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Biomedical subjects

K W Clarke

Publications and source records attributed to K W Clarke.

At least 19 recordsLinked to original sources
PubMed2006

The effect of hyoscine on dobutamine requirement in spontaneously breathing horses anaesthetized with halothane.

OBJECTIVE: To determine whether hyoscine has a sparing effect on the volume of dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses anaesthetized with halothane. STUDY DESIGN: Prospective, randomized, controlled clinical trial. ANIMALS: Twenty adult horses weighing 507 +/- 97 kg (mean +/- SD), aged 10 +/- 5 years. MATERIALS AND METHODS: Pre-anaesthetic medication in all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothane in oxygen. Horses breathed spontaneously. Flunixin (1.1 mg kg(-1) IV) was given to provide analgesia. Heart rate, ECG, invasive arterial pressure, respiratory rate, percentage end-tidal carbon dioxide, percentage end-tidal halothane and partial pressure of oxygen and carbon dioxide in arterial blood and blood pH were monitored. Dobutamine was infused by an infusion pump to maintain MAP at 70 mmHg. Horses were randomly assigned to receive saline or hyoscine (0.1 mg kg(-1)) IV 30 minutes after induction. The heart rate, MAP and volume of dobutamine infused over 30-minute periods were measured and analysed statistically using a one-way anova. RESULTS: After administration of hyoscine, heart rate increased for 10 minutes (p < 0.01) and MAP for 5 minutes (p < 0.01). There was no difference in the volume of dobutamine infused over 30 minutes between horses given hyoscine or saline, although there was a wide individual variation in dobutamine requirements. No side effects of hyoscine were seen. CONCLUSIONS: The increase in heart rate and blood pressure that occurs after 0.1 mg kg(-1) hyoscine is given IV in anaesthetized horses, is of short duration and does not significantly alter the amount of dobutamine required to maintain arterial pressure over the next 30 minutes. Clinical relevance The short duration of action of 0.1 mg kg(-1) hyoscine IV may limit its usefulness for correction of hypotension in horses anaesthetized with halothane. Further work is necessary to investigate the effects of higher or repeated doses or constant rate infusions of hyoscine.

Adjuvants, Anesthesia↗
PubMed2005

Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies.

REASONS FOR PERFORMING STUDY: Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. OBJECTIVES: To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. METHODS: Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 microg/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). RESULTS: Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t 1/2 (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. CONCLUSIONS: DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-2 adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. POTENTIAL RELEVANCE: DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.

Aging↗
PubMed2003

Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: infusion rates and cardiopulmonary side effects.

REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.

Anesthetics, Dissociative↗
PubMed2001

Minimal alveolar concentration of desflurane in combination with an infusion of medetomidine for the anaesthesia of ponies.

The minimum alveolar concentration of desflurane when combined with a continuous infusion of medetomidine at 3.5 microg/kg/hour was measured in seven ponies. Anaesthesia was induced with medetomidine (7 microg/kg intravenously) followed by ketamine (2 mg/kg intravenously) and maintained with desflurane in oxygen. The infusion of medetomidine was started 20 minutes after the induction of anaesthesia. The electrical test stimulus was applied at the coronary band (50 V, 10 ms bursts at 5 Hz for one minute), and heart rates and rhythms, arterial blood pressures, and arterial blood gas tensions were measured at intervals, just before the application of the stimulus. The mean (sd) minimum alveolar concentration of desflurane was 5.3 (1.04) per cent (range 3.2 to 6.4 per cent), 28 per cent less than the previously published value for desflurane alone after the induction of anaesthesia with xylazine and ketamine. The cardiopulmonary parameters remained stable throughout the period of anaesthesia. The mean (sd) time taken by the ponies to stand after the administration of desflurane ceased was 16.5 (6.17) (range 5.8 to 26) minutes, and the quality of recovery was good or excellent. However, one pony died shortly after standing; a postmortem examination revealed that it had chronic left atrial dilatation.

Administration, Inhalation↗
PubMed2001

Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies.

