Abstract: The anesthetic and cardiopulmonary effects of a combination of continuous intravenous infusion using a mixture of 6 g L–1 thiopental-75 g L–1 guafinesine-3 mg L–1 metedomidine (0.30 mL/kg/h) and Oxygen-Sevoflurane (OS) anesthesia (TGM-OS anesthesia) in horses were evaluated. The concentration of sevoflurane (Sevo) required maintaining surgical anesthesia was around 1.5% in TGM-OS and 3.3% in OS anesthesia. Mean Arterial Blood Pressure (MABP) was maintained at around 77 mm Hg under TGM-OS anesthesia, while dobutamine (0.43±0.13 μg kg–1) infusion was necessary to maintain MABP at 60 mmHg under OS anesthesia. No apparent complication was observed during and after anesthesia in all cases. Recovery from anesthesia under TGM-OS anesthesia was very calm and smooth. The times required for the horse to return both sternal and standing position in group under TGM-OS anesthesia tended to be shorter than group under OS anesthesia which statistical differences were p<0.05 and p<0.01, respectively. Thiopental Guafinesine-Metedomidine and Oxygen-Sevoflurane anesthesia (TGM-OS anesthesia) may be useful for prolonged equine anesthesia because of its minimal cardiopulmonary effects and good recovery from anesthesia.
INTRODUCTION
Sevoflurane (Sevo) is a halogenated inhaland anesthetic with favourable chemical and pharmaco-dynamic properties. It’s low blood solubility facilitates rapid induction and recovery from anesthesia and better control of anesthesia dept during maintenance when compared to other common used volatile anesthetic agent (Eger, 1994; Behne et al., 1999). Mean values for the Minimal Alveolar Concentration (MAC) of Sevo in horses have been reported by some researchers i.e., 2.3% by Aiada et al. (1994), 2.31% by Natalini, (2001) and 2.6-2.9% by Mizuno et al. (1996). For these reason the new inhaland agent has gained increasing interest in horse anesthesia. However, Sevo causes dose depended cardiopulmonary depression as well as hypoventilation and hypotension at the stage of surgical anesthesia (Aida et al., 1996; Grosenbauh and Muir, 1998). Assisted or controlled ventilation and administration of vasopressin should be considered during Sevo-O2 (OS) anesthesia in horses and intermittent positive ventilation has been used to improve hypoventilation during anesthesia in horses but this also leads to further cardiac depression (Yamashita et al., 2000). A low dose dobutamine infusion has been recommended to prevent or treat hypotention that develop in horses anesthetized with a volatile anesthetic agents (Donaldson, 1988; Lee et al., 1998; Swanson et al., 1985). The infusion of dobutamine in horses anesthetized with halothane, sometimes leads to the development of cardiac aritmias and tachycardia (Donaldson, 1988; Lee et al., 1998; Young et al., 1998). It has been suggested that intravenous anesthesia may be associated with lower incidence of perioperative cardiovascular emergencies and lower anesthetic risk (Johnston et al., 2002). Total Intravenous Anesthesia (TIVA) has been investigated as an alternative to inhalation anesthesia (Bettschart-Wolfansberger et al., 1996; Nolan et al., 1996; Flaherty et al., 1997; Taylor et al., 1995, 1998). This involves different drugs combination administrated either as repeated injection or as infusion. One of the most studied and familiar TIVA technique in horses is using a combination of ketamine, α2 agonist and guafinesine (Greene et al., 1986; McCarty et al., 1990; Taylor et al., 1992, 1998; Young et al., 1993). It has been reported that combination of continues intravenous infusion using a mixture of guafinesine-ketamime-xylasine and OS and guafinesine - ketamime - medetomidine could minimize cardiovascular effects by reducing requirement of Sevo for the maintenance of surgical anesthesia in horses and at this anesthesia MAPB was maintained at an appropriate level without administration of vasopressor (Yamashita et al., 2000).
Medetomidine is more specific α2 adrenoceptor agonist compared to detomidine and xylasine and it is more potent than xylasine in both behavioral and neurochemical effects (Bryant et al., 1991; Yamashita et al., 2002). It is emphasized that a mixture of GKM would be more potent than that GKX (Yamashita et al., 2000).
The purpose of this study was to evaluate the anesthetic and cardiopulmonary effects of a combination of continuous intravenous infusion using mixture of Thiopental-Guafinesine-Metedomitine and OS (low dose) anesthesia(TGM-OS anesthesia) in horses.
MATERIALS AND METHODS
This study protocol was approved by Atatürk University’s Animal Care and Use Committee. This study was conducted between 2005-2008, at the Ataturk University, Veterinary Faculty, Clinic of Surgery, Erzurum, Turkey.
