The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

The sedative effects of intramuscular (IM) alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (alfaxalone-HPCD) were evaluated in cats. The cats were treated with alfaxalone-HPCD in five occasions with a minimum 14-day interval between treatments: an IM injection of 1.0 mg/kg (IM1), 2.5 mg/kg (IM2.5), 5 mg/kg (IM5) or 10 mg/kg (IM10), or an intravenous injection of 5 mg/kg (IV5). The sedative effects were evaluated subjectively using a composite measurement scoring system (a maximum score of 16). Cardio-respiratory variables were measured non-invasively. The median sedation scores peaked at 10 min (score 9), 15 min (score 14), 10 min (score 16), 10 to 20 min (score 16) and 2 to 5 min (score 16) after the IM1, IM2.5, IM5, IM10 and IV5 treatments, respectively. The IM5 treatment produced longer lasting sedation, compared to the IV5 treatment. Durations of maintenance of lateral recumbency after the IM10 treatment (115 ± 22 min) were longer than those after the IM2.5 (40 ± 15 min), IM5 (76 ± 21 min) and IV5 treatments (50 ± 5 min). Cardio-respiratory variables remained within clinically acceptable ranges, except for each one cat that showed hypotension (<60 mmHg) after the IM10 and IV5 treatments. Tremors, ataxia and opisthotonus-like posture were observed during the early recovery period after the IM2.5, IM5, IM10 and IV5 treatments. In conclusion, IM alfaxalone-HPCD produced dose-dependent and clinically relevant sedative effect at 2.5 to 10 mg/kg in healthy cats. Hypotension may occur at higher IM doses of alfaxalone-HPCD.

ABSTRACT. 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 SpO 2 between the control and tramadol treatment. The dogs that received tramadol treatment sometimes breathed spontaneously. Therefore, their respiratory rates significantly increased, and PETCO 2 decreased during the MAC determination. In conclusion, the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dogs.

ABSTRACT. 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.KEY WORDS: canine, cardiovascular effects, sevoflurane, tramadol.J. Vet. Med. Sci. 73(12): 1603-1609, 2011 Treatment with analgesic drugs reduces the amount of anesthetics required to produce surgical anesthesia, helps to stabilize anesthesia, and decreases overall patient morbidity associated with surgery and anesthesia [17]. Opioid administration decreases the amount of volatile anesthetics required to produce general anesthesia, as evidenced by decreases in the minimum alveolar concentration (MAC) of volatile anesthetics [10,19].Tramadol is a centrally acting 'atypical' opioid analgesic and widely used in humans for control of acute and chronic pain [6,25]. Tramadol is less likely to induce tolerance in animals and humans compared with morphine because of its non-opioid mechanism of action [15]. Use of tramadol in dogs has gained popularity among veterinarians because the drug is perceived to be an effective analgesic, in easily administered, and has a longer duration of action and fewer adverse effects than most other opioids. It was demonstrated that tramadol administration decreased in the MAC of volatile anesthetics [28] and its preoperative administration provided an early pain control after ovariohysterectomy in dogs [13]. Tramadol produces a synergistic analgesic effect provided by a μ-opioid receptor affinity coupled with inhibitions of synaptic reuptake of monoamine neurotransmitters such as 5-hydroxyt...

Anesthetic and cardiorespiratory effects of nitrous oxide-oxygen-sevoflrane (GOS) anesthesia with or without a constant rate infusion (CRI) of morphine (0.2 mg/kg/hr) lidocaine (3 mg/kg/hr) and ketamine (0.6 mg/kg/hr) drug combination (MLK-CRI) were evaluated in 50 dogs undergoing hemilaminectomy. All dogs premedicated with an intravenous midazolam (0.3 mg/kg) and intramuscular morphine (0.3 mg/kg) and anesthetized with an intravenous propofol (6 mg/kg). Surgical depth of anesthesia was maintained by GOS with (n=25) or without (n=25) MLK-CRI. Total anesthesia time and extubation time were 83 ± 9 and 17 ± 12 minutes in dogs anesthetized with MLK-CRI or 105 ± 20 and 4 ± 3 minutes in dogs anesthetized without MLK-CRI. The end-tidal sevoflurane concentrations during surgery were 1.50-1.85% or 1.95-2.05% in dogs anesthetized by GOS with or without MLK-CRI, respectively. The sevoflurane requirements for maintaining surgical depth of anesthesia was reduced up to approximately 27% without severe cardiovascular suppression in the dogs receiving MLK-CRI. On the other hand, controlled ventilation was indispensable during anesthesia and extubation time was prolonged in the dogs receiving MLK-CRI. In conclusion, MLK-CRI is clinically useful for sparing with anesthetic requirement and preserving cardiac function during anesthesia, however, it should be aware of respiratory suppression and possibility of prolonged recovery in dogs receiving MLK-CRI.