OBJECTIVE: To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. ANIMALS: 10 ponies. PROCEDURE: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during anesthesia. Five ponies received atipamezole (60 microg/kg) during recovery. RESULTS: During anesthesia, mean cardiac index and heart rate increased significantly until 150 minutes, then decreased until cessation of anesthesia. Mean arterial pressure and systemic vascular resistance index increased significantly between 150 minutes and 4 hours. In 4 ponies, PaO2 decreased to < 60 mm Hg. Mean blood propofol concentrations from 20 minutes after induction onwards ranged from 2.3 to 3.5 microg/ml. Recoveries were without complications and were complete within 28 minutes with atipamezole administration and 39 minutes without atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: During total IV anesthesia of long duration with medetomidine-propofol, cardiovascular function is comparable to or better than under inhalation anesthesia. This technique may prove suitable in equids in which prompt recovery is essential; however, in some animals severe hypoxia may develop and oxygen supplementation may be necessary.

Adrenergic alpha-Antagonists↗
PubMed2001

Infusion of a combination of propofol and medetomidine for long-term anesthesia in ponies.

OBJECTIVE: To determine the minimal infusion rate of propofol in combination with medetomidine for long-term anesthesia in ponies and the effects of atipamezole on recovery. ANIMALS: 12 ponies. PROCEDURE: Ponies were sedated with medetomidine (7 microg/kg of body weight, IV). Ten minutes later, anesthesia was induced with propofol (2 mg/kg, IV). Anesthesia was maintained for 4 hours, using an infusion of medetomidine (3.5 microg/kg per hour, IV) and propofol at a rate sufficient to prevent ponies from moving after electrical stimulation. Arterial blood pressures and blood gas analysis, heart rates, and respiratory rates were monitored. For recovery, 6 ponies were given atipamezole (60 microg/kg, IV). Induction and recovery were scored. RESULTS: Minimal propofol infusion rates ranged from 0.06 to 0.1 mg/kg per min. Mean arterial blood pressure was stable (range, 74 to 86 mm Hg), and heart rate (34 to 51 beats/min) had minimal variations. Variable breathing patterns were observed. Mean PaO2 (range, 116 to 146 mm Hg) and mean PaCO2 (range, 48 to 51 mm Hg) did not change significantly with time, but hypoxemia was evident in some ponies (minimal PaO2, 47 mm Hg). Recovery was fast and uneventful with and without atipamezole (completed in 20.2 and 20.9 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of a combination of medetomidine and propofol was suitable for prolonged anesthesia in ponies. Recovery was rapid and uneventful. A combination of propofol and medetomidine may prove suitable for long-term anesthesia in horses. Monitoring of blood gases is essential because of potential hypoxemia.

Adrenergic alpha-Antagonists↗
PubMed2000

Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.

The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.

Anesthetics, Intravenous↗
PubMed1999

Desflurane and sevoflurane. New volatile anesthetic agents.

Desflurane and sevoflurane, recently licensed for use in humans, have kinetics that result in rapid induction and easy maintenance of a stable level of anesthesia. Recovery is also rapid. Cardiopulmonary effects are similar to those of isoflurane. In humans, desflurane can cause airway irritation and sympathetic stimulation, but these side effects have not caused problems in animal trials. Metabolites of sevoflurane and breakdown products from its reaction with carbon dioxide absorbents theoretically could result in hepatic and renal damage, but such toxicity has not occurred despite extensive medical use. Clinical trials in animals are now in progress.

Anesthesia, General↗
PubMed1999

Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.

The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedation reaching steady state plasma medetomidine levels of 1-1.5 ng ml(-1)within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg(-1)) i.v. The pharmacokinetics of medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.

Animals↗
PubMed1998

Effects on the intramuscular blood flow and cardiopulmonary function of anaesthetised ponies of changing from halothane to isoflurane maintenance and vice versa.

