MP3, and 50 ± 5 mmHg in Group MP6. There were no significant differences among the groups. The mean values of PaO2 were 494 ± 56 mmHg in Group M, 433 ± 97 mmHg in Group MP3, and 488 ± 66 mmHg in Group MP6; there were no significant differences among groups.
Fig. 1
Fig. 1

Mean end-tidal sevoflurane concentration during maintenance of anesthesia. Horses were maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10). *Significant difference compared with Group M (P < 0.001). Significant difference compared with Group MP3 (P = 0.003)

Table 1

Cardiovascular parameters during maintenance of anesthesia

Variable

Group

Time after connection to breathing circuit (min)

0

15

30

45

60

HR (beats/min)

M

26 ± 2

25 ± 4

26 ± 2

27 ± 1

MP3

28 ± 3

29 ± 2

29 ± 2

30 ± 2

MP6

28 ± 4

29 ± 4

29 ± 4

29 ± 3

SAP (mmHg)

M

102 ± 11

95 ± 10

104 ± 10

108 ± 6

MP3

104 ± 8

103 ± 9

105 ± 8

108 ± 6

MP6

111 ± 15

106 ± 10

109 ± 8

113 ± 8

DAP (mmHg)

M

65 ± 10

55 ± 12

60 ± 6

64 ± 5

MP3

63 ± 5

62 ± 4

63 ± 5

68 ± 4

MP6

67 ± 12

68 ± 7

71 ± 6

74 ± 7

MAP (mmHg)

M

78 ± 10

71 ± 9

75 ± 5

77 ± 3

MP3

78 ± 5

77 ± 3

78 ± 4

81 ± 6

MP6

82 ± 13

82 ± 8

85 ± 6

87 ± 7

Data are presented as mean ± SD

Horses were maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10)

None of the data across rows differed significantly from each other

HR heart rate, SAP systolic arterial blood pressure, DAP diastolic arterial blood pressure, MAP mean arterial blood pressure

The plasma propofol concentrations after induction, during maintenance, and after standing in Group MP3 and Group MP6 are shown in Table 2. The plasma propofol concentration during maintenance was calculated to be 1.1 ± 0.2 to 1.2 ± 0.2 μg/mL in Group MP3 and 2.4 ± 0.4 to 3.0 ± 0.4 μg/mL in Group MP6. Thus, the values in Group MP3 were stable and did not change significantly throughout maintenance. On the other hand, those in Group MP6 were significantly greater after 45 min of maintenance than at 15 min (P < 0.01). Moreover, the propofol concentration at each time point during maintenance was significantly greater in Group MP6 than in Group MP3. The plasma propofol concentrations after standing in Group MP3 and Group MP6 (0.4 ± 0.3 μg/mL, 0.7 ± 0.4 μg/mL, respectively) were significantly lower than those during maintenance (P < 0.01 and P < 0.01, respectively).
Table 2

Plasma propofol concentrations after induction of anesthesia, during sevoflurane maintenance, and after standing

Group

After induction (µg/mL)

Time after connection to breathing circuit (min)

After standing (µg/mL)

15 (µg/mL)

30 (µg/mL)

45 (µg/mL)

MP3

0.7 ± 0.2A

1.1 ± 0.2B

1.2 ± 0.2B

1.2 ± 0.2B

0.4 ± 0.3C

MP6

0.6 ± 0.3A

2.4 ± 0.4B*

2.7 ± 0.3BC*

3.0 ± 0.4C*

0.7 ± 0.4AD

Data are presented as mean ± SD

Horses were maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10) or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10)

Data with the same superscript letters within the same row do not differ significantly from each other

* Significant difference from Group MP3 (P < 0.05)

The number of attempts to stand and the recovery scores are shown in Fig. 2. There were no significant differences among groups; notably, all horses in Group MP3 required only one attempt to stand, and the quality of their recovery was excellent. The mean recovery times at appearance of spontaneous respiration, extubation, first movement, sternal recumbency, first attempt to stand, and standing in the three groups are shown in Table 3. There were no significant differences among the groups.
Fig. 2
Fig. 2

Number of attempts to stand (a) and recovery scores (b). Horses were maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10)

Table 3

Times from end of anesthesia to recovery events

Group

Recovery event

Appearance of spontaneous respiration (min)

Extubation (min)

First movement (min)

Sternal recumbency (min)

First attempt to stand (min)

Standing (min)

