Veterinary Anaesthesia and Analgesia, 2005, 32, 289–296
RESEARCH PAPER
A comparison of propofol, thiopental or ketamine as induction agents in goats Nikitas N Prassinos* DVM, PhD, Apostolos D Galatos* DVM, PhD, Diplomate ECVA & Dimitris Raptopoulos DVM, DrMedVet, DVA, Diplomate ECVA *Clinic of Surgery, Faculty of Veterinary Medicine, University of Thessaly, Greece Clinic of Surgery, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece
Correspondence: Nikitas N. Prassinos, Clinic of Surgery, Faculty of Veterinary Medicine, University of Thessaly, Trikalon 224, PO Box 199, GR-43100 Karditsa, Greece. E-mail:
[email protected]
Abstract Objective To compare propofol, thiopental and ketamine as induction agents before halothane anaesthesia in goats. Study design Prospective, randomized cross-over study. Animals Seven healthy adult female goats with mean (±SD; range) body mass of 38.9 ± 3.29 kg; 35–45 kg. Methods The seven animals were used on 21 occasions. Each received all three anaesthetics in a randomized cross-over design, with an interval of at least 2 weeks before re-use. Anaesthesia was induced with intravenous (IV) propofol (3 mg kg)1), thiopental (8 mg kg)1, IV) or ketamine (10 mg kg)1, IV). Following tracheal intubation, anaesthesia was maintained with halothane for 30 minutes. Indirect blood pressure, heart rate, respiratory rate and arterial blood gases were monitored. The quality of induction and recovery, recovery times and incidence of side-effects were recorded. Results Induction of anaesthesia was smooth and uneventful, and tracheal intubation was easily performed in all but two goats receiving ketamine. Changes in cardiopulmonary variables and acid–
base status were similar with all three induction agents and were within clinically acceptable limits. Mean recovery times (time to recovery of swallowing reflex and to standing) were significantly shorter, and side-effects, e.g. apnoea, regurgitation, hypersalivation and tympany, were less common in goats receiving propofol, compared with the other treatments. Conclusions and clinical relevance Propofol 3 mg kg)1 IV is superior to thiopental and ketamine as an induction agent before halothane anaesthesia in goats. It provides uneventful recovery which is more rapid than thiopental or ketamine, so reduces anaesthetic risk. Keywords anaesthesia, goat, ketamine, propofol, thiopental.
Introduction Thiopental and ketamine are popular anaesthetics in small ruminants (Gray & McDonell 1986; Riebold 1996) while propofol has been used extensively in animals and human beings. Pharmacokinetic studies in various species have revealed that propofol has a high volume of distribution, rapid metabolism and rapid clearance when given by repeated doses or continuous intravenous (IV) infusion (Langley & Heel 1988; Nolan & Reid 1991; Nolan et al. 1991; Reid et al. 1993; Hall et al. 1994; 289
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Bettschart-Wolfensberger et al. 2000). The rapid onset and short duration of action, with rapid recoveries make the drug potentially useful in ruminants, in which these features are particularly desirable. Reports on the use of propofol for induction and maintenance of anaesthesia have indicated its suitability in goats (Nolan et al. 1991; Reid et al. 1993; Pablo et al. 1997; Carroll et al. 1998). Preliminary trials with propofol in goats, which had not received pre-anaesthetic medication, indicated that a dose of 3 mg kg)1 was sufficient for induction of anaesthesia, producing satisfactory conditions for endotracheal intubation. This dose was lower than those previously described in this species. The effects of thiobarbiturates, ketamine and propofol, combined with either guaifenesin or diazepam, have been compared in sheep (Crump et al. 1994; Vesal et al. 2000), but not, to our knowledge, in goats. The aim of the current study was to compare propofol with thiopental or ketamine as induction agents before halothane anaesthesia in goats. Materials and methods With the approval of the State Veterinary Authorities, seven adult non-pregnant female mixed-bred goats were used on 21 occasions. Their body mass was 38.9 ± 3.29 kg (mean ± SD) and ranged from 35 to 45 kg. The goats were acclimatized to the facility for at least 6 months before the study. They were housed indoors, kept on straw and had free access to hay and water. The animals underwent full pre-anaesthetic screening, i.e. complete physical, haematological and serum biochemical assessments. In each animal, the right carotid artery was relocated subcutaneously at least 2 weeks before the beginning of the experiment. Each animal received all three anaesthetic techniques in a randomized cross-over design, with an interval of at least 2 weeks before re-use. The goats received no pre-anaesthetic medication, were deprived of food for 18 hours, but had free access to water for up to 2 hours before the induction of anaesthesia. The skin overlying the relocated right carotid artery, the left jugular vein and the right distal antebrachium was clipped at least 12 hours before each experiment. These areas were then infiltrated with lidocaine and prepared aseptically. A 20 SWG cannula was inserted into the relocated carotid artery and was secured in place. A second 18 SWG catheter was inserted into 290
