Comparison of the cardiopulmonary effects of anesthesia maintained by continuous infusion of ketamine and propofol with anesthesia maintained by inhalation of sevoflurane in goats undergoing magnetic resonance imaging

OBJECTIVE: To compare the cardiopulmonary effects of anesthesia maintained by continuous infusion of ketamine and propofol with anesthesia maintained by inhalation of sevoflurane in goats undergoing magnetic resonance imaging. ANIMALS: 8 Saanen goats. PROCEDURES: Goats were anesthetized twice (1-month interval) following sedation with midazolam (0.4 mg/kg, IV). Anesthesia was induced via IV administration of ketamine (3 mg/kg) and propofol (1 mg/kg) and maintained with an IV infusion of ketamine (0.03 mg/kg/min) and propofol (0.3 mg/kg/min) and 100% inspired oxygen (K-P treatment) or induced via IV administration of propofol (4 mg/kg) and maintained via inhalation of sevoflurane in oxygen (end-expired concentration, 2.3%; 1X minimum alveolar concentration; SEVO treatment). Cardiopulmonary and blood gas variables were assessed at intervals after induction of anesthesia. RESULTS: Mean +/- SD end-expired sevoflurane was 2.24 +/- 0.2%; ketamine and propofol were infused at rates of 0.03 +/- 0.002 mg/kg/min and 0.29 +/- 0.02 mg/kg/min, respectively. Overall, administration of ketamine and propofol for total IV anesthesia was associated with a degree of immobility and effects on cardiopulmonary parameters that were comparable to those associated with anesthesia maintained by inhalation of sevoflurane. Compared with the K-P treatment group, mean and diastolic blood pressure values in the SEVO treatment group were significantly lower at most or all time points after induction of anesthesia. After both treatments, recovery from anesthesia was good or excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ketamine-propofol total IV anesthesia in goats breathing 100% oxygen is practical and safe for performance of magnetic resonance imaging procedures.     

Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery

OBJECTIVE: To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. ANIMALS: 100 client-owned horses. PROCEDURE: After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. RESULTS: Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.     

Infusion of guaifenesin,ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses

OBJECTIVE: To evaluate effects of infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. DESIGN: Randomized clinical trial. ANIMALS: 40 horses. PROCEDURE: Horses were premedicated with xylazine and anesthetized with diazepam and ketamine. Anesthesia was maintained by infusion of guaifenesin, ketamine, and medetomidine and inhalation of sevoflurane (20 horses) or by inhalation of sevoflurane (20 horses). A surgical plane of anesthesia was maintained by controlling the inhaled concentration of sevoflurane. Sodium pentothal was administered as necessary to prevent movement in response to surgical stimulation. Hypotension was treated with dobutamine; hypoxemia and hypercarbia were treated with intermittent positive-pressure ventilation. The quality of anesthetic induction, maintenance, and recovery and the quality of the transition to inhalation anesthesia were scored. RESULTS: The delivered concentration of sevoflurane (ie, the vaporizer dial setting) was significantly lower and the quality of transition to inhalation anesthesia and of anesthetic maintenance were significantly better in horses that received the guaifenesin-ketamine-medetomidine infusion than in horses that did not. Five horses, all of which received sevoflurane alone, required administration of pentothal. Recovery time and quality of recovery were not significantly different between groups, but horses that received the guaifenesin-ketamine-medetomidine infusion required fewer attempts to stand. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in horses, the combination of a guaifenesin-ketamine-medetomidine infusion and inhalation of sevoflurane resulted in better transition and maintenance phases while improving cardiovascular function and reducing the number of attempts needed to stand after the completion of anesthesia, compared with inhalation of sevoflurane.     

Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies

Eight ponies were anesthetized with a solution containing 50 mg of guaifenesin, 1 mg of ketamine, and 0.5 mg of xylazine X ml-1 of 5% dextrose in water. Anesthesia was induced by IV injection (1.1 ml X kg-1), followed by continuous IV infusion at 2.75 ml X kg-1 X hr-1. Heart rate, rate-pressure product, mean pulmonary artery pressure, and standard bicarbonate were not significantly changed throughout the study. Systolic, diastolic, and mean arterial pressures and left ventricular stroke work index were significantly decreased at 5 and 15 minutes after a bolus of the anesthetic solution was injected. Systolic blood pressure returned to within the base-line range at 30 minutes, but diastolic and mean arterial pressures were significantly decreased throughout the study. Cardiac index and arterial pH were decreased at 5 minutes only. Systemic vascular resistance was significantly decreased 60 minutes after bolus injection was given. Hypoventilation, as indicated by increased PaCO2, occurred 5 minutes after bolus injection was given.     

