Ketamine In Dogs Research Articles

Effects of a synergic interaction between magnesium sulphate and ketamine on the perioperative nociception in dogs undergoing tibial plateau leveling osteotomy: a pilot study.

Magnesium Sulphate (MgSO4) is commonly used in human medicine for the management of perioperative pain in different types of procedures. However, in veterinary medicine, the use of MgSO4 has not been evaluated for its analgesic efficacy in dogs, which has generated conflicts of opinion in this area of veterinary anesthesiology. The aim of this study was to evaluate the perioperative analgesic efficacy of MgSO4 in combination with Ketamine in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO). Our hypothesis is that MgSO4 plus ketamine have a synergistic action in the management of intra-and postoperative pain. Twenty adult mixed breed dogs with average age 5.9 ± 2.6 years and weight 27.8 ± 9.2 kg were included in this prospective, clinical, randomized study. Dogs were randomly assigned to two groups. The MK group received ketamine (0.5 mg/kg as starting bolus followed by continuous infusion rate at 1 mg/kg/h). At the end of the ketamine bolus, MgSO4 (50 mg/kg over 15 min) was administered by the same route, followed by a constant rate infusion (CRI) at 15 mg/kg/h, IV. K group received a bolus of ketamine followed by a CRI at the same dosage described in MK group. Main cardiorespiratory parameters were recorded 10 min before the start of surgery (BASE), after the ketamine bolus (T1) and the MgSO4 bolus (T2), during the skin incision (SKIN), the osteotomy (OSTEOTOMY) and skin suturing (SUTURE). In the postoperative period, the short form of Glasgow Composite Pain scale (SF-CMPS) was used to assess pain at 30, 60, 120, and 180 min after extubation (Post30, Post60, Post120, and Post180, respectively). The main blood electrolytes (Mg2+, Ca2+, Na+, K+) were analyzed at BASE, T2, OSTEOTOMY, SUTURE and T3 (one hour after stopping MgSO4 infusion). Number of rescue analgesia and administration times were recorded both in the intra-and postoperative period. In K group 7 out of 10 dogs required intraoperatory rescue analgesia compared to MK group (3/10). Furthermore, mean arterial pressure (MAP) and heart rate (HR) were significantly higher at OSTEOTOMY compared to BASE time in both groups. In the postoperative period, at T120, ICMPS-SF score was higher in K group than MK group. The administration of MgSO4 could guarantee better analgesia in the perioperative period in dogs undergoing TPLO, performing a synergistic action with ketamine.

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low doses. The secondary aims were to identify associated behavioural effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, an intravenous bolus of 1 mg/kg was administered over 2 min. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 min, followed by an infusion at 0.01 mg/kg/min for 1 h. Blood samples were collected for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. Levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady-state racemic ketamine plasma concentration of 150 ng/mL was 0.028 mg/kg/min. Higher scores for behavioural effects were observed within the first five minutes following bolus administration. The most common behaviours observed were disorientation, head movements and staring eyes. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

Comparison of the cardiovascular effects of propofol and ketamine in dogs premedicated with medetomidine-vatinoxan (Zenalpha)

Comparison of the cardiovascular effects of propofol and ketamine in dogs premedicated with medetomidine-vatinoxan (Zenalpha)

Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy?

In recent years ketamine has increasingly become the focus of multimodal emergency management for epileptic seizures. However, little is known about the effect of ketamine on brain metabolites in epileptic patients. Magnetic resonance spectroscopy (MRS) is a non-invasive technique to estimate brain metabolites in vivo. Our aim was to measure the effect of ketamine on thalamic metabolites in idiopathic epileptic (IE) dogs using 3 Tesla MRS. We hypothesized that ketamine would increase the glutamine-glutamate (GLX)/creatine ratio in epileptic dogs with and without antiseizure drug treatment, but not in control dogs. Furthermore, we hypothesized that no different responses after ketamine administration in other measured brain metabolite ratios between the different groups would be detected. In this controlled prospective experimental trial IE dogs with or without antiseizure drug treatment and healthy client-owned relatives of the breeds Border Collie and Greater Swiss Mountain Dog, were included. After sedation with butorphanol, induction with propofol and maintenance with sevoflurane in oxygen and air, a single voxel MRS at the level of the thalamus was performed before and 2 min after intravenous administration of 1 mg/kg ketamine. An automated data processing spectral fitting linear combination model algorithm was used to estimate all commonly measured metabolite ratios. A mixed ANOVA with the independent variables ketamine administration and group allocation was performed for all measured metabolites. A p < 0.05 was considered statistically significant. Twelve healthy control dogs, 10 untreated IE and 12 treated IE dogs were included. No significant effects for GLX/creatine were found. However, increased glucose/creatine ratios were found (p < 0.001) with no effect of group allocation. Furthermore, increases in the GABA/creatine ratio were found in IEU dogs. MRS was able to detect changes in metabolite/creatine ratios after intravenous administration of 1 mg/kg ketamine in dogs and no evidence was found that excitatory effects are induced in the thalamus. Although it is beyond the scope of this study to investigate the antiseizure potential of ketamine in dogs, results of this research suggest that the effect of ketamine on the brain metabolites could be dependent on the concentrations of brain metabolites before administration.