the left jugular vein. Catheters were flushed with heparinized saline solution and the goats allowed a 30-minute settling period. Anaesthesia was induced with either propofol (Diprivan; AstraZeneca, Macclesfield, UK; 1% emulsion; 3 mg kg)1) (group P) thiopental (Pentothal; Abbott, Roma, Italy; 2.5% solution; 8 mg kg)1) (group T) or ketamine (Imalgene; Merial, Lyon, France; 10% solution; 10 mg kg)1) (group K), administered IV into the left jugular vein at 1 mL second)1. Once the animals were unable to stand, they were placed in left lateral recumbency and ‘blind’ endotracheal intubation was attempted. Once positioned and secured, the endotracheal tube was connected to an anaesthetic breathing circuit. Anaesthesia was maintained for 30 minutes with halothane (Fluothane; Zeneca, Macclesfield, UK) delivered in oxygen via a semi-closed circle absorption system with an out-of-circuit vaporizer; fresh gas flow was 3 L minute)1. The same vaporizer and anaesthetic circuit were used on all occasions and the soda lime was changed before each experiment. The vaporizer was initially set at 3% until the jaw relaxed and until palpebral and pelvic limb withdrawal reflexes had disappeared. The vaporizer setting was later reduced and held between 1.5 and 2% to sustain this depth of anaesthesia. During anaesthesia, the animals were kept in left lateral recumbency and did not undergo surgery. After discontinuation of halothane, the animals were left to recover undisturbed. The endotracheal tube was removed once swallowing reflex returned. Indirect systolic (SAP), diastolic (DAP) and mean (MAP) blood pressure, and heart rate (HR) were monitored using a Dinamap monitor (Critikon, Tampa, FL, USA), with the cuff (neonatal size no. 5) placed on the right thoracic limb over the radial artery, which was positioned at heart level. Readings were taken immediately before induction, at the time of breathing circuit connection, and at 5, 10, 15, 20 and 30 minutes after connection. Respiratory rate (fr) was counted by observing thoracic wall movements. Blood gas analysis (Radiometer ABL 330, Copenhagen, Denmark) was performed on arterial blood samples taken anaerobically into heparinized syringes at the same time intervals (except at 15 minutes). All samples were stored in ice-water and analysed within 2 hours of collection. Induction time (time from end-injection to recumbency), quality of induction and recovery, and the incidence of side effects, e.g. apnoea (no spontaneous breathing for more than 20 seconds), regur-
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Table 1 Criteria used to evaluate the quality of induction and recovery, and severity of regurgitation in goats induced with propofol, thiopental or ketamine and maintained with halothane (n ¼ 7) Induction quality scoring* Good ¼ smooth induction, rapidly assumes recumbency, no signs of excitement, easy tracheal intubation Fair ¼ slightly prolonged, mild excitement, reflex response to tracheal intubation Poor ¼ obvious excitement, jumps or attempts to stand after recumbency, inability to intubate trachea Recovery quality scoring* Good ¼ smooth, easy transition to alertness, resumes sternal position, stands in a reasonable amount of time and is able to walk with minimal ataxia Fair ¼ transient excitement or whole body movements, some struggling, hyper-responsiveness that disappears once goat stands unassisted but with moderate ataxia Poor ¼ stereotypical behaviour, e.g. circling, premature attempts to stand, prolonged struggling Regurgitation scoring Mild ¼ detection of ruminal contents within the pharynx or oral cavity Severe ¼ exit of rumen contents through nostrils or mouth *Modified from Lin et al. (1997) and Carroll et al. (1998).
gitation, hypersalivation, tympany, were recorded. Criteria used to evaluate the quality of induction and recovery, and the severity of regurgitation are summarized in Table 1. The presence and extent of excessive salivation and tympany were judged subjectively. The recovery period, which began with the discontinuation of halothane, was divided into four intervals: a) until the return of swallowing reflex, b) until the first head movement, c) until the animal achieved sternal recumbency, d) until the animal could stand unaided. Cardiorespiratory and blood gas data, were analysed using Kruskal–Wallis test, while the Mann– Whitney (U) test was used for between-means comparisons. One-way ANOVA and Duncan’s multiple range test were applied to determine the statistical significance of differences between the means of recovery times. All analyses were performed with the statistical package SPSS (version 11.0 for Windows, SPSS Inc., Chicago, IL, USA). A p-value <0.05 was considered significant.