Comparison of ketamine and S(+)-ketamine, with romifidine and diazepam, for total intravenous anesthesia in horses

OBJECTIVE: To compare the quality of induction and recovery, degree of muscle relaxation, clinically apparent potency and cardiopulmonary effects of racemic ketamine or S(+)-ketamine when used for total intravenous anesthesia in horses. STUDY DESIGN: Prospective randomized clinical trial ANIMALS: Sixteen healthy stallions (323 +/- 99 kg), with a mean age of 6.2 years, undergoing castration. METHODS: Horses were pre-medicated with romifidine IV, 15 minutes before induction of anesthesia. Each animal was then randomly allocated to receive either diazepam and ketamine (DK) or diazepam and S(+)-ketamine (DKS) at similar doses to induce anesthesia. For maintenance of anesthesia, 1/4 of the initial bolus of ketamine alone or S(+)-ketamine alone was administered, as required. Heart rate (HR), respiratory rate (RR) and systolic blood pressure were measured before and at 10-minute intervals during recumbency. Time from induction to lateral recumbency, time from induction to first additional dose, time from last additional dose to return to sternal posture and time from last additional dose to standing were recorded, and a subjective evaluation of quality of induction, endotracheal intubation, muscle relaxation and quality of recovery was recorded. RESULTS: The quality of the induction and duration of anesthesia were similar in both groups. HR, RR and systolic blood pressure were not significantly different between groups. Although some animals which received DKS showed some minor excitatory effects (25% of them) during the induction of anesthesia, these animals received 32% fewer doses for the maintenance of anesthesia and the recovery scores were better. CONCLUSIONS AND CLINICAL RELEVANCE: S(+)-ketamine showed some advantages over racemic ketamine, such as less anesthetic agent being required and better overall recovery from anesthesia. Further studies are needed to obtain the optimum induction dose for the S(+)-ketamine.     

Comparison of thiopentone/guaifenesin, ketamine/guaifenesin and ketamine/midazolam for the induction of horses to be anaesthetised with isoflurane

Forty-eight horses subjected to elective surgery were randomly assigned to three groups of 16 horses. After premedication with 0.1 mg/kg acepromazine intramuscularly and 0.6 mg/kg xylazine intravenously, anaesthesia was induced either with 2 g thiopentone in 500 ml of a 10 per cent guaifenesin solution, given intravenously at a dose of 1 ml/kg (group TG), or with 100 mg/kg guaifenesin and 2.2 mg/kg ketamine given intravenously (group KG), or with 0.06 mg/kg midazolam, and 2.2 mg/kg ketamine given intravenously (group KM). Anaesthesia was maintained with isoflurane. The mean (sd) end tidal isoflurane concentration (per cent) needed to maintain a light surgical anaesthesia (stage III, plane 2) was significantly lower in group KM (0.91 [0.03]) than in groups TG (1.11 [0.03]) and KG (1.14 [0.03]). The mean (sd) arterial pressure (mmHg) was significantly lower in group KG (67.4 [2.07]) than in groups TC (75.6 [2.23]) and KM (81.0 [2.16]). There were no significant differences in the logarithm of the heart rate, recovery time or quality of recovery between the three induction groups. However, pronounced ataxia was observed in the horses of group KM, especially after periods of anaesthesia lasting less than 75 minutes.     

Systemic effects of a prolonged continuous infusion of ketamine in healthy horses