Animals
In this study, two group horses were used. Group A consisted of eight
local breed aged 6.5±1.3 years and weighing 457±28 kg. Group
B consisted of eight local breed aged 7.8±2.4 years and weighing
430±30 kg.
Study Design
Animals were fasted for 12 h before experiments but water were given
ad libitum. In addition to physical examination, venous blood samples
for standart clinical haematology and serum chemistry profiles were taken
from each horse one day prior to the experiment. All horses in groups
A and B were premedicated by using 0.010 mg kg–1
of medetomidine (Domitor, Orion Pharma) intravenously and anesthetized
with 6 mg kg–1 thiopental (Veterinary Pentothal,
Rhone-Merieux). After orotracheal intubation, the horses were positioned
in left lateral recumbency and the right fascial artery was raised surgically
in to a subcutaneous position under Sevo (Sevorane, Abbot Laboratories)+O2
(OS) anesthesia in groups A and B. Anesthesia were maintained under thiopental-guafinesine
(Guailaxin, Ford-Dodge)-medetomidine (TGM)+OS (TGM-OS) anesthesia in group
A and under OS anesthesia in group B for 180 min. TGM mixture containing
75 g L–1 of guafinesine, 3 mg L–1
of medetomidine and 6 g L–1 thiopental in
serum physiologic was injected at 0.30 mL/kg/h through infusion pump (Flo-Dard
RMC 9611) and a 16 inch gouge catheter (Happycath, Medikit) placed in
the right jugular vein and surgical anesthesia was maintained by controlling
the concentration of inhaled Sevo+O2 in group A. In group B
surgical anesthesia was maintained by Sevo+O2 anesthesia. When
ABP decreased around 50 mmHg, dobutamine 0.43±13 μg/kg/min
(Dobutrex, Shionogi) was administered intravenously to maintain Arterial
Blood Pressure (ABP) around 60 mmHg. All horses in group A and B were
anesthetized for 3 h with TGM+OS anesthesia and OS anesthesia, respectively.
Sample Collection and Analysis
Heart Rate (HR) Mean Arterial Blood Pressure (MABP) and Body Temperature
(BT) were recorded by an anesthetic monitoring system (Bionet, Br3). Arterial
blood pressure was measured by connecting an 14 gauge catheter placed
into the right fascial artery to a pressure transducer. Arterial blood
samples were taken from the same catheter into a heparinized syringe and
analyzed by a blood gas analyzer (Technicon RA-TX).
All samples and data were collected each 30 min during anesthesia. Statistical analysis were made using one way ANOVA test.
RESULTS
In group A, spontaneous blinking and nystagmus were observed at the beginning of the anesthesia and they also showed a dull palpebral reflex and strong corneal reflex. In the horses of group B, corneal reflex and palpebral reflexes were observed but spontaneous nystagmus and tearing were not seen during anesthesia. Total anesthesia time, the time required for the horse to return the sternal position, the number of attempts to stand and to the standing position after the anesthesia period in group A and B are given in Table 1.
The time required for the horse to return both sternal and standing position in group A tended to be shorter than group B and statistical differences were p<0.05 and p<0.01, respectively. The attempts to stand in all group was almost equal. In group B, hypotention developed after an hour anesthesia. Six horses in group B required infusion of dobutamine (0.45±0.15 μg/kg/min) to maintain ABP during OS anesthesia.
Changes in Sevo dose, Body Temperature (BT), Heart Rate (HR), Respiratory Rate (RR), Mean Arterial Blood Pressure (MABP), partial pressure of CO2 (PaCO2), partial pressure of O2 (PaO2) and dobutamine during anesthesia in group A and B are summarised in Table 2.
The percentage Sevo required for the anesthesia in group A (approximately
1.5%) was lower than group B (approximately 3.3%) which was different
statistically (p<0.01). Mean Arterial Blood Pressure (MABP) was high
at the beginning of the anesthesia in both groups. In group A, MABP was
maintained at an appropriate level and was higher than that in group B
(p<0.01). When ABP decreased in group B, dobutamine was administered
intravenously to maintain the mean ABP at approximately 63 mmHg. BT decreased
during anesthesia in both groups. HR was at about 35 beats min–1.
in group A but it increased in group B which was different statistically
(p<0.05). RR were also different statistically between two groups as
seen in Table 2. Oxygenation was excellent in all horses
of both groups and the PaO2 levels were about 400 mmHg and
above it.