Table 2 Summary of induction and recovery quality, and occurrence of side effects in goats induced with propofol, thiopental or ketamine and maintained with halothane (n ¼ 7) Propofol Thiopental
Ketamine
Quality of good (7) good (7) good (5) fair (2) induction Quality of good (7) good (6) fair (1) good (5) fair (2) recovery Regurgitation NO mild (2) severe (2) mild (3) severe (1) Hypersalivation NO NO (3) Tympany (1) (1) (2) Apnoea NO (2) NO Numbers in parentheses denote the number of animals that showed respective signs. NO, not observed.
Table 3 Recovery times (minutes) in goats, induced with propofol, thiopental or ketamine and maintained with halothane (n ¼ 7)
Results Recovery times
Induction of anaesthesia was smooth and uneventful, and satisfactory conditions for tracheal intubation were present in all but two goats receiving ketamine (Table 2). In these, increased jaw tone was encountered after induction although endotracheal intubation was performed without the need for further doses. In all animals – with the exception of these two – induction time was 15– 30 seconds and tracheal intubation was possible within 15–20 seconds of the animals becoming recumbent. In the two exceptions, intubation was
Propofol
Thiopental
Time to recovery 4.7 ± 0.8a 11.4 ± 1.6b of swallowing reflex Time to first head 10.6 ± 2.3a 20.6 ± 3.6a,b movement Time to sternal 16.9 ± 2.3a 38 ± 7.8a recumbency Time to standing 18 ± 2.4a 43.9 ± 7.3b
Ketamine 11.7 ± 2.2b 32.6 ± 6.7b 65.3 ± 9.9b 76.9 ± 10.3c
Data in the same row with the same letter as a superscript are not different from each other (p < 0.05). Data are given as mean ± SEM.
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Table 4 Blood pressures and heart rate in goats, induced with propofol, thiopental or ketamine and maintained with halothane (n ¼ 7) Time
Propofol
Mean arterial blood pressure [kPa (mmHg)] )1 11.10 (83.43) ± 0.55 (4.10) 0 10.89 (81.86) ± 0.68 (5.13) 5 11.72 (88.14) ± 0.71 (5.30) 10 10.17 (76.43) ± 0.73 (5.52) 15 8.97 (67.43) ± 0.94 (7.04) 20 8.34 (62.71) ± 1.29 (9.68) 30 9.31 (70) ± 0.66 (4.99) Systolic blood pressure [kPa (mmHg)]à )1 14.04 (106) ± 0.66 (4.94) 0 13.76 (103) ± 0.94 (7.06) 5 14.65 (110) ± 0.84 (6.32) 10 13.64 (103) ± 0.94 (7.07) 15 12.48 (93.9) ± 1.10 (8.28) 20 11.89 (89.4) ± 1.03 (7.75) 30 12.67 (95.3) ± 0.72 (5.44) Diastolic blood pressure [kPa (mmHg)]§ )1 9.22 (69.3) ± 0.53 (3.96) 0 8.80 (66.1) ± 0.65 (4.89) 5 9.31 (70) ± 0.59 (4.43) 10 8.49 (63.9) ± 0.71 (5.36) 15 6.86 (51.6) ± 0.92 (6.89) 20 6.33 (47.6) ± 0.76 (5.69)* 30 6.63 (49.9) ± 0.48 (3.58)* Heart rate (beats minutes)1)– )1 73.1 ± 5.54 0 91.9 ± 3.55* 5 94.7 ± 3.93* 10 100 ± 4.13* 15 100 ± 3.95* 20 98 ± 4.8* 30 97.9 ± 5.32*
Thiopental
Ketamine
10.85 (81.57) 13.85 (104.1) 11.99 (90.14) 9.16 (68.86) 9.04 (68) 9.10 (68.43) 9.23 (69.43)
± ± ± ± ± ± ±
0.63 1.36 0.71 0.78 0.73 0.53 0.50
(4.76) (10.22) (5.30) (5.83) (5.49) (3.95)* (3.78)*
14.21 (107) 16.51 (124) 14.48 (109) 12.62 (94.9) 12.45 (93.6) 12.18 (91.6) 12.18 (91.6)
± ± ± ± ± ± ±
0.49 0.99 0.54 0.62 0.53 0.56 0.50