M

8 ± 6

14 ± 8

32 ± 7

36 ± 6

40 ± 6

40 ± 6

MP3

10 ± 5

17 ± 6

36 ± 11

39 ± 12

41 ± 11

41 ± 11

MP6

12 ± 5

17 ± 5

36 ± 8

42 ± 10

46 ± 14

47 ± 14

Data are presented as mean ± SD

Horses were maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10)

None of the data across rows differed significantly from each other

Discussion

We demonstrated that co-administration of medetomidine–propofol CRI during maintenance significantly reduced the sevoflurane requirement for surgical anesthesia in Thoroughbred racehorses, and that the sevoflurane requirement was significantly lower with the higher propofol infusion rate than with the lower one. Propofol, like inhalation anesthetics, directly depresses dorsal horn neuronal responses to noxious mechanical stimulation [20]. The potent anesthetic effect of propofol likely compensates for the reduction of the sevoflurane concentration. Propofol administration at a dose similar to the one we used (3.0 mg/kg/h) decreases the desflurane MAC by 28% in ponies [21] and the isoflurane end-tidal concentration by 20% in horses [22]. Villalba et al. [18] achieved a 65% reduction in the MAC of isoflurane with the administration of propofol (3.0 mg/kg/h) and medetomidine (1.25 μg/kg/h) CRI. In goats, propofol reduces isoflurane requirements by 16% at a dose of 3.0 mg/kg/h and by 34% at 6.0 mg/kg/h [23]. As in the previous study [18] we were unable to determine the individual effects of sevoflurane, propofol, and medetomidine; however, the different pharmacological interactions of the different combinations of drugs used may have caused the differences in requirements for inhalation anesthetic.

We found here that the mean plasma propofol concentrations were 1.1–1.2 μg/mL with a loading dose of 1.0 mg/kg followed by a CRI of 3.0 mg/kg/h, and 2.4–3.0 μg/mL with the same loading dose followed by a CRI of 6.0 mg/kg/h. We considered that these plasma concentrations caused significant reductions in the sevoflurane requirement. However, with CRI at 6.0 mg/kg/h the plasma propofol concentration increased significantly during the maintenance. Therefore, because accumulation of propofol or its active metabolites may occur during long-term anesthesia, we recommend propofol CRI at 3.0 mg/kg/h rather than 6.0 mg/kg/h in clinical cases.

The pharmacokinetics of CRI of propofol in horses have already been studied [24]; however, the plasma propofol concentrations required to provide anesthetic effects during sevoflurane anesthesia in horses had not, to our knowledge, been determined before our study. In goats, propofol CRI at 3.0 mg/kg/h reduces the isoflurane MAC by 16% and propofol CRI at 6.0 mg/kg/h reduces the isoflurane MAC by 34% [23]. The corresponding reported plasma concentrations of propofol were 1.2–1.8 μg/mL and 2.3–3.0 μg/mL, respectively [23], quantitatively similar to the plasma concentrations we obtained. Plasma propofol concentrations have also been reported to be 2.0–4.7 μg/mL at doses of 12 mg/kg/h in sheep [25]; 2.3–6.5 μg/mL at 9–12 mg/kg/h in ponies [14]; and 3.8–5.8 μg/mL at 24 mg/kg/h in dogs [26]. The doses of propofol used in these previous studies differ slightly from those that we used here; therefore, the reason for the difference in plasma concentrations between our results and those of these studies cannot be determined from this study and requires further investigation. Differences in propofol metabolism among species or differences in the pharmacological interactions of the different combinations of drugs used may have caused the differences in propofol plasma concentrations.

Propofol decreases arterial blood pressure in a dose-dependent manner through a direct vasodilator effect [27, 28]. However, this effect may be reduced when propofol is combined with medetomidine, most likely because the vasoconstriction caused by medetomidine counteracts the propofol-induced vasodilatation [29, 30]. Some authors have suggested that TIVA with medetomidine–propofol is associated with adequate maintenance of cardiovascular function and a reduction in the dobutamine requirement in horses [3133]. On the other hand, the combination of medetomidine and propofol CRI in a previous study resulted in an increase in MAP [18]. Inhalational anesthetics are potent dose-dependent depressors of cardiovascular function [34, 35]; therefore, the improved arterial blood pressure and lower dobutamine requirements observed when the medetomidine–propofol CRI was employed in this study may have been a consequence of the reduction in sevoflurane requirements. Nevertheless, we found no significant differences in the dobutamine requirements between horses given CRI of medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) and those given medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h). Thus, small to moderate amounts of positively inotropic agents were needed during co-administration of medetomidine and propofol because the level of improvement of cardiovascular depression was moderate during maintenance. Additionally, use of the medetomidine–propofol CRI anesthetic protocol seemed to have a plateauing effect on dobutamine requirements, but further studies are needed with different doses of propofol to demonstrate this more clearly.

