Effects of two fentanyl constant rate infusions on thermal thresholds and plasma fentanyl concentrations in awake cats

Objective

To determine the pharmacokinetics and effects on thermal thresholds (TT) of two fentanyl constant rate infusions in awake cats.

Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats

OBJECTIVE: To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device. ANIMALS: Eight healthy adult cats weighing between 3.0 and 4.9 kg. METHODS: Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmHg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 mL in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at 0.25. 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA. RESULTS: There were no significant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (DeltaT(max)) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (DeltaP(max)) was 162 +/- 189 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE: This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats.     

The effects of ketamine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVES: To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg. METHODS: Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study. RESULTS: The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.     

Effects of meperidine or saline on thermal, mechanical and electrical nociceptive thresholds in cats

ObjectiveTo measure cutaneous electrical nociceptive thresholds in relation to known thermal and mechanical stimulation for nociceptive threshold detection in cats.Study designProspective, blinded, randomized cross-over study with 1-week washout interval.AnimalsEight adult cats [bodyweight 5.1 ± 1.8 kg (mean + SD)].MethodsMechanical nociceptive thresholds were tested using a step-wise manual inflation of a modified blood pressure bladder attached to the cat’s thoracic limb. Thermal nociceptive thresholds were measured by increasing the temperature of a probe placed on the thorax. The electrical nociceptive threshold was tested using an escalating current from a constant current generator passed between electrodes placed on the thoracic region. A positive response (threshold) was recorded when cats displayed any or all of the following behaviors: leg shake, head turn, avoidance, or vocalization. Four baseline readings were performed before intramuscular injection of meperidine (5 mg kg⁻¹) or an equal volume of saline. Threshold recordings with each modality were made at 15, 30, 45, 60, 90, and 120 minutes post-injection. Data were analyzed using anova and paired t-tests (significance at p < 0.05).ResultsThere were no significant changes in thermal, mechanical, or electrical thresholds after saline. Thermal thresholds increased at 15–60 minutes (p < 0.01) and mechanical threshold increased at 30 and 45 minutes after meperidine (p < 0.05). Maximum thermal threshold was +4.1 ± 0.3 °C above baseline at 15 minutes while maximum mechanical threshold was 296 ± 265 mmHg above baseline at 30 minutes after meperidine. Electrical thresholds following meperidine were not significantly different than baseline (p > 0.05). Thermal and electrical thresholds after meperidine were significantly higher than saline at 30 and 45 minutes (p < 0.05), and at 120 minutes (p < 0.05), respectively. Mechanical thresholds were significantly higher than saline treatment at 30 minutes (p ≤ 0.05).Conclusion and clinical relevanceElectrical stimulation did not detect meperidine analgesia whereas both thermal and mechanical thresholds changed after meperidine administration in cats.     

Pharmacokinetics of alfaxalone infusions,context-sensitive half-time and recovery times in male neutered cats

Objectives

To determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%.

Dose-related thermal antinociceptive effects of intravenous hydromorphone in cats

OBJECTIVE: To describe the dose-related thermal antinociceptive effects of intravenous (i.v.) hydromorphone in cats. STUDY DESIGN: Randomized, blinded, crossover design. ANIMALS: Seven adult cats (3.5-7.4 kg), two spayed females, and five neutered males. METHODS: Hydromorphone (0.025, 0.05, or 0.1 mg kg(-1)) was administered i.v.. Skin temperature and thermal threshold were measured before and at selected time points to 720 minutes post-administration. Statistical analysis of mean thermal threshold and skin temperatures over time for each dose and between doses was by way of a split-plot model and post hoc Bonferroni t-tests. p < 0.05 was considered significant. RESULTS: A significant difference from baseline for mean thermal threshold was identified for the 0.05 mg kg(-1) dose (5-80 minutes, peak thermal threshold 46.9 +/- 6.2 degrees C) and 0.1 mg kg(-1) dose (5-200 minutes, peak thermal threshold 54.9 +/-0.2 degrees C). The thermal threshold was significantly greater after the 0.1 mg kg(-1) dose from 5 to 200 minutes compared to the 0.025 mg kg(-1) and 0.5 mg kg(-1) doses. The thermal threshold was significantly greater from 35 to 80 minutes for the 0.05 mg kg(-1) dose when compared with the 0.025 mg kg(-1) dose. Skin temperature was significantly increased from 35 to 140 minutes following the 0.1 mg kg(-1) dose. CONCLUSIONS: A dose-related antinociceptive effect was demonstrated for i.v. hydromorphone in cats. CLINICAL RELEVANCE: Hydromorphone at doses less than 0.1 mg kg(-1) has a modest antinociceptive effect and a short duration of action. At a dose of 0.1 mg kg(-1) i.v., onset of analgesia is rapid with a clinically useful duration of effect, but is associated with a rise in skin temperature.     