8.66 11.48 10.36 7.22 7.11 7.24 7.33
(65.1) (86.3) (77.9) (54.3) (53.4) (54.4) (55.1)
± ± ± ± ± ± ±
0.78 1.45 0.68 0.66 0.71 0.53 0.32
77 93.7 106 105 100 104 104
± ± ± ± ± ± ±
9.34 9.14 6.84 5.06 3.14 3.68 4.53
11.67 10.49 11.61 10.13 9.82 9.65 9.61
(87.71) (78.86) (87.29) (76.14) (73.86) (72.57) (72.29)
± ± ± ± ± ± ±
0.71 1.48 1.69 0.60 0.75 0.71 0.97
(5.36) (11.14) (12.7) (4.49) (5.63) (5.36) (7.29)
(3.71) (7.41) (4.03) (4.66) (3.96)* (4.25)* (3.73)*
13.85 (104) 12.75 (95.9) 14.29 (107) 13.47 (101) 12.75 (95.9) 12.54 (94.3) 12.10 (91)
± ± ± ± ± ± ±
0.58 1.58 1.19 0.55 0.62 0.65 0.68
(4.38) (11.9) (8.97) (4.17) (4.63) (4.89) (5.09)
(5.89) (10.9) (5.08) (5) (5.31) (3.97) (2.41)
9.56 (71.9) 9.12 (68.6) 9.35 (70.3) 7.96 (59.9) 7.58 (57) 7.64 (57.4) 6.94 (52.1)
± ± ± ± ± ± ±
0.81 1.42 1.82 0.65 0.72 0.73 0.70
(6.07) (10.7) (13.7) (4.86) (5.41) (5.46) (5.3)
73.3 94.1 101 105 105 103 94.7
± ± ± ± ± ± ±
7.3 11.6 3.23 4.93 5.12 5.39 10.3
Time: )1, before administration of induction agent; 0, at connection of anaesthetic circuit; 5, 10, 15, 20, 30, minutes after connection to the anaesthetic circuit. Data presented as mean ± SEM. *Data in the same column differ significantly from the baseline value (time: )1) (p < 0.05). Propofol: ns, Thiopental: s, Ketamine: ns. àPropofol: ns, Thiopental: s, Ketamine: ns. §Propofol: s, Thiopental: s, Ketamine: ns. –Propofol: s, Thiopental: ns, Ketamine: ns. (s), (ns): significant or not significant change over time, respectively.
achieved with a delay of 20 seconds. After tracheal intubation, the transition to inhalation anaesthesia was smooth in all cases. Recovery times were shorter in propofol recipients compared with the other two groups. The time to recovery of swallowing reflex and to standing, were significantly shorter in the P-group than in the other two. However, the time to first head movement and to sternal recumbency was only significantly different when the P- and K-groups were 292
compared (Table 3). Recovery was uneventful on all occasions with the exception of two goats in the K-group and one in the T-group, in which ‘fair’ recoveries were recorded (Table 2). Regurgitation was not observed when propofol was used. Four goats regurgitated in the T-group, at 1, 2, 12 and 21 minutes after connection to the anaesthetic circuit. In the K-group, three goats regurgitated within 1 minute of anaesthetic circuit connection and another regurgitated 4 minutes
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Table 5 Respiratory rate and blood gases in goats, induced with propofol, thiopentone or ketamine and maintained with halothane (n ¼ 7) Time
Propofol
Respiratory rate (breaths minute)1) )1 26.57 ± 1.21 0 19.14 ± 2.30* 5 20 ± 2.14* 10 18.29 ± 1.87* 15 17.71 ± 1.29* 20 15.71 ± 1.34* 30 15.43 ± 1.21* pHaà )1 7.420 ± 0.011 0 7.346 ± 0.015* 5 7.277 ± 0.019* 10 7.253 ± 0.026* 20 7.237 ± 0.036* 30 7.234 ± 0.036* Pa CO2 [kPa (mmHg)]§ )1 4.11 (30.89) ± 0.32 (2.39) 0 4.81 (36.19) ± 0.26 (1.96)a 5 5.90 (44.37) ± 0.40 (2.98)* 10 6.18 (46.47) ± 0.32 (2.42)* 20 6.60 (49.61) ± 0.45 (3.41)* 30 6.68 (50.2) ± 0.41 (3.07)a, * Pa O2 [kPa (mmHg)]– )1 11.74 (88.3) ± 0.38 (2.84)a 0 5.76 (43.3) ± 0.64 (4.82)* 5 29.79 (224) ± 6.16 (46.3)* 10 40.25 (303) ± 6.08 (45.7)* 20 39.22 (295) ± 5.71 (43)* 30 39.29 (295) ± 6.00 (45.1)*