Background: Ketamine as continuous rate infusion (CRI) provides analgesia in hospitalized horses. Objective: Determine effects of prolonged CRI of ketamine on gastrointestinal transit time, fecal weight, vital parameters, gastrointestinal borborygmi, and behavior scores in healthy adult horses. Animals: Seven adult Thoroughbred or Thoroughbred cross horses, with permanently implanted gastric cannulae. Methods: Nonblinded trial. Random assignment to 1 of 2 crossover designed treatments. Ketamine (0.55 mg/kg IV over 15 minutes followed by 1.2 mg/kg/h) or lactated Ringer's solution (50 mL IV over 15 minutes followed by 0.15 mL/kg/h) treatments. Two hundred 3 × 5 mm plastic beads administered by nasogastric tube before drug administration. Every 2 hours vital parameters, behavior scores recorded, feces collected and weighed, and beads retrieved. Every 6 hours gastrointestinal borborygmi scores recorded. Study terminated upon retrieval of 180 beads (minimum 34 hours) or maximum 96 hours. Nontransit time data analyzed between hours 0 and 34. Results: No significant (P < .05) differences detected between treatments in vital signs or gastrointestinal borborygmi. Significant (P = .002) increase in behavior score during ketamine infusion (0.381) from hours 24–34 compared with placebo (0). Ketamine caused significant delay in passage of 25, 50, and 75% of beads (ketamine = 30.6 ± 5.3, 41.4 ± 8.4, 65.3 ± 13.5 hours versus placebo = 26.8 ± 7.9, 34.3 ± 11.1, 45.8 ± 19.4 hours), and significant (P < .05) decrease in fecal weight from hours 22 (12.6 ± 3.2 versus 14.5 ± 3.8 kg) through 34 (18.5 ± 3.9 versus 12.8 ± 6.4 kg) of infusion. Conclusions and Clinical Importance: Ketamine CRI delayed gastrointestinal transit time in healthy horses without effect on vital parameters.     

Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus)

The study was conducted to evaluate the effects of romifidine alone (50 microg/kg) and a combination of romifidine (50 microg/kg) and ketamine (2.5 mg/kg) after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II). The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 +/- 6.25 s) compared to that of group I (5.2 +/- 0.54 min). Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I) and respiratory rate (more pronounced in group II), and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electrocardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.     

Cardiopulmonary effects of an intravenous infusion of guaifenesin, ketamine, and xylazine in dogs

A 5% solution of dextrose in water containing 50 mg of guaifenesin, 0.25 mg of xylazine, and 1 mg of ketamine/ml was infused IV at the rate of 2.2 ml X kg-1 X hour-1 in dogs. Heart rate, systemic vascular resistance, mean arterial blood pressure, rate-pressure product, and arterial oxygen tension were not altered significantly from baseline values during 2 hours of anesthesia. Cardiac index was significantly (P less than 0.05) decreased from base-line values. Hypoventilation resulted in increased arterial carbon dioxide tension and decreased arterial pH. After the dogs were given glycopyrrolate, cardiac index returned to base line, and heart rate, mean arterial pressure, and rate-pressure product were significantly greater (P less than 0.05) than base-line values.     

Prolongation of anesthesia with xylazine, ketamine, and guaifenesin in horses: 64 cases (1986-1989)

On 74 occasions, 54 horses and 6 foals were anesthetized with xylazine and ketamine or xylazine, guaifenesin, and ketamine, with or without butorphanol. On 64 occasions, anesthesia was prolonged for up to 70 minutes (34 +/- 15 min) by administration of 1 to 9 supplemental IV injections of xylazine and ketamine at approximately a third the initial dosage. All horses except 5 were positioned in lateral recumbency, and oxygen was insufflated. In adult horses, the time from induction of anesthesia to the first supplemental xylazine and ketamine injection was 13 +/- 4 minutes and the time between supplemental injections was 12.1 +/- 3.7 minutes. These results were consistent with predicted plasma ketamine concentration calculated from previously published pharmacokinetic data for ketamine in horses. Respiratory and heart rates and coccygeal artery pressure remained consistent for the duration of anesthesia. The average interval between the last injection of ketamine and assumption of sternal position was approximately 30 minutes, and was the same regardless of the number of supplemental injections. The time to standing was significantly longer (P less than 0.05) in horses given 2 supplemental injections, compared with those not given any or only given 1, but was not longer in horses given 3 supplemental injections. Recovery was considered unsatisfactory in 5 horses, but did not appear to be related to prolongation of anesthesia.     

Effects of ketamine infusion on halothane minimal alveolar concentration in horses.

Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron-impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (MAC; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 microgram/ml decreased halothane MAC. The degree of MAC reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 +/- 2.7 micrograms/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane MAC reduction. Cardiac output increased significantly during ketamine infusions and halothane MAC reduction. Our findings suggest that plasma ketamine concentrations > 1.0 micron/ml reduce halothane MAC and produce beneficial hemodynamic effects.     

Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses

OBJECTIVE: To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. ANIMALS: 8 adult horses. PROCEDURES: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius. RESULTS: No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.     