Anesthetic and clinical assessments of I/V propofol versus ketamine in Dogs premedicated with diazepam

The present anesthetic investigation was aimed to evaluate anesthetic clinico-physiological and hematobiochemical effects in addition to the anesthetic properties of propofol or ketamine premedicated with diazepam . For this purpose, 12 apparently healthy dogs were randomly divided into Two groups: A and B. All dogs were premedicated with Diazepam (0.2mg/kg Bwt/IM) then intravenous anesthesia was induced in group A with propofol intravenous (1mg/kg Bwt) ,while group B with ketamine intravenous (5 mg/kg Bwt). Blood samples were collected from the Two groups 15 minutes before anesthesia induction, then at (15, 30, 45 and 60) minutes after treatments for the hemato-biochemical evaluation, and for clinico-physiological observations. A slight alteration in some physiological parameters and hemato-biochemical values was observed after anesthesia induction, but it still safe to induce general anesthesia in dogs. in conclusion, the present anesthetic investigation showed the longest period of anesthesia with complete muscle relaxation following intravenous ketamine injection than propofol in premedicated dogs with diazepam.

Sedative effects and changes in cardiac rhythm with intravenous premedication of medetomidine, butorphanol and ketamine in dogs

ObjectiveTo determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs. Study designProspective, blinded, randomized clinical trial. AnimalsA total of 116 client-owned healthy dogs undergoing elective surgery. MethodsDogs were randomly allocated one of four groups: group M, medetomidine 5 μg kg–1; group B, butorphanol 0.2 mg kg–1; group MB, medetomidine 5 μg kg–1 and butorphanol 0.2 mg kg–1; or group MBK, medetomidine 5 μg kg–1, butorphanol 0.2 mg kg–1 and ketamine 1 mg kg–1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg–1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test. ResultsSedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks.Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg–1) than in group M (2.6 ± 0.6 mg kg–1). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg–1) and MBK (0.9 ± 0.8 mg kg–1), both groups required significantly less propofol than group M. Conclusion and clinical relevance:Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs.

Evaluation of the analgesic effect of fentanyl–ketamine and fentanyl–lidocaine constant rate infusions in isoflurane-anesthetized dogs undergoing thoracolumbar hemilaminectomy

ObjectiveTo evaluate anesthetic conditions and postoperative analgesia with the use of intraoperative constant rate infusions (CRIs) of fentanyl–lidocaine or fentanyl–ketamine in dogs undergoing thoracolumbar hemilaminectomy. Study designProspective, randomized, blinded, clinical study. AnimalsA total of 32 client-owned dogs. MethodsDogs were premedicated with fentanyl (5 μg kg–1) administered intravenously (IV), anesthesia was induced with IV alfaxalone and maintained with isoflurane. Fentanyl (0.083 μg kg–1 minute–1) was infused IV with either ketamine (0.5 mg kg–1; then 40 μg kg–1 minute–1; group KF) or lidocaine (2 mg kg–1; then 200 μg kg–1 minute–1; group LF) assigned randomly. Heart rate, noninvasive arterial pressures, respiratory rate, esophageal temperature, end-tidal partial pressure of carbon dioxide and isoflurane concentration were recorded throughout anesthesia. Maintenance of anesthesia, recovery and postoperative pain (Glasgow Composite Pain Scale) were scored. Cardiopulmonary data were analyzed using a two-way anova with repeated measures, demographics of the two groups with a t test, and scores with Mann–Whitney U test, with p < 0.05. ResultsAll dogs recovered from anesthesia without complications. No significant difference was found between groups for cardiopulmonary variables, total anesthesia time, sedation score and requirement for postoperative sedation or for rescue analgesia. Anesthetic maintenance score was of lower quality in KF than in LF [median (interquartile range): 0 (0–0.5) versus 0 (0–0); p = 0.032)], but still considered ideal. Recovery score was higher and indicative of less sedation in LF than in KF [1 (1–1.5) versus 0.5 (0–1); p < 0.0001]. Pain score was higher in KF than in LF [2 (1–3) versus 1 (1–2); p = 0.0009]. Conclusions and clinical relevanceBoth CRIs of KF and LF provided adequate anesthetic conditions in dogs undergoing thoracolumbar hemilaminectomy. Based on requirement for rescue analgesia, postoperative analgesia was adequate in both groups.

