The pharmacokinetics of thiopentone

The pharmacokinetics of thiopentone was studied in six mongrel dogs using a high-performance liquid chromatographic method for measurement of the drug in the plasma. An intravenous bolus dose (20 mg/kg) of 2.5% thiopentone sodium solution was injected into the cephalic vein. While the two- and three-compartment models were used in the analysis of the experimental data, the disposition curve was adequately described by a biexponential equation. Plasma protein binding of thiopentone was determined in vitro using the equilibrium dialysis technique. The drug was bound to a moderately high extent (73.8 ± 4.1%). The half-time of the initial phase, which comprises distribution/redistribution, was 14.9 ± 3.3 mins. The apparent volume of distribution was quite high for an organic acid (843 ± 194 ml/kg). This may be attributed to the high lipid solubility of the thiobarbiturate. The half-life was 6.99 ± 2.18 h and a body clearance value of 1.51 ± 0.60 ml/kg-min was obtained. It can be concluded from this study that the half-time of the distribution/redistribution phase approximates the duration of anaesthetic effect. Consequently, physiological conditions and disease states which influence distribution/redistribution rather than those affecting hepatic biotransformation of the drug are likely to affect anaesthesia.     

Pharmacokinetics of thiopentone in the horse

Abass, B.T., Weaver, B.M.Q., Staddon, G.E., Waterman, A.W. Pharmacokinetics of thiopentone in the horse. J. vet. Pharmacol. Therap . 17 , 331–338.
The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre-medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three-compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half-life 1.4 ± 1.2 min (mean ± SD) and 1.3 ± 0.7 min, respectively, was obtained, which was followed by a second comparatively slower redistribution phase, half-life 16 ± 12 min and 11 ± 5 min, respectively. The volume of distribution for the drug was large, especially in the ponies which received isoflurane (1127 ± 86 ml/kg). compared to the horses which received halothane (742 ± 89 ml/kg). The drug had a somewhat shorter elimination half-life in the horses (147 ± 21 min) than in the ponies (222 ± 44 min), but no obvious difference in clearance of the drug was observed between the horses (3.5 ± 0.5 ml/min/kg) and ponies (3.6 ± 0.8 ml/min/kg).     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.     

Endocrine and metabolic responses to halothane and pentobarbitone anaesthesia in sheep

Some metabolic and endocrine responses to anaesthesia in sheep were studied. Adult sheep were anaesthetised with thiopentone and halothane (n=9), acepromazine, thiopentone and halothane (n=8) and pentobarbitone (n=10) on separate occasions. Routine cardiovascular monitoring was carried out and blood samples were taken for assay of cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Halothane anaesthesia induced hypotension, hypercapnia and respiratory acidosis. Sheep anaesthetised with pentobarbitone were also hypercapnic and acidotic but did not develop hypotension. Plasma cortisol, ACTH and AVP (mean maximum values: cortisol: 83 ng/ml, ACTH 278 ng/ml, AVP 135 pg/ml), increased during halothane anaesthesia but did not change significantly from control values during pentobarbitone anaesthesia (mean maximum values: cortisol: 30 ng/ml, ACTH 71 ng/ml, AVP 7.8 pg/ml). Glucose tended to increase during both halothane and pentobarbitone anaesthesia but lactate decreased. It is not clear what facet of halothane anaesthesia evokes the stress response but it may be associated with cardiovascular depression.     

Metocurine pharmacokinetics and pharmacodynamics in goats

Non-depolarizing muscle relaxants can facilitate surgery and anaesthesia in numerous species, and volatile inhalational anaesthetics such as isoflurane potentiate their action. We studied the effect of isoflurane on the pharmacodynamics and pharmacokinetics of metocurine in six goats. Each was studied twice: once during barbiturate-opiate anaesthesia and once during isoflurane anaesthesia. The evoked response to sciatic nerve stimulation was measured using a force transducer attached to the hoof. Metocurine was infused until approximately 80–90% blockade. Plasma metocurine concentration was determined by high-performance liquid chromatography. Isoflurane increased the potency of metocurine significantly; IC₅₀ (the concentration in the effect compartment at 50% paralysis) was 70 ± 15 ng/mL during isoflurane anaesthesia and 129 ± 42 ng/mL during barbiturate-opiate anaesthesia ( P < 0.03). Volume of distribution (63 ± 18 mL/kg), clearance (1.6 ± 0.4 mL/min±kg) and elimination half-life (99 ± 9 min) during barbiturate-opiate anaesthesia were not significantly different during isoflurane anaesthesia: 64 ± 25 mL/kg, 1.5 ± 0.7 mL/kgmin, 116 ± 16 min respectively. We conclude that, relative to barbiturate-opiate anaesthesia, isoflurane potentiates metocurine in goats.     

