Effects of toxic doses of phenylbutazone in ponies

Toxic doses of phenylbutazone (10 mg/kg of body weight) were administered to 10 ponies once daily for 14 days. Clinical signs of toxicosis similar to those seen in other species included CNS depression, anorexia, oral ulcers, and soft feces. Six ponies died in 7 to 20 days; 1 pony was euthanatized during an acute abdominal crisis; and 3 ponies survived the study. At necropsy, the major lesions were oral and gastrointestinal ulcerations and renal changes.     

Effects of hypoxia on endocrine and metabolic responses to anaesthesia in ponies

Some metabolic and endocrine effects of hypoxaemia were studied during halothane anaesthesia in six ponies. Each was anaesthetised twice; on one occasion a 20-minute period of hypoxaemia (arterial oxygen tension between 4.4 and 5.8 [mean 5.3] kPa) was imposed during 120 minutes of anaesthesia. On the second occasion arterial oxygen tension was maintained above 17 kPa throughout. Routine cardiovascular monitoring was performed and blood samples were taken to measure haematocrit, cortisol, insulin, glucose and lactate. Anaesthesia was associated with hypotension in both groups (mean ABP < 70 mmHg) but pulse rate changed little from control. Hypercapnia (PaCO2 > 7.0 kPa) developed in the normoxic group and acidosis was more severe than in the hypoxic group. Haematocrit changed little but was higher in the hypoxic group after the hypoxic period (0.39[0.06] vs 0.32[0.06] litre litre(-1)). Plasma cortisol increased significantly during anaesthesia in both groups (maximum values: hypoxic group 418[96], normoxic group 492[102] nmol litre(-1)) and there was no significant difference between them. Glucose concentration increased in the hypoxic group and was significantly higher than in the normoxic group during the hypoxic period (8.8[1.5] vs 6.4[1.5] mmol litre(-1)). Insulin decreased in both groups but this was significant only in the normoxic group (from 34[19] to a nadir of 12[9] iu ml(-1)) and the groups were not significantly different. Lacticacidaemia developed in both groups but was more severe in the hypoxic group (maximum values 2.3[0.6] and 1.3[0.5] mmol litre(-1)). It was concluded that 20 minutes of hypoxia during halothane anaesthesia in ponies did not markedly alter the stress response already induced by anaesthesia.     

Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies

The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-time curve were common. Double peaks were also encountered when phenylbutazone was given to ponies deprived of food prior to, and allowed access to hay after, dosing. In this circumstance, mean times to peak concentration were much shorter (3.8 +/- 1.3 h after morning dosing and 5.3 +/- 1.5 h followed afternoon dosing). Absorption was more regular and double peaks were less apparent when food was withheld both before and after dosing. In order to explain these findings, it is tentatively postulated that, whereas some of the administered dose of phenylbutazone may be absorbed quickly, some may become adsorbed on to the feed and subsequently released by fermentative digestion in the large intestine and/or caecum. The consequences of delayed absorption in fed animals for toxicity and clinical efficacy, and for the use of phenylbutazone in equestrian sports, are considered. Delayed absorption in ponies given access to hay was not accompanied by a significant reduction in total absorption. Bioavailability was estimated to be approximately 69% in fed and 78% in unfed ponies. Estimates of bioavailability gave similar values for morning (72%) and afternoon (71%) dosing.     

Effects of a phenylbutazone paste in ponies: model of acute nonimmune inflammation

In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges. There were no significant (P less than 0.05) differences in exudate protein concentration and leukocyte numbers between the treatment groups, but the group given PBZ had significantly reduced exudate concentrations of eicosanoids 6-keto-prostaglandin F 1 alpha (the stable metabolite of prostacyclin) at 4, 8, and 12 hours; thromboxane B2 at 8, 12, and 24 hours; and bicyclic prostaglandin E2 at 8 hours. The maximal depression of eicosanoid synthesis occurred at times of peak exudate concentrations of PBZ (8 and 12 hours). Phenylbutazone was cleared more slowly from exudate than from plasma. Changes in surface skin temperature were measured by infrared thermometry. Lesional temperatures were recorded 1 cm below the base of the incision line, and mean increases were significantly (P less than 0.05) less in PBZ-treated than in placebo-treated ponies between 4 and 24 hours. The importance of the findings for the clinical efficacy of this dosage schedule is considered.     