| Table 1: | Mean values (±SD ) of sternal position, attempts to stand and standing position |
| *p<0.05, **p<0.01 | |
| Table 2: | Mean values (±SD) of sevoflurane (Sevo), Body Temperature (BT), Heart Rate (HR), Respiratory Rate (RR), Arterial Blood Pressure (ABP), partial pressure of CO2 (PaCO2), partial pressure of O2 (PaO2) and dobutamin during anesthesia period |
| *p<0.05, **p<0.01 | |
DISCUSSION
Volatile anesthetic agents are widely used in various species for their hypnotic properties. For prolonged procedures, horses are commonly anesthetized with volatile anesthetic agents and these agents produce dose related cardiopulmonary depression (Steffy and Howland, 1978) and provide poor analgesia. Cardiovascular problems contribute greatly to the high mortality rate in horses (Jonston et al., 2002). In order to optimize anesthesia, the amount of inhalation agents should be minimized and additional analgesia provided. TIVA can be used as an alternative to inhalation anesthesia to maintain better cardiopulmonary performance (McMurphy et al., 2002). α2 adrenoreceptor agonist are potent analgesics and reduce Minimal Alveolar Concentration (MAC) of inhalation agent (Steffey and Pascoe, 2002).
Intravenous agents commonly used in horses, such as ketamine, which has known analgesic properties (Wright, 1982). TIVA is commonly used for short anesthetic procedures because of potential drug accumulation in the body. The combination of inhalation and injectable agents allows benefits from both forms of anesthesia, reducing such undesirable effects as cardiopulmonary depression and prolonged recovery because of surgical anesthesia over a long time (Spadavecchia et al., 2002; Kushiro et al., 2005). In this method, sedative, analgesic and injectable anesthetic drugs were combined and used either as repeated injection or as infusion. The most commonly used TIVA combination is ketamine-any α2 agonist and guafinesine (Bettschart-Wolfansberger et al., 1996; Nolan et al., 1996; Flaherty et al., 1997; Taylor et al., 1998). Ketamine is widely used for intravenous induction and maintenance of general anesthesia in horses (Muir and Sams, 1992). Because recovery from ketamine is not smooth and muscle rigidity occurs, this drug is not recommended as the sole intravenous agent (Muir et al., 1977), even during inhalation anesthesia (Serteyn et al., 1987; Muir and Sams, 1992). Therefore, ketamine is commonly combined with guafinesine, any α2 agonist, which all having good myorelaxant properties (Greene et al., 1986). In the present study, induction of anesthesia (in groups A and B) and during maintenance of anesthesia in group A medetomidine which has more α2 agonist effect than xylasine (England and Clarke, 1996) and thiopental which has better effect on muscle relaxation than ketamine, were preferred as anesthetic mixture. When earlier studies examined 2.3% by Aiada et al. (1994), 2.31% by Natalini (2001) and 2.6-2.9% by Mizuno et al. (1996) the amount of Sevo used were between 2.31 and 2.9%. But in the present study, the amount of Sevo used were in between 2.9-3.7% in group B except first 30 min of the anesthesia period. This situation occured due to reduction in the preanesthetic effects which was used in group B. As a matter of fact this is confirmed with the result obtained from group A. Young et al. (1993) reported their experiences with guafinesine (100 g L–1), ketamine (2 g L–1) and xylasine (1 g L–1) anesthesia in horses undergoing various types of surgery and they found that the average infusion rate to maintain anesthesia was 1.1 mL/kg/h. In GKX-OS anesthesia , the dose rates of guafinesine, ketamine and xylazine were 30 mg/kg/h, 1.2 mg/kg/h and 0.3 mg/kg/h, respectively (Yamashita et al., 1997). The dose rates of guafinesine, ketamine and medetomidine were 25 mg/kg/h, 1.0 mg/kg/h and 0.00125 mg/kg/h, respectively in GKM-OS anesthesia (Yamashita et al., 2000). Anesthesia was maintained by Taylor et al. (2001) with IV infusion of detomidine (0.04 mg mL–1), ketamine (4 mg mL–1) and guafinesine (100 mg mL–1) (DKG) for 140 min.
In the present study, the dose rates of guafinesine and medetomidine were 22.5 and 0.0009 mg/kg/h, respectively.
Induction of anesthesia with xylasine (Mama et al., 1995) and xylasine premedicated horses (Mama et al., 1996) were associated with spontaneous uncoordinated and coordinated muscle activity immediately after recumbency of some horses. This behavior is in contrast to the smooth quiet induction of anesthesia recorded in ponies (Nolan and Hall, 1985). In the present study, in both groups, medetomidine (0. 010 mg kg–1) and thiopental (6 mg kg–1) were used induction period. Induction of anesthesia was smooth and uneventful and satisfactory conditions for tracheal intubation were present in both groups. But in both groups, apnea occured after thiopental administration in a total of 7 horses, in this situation, mechanical ventilation were applied to these 7 horses. Apnea was expected complication after thiopental infusion (Alon et al., 1993; Murison, 2001).