Use of guaiacol glycerine ether in clinical anaesthesia in the horse

A total of 103 anaesthetic inductions were performed in horses for a variety of elective procedures. All cases were premedicated with acepromazine maleate (0.02 to 0.05 mg/kg body weight [bwt] intramuscularly [im]). In 50 cases (Group A) anaesthesia was induced by a single intravenous (iv) bolus of thiopentone sodium (11.1 mg/kg bwt or 1 g/90 kg bwt) followed immediately by a bolus of suxamethonium chloride (0.1 mg/kg bwt). In 53 cases (Group B) anaesthesia was induced using iv guaiacol glycerine ether (GGE) (approximately 50 mg/kg bwt) followed by a bolus of thiopentone at half the usual dose rate (5.6 mg/kg bwt or 1 g/180 kg bwt). Induction of anaesthesia was uneventful in both groups although in Group B it was particularly smooth. Following endotracheal intubation anaesthesia was maintained with halothane in oxygen administered via a circle system. The duration of anaesthesia was comparable between the two groups; however, the mean (+/- sd) time to standing in Group B, 35 +/- 22 mins, was significantly shorter than in Group A, 48 +/- 25 mins. The use of the GGE/thiopentone technique is discussed.     

Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog

Ventilatory effects at induction of anaesthesia were studied following intubation in 66 dogs anaesthetised using thiopentone (10 mg/kg) or propofol (4 mg/kg, injected rapidly or 4 mg/kg, injected slowly). Acepromazine and morphine preanaesthetic medication was administered, and anaesthesia was maintained with halothane in nitrous oxide and oxygen. The time from connection of the breathing system to the first breath was measured. Apnoea was defined as cessation of spontaneous respiration for 15 seconds or longer. Respiratory rate and minute volume were measured for the first five minutes of anaesthesia. Propofol was associated with a greater incidence of apnoea than thiopentone (59 per cent and 64 per cent compared with 32 per cent), but this difference was not statistically significant. Time to first breath was significantly longer with propofol than thiopentone and longest with the slower injection of propofol (P<0.05) (median of four seconds for thiopentone, 19.5 seconds for the propofol rapid injection, and 28.8 seconds for the propofol slow injection). In conclusion, the induction agent and speed of injection affect the incidence and duration of post-intubation apnoea.     

THIAMBUTENE AND ACEPROMAZINE AS ANALGESIC AND PREANESTHETIC AGENTS IN HORSES AND SHEEP

Investigations into the analgesic effect of thiambutene and its value as a pre-anaesthetic agent were carried out in the horse and the sheep. Special emphasis was placed on the post-anaesthetic recovery period.
Thiambutene produced analgesia in both species. Toxic effects such as muscle tremor and hyperkinesia occurred with high doses. Prior administration of acepromazine increased the tolerated doses of thiambutene, and satisfactory neuroleptanalgesic states were produced.
Combined use of thiambutene and acepromazine in pre-anaesthetic medication reduced the dose of thiopentone required for anaesthesia in both species and significantly improved post-anaesthetic recovery.
Administration of nalorphine in both species reduced the duration of the recovery period. In the horse, even after prolonged thiopentone anaesthesia, nalorphine produced a shorter, quieter recovery.
It was concluded that pre-anaesthetic medication with thiambutene and acepromazine facilitated thiopentone anaesthesia and greatly reduced the problems of post-anaesthetic recovery in horses.     

EVALUATION OF EXPERIMENTALLY INDUCED CANINE HEPATIC CIRRHOSIS USING DUPLEX DOPPLER ULTRASOUND

Portal blood flow was measured with duplex Doppler ultrasound in ten normal dogs and in ten dogs with hepatic cirrhosis induced by common bile duct ligation 4 weeks previously. Mean portal blood flow velocity in the 10 dogs with experimentally induced hepatic cirrhosis was markedly reduced (9.2 ± 1.70 cm/sec vs. normal 18.1 ± 7.6 cm/sec, p < 0.01). Mean portal blood flow was also significantly decreased compared to normal (17.2 ± 4.9 cc/min/kg versus normal 31.06 ± 9.1 cc/min/kg, p < 0.01) while portal vein diameter remained unchanged. The dogs with induced hepatic cirrhosis developed extensive extrahepatic portosystemic shunting that was confirmed at necropsy. It was concluded that decreased portal velocity and portal flow which resulted from hepatic cirrhosis was detectable noninvasively with Doppler ultrasound.     

Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats

Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C _p= Be ^-βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.     

Effects of plasma expansion on the pituitary-adrenocortical response to halothane anaesthesia in sheep

The study aimed to investigate the stimulus to adrenocortical activity that is induced by halothane anaesthesia. Groups of 7 sheep were anaesthetised with thiopentone and halothane (TH) or acepromazine, thiopentone and halothane (ATH). During 120 min of anaesthesia hypotension was prevented (mean arterial blood pressure kept at pre-anaesthetic level) by infusion of a modified gelatine plasma replacer given to effect (0.34–1.1 litres with TH and 1.1–3.1 litres with ATH). Pulse rate, arterial blood pressure and gases were measured and sequential samples withdrawn for analysis of plasma cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Heart rate increased in the ATH but not the TH group. All sheep were well oxygenated but developed hypercapnia and respiratory acidosis. In both groups, cortisol increased more than 2-fold 20 min after the end of anaesthesia but there were no significant changes in ACTH. AVP was measured in the TH group only and increased 3-fold at the end of anaesthesia. Glucose and lactate remained stable except for lactate in the TH group which decreased during anaesthesia. These data indicate that hypotension is a major component of the stimulus inducing adrenocortical activity during halothane anaesthesia. However, maintenance of normotension did not entirely depress the response; halothane itself or decreased perfusion may also contribute.     

Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub-anesthetic dose together with xylazine to calves prior to castration

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V_c = 132.82 ± 68.23 mL/kg), distribution clearance (CL_D = 15.49 ± 2.56 mL/min/kg), volume of the peripheral compartment (V_T = 257.05 ± 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL_2M = 8.56 ± 7.37 mL/kg/min) and ketamine clearance by other routes (CL_o = 16.41 ± 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.     

Pharmacokinetics of sulphadimidine in normal and febrile dogs

Pharmacokinetic parameters which describe the distribution and elimination of sulphadimidine were determined in normal dogs and dogs in which fever was produced by an intravenous injection of escherichia and staphylococcal species of bacteria. Sulphadimidine was injected as a single intravenous bolus at the dose of 100 mg/kg and the kinetics of the drug were described in terms of the bi-exponential expression: C_p = Ae ^{-α t} + Be ^{-β t} . The distribution half-times of the drug were 1.52 h in the normal and 0.81 h in the febrile dogs. The drug distribution was significantly more rapid ( P < 0.05) in febrile than in normal dogs. Average ± SD values for the half-lives of the drug were 16.2 ± 5.7 h in normal and 16.7 ± 4.7 h in the febrile dogs. The apparent volume of distribution ( V ' _d (area)) was 628 ± 251 ml/kg in the normal dogs, and was not statistically different from 495 ± 144 ml/kg in the febrile dogs. The volume of the central compartment ( V ' _c ) was 445 ± 55 ml/kg in normal dogs and this was significantly higher ( P < 0.01) than the V ' _c of 246 ± 72 ml/kg in the febrile dogs. The body clearance was 22.4 ± 4.8 and 20.2 ± 3.6 ml/hour. kg in the normal and febrile dogs, respectively. The investigation revealed that the dosage regimen of sulphadimidine did not differ significantly between normal and febrile dogs.     

Pharmacokinetics of pentobarbital and thiamylal as combined anesthetics in sheep

This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t 1/2 beta, and ClB for either drug were not affected by the other when given in combination. The t 1/2 alpha was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer-generated curves, associated with the two-compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein-binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra-additive is attributed to a shift of awakening time from the distribution (alpha) phase, when given independently, to the elimination (beta) phase when administered in combination.     

The Stress Responses Involved in General Anaesthesia in Cattle

Anaesthesia was induced in four adult Friesian cows with intravenous thiopentone (10 mg/kg) after either intramuscular saline (2ml), acepromazine (0.05mg/kg) or xylazine pre- medication (0.05 mg/kg). At least 4 weeks was allowed to alapse between each anaesthetic in each cow. The stress involved in induction of and recovery from anaesthesia was assessed by measuring pulse and respiration rates, plasma cortisol and glucose concentrations, total plasma protein concentration and haematocrit at 10–15 minute intervals from 60 min prior to premedication to the time when the animals stood after anaesthesia. Recovery from anaesthesia was associated with an increase in cortisol concentration. This response was significantly attenuated by premedication with xylazine but not acepromazine. Xylazine produced a marked hyperglycaemia in comparison to the other premedicants. Anaesthesia was associated a marked increase in pulse rate and slight increase in haematocrit, but these changes were not markedly affected by the premedication given. Recovery from anaesthesia was deemed to be the most stressful period of short-term general anaesthesia.     