Thiopental
Ketamine
25.71 20.86 19.71 15.71 18.29 19.43 16.57
± ± ± ± ± ± ±
1.71 1.89 2.16 2.41 4.01 3.8 2.61
26.57 26.57 30.86 27.71 24.29 21.71 25.71
± ± ± ± ± ± ±
1.21 2.89 6.98 5.41 5.46 5.51 7.82
7.431 7.363 7.261 7.222 7.193 7.17
± ± ± ± ± ±
0.020 0.029 0.024* 0.022* 0.033* 0.044*
7.406 7.292 7.225 7.186 7.149 7.128
± ± ± ± ± ±
0.027 0.026* 0.029* 0.037* 0.034* 0.046*
4.35 (32.7) 5.66 (42.53) 7.39 (55.54) 8.17 (61.44) 7.78 (58.53) 8.61 (64.73)
± ± ± ± ± ±
0.24 0.56 0.78 1.07 0.80 0.94
(1.84) (4.2)a,b,* (5.83)* (8.05)* (5.98)* (7.04)a,b,*
4.49 6.23 7.14 7.33 8.00 9.24
(33.74) (46.86) (53.69) (55.09) (60.16) (69.46)
± ± ± ± ± ±
0.44 0.47 0.66 0.51 0.68 0.83
(3.34) (3.53)b,* (4.93)* (3.85)* (5.15)* (6.21)b,*
13.40 (101) 7.50 (56.4) 25.17 (189) 40.36 (303) 37.21 (280) 35.72 (269)
± ± ± ± ± ±
0.40 1.06 4.36 5.20 5.65 5.82
(3.01)b (8)* (32.8)* (39.1)* (42.5)* (43.8)*
12.30 (92.5) 7.22 (54.3) 29.98 (225) 33.58 (252) 29.90 (225) 31.34 (236)
± ± ± ± ± ±
0.66 0.81 4.30 4.27 5.04 5.22
(4.99)a,b (6.08)* (32.3)* (32.1)* (37.9)* (39.3)*
Time: )1, before administration of induction agent; 0, at connection of anaesthetic circuit; 5, 10, 15, 20, 30, minutes after connection to the anaesthetic circuit. Data presented as mean ± SEM. *Data in the same column differ significantly from the baseline value (time: )1) (p < 0.05). Data in the same row with no letter or with the same letter as a superscript are not different from each other (p < 0.05). Propofol: s, Thiopental: ns, Ketamine: ns. àPropofol: s, Thiopental: s, Ketamine: s. §Propofol: s, Thiopental: s, Ketamine: s. –Propofol: s, Thiopental: s, Ketamine: s. (s), (ns): significant or not significant change over time, respectively.
after tracheal extubation. Regurgitation was ‘mild’ in all cases with the exception of one goat in the K-group and two goats in the T-group. Hypersalivation occurred in three goats induced with ketamine: 5 minutes after anaesthetic circuit connection, at extubation and at 20 minutes after extubation. Mild tympany occurred in two goats in the K-group and in one goat in each of the other groups. Post-induction apnoea was not observed in any group. However, apnoea lasting 25–30 seconds was observed in two goats induced with thiopental, at 15 and 25 minutes after connection
to the anaesthetic circuit. A summary of these results is given in Table 2. Blood pressures tended to decrease over time and occasionally reached levels significantly lower than pre-injection values (Table 4). Heart rate increased and fr decreased in all three groups. However, changes were significant in the P-group only (Tables 4 & 5). Arterial O2 tensions (PaO2) were minimal at the time of breathing system connection, when significant hypoxaemia was present. However, cyanosis was not detected. Thereafter PaO2 increased significantly in all three groups (Table 5).