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α2-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal. Study designRandomized, masked crossover study. AnimalsA total of eight purpose-bred Beagle dogs aged 3 years. MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg–1) and butorphanol (100 μg kg–1) premedication with vatinoxan (500 μg kg–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg–1). Atipamezole (100 μg kg–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed. ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB. Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.

Enantioselective determination of ketamine in dog plasma by chiral liquid chromatography-tandem mass spectrometry.

Ketamine is an N-methyl-d-aspartate receptor antagonist that is usually used clinically as a racemic mixture. Its two enantiomers exhibit different pharmacological activities. To determine whether the enantiomers have different pharmacokinetic profiles, a chiral liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of ketamine enantiomers in dog plasma. The enantiomers of ketamine were extracted from 50 μL of plasma by methyl tert-butyl ether. Adequate chromatographic retention and baseline resolution of the enantiomers were achieved within a runtime of 5 min on a chiral column coated with polysaccharide derivatives, using a gradient mobile phase of acetonitrile and 10 mm ammonium bicarbonate aqueous solution. Ketamine enantiomers were detected by mass spectrometry with multiple reaction monitoring mode using the transitions of m/z 238.3 → 125.9 for the analytes and m/z 237.1 → 194.1 for carbamazepine (internal standard). The method was linear over the concentration range from 0.5 to 500 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was 0.5 ng/mL. The intra- and inter-day precision was <7.3% and 8.5% for R- and S-ketamine, respectively. The accuracy was 92.9-110.4% for R-ketamine and 99.8-102.4% for S-ketamine. The method was successfully applied to characterize the stereoselective pharmacokinetic profiles of ketamine in beagle dogs.

Evaluation of the cardiorespiratory effects of the alpha-2 adrenoceptor agonists xylazine, medetomidine and dexmedetomidine in combination with ketamine in dogs

In this study, we compared the effects of xylazine, medetomidine and dexmedetomidine in combination with ketamine on heart rate, respiratory rate, blood gas values, temperature and sedation scores. A total of 30 dogs were evaluated. The dogs were randomly allocated into three anaesthesia groups, each of which included ten dogs. The first group, denoted the xylazine/ketamine group, intravenously received xylazine (0.5 mg/kg) for premedication and ketamine (5 mg/kg) for induction. The second group, the medetomidine/ketamine group, intravenously received medetomidine (10 µg/kg) followed by ketamine (5 mg/kg). The third group received the dexmedetomidine/ketamine combination. This group intravenously received dexmedetomidine (3 µg/kg) for premedication and ketamine (5 mg/kg). Heart rate, respiratory rate, oxygen saturation, blood gas parameters and temperature were recorded for all patients immediately before sedation onset (T&lt;sub&gt;0&lt;/sub&gt;), five minutes after sedation onset (T&lt;sub&gt;1&lt;/sub&gt;) and five minutes after endotracheal intubation following ketamine injection (T&lt;sub&gt;2&lt;/sub&gt;). The end tidal carbon dioxide level was recorded at T&lt;sub&gt;2&lt;/sub&gt;. A significant decrease in heart rate occurred following premedication in all groups. However, the decrease was most marked in the medetomidine/ketamine group. An increase was observed in venous partial pressure of carbon dioxide values at T&lt;sub&gt;2&lt;/sub&gt; in the xylazine/ketamine group compared to the medetomidine/ketamine and dexmedetomidine/ketamine groups. The end tidal carbon dioxide levels were higher in the medetomidine/ketamine group than in the other two groups, and oxygen saturation of haemoglobin levels in the same group were found to be lower than in the others. It was determined that none of α&lt;sub&gt;2&lt;/sub&gt;-agonists, namely xylazine, medetomidine or dexmedetomidine, had superior properties over the others. If medetomidine is used, special care should be taken because of the rapid decrease in heart rate.

Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose and select physiologic effects

ObjectiveTo determine the intubation dose and select physiologic effects of alfaxalone alone or in combination with midazolam or ketamine in dogs. Study designProspective, clinical study. AnimalsFifty-three healthy client-owned dogs [mean±standard deviation (SD)] 5.1±1.8 years, 27±15.4 kg, scheduled for elective orthopedic surgery. MethodsAfter premedication with acepromazine (0.02 mg kg–1) and hydromorphone (0.1 mg kg–1) intramuscularly, alfaxalone (0.25 mg kg–1) was administered intravenously over 15 seconds followed immediately by 0.9% saline (AS), midazolam (0.3 mg kg–1; AM), ketamine (1 mg kg–1; AK1), or ketamine (2 mg kg–1; AK2). Additional alfaxalone (0.25 mg kg–1 increments) was administered as required to permit endotracheal intubation. The incidence of apnea and the time from intubation until spontaneous movement were recorded. Heart rate (HR) and blood pressure were recorded 15 minutes after premedication, after intubation and 2, 5, 10 and 15 minutes thereafter. Blood was collected for measurement of serum glucose and insulin concentrations before induction, after intubation and at 2, 5, 10 and 50 minutes. Data were analyzed by split-plot anova with Bonferroni adjustment for the number of group comparisons. ResultsMean±SD alfaxalone mg kg–1 doses required for endotracheal intubation were AS (1.0±0.4), AM (0.4±0.2), AK1 (0.5±0.3) and AK2 (0.5±0.4) (p=0.0005). Differences in cardiopulmonary variables among groups were minor; HR decreased in AS, while in other groups, HR increased transiently postintubation. Incidence of apnea in AS was 54% with no significant difference among groups. Midazolam significantly prolonged time from intubation until spontaneous movement (p<0.002). Conclusions and clinical relevanceMidazolam and ketamine reduced the alfaxalone dose required for endotracheal intubation. Serum glucose and insulin concentrations were not influenced by administration of alfaxalone alone or when administered with midazolam or ketamine.

Subarachnoid injection of ifenprodil and ketamine association improves the anti-hyperalgesic action of ketamine in dogs

To test clinically whether a small dose of ifenprodil can enhance the anti-hyperalgesic effect of ketamine in dogs, a prospective randomized cross-over study was done with eight mongrel dogs (weighing 16.9 ± 3.7kg). Animals received two distinct treatments: ketamine (0.3mg kg-1; KT) and an ifenprodil plus ketamine combination (0.03mg kg-1 and 0.3mg kg-1, respectively; IKT). Dogs were anesthetized with propofol (5mg kg-1 intravenously) and a subarachnoid needle was placed between the 5th and 6th lumbar vertebrae. Five minutes after subarachnoid injection of KT or IKT, an incision including cutaneous and subcutaneous tissues was made on the common pad of one hind limb and was immediately closed with a simple interrupted suture pattern. The dogs were treated again 20 days later, using the contralateral pad and the opposite treatment. Sedation score (SS), lameness score (LS), heart rate (HR), respiratory rate (fR), and mechanical nociceptive threshold using von Frey filaments, were evaluated before anesthesia and at 1, 1.5, 2, 3, 4, 8, 12, and 24 hours after subarachnoid injection. There were no differences in SS, LS, HR or fR between treatments. The intensity of hyperalgesia was higher in KT than in IKT for 24 hours. The anti-hyperalgesic effect of IKT remained without statistical significant difference between 1 and 24 h. Prior subarachnoid administration of ifenprodil enhances the anti-hyperalgesic effect of subarachnoid ketamine in dogs. Ifenprodil can be co-administrated with ketamine to enhance its anti-hyperalgesic effect and to reduce acute post-incisional hyperalgesia without motor impairment and sedation.