Pharmacokinetics of tobramycin in the camel

A/Hadi, A.A., Wasfi, I.A., Gadir, F.A., Amiri, M.H., Bashir, A.K. Baggot, J.D. Pharmacokinetics of tobramycin in the camel. J. vet. Pharmacol. Therap. 17 . 48–51.
The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m. administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 ± 21 min and the mean residence time was 254 ± 26 min. The apparent volume of distribution (area method) was 245 ± 21 ml/kg. while volume of the central compartment of the two-compartment pharmaco-kinetic model was 110 ± 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 ± 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 ± o.59 g/ml at 20–30 min; the absorption half-life was 3.9 ± 0.9 min. The systemic availability of tobramycin was 90.7 ± 14.4%. The apparent half-life was 201 ±40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 g/ml with peak serum concentration approaching, but not exceeding, 10 g/ml.     

Anesthesia in Sheep With Propofol or With Xylazine-Ketamine Followed by Halothane

Objective- This study evaluates the clinical usefulness and anesthetic effect of propofol, and compares these effects with those of xylazine-ketamine-halothane anesthesia in sheep.
Study Design- Prospective, randomized, clinical trial. Animals or Sample Population- Fourteen healthy adult male sheep.
Methods- Sheep were randomly assigned to two different drug regimens: (1) Bolus injection of propofol (3 mg/kg, intravenously [IV]) followed by continuous intravenous infusion and (2) xylazine (0.11 mg/kg, IV) and ketamine (2.2 mg/kg, IV) for induction followed by halothane anesthesia. Heart rate, respiratory rate, and arterial blood pressures were monitored during anesthesia. Venous blood samples were collected for blood gas analysis. Quality of induction and recovery were also recorded.
Results- The average dose of propofol used to induce and maintain anesthesia was 6.63 ±2.06 mg/kg and 29.3 ±11.7 mg/kg/hr (0.49 ±0.20 mg/kg/min), respectively. The duration of propofol anesthesia was 45.3 ±13.2 minutes and recovery to standing occurred in 14.7 ±5.7 minutes. Sheep receiving xylazine-ketamine-halothane were anesthetized for 35.9 ±4.0 minutes and recovery to standing occurred within 28.5 ±7.5 minutes. Sheep anesthetized with propofol had a significantly higher heart rate, diastolic blood pressure and Pvo₂, and a lower Pvco₂ at 30 minutes and lower BE at 15 and 30 minutes than sheep anesthetized with xylazine-ketamine-halothane.
Conclusions- Propofol anesthesia was characterized by a smooth induction, effective surgical anesthesia and rapid recovery which was comparable to anesthesia with xylazine-ketamine-halothane.
Clinical Relevance- Propofol may be indicated in situations when it is desirable to maintain anesthesia with an intravenous infusion followed by a rapid recovery in healthy sheep.     

Comparative pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous administration to sheep and goats

The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination was studied after intravenous administration of single doses (20 mg/kg per kg body weight) to five sheep and six goats. The objective was to determine whether there are differences between sheep and goats in the disposition of amoxicillin and clavulanic acid. The plasma concentration-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in sheep and goats. The elimination half-lives of amoxicillin were 1.43 ± 0.16 h in sheep and 1.13 ± 0.19 h in goats, and of clavulanic acid were 1.16 ± 0.01 h and 0.85 ± 0.09 h in sheep and goats respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. Body clearances of amoxicillin were 0.09 ± 0.01 L/h kg in sheep and 0.11 ± 0.01 L/h kg in goats, and of clavulanic acid were 0.07 ± 0.01 L/h kg and 0.12 ± 0.01 L/h kg in sheep and goats respectively. The half-lives and body clearances of amoxicillin and clavulanic acid differed significantly between sheep and goats. It was concluded that the disposition of amoxicillin and clavulanic acid administered intravenously as an amoxicillin/clavulanic acid combination to sheep and goats differed between the two ruminant species. Even though the differences in disposition kinetics of both drugs were statistically significant, the same intravenous dosing rate of this antimicrobial combination can generally be used in sheep and goats.     