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The changes in mean arterial oxygen saturation (SaO2) followed a similar pattern. Arterial blood pH (pHa) decreased and mean arterial carbon dioxide tensions (PaCO2) increased significantly over time in all three groups. Thirty minutes after connection to the anaesthetic circuit, hypercapnia was present in all three groups; PaCO2 was significantly higher in ketamine recipients, compared with those given propofol (Table 5). No significant changes were observed in bicarbonate concentration, total carbon dioxide concentration, base excess, standard base excess and standard bicarbonate concentrations in all three groups. Discussion Rapid-sequence induction of anaesthesia and tracheal intubation is particularly desirable in small ruminants in which the risk of aspiration pneumonia after regurgitation during induction is high. In the study reported here, thiopental at 8 mg kg)1 and propofol at 3 mg kg)1 provided a smooth and uneventful induction of anaesthesia, combined with satisfactory conditions for rapid tracheal intubation and smooth transition to inhalational anaesthesia. Thiopental is renowned for producing a smooth, rapid induction of anaesthesia in sheep and goats (Gray & McDonell 1986). Similar conditions were also achieved with propofol at 4 mg kg)1 (Reid et al. 1993), while a median effective dose of 5.1 mg kg)1 produced conditions for successful intubation in goats (Pablo et al. 1997). Ketamine (10 mg kg)1) was also effective, although intubation conditions were unsatisfactory in two of seven animals because of increased jaw tone; ketamine causes increased tonic-clonic muscle activity when used alone in ruminants (Riebold 1996; Hall et al. 2001) and for this reason, should be combined with sedative tranquillizers, such as xylazine or diazepam. However, ruminants are not always sedated before induction of anaesthesia, in order to avoid prolonged recoveries and, or an increased risk of regurgitation. It is noted that orotracheal intubation was eventually achieved in these two animals. Myoclonic activity and other forms of excitement have been associated with propofol in people and animals (Langley & Heel 1988; Morgan & Legge 1989; Cullen & Reynoldson 1993). Myoclonic activity of the face and limbs has also been reported in propofol-induced goats (Pablo et al. 1997). These authors, using doses of 3.2–7.8 mg kg)1, found that the incidence of myoclonus was un-associated 294
with dose. Opisthotonos and muscular spasms were also encountered in one of seven goats 1–7 minutes after having received propofol (4 mg kg)1) (Bettschart-Wolfensberger et al. 2000). Pablo et al. (1997) speculated that higher doses of propofol might eliminate or minimize myoclonic activity. However, no signs of myoclonic activity were observed in the current study despite the low propofol dose used. Other authors using goats that either had (Carroll et al. 1998) or had not received (Reid et al. 1993) pre-anaesthetic medication have not observed such signs. The dose of propofol used in the current study was lower than that used by Reid et al. (1993), Pablo et al. (1997) and Bettschart-Wolfensberger et al. (2000) who also avoided the use of preanaesthetic medication. Indeed, the dose examined in the current study is lower than that used in sedated goats (4.3 mg kg)1) by Carroll et al. (1998). Pablo et al. (1997) speculated that differences between induction doses of propofol might be an effect of administration rate. However, administration rates in the present study were the same as those used by Pablo et al. (1997). These workers also commented that the dose of 3.0 mg kg)1 should be used with caution in docile or pet goats. The animals used in the present study were acclimatized for at least six months before the study, and, therefore, were accustomed to the operating room and personnel. Similar (3.5 ± 0.5 mg kg)1) or lower (2.0–2.5 mg kg)1) doses have been used in unsedated (Waterman 1988) and sedated sheep (Alon et al. 1993; Vesal et al. 2000), respectively. Passive regurgitation of rumen contents can occur at any time during anaesthesia when the cardia relaxes, while in lightly anaesthetized ruminants active regurgitation occurs during attempted tracheal intubation (Riebold 1996). Reid et al. (1993) reported regurgitation in two of five goats anaesthetized with propofol and halothane. However, this problem was not associated with propofol use by other authors (Pablo et al. 1997; Carroll et al. 1998; Bettschart-Wolfensberger et al. 2000). Regurgitation did not occur when goats were induced with propofol in the study reported here, while it occurred in four of seven animals in both the thiopental and the ketamine groups. In four goats (one given thiopental and three given ketamine) regurgitation occurred within one minute of connection to the anaesthetic circuit, and in another goat (thiopental) it occurred 2 minutes later. Regurgitation was clinically inconsequential