Interactions between chloramphenicol, acepromazine, phenylbutazone, rifampin and thiamylal in the horse

The potential for interactions between chloramphenicol, phenylbutazone, acepromazine and thiamylal and chloramphenicol, rifampin, and phenylbutazone were evaluated in two groups of experiments. In the first, five horses were given thiamylal intravenously (iv) (6.6 mg/kg) after pretreatment with acepromazine, and the time of recumbency was determined. Administration of chloramphenicol iv (25 mg/kg) 1 h prior to anaesthesia significantly lengthened the recumbency time from 21.8 +/- 4.8 mins to 36.0 +/- 8.3 mins. There was an apparent but not statistically significant decrease in recumbency time when phenylbutazone (4.4 mg/kg) was administered iv daily for 4 days prior to anaesthesia. In the second series of experiments, phenylbutazone (4.4 mg/kg), chloramphenicol (25 mg/kg) and rifampin (10 mg/kg) were administered in various sequences to five different horses. Chloramphenicol pretreatment produced a significant decrease in the elimination rate and rifampin a significant increase in the elimination rate of phenylbutazone. The half-life of elimination of phenylbutazone alone was about 4 h. Following four days pretreatment with rifampin it was approximately 2.7 h, it was approximately 5.6 h and 9.5 h, respectively, when chloramphenicol was administered in one dose 1 h before or two doses 12 h and 1 h before phenylbutazone.     

The stress response to anaesthesia in ponies: barbiturate anaesthesia

Information on the equine stress response to anaesthesia and surgery is sparse but offers a promising approach to elucidating the high anaesthetic risk in this species. Previous work has shown that halothane anaesthesia induces substantial metabolic and endocrine changes. This paper reports the effects of barbiturate anaesthesia. Anaesthesia was induced with thiopentone in six ponies and no further agents were given. They stood within 30 mins. On another occasion, these animals, and three further ponies, were anaesthetised with pentobarbitone and anaesthesia was maintained for 2 h. No surgery was performed on either occasion. Plasma concentrations of glucose, lactate, non esterified fatty acids, cortisol, insulin, catecholamines and adrenocorticotrophic hormone were measured at the same time intervals in both groups before, during and after anaesthesia. There were no significant changes in hormones or metabolites during either period of anaesthesia and normotension was maintained. This was in marked contrast to the substantial stress response and hypotension under halothane anaesthesia in the same ponies. These results suggest that barbiturates may induce less of a stress response than halothane in horses. Recovery after 2 h of pentobarbitone anaesthesia was poor, precluding its clinical use. The need for a non-cumulative intravenous agent or a non-hypotensive volatile agent for use in equine anaesthesia is discussed.     

Doxapram infusion during halothane anaesthesia in ponies

Doxapram, 0.05 mg/kg bodyweight/min, was infused during the second hour of 2 h halothane anaesthesia in six ponies. Two of the ponies were anaesthetised on a second occasion as controls and given 5 per cent dextrose in place of the doxapram. Respiratory depression typical of halothane anaesthesia in ponies developed in the first hour of anaesthesia and continued during the second hour in the control animals. During doxapram infusion arterial carbon dioxide tension decreased and pH increased. Arterial blood pressure increased but there was no change in pulse rate, the electrocardiogram or arterial oxygen tension. Anaesthesia lightened during doxapram infusion necessitating an increase in the vapouriser setting in order to prevent arousal. Recovery from anaesthesia appeared unaffected by the doxapram infusion.     

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study ( n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg ( n = 5) or 4.4 mg/kg ( n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases ( P <0.05) in total body clearance ( CL _B; 29.2 ± 3.9 vs. 43.8 ± 8.1 mL/ h-kg) and the volume of distribution, calculated by area ( V _d(area); 0.18 ± 0.05 vs. 0.25 ± 0.03 L/kg) or at steady-state ( V _d(SS); 0.17±0.04 vs. 0.25 ± 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly ( P <0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.     