S-ketamine versus racemic ketamine in dogs: their relative potency as induction agents

ObjectiveTo determine the potency ratio between S-ketamine and racemic ketamine as inductive agents for achieving tracheal intubation in dogs. Study designProspective, randomized, ‘blinded’, clinical trial conducted in two consecutive phases. Animals112 client-owned dogs (ASA I or II). MethodsAll animals were premedicated with intramuscular acepromazine (0.02 mg kg−1) and methadone (0.2 mg kg−1). In phase 1, midazolam (0.2 mg kg−1) with either 3 mg kg−1 of racemic ketamine (group K) or 1.5 mg kg−1 of S-ketamine (group S) was administered IV, for induction of anaesthesia and intubation. Up to two additional doses of racemic (1.5 mg kg−1) or S-ketamine (0.75 mg kg−1) were administered if required. In phase 2, midazolam (0.2 mg kg−1) with 1 mg kg−1 of either racemic ketamine (group K) or S-ketamine (group S) was injected and followed by a continuous infusion (1 mg kg minute−1) of each respective drug. Differences between groups were statistically analyzed via t-test, Fisher exact test and ANOVA for repeated measures. ResultsDemographics and quality and duration of premedication, induction and intubation were comparable among groups. During phase 1 it was possible to achieve tracheal intubation after a single dose in more dogs in group K (n = 25) than in group S (n = 16) (p = 0.046). A dose of 3 mg kg−1 S-ketamine allowed tracheal intubation in the same number of dogs as 4.5 mg kg−1 of racemic ketamine. The estimated potency ratio was 1.5:1. During phase 2, the total dose (mean ± SD) of S-ketamine (4.02 ±1.56 mg kg−1) and racemic ketamine (4.01 ± 1.42) required for tracheal intubation was similar. Conclusion and clinical relevanceRacemic and S-ketamine provide a similar quality of anaesthetic induction and intubation. S-ketamine is not twice as potent as racemic ketamine and, if infused, the potency ratio is 1:1.

Decreased postoperative C‐reactive protein production in dogs with pyometra through the use of low‐dose ketamine

To determine the effects of subanesthetic ketamine in dogs with pyometra on C-reactive protein (CRP) concentrations following surgery. Prospective, nonconcealed, alternating allocation controlled trial. Veterinary teaching hospital. Sixteen dogs diagnosed with pyometra. The tentative diagnosis of canine pyometra was based on compatible history, physical examination findings, ultrasonographic findings, and hematological evaluation. Two different anesthesia and analgesic protocols with and without low-dose ketamine were used during and following ovariohysterectomy in 16 female dogs (n = 8 per group) that were diagnosed with naturally occurring pyometra. Dogs were sequentially allocated to treatment groups in an alternating fashion without concealment. Serum was collected before, 24, and 48 hours after surgery for CRP measurement. Perioperative physical parameters in the 2 groups of dogs were similar. The serum concentrations of CRP in both groups were essentially the same before surgery, but significantly increased in the control group and decreased in ketamine group at 48 hours after surgery. Low-dose ketamine attenuated the postoperative concentration of serum CRP in dogs with pyometra compared with dogs that did not receive ketamine in the perioperative period. Further studies are warranted to determine the clinical implications of these findings.

Evaluation of anaesthetic stress following administration of dexmedetomidine and its combinations with midazolam, fentanyl and ketamine in dogs

The study was conducted on 16 apparently healthy adult dogs of either sex, randomly divided into 4 groups, each containing 4 animals. Animals of group A received dexmedetomidine (20 µg/kg) alone. Midazolam (0.2 mg/kg), fentanyl (4 µg/kg) + midazolam (0.2 mg/kg) and ketamine (10 mg/kg) + fentanyl (4 µg/kg) + midazolam (0.2 mg/kg) were administered along with dexmedetomidine (20 µg/kg) in the animals of groups B, C and D, respectively. All the drugs were given simultaneously by intramuscular route. Differential leucocytic count, plasma glucose, insulin and cortisol were measured at baseline (0 min) and at 30, 60 and 120 min after the drug administration. Neutrophilia was observed only for a very short period. Plasma insulin levels significantly decreased whereas a significant increase in the plasma glucose towards the end of the study period was observed except in group C in which it decreased. Cortisol levels were nonsignificantly lower than the base values throughout the study in all the groups. It could be concluded that dexmedetomidine and its combinations with midazolam, fentanyl and ketamine do not threaten homeostasis and can obtund the stress response associated with handling and anaesthetic procedures in dogs.

Relative potency of ketamine and S(+)‐ketamine in dogs

The aim of this study was to determine the relative potency of racemic ketamine and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)-ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter with S(+)-ketamine. It was concluded that the potency ratio between ketamine and S(+)-ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.