The cardiovascular and respiratory effects of medetomidine and thiopentone anaesthesia in dogs breathing at an altitude of 1486 m

The purpose of this study was to evaluate the cardio-respiratory effects of the combination of medetomidine and thiopentone followed by reversal with atipamezole as a combination for anaesthesia in 10 healthy German Shepherd dogs breathing spontaneously in a room at an altitude of 1486 m above sea level with an ambient air pressure of 651 mmHg. After the placement of intravenous and intra-arterial catheters, baseline samples were collected. Medetomidine (0.010 mg/kg) was administered intravenously and blood pressure and heart rate were recorded every minute for 5 minutes. Thiopentone was then slowly administered until intubation conditions were ideal. An endotracheal tube was placed and the dogs breathed room air spontaneously. Blood pressure, pulse oximetry, respiratory and heart rate, capnography, blood gas analysis and arterial lactate were performed or recorded every 10 minutes for the duration of the trial. Thiopentone was administered to maintain anaesthesia. After 60 minutes, atipamezole (0.025 mg/kg) was given intramuscularly. Data were recorded for the next 30 minutes. A dose of 8.7 mg/kg of thiopentone was required to anaesthetise the dogs after the administration of 0.010 mg/kg of medetomidine. Heart rate decreased from 96.7 at baseline to 38.5 5 minutes after the administration of medetomidine (P < 0.05). Heart rate then increased with the administration of thiopentone to 103.2 (P < 0.05). Blood pressure increased from 169.4/86.2 mmHg to 253.2/143.0 mmHg 5 minutes after the administration of medetomidine (P < 0.05). Blood pressure then slowly returned towards normal. Heart rate and blood pressure returned to baseline values after the administration of atipamezole. Arterial oxygen tension decreased from baseline levels (84.1 mmHg) to 57.8 mmHg after the administration of medetomidine and thiopentone (P < 0.05). This was accompanied by arterial desaturation from 94.7 to 79.7% (P < 0.05). A decrease in respiratory rate from 71.8 bpm to 12.2 bpm was seen during the same period. Respiratory rates slowly increased over the next hour to 27.0 bpm and a further increases 51.4 bpm after the administration of atipamezole was seen (P < 0.05). This was maintained until the end of the observation period. Arterial oxygen tension slowly returned towards normal over the observation period. No significant changes in blood lactate were seen. No correlation was found between arterial saturation as determined by blood gas analysis and pulse oximetry. Recovery after the administration of atipamezole was rapid (5.9 minutes). In healthy dogs, anaesthesia can be maintained with a combination of medetomidine and thiopentone, significant anaesthetic sparing effects have been noted and recovery from anaesthesia is not unduly delayed. Hypoxaemia may be problematic. Appropriate monitoring should be done and oxygen supplementation and ventilatory support should be available. A poor correlation between SpO2 and SaO2 and ETCO2 and PaCO2 was found.     

Endocrine and metabolic responses in sheep during halothane and pentobarbitone anaesthesia with dobutamine infusion

The study investigated the stimulus to pituitary-adrenocortical activity (PACA) during halothane anaesthesia. Groups of six sheep were anaesthetized with thiopentone/halothane (TH group), acepromazine/thiopentone/halothane (ATH group) or pentobarbitone (P group). Dobutamine was infused in the TH and ATH groups to prevent hypotension (0.3–1.4 μg/kg/min) and in the P group at 0.05 μg/kg/min. Pulse rate, arterial blood gases and pressure (ABP) were measured and sequential blood samples taken for assay of cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Pulse rate increased in all groups. Arterial blood pressure decreased by 13% in TH, by 24% in ATH and remained stable in P. All three groups developed hypercapnia and acidosis but were well oxygenated. Cortisol increased in all groups; with ATH the sevenfold rise occurred earlier than with either TH (sixfold rise) or P (fivefold rise). Adrenocorticotrophic hormone changes were as for cortisol but AVP increases were not consistent. Glucose and lactate were stable, but lactate was lowest with ATH. Dobutamine infusion failed to prevent hypotension during halothane anaesthesia and PACA appeared proportional to the hypotension. Dobutamine may have stimulated ACTH and cortisol release after 120 min. Halothane-induced hypotension may cause adrenocortical activity but a direct effect of halothane cannot be ruled out.