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in all cases, because endotracheal intubation had been performed. However, it emphasizes the importance of using rapid-acting induction agents, which produce – with minimum delay – satisfactory conditions for endotracheal intubation in ruminants. On the basis of this criterion, propofol and thiopental were equally effective. However, no regurgitation occurred in propofol-treated animals. Moreover, propofol compared favourably with ketamine as an induction agent as the results of the present study indicate that intubation conditions were poorer with ketamine. In delaying intubation – at a time when regurgitation can and does occur – ketamine increases the risk of aspiration, and while laryngeal and swallowing reflexes are maintained, aspiration is still possible during ketamine anaesthesia (Gray & McDonell 1986). Therefore, ketamine should be used with care when inducing anaesthesia in unsedated goats. Hypersalivation occurred in three goats of the ketamine group which was not surprising: ketamine is a recognized sialogogue (Hall et al. 2001). Apnoea occurs after thiopental (Green 1979) or ketamine injection (Thurmon et al. 1973) in small ruminants. It also occurs after propofol is used in human beings (Langley & Heel 1988), and in various animal species (Watkins et al. 1987; Morgan & Legge 1989; Cullen & Reynoldson 1993; Murison 2001) including goats (Reid et al. 1993; Pablo et al. 1997; Bettschart-Wolfensberger et al. 2000). In the present study, apnoea occurred in two goats induced with thiopental although positive pressure ventilation was unnecessary because it was transient. Pablo et al. (1997) reported apnoea in 27 of 28 goats given propofol and suggested that this was attributable to rapid administration, which results in a higher plasma concentration in a short period of time. In contrast, Murison’s (2001) study in dogs indicated an increased incidence and duration of post-intubation apnoea with slow propofol injection rates. Moreover, Rolly et al. (1985) using different rates for IV propofol injection in human beings, concluded that apnoea was not influenced by administration rate. Pablo et al. (1997) reported a high incidence of apnoea in goats receiving propofol at five different dose rates. In most of these animals, the propofol dose was higher than that used in the present study; only two goats had received similar doses (3.2 mg kg)1). Therefore, most animals developing apnoea received doses greater than that used in the current study. The propofol administration rate in
the present study was the same as that used by Pablo et al. (1997) which indicates that the incidence of apnoea is a dose, rather than a rate of administration effect. All induction agents in the current study produced hypoxaemia. However, its duration was unknown, as on all occasions the inspired oxygen concentration was almost 100% after connection to the anaesthetic circuit. Consequently, PaO2 increased with time. Marked hypoxaemia was also encountered within 2 minutes of propofol administration by Bettschart-Wolfensberger et al. (2000). Hypercapnia was also observed after induction in all three groups, with PaCO2 increasing progressively with time, and peaking 30 minutes after connection to the circuit. The peak value was significantly lower in propofol, compared with ketamine recipients. Both hypoxaemia and hypercapnia were apparently the result of drug-induced respiratory depression. A rapid recovery is desirable in ruminants because extended recumbency enhances the risk of tympany and hypoxaemia. Rapid recovery of swallowing reflex minimizes the risk of aspiration of regurgitated rumen contents. In the present study, recovery times (time to recovery of swallowing reflex and to standing) were significantly shorter after propofol compared with thiopental or ketamine. Recovery times after propofol in the present study are consistent with the pharmacokinetic data available for goats (Nolan et al. 1991; Reid et al. 1993; Bettschart-Wolfensberger et al. 2000). Longer recovery times after ketamine were expected since ketamine alone, or in combination with xylazine is occasionally associated with prolonged recoveries (Gray & McDonell 1986; Dehghani et al. 1991). Mean recovery times after propofol were longer than those reported elsewhere (Nolan et al. 1991; Reid et al. 1993) and may be attributed to the absence of surgical stimulation. Recovery from anaesthesia was smooth and uneventful in all cases, with the exception of two goats receiving ketamine and one given thiopental. The quality of recovery after propofol was similar to that reported by other workers (Nolan et al. 1991; Carroll et al. 1998). The results of the present study indicate that IV propofol at 3 mg kg)1 is a satisfactory induction agent before halothane anaesthesia in unsedated goats. It also provides uneventful and rapid recovery from anaesthesia, thus reducing risks associated with anaesthesia in this species. Apnoea, regurgi-
