Comparison of pharmacokinetics of tramadol between young and middle-aged dogs.

This study aimed to compare the pharmacokinetics of tramadol between young and middle-aged dogs. Tramadol (4 mg/kg) was administered intravenously (IV) to young and middle-aged dogs (2 and 8-10 years, respectively). Plasma concentrations of tramadol were measured using high-performance liquid chromatography (HPLC), and its pharmacokinetics best fit a two-compartment model. The volume of distribution (Vd), elimination half-life (t1/2,ß) and total body clearance (CLtot) of the young group were 4.77 ± 1.07 l/kg, 1.91 ± 0.26 hr and 29.9 ± 7.3 ml/min/kg, respectively, while those of the middle-aged group were 4.73 ± 1.43 l/kg, 2.39 ± 0.97 hr and 23.7 ± 5.4 ml/min/kg, respectively. Intergroup differences in the t1/2,ß and CLtot were significant (P<0.05). In conclusion, tramadol excretion was significantly prolonged in middle-aged dogs.

Effects of a single bolus intravenous dose of tramadol on minimum alveolar concentration (MAC) of sevoflurane in dogs.

Tramadol is an atypical opioid analgesic widely used in small animal practice. This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg, IV) at 7 days interval. The sevoflurane MAC was determined using a tail clamp method in each dog ventilated with positive pressure ventilation. The tramadol administration produced a significant reduction in the sevoflurane MAC by 22.3 ± 12.2% (1.44 ± 0.28% with tramadol versus 1.86 ± 0.30% without tramadol, P=0.010). This MAC reduction had been determined from 122 ± 19 to 180 ± 41 min following the tramadol administration. During this period, the plasma concentrations of tramadol and its metabolite, O-desmethyltramadol (M1), decreased from 429 ± 64 to 332 ± 55 ng/ml and from 136 ± 24 to 114 ± 68 ng/ml, respectively, but these changes were not statistically significant. There was no significant difference in heart rate, mean arterial blood pressure and SpO2 between the control and tramadol treatment. The dogs that received tramadol treatment sometimes breathed spontaneously. Therefore, their respiratory rates significantly increased, and PETCO2 decreased during the MAC determination. In conclusion, the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dogs.

Anesthetic and cardiorespiratory effects of propofol, medetomidine, lidocaine and butorphanol total intravenous anesthesia in horses.

Anesthetic and cardiorespiratory effects of medetomidine, lidocaine, butorphanol and propofol total intravenous anesthesia (MLBP-TIVA) were evaluated in horses undergoing an experimental surgery. Ten horses were premedicated with an intravenous injection (IV) of medetomidine (5 µg/kg) and butorphanol (20 µg/kg). Anesthesia was induced by administration of 1% propofol (3 mg/kg, IV) at a rate of 1 mg/kg/min (n=5, group-1) or 2% propofol administered at a rate of 6 mg/kg/min (n=5, group-2) following administration of lidocaine (1 mg/kg, IV) and then maintained by infusions of propofol, medetomidine (3.5 µg/kg/hr), lidocaine (3 mg/kg/hr) and butorphanol (24 µg/kg/hr). The mean durations of anesthesia and propofol infusion rate required for maintaining surgical anesthesia were 130 ± 17 min and 0.10 ± 0.01 mg/kg/min in group 1 and 129 ± 14 min and 0.10 ± 0.02 mg/kg/min in group 2. Four horses in group 1 and 2 horses in group 2 paddled following recumbency during induction of anesthesia. The median quality scores for induction (0-4: poor-excellent) and recovery (0-5: unable to stand-excellent) were 3 and 4 for both groups, respectively. Transition to anesthesia (the first 20-min period after induction) was uneventful in group 2, while all horses showed a light plane of anesthesia in group 1. The quality score (0-3: poor-excellent) for the transition to anesthesia in group 2 was significantly higher than in group 1 (median 3 versus 1, P=0.009). Heart rate and arterial blood pressure were maintained within acceptable ranges, but hypercapnia occurred during anesthesia in both groups. In conclusion, MLBP-TIVA may provide clinically useful surgical anesthesia in horses. A rapid induction with propofol may improve the qualities of induction and transition to MLBP-TIVA.

Cardiovascular effects of tramadol in dogs anesthetized with sevoflurane.

Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (P<0.0001). Compared with baseline value, mean ABP increased significantly at 5 min (119% of baseline value, P=0.003), 10 min (113%, P=0.027), and 15 min (111%, P=0.022). SVR also increased significantly at 5 min (128%, P<0.0001), 10 min (121%, P=0.026), 30 min (114%, P=0.025), 45 min (113%, P=0.025) and 60 min (112%, P=0.048). Plasma concentrations of tramadol were weakly correlated with the percentage changes in mean ABP (r=0.642, P<0.0001) and SVR (r=0.646, P<0.0001). There was no significant change in heart rate, cardiac output, cardiac index, stroke volume, pulmonary arterial pressure, right atrial pressure and pulmonary capillary wedge pressure. In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.

Evaluation of bispectral index (BIS) as an indicator of central nervous system depression in horses anesthetized with propofol.

The bispectral index (BIS) was evaluated as an indicator of central nervous system (CNS) depression in horses anesthetized with propofol. Five non-premedicated horses were anesthetized with 7 mg/kg, IV propofol and the minimum infusion rate (MIR) of propofol required to maintain anesthesia was determined during intermittent positive pressure ventilation in each horse. The BIS was determined 20 min later and after stabilization at 2.0 MIR, 1.5 MIR, and 1.0 MIR. The BIS was also recorded after the cessation of propofol infusion when the horses regained spontaneous breathing and swallowing reflex. The MIR and plasma concentration (Cp) of propofol were 0.20 +/- 0.03 mg/kg/min and 17.5 +/- 4.0 microg/ml, respectively. The BIS value and Cp were 59 +/- 13 and 26.7 +/- 8.6 microg/ml at 2.0 MIR, 63 +/- 9 and 22.9 +/- 9.7 microg/ml at 1.5 MIR, 64 +/- 13 and 20.1 +/- 5.9 microg/ml at 1.0 MIR, 64 +/- 24 and 13.0 +/- 2.8 microg/ml at return of spontaneous breathing, and 91 +/- 4 and 11.0 +/- 3.4 microg/ml when the swallowing reflex returned, respectively. The BIS value was significantly less in anesthetized horses compared to horses once swallowing returned (p=0.025). The BIS value was significantly correlated with the propofol Cp (r=-0.625, p=0.001). There was not a significant difference in the BIS values during the MIR multiples of propofol. The BIS was a useful indicator of awakening but did not indicate the degree of CNS depression during propofol-anesthesia in horses.

Effect of age on minimum alveolar concentration (MAC) of sevoflurane in dogs.

It is well known that the minimum alveolar concentration (MAC) of inhalation anesthetic decreases with increasing age. However, there is limited information regarding the effect of age on MAC in dogs. This study was designed to determine the effect of age on sevoflurane MAC in dogs. MAC was determined in 6 young (2 years old) and 6 old beagle dogs (8 to 10 years old) under artificial ventilation. Anesthesia was induced via mask induction and maintained with sevoflurane in oxygen, and MAC was determined by using a tail clamp method. The sevoflurane MAC for the older dogs was significantly less than that for the younger dogs (1.86 +/- 0.29% vs 2.25 +/- 0.15%, P=0.007). The MAC of sevoflurane is profoundly affected by age in dogs.

Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs.

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.

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.

Minimally invasive determination of cardiac output by transthoracic bioimpedance, partial carbon dioxide rebreathing, and transesophageal Doppler echocardiography in beagle dogs.

Minimally invasive cardiac output was determined using transthoracic bioimpedance (BICO), partial carbon dioxide rebreathing (NICO) and transesophageal Doppler echocardiography (TEECO) and compared to thermodilution (TDCO) in 6 beagle dogs. The dogs were 2 years old, weigh between 9.1-13.0 kg and were anesthetized with nitrous oxide-oxygen-sevoflurane. All dogs were administered a neuromuscular blocking drug and artificially ventilated during anesthesia. Thirty paired measurements of TDCO and each non-invasive method were collected during low, intermediate, and high values of cardiac output achieved by varying the depth of anesthesia and the administration of dobutamine. Cardiac output values ranged from 1.10-2.50 L/min for BICO compared to 0.81-4.88 L/min for TDCO; 0.70-2.60 L/min for NICO compared to 0.89-4.45 L/min for TDCO; and 0.59-4.37 L/min for TEECO compared to 0.57-4.15 L/min for TDCO. The limits of agreement and percentage error were -0.58 +/- 1.56 L/min and +/- 75.4% for BICO, -1.04 +/- 1.08 L/min and +/- 56.0% for NICO, and 0.03 +/- 0.26 L/min and +/- 12.3% for TEECO compared to TDCO. In conclusion, TEECO provided the best agreement to TDCO in sevoflurane anesthetized beagle dogs.

Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine-medetomidine-propofol in horses.

OBJECTIVE: To evaluate the cardiovascular effects of total IV anesthesia with propofol (P-TIVA) or ketamine-medetomidine-propofol (KMP-TIVA) in horses. ANIMALS: 5 Thoroughbreds. PROCEDURES: Horses were anesthetized twice for 4 hours, once with P-TIVA and once with KMP-TIVA. Horses were medicated with medetomidine (0.005 mg/kg, IV) and anesthetized with ketamine (2.5 mg/kg, IV) and midazolam (0.04 mg/kg, IV). After receiving a loading dose of propofol (0.5 mg/kg, IV), anesthesia was maintained with a constant rate infusion of propofol (0.22 mg/kg/min) for P-TIVA or with a constant rate infusion of propofol (0.14 mg/kg/min), ketamine (1 mg/kg/h), and medetomidine (0.00125 mg/kg/h) for KMP-TIVA. Ventilation was artificially controlled throughout anesthesia. Cardiovascular measurements were determined before medication and every 30 minutes during anesthesia, and recovery from anesthesia was scored. RESULTS: Cardiovascular function was maintained within acceptable limits during P-TIVA and KMP-TIVA. Heart rate ranged from 30 to 40 beats/min, and mean arterial blood pressure was > 90 mm Hg in all horses during anesthesia. Heart rate was lower in horses anesthetized with KMP-TIVA, compared with P-TIVA. Cardiac index decreased significantly, reaching minimum values (65% of baseline values) at 90 minutes during KMP-TIVA, whereas cardiac index was maintained between 80% and 90% of baseline values during P-TIVA. Stroke volume and systemic vascular resistance were similarly maintained during both methods of anesthesia. With P-TIVA, some spontaneous limb movements occurred, whereas with KMP-TIVA, no movements were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiovascular measurements remained within acceptable values in artificially ventilated horses during P-TIVA or KMP-TIVA. Decreased cardiac output associated with KMP-TIVA was primarily the result of decreases in heart rate.

Evaluation of total intravenous anesthesia with propofol or ketamine-medetomidine-propofol combination in horses.

Objective-To compare the anesthetic and cardiorespiratory effects of total IV anesthesia with propofol (P-TIVA) or a ketamine-medetomidine-propofol combination (KMP-TIVA) in horses. Design-Randomized experimental trial. Animals-12 horses. Procedure-Horses received medetomidine (0.005 mg/kg [0.002 mg/lb], IV). Anesthesia was induced with midazolam (0.04 mg/kg [0.018 mg/lb], IV) and ketamine (2.5 mg/kg [1.14 mg/lb], IV). All horses received a loading dose of propofol (0.5 mg/kg [0.23 mg/lb], IV), and 6 horses underwent P-TIVA (propofol infusion). Six horses underwent KMP-TIVA (ketamine [1 mg/kg/h {0.45 mg/lb/h}] and medetomidine [0.00125 mg/kg/h {0.0006 mg/lb/h}] infusion; the rate of propofol infusion was adjusted to maintain anesthesia). Arterial blood pressure and heart rate were monitored. Qualities of anesthetic induction, transition to TIVA, and maintenance of and recovery from anesthesia were evaluated. Results-Administration of KMP IV provided satisfactory anesthesia in horses. Compared with the P-TIVA group, the propofol infusion rate was significantly less in horses undergoing KMP-TIVA (0.14 +/- 0.02 mg/kg/min [0.064 +/- 0.009 mg/lb/min] vs 0.22 +/- 0.03 mg/kg/min [0.1 +/- 0.014 mg/lb/min]). In the KMP-TIVA and P-TIVA groups, anesthesia time was 115 +/- 17 minutes and 112 +/- 11 minutes, respectively, and heart rate and arterial blood pressure were maintained within acceptable limits. There was no significant difference in time to standing after cessation of anesthesia between groups. Recovery from KMP-TIVA and P-TIVA was considered good and satisfactory, respectively. Conclusions and Clinical Relevance-In horses, KMP-TIVA and P-TIVA provided clinically useful anesthesia; the ketamine-medetomidine infusion provided a sparing effect on propofol requirement for maintaining anesthesia.