The disposition and local effects of intra-articular morphine in normal ponies

Morphine (15 mg in 5 ml saline) was injected into the left, and 5 ml saline into the right, tarsocrural joint of 8 ponies. Venous blood samples were collected before and at 0.5, 1, 2, 6 and 24 h after the intra-articular morphine injection and analysed for morphine and its metabolites. Synovial fluid was sampled from both tarsocrural joints before and 24 h after injection. Synovial white blood cell and red blood cell counts, protein and hyaluronate concentrations were measured in all the samples; and the synovial fluid morphine concentration from the left tarsocrural joint was measured 24 h after the injection. The peak mean plasma morphine concentration (7.1 μg/l) was detected in samples taken 0.5 h after the intra-articular morphine injection, but neither morphine nor its metabolites were found in plasma 6 h or more post injection. Morphine was detected in the synovial fluid of each pony 24 h after the injection. The plasma morphine or morphine-6-glucuronide concentrations were lower than those likely to have any systemic effect. The synovial fluid white blood cell count and protein concentration were increased and hyaluronate concentration decreased in samples taken 24 h after the intra-articular morphine injection, compared to the pre-injection samples. No differences were found between morphine and saline injected joints. It was concluded that morphine did not irritate the joint more than saline.     

The effect of guaiphenesin on romifidine/ketamine anaesthesia in ponies

The purpose of this study was to investigate the effect of a single dose (50 mg/kg) of guaiphenesin on recumbency time, surgical conditions and the ‘quality’ of anaesthesia in ponies anaesthetised for castration. Sixteen ponies were sedated with romifidine 100 μg/kg and anaesthetised with ketamine (2.2 mg/kg). Ponies allocated to Group A received no treatment and those in Group B were given 50 mg/kg of a 15% guaiphenesin solution. Guaiphenesin was given as a rapid iv injection immediately after induction of anaesthesia. All ponies were subsequently castrated. The mean (± se) time of recumbency in Group A was 20.9 ± 1.37 min and in Group B 27.2 ± 2.1 min to (P<0.05). Subjective assessment scores for the quality of surgical conditions and anaesthesia itself were significantly greater (indicating better conditions) in ponies receiving guaiphenesin, although there was no difference between groups in the quality of recovery.     

Pharmacokinetics of phenylbutazone in two age groups of ponies: a preliminary study

A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.     

Effects of glucose infusion on the endocrine, metabolic and cardiorespiratory responses to halothane anaesthesia of ponies.

Glucose was infused intravenously into six ponies during halothane anaesthesia, to evaluate its effect on their endocrine response to anaesthesia. The ponies were premedicated with acepromazine, and anaesthesia was induced with thiopentone and maintained with halothane in oxygen for two hours. Glucose was infused to maintain the plasma glucose concentration above 20 mmol/litre. Anaesthesia was associated with hypothermia, a decrease in haematocrit, hypotension, hyperoxaemia, respiratory acidosis and an increase in the plasma concentrations of lactate and arginine vasopressin. The concentration of beta-endorphin in plasma increased transiently after 20 minutes but there were no changes in concentrations of adrenocorticotrophic hormone, dynorphin, cortisol or catecholamines. These data suggest that the glucose infusion attenuated the normal adrenal response of ponies to halothane anaesthesia.     

The effect of phenylbutazone on the plasma disposition of penicillin G in the horse

A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.     

