Effects of thiopentone and propofol on lower oesophageal sphincter and barrier pressure in the dog

The effects of thiopentone and propofol on oesophageal pressures were examined in 39 bitches. The dogs were premedicated with either atropine (n = 13), acepromazine maleate (n = 13) or a combination of atropine and acepromazine. Anaesthesia was induced with either thiopentone (15 dogs) or propofol (24 dogs), both given intravenously. Immediately following the induction of anaesthesia, gastric pressure and lower oesophageal sphincter pressure (LOSP) were measured and oesophageal barrier pressure determined. There were no significant differences attributable to the premedication regimens used but both LOSP and barrier pressure were significantly lower in the dogs anaesthetised with propofol compared to the animals given thiopentone (LOSP 12-2 ± 4-2 cm H₂O propofol group versus 26-8 ± 6-5 cm H₂O thiopentone group).     

Effect of yohimbine on xylazine-ketamine anesthesia in cats

Xylazine and ketamine are an anesthetic combination used in feline practice for routine surgical procedures. In a controlled study, we evaluated the effects of yohimbine, an antagonist of xylazine, on the anesthesia induced by this anesthetic combination in cats. Two intramuscular doses of xylazine and ketamine (2.2 mg of xylazine/kg plus 6.6 mg of ketamine/kg and 4.4 mg of xylazine/kg plus 6.6 mg of ketamine/kg) caused approximately 60 and 100 minutes of anesthesia, respectively, in control cats. When yohimbine (0.1 mg/kg) was given intravenously 45 minutes after ketamine administration, the cats regained consciousness within 3 minutes. They were ambulatory 1 to 2 minutes after regaining consciousness. Yohimbine also reversed the bradycardia and respiratory depression elicited by xylazine-ketamine. The results indicated that yohimbine may be useful for controlling the duration of xylazine-ketamine anesthesia in cats.     

Effect of anesthetic induction with propofol,alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation

ObjectiveTo compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats.Study designProspective, masked, randomized clinical trial.AnimalsA total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures.MethodsFollowing baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg^?1) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant.ResultsMean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg).Conclusions and clinical relevancePropofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.     

Effects of thiopentone,propofol and alfaxalone on laryngeal motion during oral laryngoscopy in healthy dogs

Objective

To compare the effects of thiopentone, propofol and alfaxalone on arytenoid cartilage motion and establish the dose rates to achieve a consistent oral laryngoscopy examination.

Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats

Zonca, A., Ravasio, G., Gallo, M., Montesissa, C., Carli, S., Villa, R., Cagnardi, P. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats. J. vet. Pharmacol. Therap.  35 , 580–587. The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as ‘ketofol’, frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV‐visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two‐compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half‐life (t_1/2λ2 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half‐life (t_1/2λ2 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol’s long elimination half‐life and low clearance is negligible when the drug is administered as short‐term and low‐dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism.     

Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats

The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group), ketamine 10 mg/kg intravenously (KetIV group) or propofol 4 mg/kg intravenously (PropIV group). Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms.     

Effects of propofol on the electrocardiogram and systolic blood pressure of healthy cats pre-medicated with acepromazine

OBJECTIVE: To obtain and analyze the electrocardiogram and systolic blood pressure of cats before, during, and after a continuous infusion of propofol. STUDY DESIGN: Prospective, uncontrolled experimental trial. ANIMALS: Twenty healthy adult crossbred male and female cats aged between 3 and 5 years, weighing 2.8-5.0 kg (mean 3.9 kg). METHODS: Cats were pre-medicated with acepromazine 0.1 mg kg(-1) subcutaneously and anesthesia was induced with intravenous (IV) propofol 6 mg kg(-1) and maintained with a continuous infusion of propofol at 0.5 mg kg(-1) minute(-1) for 60 minutes. Electrocardiographic parameters and systolic blood pressure obtained by Doppler ultrasound were recorded before pre-medication (T0), 30 (T30), and 60 (T60) minutes after beginning the continuous infusion, and 30 minutes after its cessation (T90). Repeated measures anova was used to perform statistical analysis. RESULTS: A significant decrease in heart rate was observed at all time points when compared with T0 values. The PR interval increased significantly at T60 and T90. Systolic blood pressures during anesthesia were significantly lower than at T0 and T90. CONCLUSION AND CLINICAL RELEVANCE: The changes seen were not clinically important in normal cats but given the reduction in heart rate and systolic blood pressure, careful consideration should be given before using this technique in patients in which hypotension or a reduction in heart rate would be poorly tolerated.     