Good quality recovery from anesthesia is important in horses, as in other species, and it depends on a number of factors, including, but not limited to, the sedative and anesthetic drugs used, the duration of anesthesia, the degree of postoperative pain, the horse’s temperament, and any limitations to standing caused by surgery or anesthesia-induced myopathy or neuropathy [36, 37]. Both propofol and medetomidine have been associated with a good quality of recovery. In horses, propofol produces high-quality anesthetic recoveries that are smooth and calm in the attempt to stand [38, 39]. Alpha-2 adrenoceptor agonists administered at the end of anesthesia improve the quality of recovery in horses [40] and, when compared with lidocaine, medetomidine is considered to provide better recoveries following sevoflurane anesthesia [11]. We found here that propofol administered at a loading dose of 1.0 mg/kg followed by CRI at 3.0 mg/kg/h gave the best recovery quality. We were unable to find any previous studies in the available literature on the relationship between propofol plasma concentration and time to recovery from inhalation anesthesia. Boscan et al. noted that plasma propofol concentration appeared to be correlated with recovery quality and that better recoveries were associated with lower propofol plasma concentrations [24]. When our horses stood, their mean plasma propofol concentrations were approximately 0.4 μg/mL for horses given CRI of medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) and 0.7 μg/mL for those given medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h). There were no significant differences in the number of attempts to stand or in recovery scores between the two infusion rates; however, the differences in plasma propofol concentrations after standing might have had a non-significant effect on recovery quality.

Conclusions

Compared with a CRI of medetomidine alone, CRIs of medetomidine and propofol reduced the sevoflurane requirement for surgical anesthesia as the propofol dose increased; additionally, it provided good maintenance of cardiovascular function. Specifically, CRI of medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) produced excellent recovery quality and could be an especially useful addition to sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.

Abbreviations

ANOVA: 

analysis of variance

CRI: 

constant rate infusion

DAP: 

diastolic arterial blood pressure

ETSEVO

end-tidal sevoflurane concentrations

HR: 

heart rate

IV: 

intravenous

MAP: 

mean arterial blood pressure

P: 

probability

PaCO2

arterial carbon dioxide tension

PaO2

arterial oxygen partial tension

SAP: 

systolic arterial blood pressure

SD: 

standard deviation

Declarations

Authors’ contributions

HT, HI, and MO designed the study. HT, AO, DA, HI, and YK performed the anesthesia. HT, HI, and YM participated in data acquisition and interpretation and analysis of results. All authors participated in writing and editing of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Informed consent from owners and trainers was obtained before arthroscopic surgery.

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Authors’ Affiliations

(1)
Racehorse Clinic, Miho Training Center, Japan Racing Association, 2500-2 Mikoma, Miho-mura, Inashiki-gun Ibaraki, 300-0493, Japan
(2)
Analytical Chemistry Section, Laboratory of Racing Chemistry, 1731-2 Tokami-cyo, Utsunomiya-shi Tochigi, 320-0851, Japan
(3)
Equine Research Institute, Japan Racing Association, 1400-4 Shiba, Shimotsuke Tochigi, 329-0412, Japan