The effects on intramuscular blood flow and cardiopulmonary parameters of changing from anaesthesia with halothane to isoflurane and vice versa were investigated in six ponies (small horses). Anaesthesia was induced with xylazine, ketamine and diazepam, maintained for one hour with halothane at an end tidal concentration of 1 per cent and then with isoflurane at 1.5 per cent for a further hour (halo/iso). On another occasion the order in which the volatile agents were administered was reversed (iso/halo). After one hour of anaesthesia the mean (sd) arterial blood pressure (MAP) and cardiac output (CO) of the ponies on the two occasions did not differ significantly (iso/halo, MAP 43 [5] mmHg, CO 10.9 [2.4] litre/min; halo/iso, MAP 53 [8] mmHg, CO 8.9 [2.3] litre/min). On changing the anaesthetic, MAP rose similarly in both groups. In the halo/iso group CO remained stable (8.64 [1.4] litre/min after the hour of isoflurane), but in the iso/halo group, CO decreased significantly on the administration of halothane (6.16 [1.3] litre/min after the second hour). When halothane replaced isoflurane, the intramuscular blood flow in both the upper and lower triceps brachii decreased significantly by 23 to 35 per cent, but when isoflurane replaced halothane the changes were not significant. It is concluded that CO and intramuscular blood flow both deteriorated when isoflurane was replaced by halothane. When isoflurane replaced halothane, cardiopulmonary function did not deteriorate further, but any improvement was not statistically significant.

Anesthetics, Inhalation↗
PubMed1998

Single chamber atrial pacing: an underused and cost-effective pacing modality in sinus node disease.

OBJECTIVE: To determine the safety and cost effectiveness of single chamber atrial pacing in patients with sinus node disease. DESIGN: Retrospective follow up study. SETTING: Tertiary referral centre. PATIENTS: 81 patients with single chamber atrial pacemakers implanted between 1992 and 1996. MAIN OUTCOME MEASURES: The development of high grade atrioventricular block resulting in a further pacemaker procedure. The cost savings of changing our current pacing practice to conform with British Pacing and Electrophysiology Group guidelines. RESULTS: During the follow up period, four patients (5.8%) required a further procedure to upgrade their atrial pacemaker to a dual chamber system owing to the development of high grade atrioventricular block. In 1995 and 1996, 343 pacemakers were implanted in patients with sinus node disease; 19 (5.5%) received single chamber atrial pacemakers and 271 (79%) dual chamber pacemakers. If the current pacing practice was changed so that all patients received single chamber atrial pacemakers, with revision for symptomatic atrioventricular block, savings in excess of 206,000 Pounds would have been made in the two year period. CONCLUSIONS: Atrial pacing in patients with sinus node disease is underused. The need for patients to undergo further procedures owing to the development of atrioventricular block is small and significant cost savings could be made by changing pacemaker practice.

Adult↗
PubMed1998

Effects of dopamine, dobutamine, dopexamine, phenylephrine, and saline solution on intramuscular blood flow and other cardiopulmonary variables in halothane-anesthetized ponies.

OBJECTIVE: To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia. ANIMALS: 8 ponies. PROCEDURE: Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppler flowmetry) in nondependent and dependent triceps brachii muscles and cardiopulmonary variables were measured. RESULTS: Phenylephrine at all dosages failed to improve IMBF or cardiac index (CI), but increased mean arterial pressure (MAP) and systemic vascular resistance (SVR); 2 ponies had forelimb lameness on recovery. Dopamine (10 microg/kg/min) increased CI, MAP, and IMBF in the dependent muscle. A higher dose (20 microg/kg/min) caused cardiac arrhythmias and muscular tremor. Dobutamine increased Cl, MAP, and IMBF of both forelimbs, effects being significant for 2.5 microg/kg/min, with further improvement as the dosage increased. In 2 ponies, 10 microg of dobutamine/kg/min caused cardiac arrhythmias. Dopexamine (1 and 5 microg/kg/min) increased CI, MAP, and IMBF in the nondependent muscle, and 10 microg/kg/min caused muscular tremor, sweating, and arrhythmias. SVR was reduced after infusion of dopamine, dobutamine, or dopexamine. CONCLUSION: During anesthesia of equids, an increase in Cl and MAP is necessary to improve IMBF in the dependent forelimb. CLINICAL RELEVANCE: Of the agents investigated, dobutamine proved the most consistent in improving IMBF.

Anesthetics, Inhalation↗
PubMed1996

Cardiopulmonary effects of desflurane in ponies, after induction of anaesthesia with xylazine and ketamine.