Evaluation of analgesia provided by the administration of epidural ketamine in dogs with a chemically induced synovitis

Objective To determine if epidural ketamine provides analgesia in dogs with a chemically induced synovitis.Study design Prospective randomized experimental trial.Animals Thirty-two healthy, adult mongrel dogs (13–30 kg).Methods (Part I) Synovitis was induced in the right stifle of 16 dogs and allowed to develop for 12 hours. Epidural injection at the lumbosacral space of either ketamine (2 mg kg−1; n = 8) or placebo (n = 8) was performed. Limb use and pain were measured using a force platform and numerical rating scale (NRS). Assessments were performed before and at 12, 14, 16, 18, 20, and 24 hours after the induction of synovitis. (Part II) Epidural injection of either ketamine (n = 8) or placebo (n = 8) was performed immediately before the induction of synovitis. Analgesia was assessed as in Part I. Assessments occurred before and at 2, 4, 6, 8, and 12 hours after the induction of synovitis.Results (Part I) Vertical ground reaction forces (VGRF) significantly decreased and NRS scores of total pain significantly increased after the induction of synovitis in all dogs (p < 0.05). No significant differences in VGRF or NRS scores were measured between treatment groups at any assessment period. (Part II) Dogs that received ketamine had significantly lower NRS scores 2 hours after treatment (p < 0.05). NRS scores did not differ between groups at any other evaluation. VGRF did not differ significantly between treatment groups at any assessment period.Conclusion Epidural ketamine at a dose of 2 mg kg−1 administered after the development of synovitis does not provide significant levels of analgesia. Administration of ketamine before the induction of synovitis significantly decreased the NRS score 2 hours post-induction.Clinical relevance Administration of epidural ketamine before tissue injury may provide analgesia of short duration in dogs.

The evaluation of analgesia provided by epidural ketamine in dogs with chemically induced synovitis

Ketamine, a noncompetitive NMDA receptor antagonist, has been shown to provide analgesia in some species. To target the NMDA receptor specifically and to potentially minimize some untoward side-effects, ketamine had been used epidurally. The objective of this study was to determine the analgesic effect of epidurally administered ketamine in dogs with chemically induced synovitis. Sixteen healthy dogs were used. Dogs were anesthetized with propofol (4 mg kg−1 IV). Synovitis was induced by injecting 1 mL of sodium urate crystal solution (10 mg mL−1) into the right stifle. Dogs were allowed to recover and the synovitis was allowed to develop for 12 hours. The dogs were then anesthetized again using propofol (4 mg kg−1 IV). Lumbosacral epidural injections were performed with each dog receiving either 2 mg kg−1 of ketamine (20 mg mL−1) or an equal volume of placebo (sterile water containing not more than 0.1 mg mL−1 benzethonium chloride). Analgesia was assessed at baseline and then at 12, 14, 16, 18, 20, and 24 hours after induction of synovitis. Ground reaction forces (peak vertical force and impulse area) and overall pain were measured using a force platform and a pain scoring system (numerical rating scale). Analysis of the data by Repeated Measures anova showed that the dogs developed a significant lameness between the baseline and 12 hours. However, no significant difference in ground reaction forces or total pain score was demonstrated between the treatment and control groups at any other time. In conclusion, ketamine administered epidurally at a dose of 2 mg kg−1 did not provide significant analgesia in dogs with chemically induced synovitis.

Romifidine or xylazine combined with ketamine in dogs premedicated with methotrimeprazine

The cardiorespiratory and analgesic effects of romifidine or xylazine combined with ketamine was investigated in dogs. Dogs were premedicated with 1.0 mg/kg of methotrimeprazine IV, followed by 0.1 mg/kg of romifidine (n = 8) or 1.0 mg/kg of xylazine (n = 8) and 15 mg/kg of ketamine IM, using a double blind randomised design. Dogs of both groups developed hypothermia, bradycardia, slight hypotension and reduction in respiratory rate and minute volume. There were minimal changes in end tidal CO2 and O2 saturation. There were no differences either in time or between the groups in pH, PaO2, and blood biochemistry. The reflexes to pain were reduced until 30-45 minutes of anaesthesia in both groups. Twelve bitches were divided in two groups as above and underwent ovariohysterectomy. Recovery was longer after romifidine/ketamine when compared to xylazine/ketamine in both studies. Although these anaesthetic protocols produced minimal cardiorespiratory changes, the quality of anaesthesia was not ideal for ovariohysterectomy.

Spinal conduction block by intrathecal ketamine in dogs.

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.