References

  1. Aida H, Steffey EP, Pascoe JR, Yarbrough TB, Takahashi T, Hiraga A, et al. Use of sevoflurane for anesthetic management of horses during thoracotomy. Am J Vet Res. 2000;61:1430–7.View ArticleGoogle Scholar
  2. Carroll GL, Hooper RN, Rains CB, Martinez EA, Matthews NS, Hartsfield SM, Beleau MH. Maintenance of anaesthesia with sevoflurane and oxygen in mechanically-ventilated horses subjected to exploratory laparotomy treated with intra- and post operative anaesthetic adjuncts. Eq Vet J. 1998;30:402–7.View ArticleGoogle Scholar
  3. Wallin RF, Regan BM, Napoli MD, Stern IJ. Sevoflurane: a new inhalational anesthetic agent. Anesth Analg. 1975;54:758–66.View ArticleGoogle Scholar
  4. Aida H, Mizuno Y, Hobo S, Yoshida K, Fujinaga T. Cardiovascular and pulmonary effects of sevoflurane anesthesia in horses. Vet Surg. 1996;25:164–70.View ArticleGoogle Scholar
  5. Driessen B, Nann L, Benton R, Boston R. Differences in need for hemodynamic support in horses anesthetized with sevoflurane as compared to isoflurane. Vet Anaesth Analg. 2006;33:356–67.View ArticleGoogle Scholar
  6. Grosenbaugh DA, Muir WW. Cardiorespiratory effects of sevoflurane, isoflurane, and halothane anesthesia in horses. Am J Vet Res. 1998;59:101–6.PubMedGoogle Scholar
  7. Valverde A. Balanced anesthesia and constant-rate infusions in horses. Vet Clin North Am Eq Pract. 2013;29:89–122.View ArticleGoogle Scholar
  8. Bettschart-Wolfensberger R, Clarke KW, Vainio O, Aliabadi F, Demuth D. Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation. Res Vet Sci. 1999;67:41–6.View ArticleGoogle Scholar
  9. Creighton CM, Lemke KA, Lamont LA, Horney BS, Riley CB. Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on cardiopulmonary function and depth of anesthesia in horses anesthetized with isoflurane. J Am Vet Med Assoc. 2012;240:991–7.View ArticleGoogle Scholar
  10. Grimsrud KN, Mama KR, Steffey EP, Stanley SD. Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse. Vet Anaesth Analg. 2012;39:38–48.View ArticleGoogle Scholar
  11. Ringer SK, Kalchofner K, Boller J, Fürst A, Bettschart-Wolfensberger RA. Clinical comparison of two anaesthetic protocols using lidocaine or medetomidine in horses. Vet Anaesth Analg. 2007;34:257–68.View ArticleGoogle Scholar
  12. Tokushige H, Ohta M, Okano A, Kuroda T, Kakizaki M, Ode H, et al. Effects of medetomidine constant rate infusion on sevoflurane requirement, cardiopulmonary function, and recovery quality in thoroughbred racehorses undergoing arthroscopic surgery. J Eq Vet Sci. 2015;35:83–7.View ArticleGoogle Scholar
  13. Bettschart-Wolfensberger R, Freeman SL, Jäggin-Schmucker N, Clarke KW. Infusion of a combination of propofol and medetomidine for long-term anesthesia in ponies. Am J Vet Res. 2001;62:500–7.View ArticleGoogle Scholar
  14. Nolan A, Reid J, Welsh E, Flaherty D, McCormack R, Monteiro AM. Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study. Res Vet Sci. 1996;60:262–6.View ArticleGoogle Scholar
  15. Oku K, Ohta M, Katoh T, Moriyama H, Kusano K, Fujinaga T. Cardiovascular effects of continuous propofol infusion in horses. J Vet Med Sci. 2006;68:773–8.View ArticleGoogle Scholar
  16. Bettschart-Wolfensberger R, Freeman S, Bettschart R, Fürst A, Clarke K. Assessment of a medetomidine–propofol total intravenous anaesthesia (TIVA) for clinical anaesthesia in equidae. Vet Anaesth Analg. 2002;27:112–6.Google Scholar
  17. Pablo J, Bailey J, Nicklin C. Evaluation of guaifenesin-propofol and sevoflurane in premedicated horses. In: Proceedings of the 6th international conference of veterinary anaesthesia; 1977. p. 123.Google Scholar
  18. Villalba M, Santiago I, Gómez IA. Effects of a constant rate infusion of medetomidine–propofol on isoflurane minimum alveolar concentrations in horses. Vet J. 2014;202:329–33.View ArticleGoogle Scholar
  19. Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in premedicated horses. Am J Vet Res. 1996;57:512–6.PubMedGoogle Scholar