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in cats

OBJECTIVE: To compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with propofol (loading dose, 6.6 mg/kg; constant rate infusion [CRI], 0.22 mg/kg/min) and instrumented for blood collection and measurement of blood pressures and cardiac output. Cats were maintained at this CRI for a further 60 minutes, and blood samples and measurements were taken. A noxious stimulus was applied for 5 minutes, and blood samples and measurements were obtained. Propofol concentration was decreased to 0.14 mg/kg/min, and ketamine (loading dose, 2 mg/kg; CRI, 23 microg/kg/min) was administered. After a further 60 minutes, blood samples and measurements were taken. A second 5-minute noxious stimulus was applied, and blood samples and measurements were obtained. RESULTS: Mean arterial pressure, central venous pressure, pulmonary arterial occlusion pressure, stroke index, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, partial pressure of oxygen in mixed venous blood, pH of arterial blood, PaCO2, arterial bicarbonate concentration, and base deficit values collected during propofol were not changed by the addition of ketamine and reduction of propofol. Compared with propofol, ketamine and reduction of propofol significantly increased mean pulmonary arterial pressure and venous admixture and significantly decreased PaO2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by CRI for maintenance of anesthesia induced stable hemodynamics and could prove to be clinically useful in cats.     

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in healthy cats

This study was designed to compare the cardiovascular effects of equipotent maintenance of anesthetic doses (determined in a previous study) of propofol and propofol/ketamine, administered with and without noxious stimulation. Six healthy adult cats were anesthetized with propofol (loading dose 6.6 mg kg^?1, infusion 0.22 mg kg^?1 minute^?1), and instrumented to allow determination of blood gas and acid–base balance and measurement of blood pressures and cardiac output. The propofol infusion was continued for a further 60 minutes after which measurements were taken prior to and during application of a noxious stimulus. The propofol infusion was decreased to 0.14 mg kg^?1 minute^?1, and ketamine (loading dose 2 mg kg^?1, infusion 23 µg kg minute^?1) was administered. After a further 60 minutes, measurements were again taken prior to and during application of a noxious stimulus. The data were analyzed, using several Repeated Measures anova (first, ketamine/propofol and noxious stimulation were each treated as within‐subject factors; secondly, the levels of these two factors were combined into a single within‐subject factor). Mean arterial pressure, CVP, PAOP, SI, CI, SVRI, PVRI, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, PvO₂, pHa, PaCO₂, bicarbonate concentration, and BD values collected during propofol administration were not changed by addition of ketamine and reduction of propofol concentration or by application of a noxious stimulus under propofol alone. Application of a noxious stimulus under propofol alone did, however, significantly increase HR and PaO₂, and these responses were not blunted by the addition of ketamine. Compared with propofol, administration of ketamine and reduction of propofol concentration significantly increased PAP and venous admixture, and significantly decreased PaO₂. Although application of a noxious stimulus to cats under propofol alone did not significantly change CVP, SI, CI, PVRI, oxygen delivery index, and oxygen consumption index, significant differences were found in these variables between propofol and propofol/ketamine. In conclusion, propofol alone provided cardiopulmonary stability; addition of ketamine did not improve hemodynamics but did decrease oxygenation.     