Adrenocortical and metabolic responses to dobutamine infusion during halothane anaesthesia in ponies

The study investigated whether hypotension in halothane-anaesthetised ponies is the stimulus inducing an endocrine stress response by assessing the effect of maintenance of normotension with a dobutamine infusion. Groups of six ponies were studied. After premedication with acepromazine (0.04 mg/kg) anaesthesia was induced with thiopentone (10 mg/kg) and maintained for 120 min with halothane (group AN). Dobutamine was infused to effect (1.1–4.4 μg/kg/min) to maintain arterial pressure at pre anaesthetic levels. The conscious group (CON) were prepared as for AN and then received only dobutamine infusion 1.0 μg/kg/min for 120 min. Arterial blood pressure, pH, oxygen and carbon dioxide tension, pulse rate, haematocrit, and plasma cortisol, glucose and lactate concentrations were measured before, at 20 min intervals during anaesthesia, and 20 and 120 min after anaesthesia ceased. Blood pressure remained close to control in both groups. The AN group became hypercapnic and acidotic, pulse rate and haematocrit increased, cortisol increased more than twofold and plasma glucose and lactate did not change. All values remained at control in the CON group except for small increases in haematocrit and decreases in pulse rate. Maintenance of normotension during halothane anaesthesia did not blunt the adrenocortical response to anaesthesia nor did the same dose of dobutamine alone increase plasma cortisol. Hypotension appears not to be the sole stimulus to equine adrenocortical activity during halothane anaesthesia.     

Effects of naloxone on endotoxin-induced changes in ponies

The value of naloxone (1 mg/kg of body weight/hr for 4 hrs), a beta-endorphin antagonist, was assessed in the management of endotoxin-induced shock in ponies. Three groups of 5 ponies each were used: controls, ponies given Escherichia coli endotoxin put untreated, and ponies given endotoxin and then treated with naloxone. Endotoxin-induced changes in hemodynamics, blood chemical values, regional blood flow, plasma enzymes, and energy supplies were measured at selected times during the first 6 hours after endotoxin was given. There was no evidence that beta-endorphins released during shock were responsible for the hemodynamic changes, blood flow changes, plasma enzyme changes, or energy deficits, because naloxone, at this dosage level, did not prevent these endotoxin-induced changes.     

In vitro anion transport alterations and apoptosis induced by phenylbutazone in the right dorsal colon of ponies

OBJECTIVES: To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo. ANIMALS: 8 adult ponies. PROCEDURE: Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO3- were exposed to PBZ, bumetanide, or indomethacin. Bidirectional Cl- fluxes were determined. After a baseline flux period, prostaglandin E2 (PGE2) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed. RESULTS: Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE2. After PGE2 was added, Cl- secretion increased significantly in tissues in HCO3- -free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE2. Bumetanide did not affect baseline short circuit current and Cl- fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin. CONCLUSIONS AND CLINICAL RELEVANCE: Prostaglandin-induced Cl- secretion appeared to involve a transporter that might also secrete HCO3-. Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis; PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl- and HCO3- secretion.     

Effects of phenylbutazone on bone activity and formation in horses

OBJECTIVE: To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses. ANIMALS: 12 healthy 1- to 2-year-old horses. PROCEDURES: Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ. RESULTS: MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses.     

Alfaxalone in cyclodextrin for induction and maintenance of anaesthesia in ponies undergoing field castration

Objective  To evaluate the induction and maintenance of anaesthesia using alfaxalone following pre-anaesthetic medication with romifidine and butorphanol in ponies undergoing castration in the field.
Study design  Prospective clinical study.
Animals  Seventeen male ponies weighing 169 ± 29 kg.
Methods  The ponies were sedated with romifidine and butorphanol intravenously (IV). Induction time was recorded following administration of alfaxalone 1 mg kg⁻¹ and diazepam 0.02 mg kg⁻¹ IV. If movement during surgery occurred, alfaxalone 0.2 mg kg⁻¹ was administered IV. The quality of anaesthetic induction, and recovery were scored on a subjective scale of 1 (good) to 5 (poor). The number of attempts to attain sternal recumbency and standing, quality of recovery and times from induction to end of surgery, first head lift, sternal recumbency and standing were recorded.
Results  Induction quality was good [median score (range) 1 (1–3)] with a mean ± SD time of 29 ± 6 seconds taken to achieve lateral recumbency. Ten ponies required incremental doses of alfaxalone during surgery. Mean times to the end of surgery, first head lift, sternal recumbency and standing were 26 ± 9 minutes, 31 ± 9 minutes, 33 ± 9 minutes and 34 ± 9 minutes respectively. The number of attempts to attain sternal recumbency was 1(1–1) and to attain standing was 1(1–2). Quality of recovery was good, with a recovery score of 1(1–2).
Conclusions and clinical relevance  Alfaxalone provided smooth induction and recovery characteristics and was considered suitable for maintenance of anaesthesia for castration in ponies.     