  20. Antognini JF, Wang XW, Piercy M, Carstens E. Propofol directly depresses lumbar dorsal horn neuronal responses to noxious stimulation in goats. Can J Anaesth. 2000;47:273–9.View ArticleGoogle Scholar
  21. Bettschart-Wolfensberger R, Jäggin-Schmucker N, Lendl C, Bettschart RW, Clarke KW. Minimal alveolar concentration of desflurane in combination with an infusion of medetomidine for the anaesthesia of ponies. Vet Rec. 2001;148:264–7.View ArticleGoogle Scholar
  22. Neges K, Bettschart-Wolfensberger R, Müller J, Fürst A, Kästner S. The isoflurane sparing effect of a medetomidine constant rate infusion in horses. Vet Anaesth Analg. 2003;30:92–3.View ArticleGoogle Scholar
  23. Dzikiti BT, Stegmann FG, Cromarty D, Dzikiti LN, Hellebrekers LJ. Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats. Vet Anaesth Analg. 2011;38:44–53.View ArticleGoogle Scholar
  24. Boscan P, Rezende ML, Grimsrud K, Stanley SD, Mama KR, Steffey EP. Pharmacokinetic profile in relation to anaesthesia characteristics after a 5% micellar microemulsion of propofol in the horse. Br J Anaesth. 2010;104:330–7.View ArticleGoogle Scholar
  25. Correia D, Nolan AM, Reid J. Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum. Res Vet Sci. 1996;60:213–7.View ArticleGoogle Scholar
  26. Nolan A, Reid J. Pharmacokinetics of propofol administered by infusion in dogs undergoing surgery. Br J Anaesth. 1993;70:546–51.View ArticleGoogle Scholar
  27. Bentley GN, Gent JP, Goodchild CS. Vascular effects of propofol: smooth muscle relaxation in isolated veins and arteries. J Pharm Pharmacol. 1989;41:797–8.View ArticleGoogle Scholar
  28. Goodchild CS, Serrao JM. Cardiovascular effects of propofol in the anaesthetized dog. Br J Anaesth. 1989;63:87–92.View ArticleGoogle Scholar
  29. Thurmon JC, Ko JC, Benson GJ, Tranquilli WJ, Olson WA. Hemodynamic and analgesic effects of propofol infusion in medetomidine-premedicated dogs. Am J Vet Res. 1994;55:363–7.PubMedGoogle Scholar
  30. Bufalari A, Short CE, Giannoni C, Vainio O. Comparative responses to propofol anaesthesia alone and with alpha 2-adrenergic medications in a canine model. Acta Vet Scand. 1996;37:187–201.PubMedGoogle Scholar
  31. Bettschart-Wolfensberger R, Bowen MI, Freeman SL, Feller R, Bettschart RW, Nolan A, Clarke KW. Cardiopulmonary effects of prolonged anesthesia via propofol–medetomidine infusion in ponies. Am J Vet Res. 2001;62:1428–35.View ArticleGoogle Scholar
  32. Bettschart-Wolfensberger R, Kalchofner K, Neges K, Kästner S, Fürst A. Total intravenous anaesthesia in horses using medetomidine and propofol. Vet Anaesth Analg. 2005;32:348–54.View ArticleGoogle Scholar
  33. Umar MA, Yamashita K, Kushiro T, Muir WW 3rd. Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine–medetomidine–propofol in horses. Am J Vet Res. 2007;68:121–7.View ArticleGoogle Scholar
  34. Steffey EP, Howland D Jr, Giri S, Eger EI 2nd. Enflurane, halothane, and isoflurane potency in horses. Am J Vet Res. 1977;38:1037–9.PubMedGoogle Scholar
  35. Steffey EP, Howland D Jr. Cardiovascular effects of halothane in the horse. Am J Vet Res. 1978;39:611–5.PubMedGoogle Scholar
  36. Young SS, Taylor PM. Factors influencing the outcome of equine anaesthesia: a review of 1,314 cases. Eq Vet J. 1993;25:147–51.View ArticleGoogle Scholar
  37. Yamashita K, Muir WW, Tsubakishita S, Abrahamsen E, Lerch P, Izumisawa Y, Kotani T. Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. J Am Vet Med Assoc. 2002;221:1150–5.View ArticleGoogle Scholar
  38. Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol as a general anesthetic for horses. Vet Surg. 1995;24:188–94.View ArticleGoogle Scholar
  39. Oku K, Yamanaka T, Ashihara N, Kawasaki K, Mizuno Y, Fujinaga T. Clinical observations during induction and recovery of xylazine–midazolam–propofol anesthesia in horses. J Vet Med Sci. 2003;65:805–8.View ArticleGoogle Scholar
  40. Santos M, Fuente M, Garcia-Iturralde R, Herran R, Lopez-Sanroman J, Tendillo FJ. Effects of alpha-2 adrenoceptor agonists during recovery from isoflurane anaesthesia in horses. Eq Vet J. 2003;35:170–5.View ArticleGoogle Scholar

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