Anesthetic and cardiopulmonary effects of total intravenous anesthesia using a midazolam, ketamine and medetomidine drug combination in horses

The anesthetic and cardiopulmonary effects of midazolam, ketamine and medetomidine for total intravenous anesthesia (MKM-TIVA) were evaluated in 14 horses. Horses were administered medetomidine 5 microg/kg intravenously as pre-anesthetic medication and anesthetized with an intravenous injection of ketamine 2.5 mg/kg and midazolam 0.04 mg/kg followed by the infusion of MKM-drug combination (midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.1 mg/ml). Nine stallions (3 thoroughbred and 6 draft horses) were castrated during infusion of MKM-drug combination. The average duration of anesthesia was 38 +/- 8 min and infusion rate of MKM-drug combination was 0.091 +/- 0.021 ml/kg/hr. Time to standing after discontinuing MKM-TIVA was 33 +/- 13 min. The quality of recovery from anesthesia was satisfactory in 3 horses and good in 6 horses. An additional 5 healthy thoroughbred horses were anesthetized with MKM- TIVA in order to assess cardiopulmonary effects. These 5 horses were anesthetized for 60 min and administered MKM-drug combination at 0.1 ml/kg/hr. Cardiac output and cardiac index decreased to 70-80%, stroke volume increased to 110% and systemic vascular resistance increased to 130% of baseline value. The partial pressure of arterial blood carbon dioxide was maintained at approximately 50 mmHg while the arterial partial pressure of oxygen pressure decreased to 50-60 mmHg. MKM-TIVA provides clinically acceptable general anesthesia with mild cardiopulmonary depression in horses. Inspired air should be supplemented with oxygen to prevent hypoxemia during MKM-TIVA.     

Cardiopulmonary effects of romifidine and detomidine used as premedicants for ketamine/halothane anaesthesia in ponies

The cardiopulmonary effects of romifidine at 80 microg/kg (R80) or 120 pg/kg (R120), and detomidine at 20 pg/kg (D20) when used as premedicants for ketamine/halothane anaesthesia were investigated in six ponies. Using a blinded crossover design, acepromazine (0-04 mg/kg) was administered followed by the alpha-2 agonist. Anaesthesia was induced with ketamine at 2.2 mg/kg and maintained with halothane (expired concentration 1.0 per cent) in oxygen for three hours. During anaesthesia, arterial blood pressure, cardiac index, PaO2 and PmvO2 decreased, and systemic vascular resistance and PaCO2 increased. The cardiac indices for R80, R120 and D20 were, respectively, 39, 39 and 32 ml/kg/minute at 30 minutes and 29, 29 and 26 ml/kg/minute at 180 minutes. The alpha-2 agonists had similar cardiovascular effects, but PaO2 was significantly lower with R120. The quality of anaesthesia was similar in all three groups.     

Cardiovascular effects of continuous propofol infusion in horses

We examined the influence of propofol infusion on cardiovascular system at the rate of 0.14, 0.20 and 0.30 mg/kg/min in six adult Thoroughbred horses. The cardiovascular parameters were heart rate (HR), mean arterial pressure (MAP), mean right atrial pressure (MRAP), stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), pre-ejection period (PEP) and ejection time (ET). In order to keep the ventilation conditions constantly, intermittent positive pressure ventilation was performed, and the partial arterial CO(2) pressure was maintained at 45 to 55 mmHg during maintenance anesthesia. SV showed a significant dose-dependent decrease however, CO did not show significant change. SVR decreased significantly at higher dose. PEP was prolonged and PEP/ET increased significantly at the highest dose. From these results, it became clear that SV decreases dose-dependently due to decrease of cardiac contractility during anesthesia with continuous propofol infusion in horses. On the other hand, since MAP and CO did not show significant changes, total intravenous anesthesia with propofol was suggested to be suitable for long-term anesthesia in horses.     

Comparison of recoveries from halothane vs isoflurane anesthesia in horses.

Recovery from isoflurane anesthesia was shorter, with no difference in quality, compared with halothane anesthesia in 2 groups of horses. In 1 group, 12 horses scheduled for elective arthroscopy were randomly assigned to receive halothane or isoflurane for maintenance of anesthesia during surgery. In the other group, 6 horses received anesthesia only, on 2 occasions, with halothane on 1 occasion, and isoflurane on the other. Difference in the quality of recovery was not seen between isoflurane and halothane anesthesia in either group. In the group that had surgery, recovery to sternal position was significantly shorter when isoflurane was used. In the group not treated surgically, recovery to sternal and standing positions was significantly shorter with isoflurane.     