Effects of aflatoxins in young ponies

Sixteen clinically normal, healthy ponies were randomly assigned to 4 groups and given aflatoxin B1 in doses of 0.045, 0.030, 0.015, and 0 (control) mg/kg of body weight per day for 21 days (or total doses of 0.945, 0.630, 0.315, and 0 mg/kg). The animals were allowed to recover for 3 months and then were reassigned to 4 treatment groups such that each group during the 2nd trial included a pony from each of the groups of the 1st trial. The animals in the new groups were intubated and were given aflatoxin in doses of 0.4, 0.2, 0.1, and 0 (control) mg/kg/day for 5 days ( or total doses of 2.0, 1.0, 0.5, and 0 mg/kg). Venous blood samples were drawn every other day to monitor for toxicosis; examinations were made for RBC and WBC counts, hemoglobin concentration, PCV, serum urea nitrogen, prothrombin time, and serum concentrations of aspartate aminotransferase, iditol dehydrogenase, alkaline phosphatase, albumin, gamma-glutamyl transferase, and arginase. There were no significant differences between treatment groups and controls (given no aflatoxin) in the toxicologic values examined for during the 1st trial. During the 2nd experiment, 2 of the ponies in the large-dose treatment gorup (2.0 mg/kg) demonstrated increased serum enzyme activities. These animals had been in the large-dose (0.945 mg/kg) and median-dose (0.63 mg/kg) groups during the 1st trial. Arginase, iditol dehydrogenase, and gamma-glutamyl transpeptidase activities became increased on the 4th day of treatment and continued to increase until the 6th day of the experiment (1 day after treatment was terminated). These enzymes approached control group values at 10 days after cessation of treatment. These increases were indicative of hepatocellular toxicity. It was concluded that the possibility of equine aflatoxicosis exists although ponies given high quality rations appear to be less susceptible than some other species. Prior exposure to aflatoxins may predispose to clinical toxicity on subsequent exposure, despite lack of expression of clinical signs.     

Endocrine and metabolic responses to plasma volume expansion during halothane anaesthesia in ponies

The study was designed to contribute to identification of the stimulus to adrenocortical activity during halothane anaesthesia in equidae . Two groups of six ponies were premedicated with acepromazine before induction of anaesthesia with thiopentone and maintenance for 120 min with halothane in oxygen. In group H Haemaccel® modified gelatine plasma replacer was infused (48 ± 13 mL/kg) to maintain mean arterial blood pressure (MABP) close to preanaesthetic values. In group DH, blood pressure was maintained close to preanaesthetic levels with a lower dose of Haemaccel® (10 mL/kg) combined with an infusion of dobutamine. Measurements were made before anaesthesia, at 20 min intervals during anaesthesia and 20 and 120 min after anaesthesia. MABP and blood gases, pulse and respiratory rates were measured, and blood was withdrawn for assay of cortisol, adrenocorticotrophic hormone (ACTH), glucose and lactate. Ponies in both groups became hyperoxic, hypercapnic and developed a respiratory acidosis; pulse rate increased in both groups but this was more marked in group H. Haematocrit decreased by 50% in H and by 20% in DH. Cortisol and ACTH did not change significantly during anaesthesia in either group and the area under the time curve ( AUC _(0–140)) was lower in the DH group. Plasma glucose and lactate remained stable. After the H treatment all ponies had a watery nasal discharge and one pony died from endotoxaemia. This investigation demonstrated that the adrenocortical response to halothane anaesthesia in ponies can be ameliorated by manipulation of ABP using plasma expansion with or without inotrope infusion; however, low dose Haemaccel® with dobutamine was safer and more practical. It is suggested that, although hypotension is not the sole stimulus to adrenocortical activity during halothane anaesthesia, it may contribute, probably through an effect on tissue perfusion.