Effects of diazepam, ketamine, and their combination on intraocular pressure in normal dogs

Ketamine has been implicated as causing increases in intraocular pressure. The purpose of this study is to document the effects of ketamine, diazepam, and their combination on intraocular pressure (IOP) in normal, unpremedicated dogs. Random-source dogs were assigned to one of five groups of 10 dogs each: ketamine 5 mg kg^–1 (KET5), ketamine 10 mg kg^–1 (KET10), diazepam 0.5 mg kg^–1 (VAL), ketamine 10 mg kg^–1 with diazepam 0.5 mg kg^–1 (KETVAL), saline 0.1 mL kg^–1 (SAL), all given intravenously. A baseline IOP was measured before injection, immediately after injection, and at 5, 10, 15, and 20 minutes following injection. IOP was increased over baseline immediately after injection in the KET5, KET10, and KETVAL groups; at 5, 10, and 15 minutes in the KET5 group; and at 20 minutes in the KETVAL group. The mean IOP change compared to SAL increased immediately after injection and at 5 minutes in the KET5, KET10, and KETVAL groups; at 10 and 15 minutes in the KET5 group, and at 20 minutes in the KETVAL group. The mean IOP increased up to 5.7, 3.2, and 3.1 mm Hg over mean baseline in the KET5, KET10, and KETVAL groups, respectively. All dogs in the KET5 group and the majority in the KETVAL and KET10 groups had an increase in their IOP over baseline. Ketamine caused a clinically and statistically significant elevation in IOP over baseline and compared to SAL. The concurrent addition of diazepam did not blunt this increase. Ketamine should be avoided in dogs with corneal trauma, glaucoma, or in those undergoing intraocular surgery.     

Effects of atropine, acepromazine, meperidine, and xylazine on gastroesophageal sphincter pressure in the dog

Gastroesophageal sphincter (GES) pressure was 47.9 +/- 1.2 mm of Hg in nontreated dogs. Treatment with atropine, acepromazine, and xylazine reduced GES pressure to 13.2 +/- 2.03, 18.6 +/- 2.14, and 11.7 +/- 1.19 mm of Hg, respectively. Treatment with meperidine resulted in phasic contractions with minimum and maximum pressures of 27.9 +/- 4.55 and 98.9 +/- 9.16 mm of Hg, respectively. Drugs used in anesthetic procedures can reduce GES pressure in dogs.     

Effect of diuretics on ketamine and sulfanilate elimination in cats

Rate constants of elimination were used to evaluate potential effects of diuretic agents on the elimination of ketamine from the blood of cats. Furosemide, mannitol, and aminophylline did not significantly alter the ketamine elimination rate constants, although the diuretics had a tendency to prolong elimination. This tendency of furosemide was further substantiated by observing the effect of furosemide on glomerular filtration. The rate of sulfanilate elimination, used as an indicator of glomerular filtration, was significantly decreased in the cats that were administered furosemide. Possible mechanisms for the influence of furosemide on the renal excretion of ketamine are discussed.     

Comparison of the effects of thiopentone and propofol on the electrocardiogram of dogs

Sixty-four dogs were randomly assigned to receive either thiopentone or propofol and their electrocardiograms were recorded immediately before and shortly after they were anaesthetised. Thiopentone caused a marked increase in QT and JT intervals, a flattening of the T-wave and an increase in precordial QT dispersion. Propofol induced a less marked increase in QT and JT intervals, corrected for heart rate. Both agents induced an increase in heart rate and a decrease in heart rate variability, consistent with reduced vagal tone. Shortly after anaesthesia was induced, thiopentone affected ventricular repolarisation to a far greater extent than propofol, changes which suggest that it may be more likely to induce re-entrant ventricular arrhythmogenesis and could be associated with an increase in sympathetic tone. Propofol may therefore be more suitable than thiopentone for dogs with a susceptibility to ventricular arrhythmias or a long QT interval.     