Cardiopulmonary responses of swine to intravenous infusion of guaifenesin, ketamine, and xylazine

Swine were anesthetized with a 5% solution of dextrose in water containing 50 mg of guaifenesin, 1 mg of ketamine, and 1 mg of xylazine X ml-1 (G-K-X) infused IV at a rate of 2.2 ml X kg-1 X hr-1. Mean arterial blood pressure and systemic vascular resistance were significantly increased from base-line values throughout the 2 hours of G-K-X infusion. Cardiac index decreased significantly initially, but returned to near base line at 30 minutes. Fifteen minutes after G-K-X infusion was discontinued, cardiac index was not significantly different from base line. Heart rate decreased significantly from base line 90 minutes after infusion of G-K-X began and remained so throughout the study. However, the mean heart rate remained within the acceptable range for swine. Rate-pressure product was not significantly altered. The PaCO2 decreased, and arterial pH increased significantly from base line, supporting our clinical impression that pigs breathe well when anesthetized with G-K-X. We conclude that G-K-X is a satisfactory combination of drugs for induction and maintenance of surgical anesthesia in healthy swine for a period of 2 hours.     

Pharmacodynamic effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses

Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, nonesterified fatty acids, and muscle enzyme levels were measured, as were plasma concentrations of KET and its metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Levels of sedation and muscle tension were scored. Respiration and heart rate significantly increased during the early infusion phase. Glucose and cortisol significantly varied both during and after infusion. During CRI all horses scored 0 on sedation. All but one horse scored 0 on muscle tension, with one mare scoring 1. All other parameters remained within or close to physiological limits without significant changes from pre-CRI values. The mean plasma concentration of KET during the 1.5 mg/kg/h KET CRI was 235 ng/mL. The decline of its plasma concentration-time curve of both KET and norketamine (NKET) following the CRI was described by a two-compartmental model. The metabolic cascade of KET was NKET, hydroxynorketamine (HNK), and 5,6-dehydronorketamine (DHNK). The KET median elimination half-lives (t1/2alpha and t1/2beta) were 2.3 and 67.4 min, respectively. The area under the KET plasma concentration-time curve (AUC), elimination was 76.0 microg.min/mL. Volumes of C1 and C2 were 0.24 and 0.79 L/kg, respectively. It was concluded that a KET CRI of 1.5 mg/kg/h can safely be administered to healthy conscious horses for at least 6 h, although a slight modification of the initial infusion rate regimen may be indicated. Furthermore, in the horse KET undergoes very rapid biotransformation to NKET and HNK and DHNK were the major terminal metabolites.     

Anesthetic and cardiovascular effects of balanced anesthesia using constant rate infusion of midazolam-ketamine-medetomidine with inhalation of oxygen-sevoflurane (MKM-OS anesthesia) in horses

The anesthetic sparring and cardiovascular effects produced by midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.05 mg/ml (0.025 ml/kg/hr) drug infusion during sevoflurane in oxygen (MKM-OS) anesthesia was determined in healthy horses. The anesthetic sparring effects of MKM-OS were assessed in 6 healthy thoroughbred horses in which the right carotid artery was surgically relocated to a subcutaneous position. All horses were intubated and ventilated with oxygen using intermittent positive pressure ventilation (IPPV). The end-tidal concentration of sevoflurane (ET(SEV)) required to maintain surgical anesthesia was approximately 1.7%. Heart rate and mean arterial blood pressure averaged 23-41 beats/min and 70-112 mmHg, respectively. All horses stood between 23-44 min after the cessation of all anesthetic drugs. The cardiovascular effects of MKM-OS anesthesia were evaluated in 5 healthy thoroughbred horses ventilated using IPPV. Anesthesia was maintained for 4 hr at an ET(SEV) of 1.7%. Each horse was studied during left lateral (LR) and dorsal recumbency (DR) with a minimum interval between evaluations of 1 month. Cardiac output and cardiac index were maintained between 70-80% of baseline values during LR and 65-70% of baseline values during DR. Stroke volume was maintained between 75-85% of baseline values during LR and 60-70% of baseline values during DR. Systemic vascular resistance was not different from baseline values regardless of position. MKM-OS anesthesia may be useful for prolonged equine surgery because of its minimal cardiovascular depression in both of lateral and dorsal recumbency.