Cardiopulmonary parameters were measured in 12 ponies (small horses) before anaesthesia and, following induction with xylazine and ketamine, during maintenance of anaesthesia with desflurane. In six of the ponies (group A) anaesthesia was maintained for three hours with desflurane at an end-tidal concentration of 7.4 per cent. In the other six ponies (group B), anaesthesia was maintained in the same way for one hour and then the effects of end-tidal desflurane concentrations of 7.4 per cent and 9.6 per cent with and without artificial ventilation were investigated. In group A ponies the arterial blood pressure and the systemic vascular resistance index (SVRI) decreased significantly during the first 45 minutes of anaesthesia but recovered with time. The cardiac index and heart rates were unchanged throughout the measurement period but arterial carbon dioxide tensions increased significantly. In group B ponies, with either mode of ventilation, increasing desflurane concentration resulted in decreases in arterial blood pressure, cardiac index and mixed venous oxygen tension, although the changes were not always statistically significant. There were marked individual differences in the cardiovascular responses to the high desflurane concentrations, the minimum mean arterial blood pressure ranging from 35 to 62 mm Hg, and the cardiac index from 23 to 50 ml/kg/min. The study concludes that during maintenance of anaesthesia with end tidal concentrations of desflurane of 7.4 per cent, cardiac index is well maintained and the initial fall in arterial blood pressures results from a fall in SVRI. However, increasing the concentration of desflurane causes a fall in blood pressure due to cardiac depression.

Anesthesia, Intravenous↗
PubMed1996

Cardiopulmonary effects of combinations of medetomidine hydrochloride and atropine sulphate in dogs.

Medetomidine and xylazine are alpha 2 adrenoceptor agonists which are used as sedatives and premedicants in small animals. However, bradycardia is a side effect and the use of atropine sulphate has been recommended to counteract it. This study investigated the effects of combining medetomidine (40 micrograms/kg) and atropine (30 micrograms/kg) on the cardiopulmonary function of six dogs. Medetomidine administered alone caused severe bradycardia, but hypertension was mild and transient. Medetomidine and atropine administered together caused an initial bradycardia, but within 15 minutes there was tachycardia accompanied by a mean arterial blood pressure of 210 mm Hg. When atropine was administered 30 minutes before medetomidine, tachycardia and hypertension were observed within five minutes of the medetomidine injection. Thus, although atropine will counteract medetomidine-induced bradycardia, its use results in prolonged and severe hypertension, in association with the tachycardia. Although atropine may be life-saving when bradycardia is profound, its indiscriminate use in combination with alpha 2 adrenoceptor agonists may be disadvantageous.

Adrenergic alpha-Agonists↗
PubMed1996

Alpha 2 adrenoceptor agonists in the horse--a review.

In recent years the usefulness of the alpha 2 adrenoceptor agonist drugs has been recognized in equine practice. Several agents have become available and are now licensed for use in a number of countries. The principle actions of all alpha 2 adrenoceptor agonists are similar, in that they produce a reduction in heart rate and alteration of heart rhythm, an initial hypertension followed by a prolonged hypotension, a decrease in the cardiac output and respiratory depression. For clinical purposes, these agents produce sedation and analgesia, they are useful for premedication and markedly potentiate the effects of other sedative/analgesic agents. Differences in receptor specificity between the alpha 2 adrenoceptor agonists results in the distinguishing characteristics of the individual agents, particularly with respect to their duration of action, sedative effect and analgesic properties; their cardiopulmonary effects are however similar, when equipotent sedative doses are administered. When used in combination with other agents, the alpha 2 adrenoceptor agonists all appear to act in a similar manner, with the greatest difference being related to their duration of action.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Cardiopulmonary effects of medetomidine in sheep and in ponies.

Medetomidine was administered intravenously to six sheep at 5, 10 and 20 micrograms kg-1 and to one horse and four ponies at 5 and 10 micrograms kg-1. In both species medetomidine resulted in significant decreases in heart rate and cardiac output and, initially, in an increase in arterial blood pressure. In the ponies this increase in blood pressure was followed by a significant and prolonged decrease, but in the sheep the secondary decrease in blood pressure was not statistically significant. In the sheep, the three doses of medetomidine resulted in profound and significant decreases in arterial oxygen tensions, which were significantly dose related, but in the ponies the arterial blood oxygen tensions were not significantly decreased. In both species medetomidine caused a small but significant increase in arterial blood carbon dioxide tensions.

Animals↗