In the present study, heart rate increased at the beginning of the anesthesia in both groups (first 30 min). An increase in heart rate after thiopental injection (Taylor, 1990) and sevoflurane in horses (Aida et al., 2000; Grosenbagh and Muir, 1998) has also been reported. The results observed in the present study could also be due to the usage of both thiopental and sevoflurane but this station could also be the results of reflex tachicardia occured response to hypotention. In present study, ABP decreased including in the induction period in both groups. However, differences between group A and B with regard to ABP were different statistically (p<0.05). This situation could be due to thiopental used during anesthesia period in group A and high dose sevoflurane used during anesthesia period in group B. Higher ABP obtained in group A compared to group B could be due to mixture of TGM used in group A which provaked reduction of the amount of sevoflurane concentration. In group B, increased heart rate was observed in a whole anesthesia period. This finding corresponds with above mentioned studies (Aida et al., 2000; Grosenbaugh and Muir, 1998). During general anesthesia, movement reported to occur in horses and this controlled with thiopental (Bettschart- Wolfensberger et al., 2005; Ringer et al., 2007). In the present study, movement were not seen in both groups. This situation could be due to continuously usage of thiopental in group A and usage of a high dose sevoflurane in group B. Due to cardiovascular depression, postanesthetic myopathy, colitis and lameness reported to occur in horses and this can be impeded through holding ABP about 65-70 mmHg or above level (Grandy et al., 1987; Lindsay et al., 1989). For this purpose, dobutamine reported to be used at 1-5 μg/kg/min dose (Carrol et al., 1998; Mizuno et al., 1996; Spadavecchia et al., 2002). In the present study, ABP did not reduce in a dangerous level. But, in 6 horses in group B, ABP decreased under 50 mmHg level. Therefore, dobutamine were used at 0.43±13 μg/kg/min dose. So that, ABP in these horses increased to above 60 mmHg. In present study infusion period of the dobutamine were not fixed. When ABP reached to above 60 mmHg or tachicardia occured, infusion of this drug ended.
Heart rate were statistically different between two groups in this study at the end of anesthesia. Furthermore, although it was not statistically important heart rate increased in group B more in the other period of anesthesia. This increase thought to be due to positive chronotropic effect of dobutamine. Furthermore, in group B reductive effect of the used premedican drugs due to time may also play role in the increase of heart rate. Because in group A, mixture was used as infusion. Respiration rate in this study in first 15 min after induction period decreased. Because thiopental are respiratory system depressor (Bennett et al., 1998; Taylor, 1990) in this period mechanical ventilation were applied, then spontane respiration continued. In present study, mechanical ventilation were applied only in the beginning of the anesthesia in both groups and later on this application did not require. This station could be due to the anesthetics used in this study were just enough with concern to dose for the anesthesia. In OS anaesthesia, the Sevo has been reported to be used from 2.0 to 3.0% (Carroll et al., 1998; Mizuno et al., 1996; Yamashita et al., 1997). In the present study, 3.3% Sevo required to maintain surgical anesthesia in group B. Under TGM-OS (Group A) anesthesia, 1.5% Sevo required to maintain surgical anesthesia, which was only about 50 % of that under OS anesthesia (Group B). In short time sevoflurane anesthesia (depending on induction agents) recovery time from anesthesia has been reported to be around 8-18 min(Aida et al., 1994, 1996; Hikasa et al., 1994; Matthews et al., 1998; Mizuno et al., 1996). In horses under OS anesthesia, time to standing was reported to be 65±27 min. in 8 horses anesthetized for 296±31 min (Carrol et al., 1998), 2 h in a horse anesthetized for 7 h for internal fixation (Mizuno et al., 1996) and 32±6 min in 5 horses anesthetized for 151±32 min (Yamashita et al., 1997). In the present study, standing time in group A was 38±12 min and in group B was 45±17 min anesthetized for 180 min. When anesthesia period taken into consideration, these recovery time were in parallel with the previous studies. However, in the present study standing time were shorter in group A compared to group B.
In conclusion, the infusion of thiopental (6 g L–1)-guafinesine (75 g L–1)-medetomidine (3 mg L–1) combination at 0.30 mL/kg/ h dose in horses receiving low concentrations of sevoflurane appears to be a safe technique for producing prolonged anesthesia. Compared with the use of sevoflurane alone, the combined infusion-inhalation technique produced more stable anesthesia, cardiopulmonar function was adequate, sympatomimetic drugs were not required. Recovery was normally rapid and of good quality.
ACKNOWLEDGMENTS
This study was supported by Fund of Scientific Research Projects of Ataturk University (BAP2003284). Thanks to Dr. Ekrem Lacin for statistical analysis, at the Department of Animal Sciences in Faculty of Veterinary,