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tation, hypersalivation and tympany were rarely, if ever, encountered. It is concluded that propofol is superior to thiopental and ketamine as an induction agent in goats. References Alon E, Ball RH, Gillie MH et al. (1993) Effects of propofol and thiopental on maternal and fetal cardiovascular and acid–base variables in the pregnant ewe. Anesthesiology 78, 562–576. Bettschart-Wolfensberger R, Semder A, Alibhai H et al. (2000) Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (DisoprivanÒ) in comparison to propofol solved in polysorbate 80 in goats. Vet Med A 47, 341–350. Carroll GL, Hooper RN, Slater MR et al. (1998) Detomidine-butorphanol-propofol for carotid artery translocation and castration or ovariectomy in goats. Vet Surg 27, 75–82. Crump KT, Dunlop CI, Hick LH et al. (1994) Recovery from anesthesia in sheep following induction with thiamylal, ketamine or propofol. In: Proceedings of the 5th International Congress of Veterinary Anesthesia, Guelph, Canada, pp. 85 (abstract). Cullen LK, Reynoldson JA (1993) Xylazine or medetomidine premedication before propofol anaesthesia. Vet Rec 132, 378–383. Dehghani S, Sharifnia N, Yahyaei MR et al. (1991) Clinical, haematological and biochemical effects of xylazine, ketamine and their combination in caprine and feline. In: Proceedings of the 4th International Congress of Veterinary Anesthesia, Utrecht, The Netherlands, pp. 129–133. Gray PR, McDonell WN (1986) Anesthesia in goats and sheep. Part II. General anesthesia. Comp Cont Educ Pract 8, S127–S135. Green CJ (1979) Animal Anaesthesia. Laboratory Animals Ltd, London, UK, pp. 183. Hall LW, Clarke KW, Trim CM (2001) Veterinary Anaesthesia (10th edn). WB Saunders, London, UK, pp. 128– 129, 352. Hall LW, Lagerweij E, Nolan AM et al. (1994) Effect of medetomidine on the pharmacokinetics of propofol in dogs. Am J Vet Res 55, 116–120. Langley MS, Heel RC (1988) Propofol. A review of its pharmacodynamic and pharmacokinetic properties and
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use as an intravenous anaesthetic. Drugs 35, 334– 372. Lin H-C, Purohit RC, Powe TA (1997) Anesthesia in sheep with propofol or with xylazine-ketamine followed by halothane. Vet Surg 26, 247–252. Morgan DWT, Legge K (1989) Clinical evaluation of propofol as an intravenous anaesthetic agent in cats and dogs. Vet Rec 124, 31–33. Murison PJ (2001) Effect of propofol at two injection rates or thiopental on post-intubation apnoea in the dog. J Small Anim Pract 42, 71–74. Nolan A, Reid J (1991) A pharmacokinetic study of propofol in the dog. In: Proceedings of the 4th International Congress of Veterinary Anaesthesia, Utrecht, The Netherlands, pp. 40 (abstract). Nolan AM, Reid J, Welsh E (1991) The use of propofol as an induction agent in goats. J Vet Anaesth 18, 53–54 (abstract). Pablo LS, Bailey JE, Ko JCH (1997) Median effective dose of propofol required for induction of anesthesia in goats. J Am Vet Med Assoc 211, 86–88. Reid J, Nolan AM, Welsh E (1993) Propofol as an induction agent in the goat: a pharmacokinetic study. J Vet Pharmacol Therap 16, 488–493. Riebold TW (1996) Ruminants. In: Lumb & Jones, Veterinary Anesthesia (3rd edn). Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins, Baltimore, USA, pp. 610–626. Rolly G, Versichelen L, Huyghe L et al. (1985) Effect of speed of injection on induction of anaesthesia using propofol. Br J Anaesth 57, 743–746. Thurmon JC, Kumar A, Link RP (1973) Evaluation of ketamine hydrochloride as an anesthetic in sheep. J Am Vet Med Assoc 162, 293–297. Vesal N, Navid N, Sadjadi G (2000) Evaluation of propofol, ketamine and thiopental as anesthetic induction agent in sheep. In: Proceedings of the 7th World Congress of Veterinary Anaesthesia, Berne, Germany, pp. 107 (abstract). Waterman AE (1988) Use of propofol in sheep. Vet Rec 122, 260. Watkins SB, Hall LW, Clarke KW (1987) Propofol as an intravenous anaesthetic agent in dogs. Vet Rec 120, 326–329. Received 6 January 2003; accepted 17 July 2003
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