Effect of variable-dose propofol alone and in combination with two fixed doses of ketamine for total intravenous anesthesia in cats

OBJECTIVE: To determine the minimum infusion rate (MIR50) for propofol alone and in combination with ketamine required to attenuate reflexes commonly used in the assessment of anesthetic depth in cats. ANIMALS: 6 cats. PROCEDURE: Propofol infusion started at 0.05 to 0.1 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine (low-dose ILD] constant rate infusion [CRI] of 23 microg/kg/min or high-dose [HD] CRI of 46 microg/kg/min), and after 15 minutes, responses of different reflexes were tested. Following a response, the propofol dose was increased by 0.05 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine, and after 15 minutes, reflexes were retested. RESULTS: The MIR50 for propofol alone required to attenuate blinking in response to touching the medial canthus or eyelashes; swallowing in response to placement of a finger or laryngoscope in the pharynx; and to toe pinch, tetanus, and tail-clamp stimuli were determined. Addition of LD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, finger, toe pinch, and tetanus stimuli but did not change those for laryngoscope or tail-clamp stimuli. Addition of HD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, toe pinch, tetanus, and tail-clamp stimuli but did not change finger or laryngoscope responses. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol alone or combined with ketamine may be used for total IV anesthesia in healthy cats at the infusion rates determined in this study for attenuation of specific reflex activity.     

Milrinone and theophylline act as lower oesophageal sphincter relaxing agents: a comparative pharmacodynamic study in the rabbit

This study demonstrates that the inotropic agent milrinone and the bronchodilator drug theophylline exert a relaxing effect on the rabbit lower oesophageal sphincter in vitro . The relaxing effect of milrinone and theophylline, which is concentration-dependent, involves a second messenger 3',5'-cyclic adenosine monophosphate pathway and most probably it is accomplished through inhibition of phosphodiesterase (PDE) type III, as according to the obtained results it is not significantly modified either by nicotinic acid, an inhibitor of adenylate cyclase, or by the inhibitor of nitric oxide-synthetase N _ω-nitro- l -arginine methylester and the purinergic antagonist suramin; moreover, it persists under non-adrenergic non-cholinergic conditions and it is both hexamethonium- and tetrodotoxin-insensitive. Both milrinone and theophylline display equal efficacy, comparable to that of the calcium blocker verapamil and the non-selective PDE inhibitor papaverine, but milrinone appears 50 times more potent than theophylline and three times less potent than verapamil, as, according to the pIC₅₀ values the potency rank of order is found to be verapamil (5.56) > milrinone (5.12) > theophylline (3.42). The here obtained pharmacodynamic profiles of the drugs suggest that both milrinone and theophylline may be considered as potent relaxing agents of the lower oesophageal sphincter.     

Comparison of diazepam–ketamine and thiopentone for induction of anaesthesia in healthy dogs

Objective To compare the anaesthetic and cardiopulmonary effects of a diazepam–ketamine combination with thiopentone for induction of anaesthesia in dogs. Animal population Twenty healthy dogs of various breeds weighing between 3.8 and 42.6 kg undergoing major orthopaedic or soft tissue surgery. Materials and methods Pre‐anaesthetic medication in all cases was intramuscular acepromazine and methadone given 30 minutes before induction of anaesthesia. Each animal was then randomly assigned to receive either thiopentone or diazepam and ketamine. Quality of conditions for, and time to tracheal intubation were recorded. Anaesthesia was maintained with halothane in oxygen and nitrous oxide. Heart rate, respiratory rate, systolic blood pressure, end tidal carbon dioxide tensions and oxygen saturation were recorded at 10 minute intervals throughout surgery. The quality of recovery from anaesthesia was assessed. Results The quality of induction in both groups was satisfactory. The total mean time (± SD) to tracheal intubation (162 ± 84 seconds) was significantly longer in dogs receiving diazepam and ketamine compared to dogs receiving thiopentone (62 ± 28 seconds). Heart rate, systolic blood pressure and end tidal carbon dioxide concentration were not significantly different between groups. Respiratory rate was significantly higher in the diazepam–ketamine group between 0 and 30 minutes. The quality of recovery was similar in each group. Conclusions There appear to be fewer differences between the induction agents examined in this study than was previously believed. No pressor, or other cardiovascular stimulating effects were detected in the dogs that received diazepam and ketamine. Clinical relevance The absence of obvious differences between groups suggests that pre‐anaesthetic medication, inhaled anaesthetics and the physiological effects of surgery itself probably had a greater effect on the variables studied than the induction agent used. Further studies are required to determine whether diazepam and ketamine offers significant advantages over other induction agents in the unhealthy dog.