Cardiopulmonary effects of dexmedetomidine and ketamine infusions with either propofol infusion or isoflurane for anesthesia in horses

ObjectiveTo examine the cardiopulmonary effects of two anesthetic protocols for dorsally recumbent horses undergoing carpal arthroscopy.Study designProspective, randomized, crossover study.AnimalsSix horses weighing 488.3 ± 29.1 kg.MethodsHorses were sedated with intravenous (IV) xylazine and pulmonary artery balloon and right atrial catheters inserted. More xylazine was administered prior to anesthetic induction with ketamine and propofol IV. Anesthesia was maintained for 60 minutes (or until surgery was complete) using either propofol IV infusion or isoflurane to effect. All horses were administered dexmedetomidine and ketamine infusions IV, and IV butorphanol. The endotracheal tube was attached to a large animal circle system and the lungs were ventilated with oxygen to maintain end-tidal CO₂ 40 ± 5 mmHg. Measurements of cardiac output, heart rate, pulmonary arterial and right atrial pressures, and body temperature were made under xylazine sedation. These, arterial and venous blood gas analyses were repeated 10, 30 and 60 minutes after induction. Systemic arterial blood pressures, expired and inspired gas concentrations were measured at 10, 20, 30, 40, 50 and 60 minutes after induction. Horses were recovered from anesthesia with IV romifidine. Times to extubation, sternal recumbency and standing were recorded. Data were analyzed using one and two-way anovas for repeated measures and paired t-tests. Significance was taken at p=0.05.ResultsPulmonary arterial and right atrial pressures, and body temperature decreased from pre-induction values in both groups. PaO₂ and arterial pH were lower in propofol-anesthetized horses compared to isoflurane-anesthetized horses. The lowest PaO₂ values (70–80 mmHg) occurred 10 minutes after induction in two propofol-anesthetized horses. Cardiac output decreased in isoflurane-anesthetized horses 10 minutes after induction. End-tidal isoflurane concentration ranged 0.5%–1.3%.Conclusion and clinical relevanceBoth anesthetic protocols were suitable for arthroscopy. Administration of oxygen and ability to ventilate lungs is necessary for propofol-based anesthesia.     

Combination of dexmedetomidine with buprenorphine enhances the antinociceptive effect to a thermal stimulus in the cat compared with either agent alone

ObjectiveTo evaluate the sedative and antinociceptive effects of combinations of dexmedetomidine and buprenorphine in cats.Study designExperimental randomized study.AnimalsTwelve purpose-bred neutered domestic short-hair cats (4 male and 8 female) weighing 4.6 kg (range 3.7–5.5 kg) aged from 2 to 5 years.MethodsSix cats per group were administered buprenorphine (B) at 10 (B10) or 20 μg kg^?1 (B20) or dexmedetomidine (D) at 20 (D20) or 40 μg kg^?1 (D40) or a combination of B10/D20. A feline thermal nociceptive threshold testing device was used to evaluate the antinociceptive effects of the drugs before and up to 24 hours after drug treatment. Sedation was scored using a 100 mm visual analogue scale (VAS).ResultsThermal thresholds increased significantly after administration of all but D20. Area under the curve (AUC, hours °C) for the first 6 hours (mean ± SD) for B20 (281 ± 17.8) was significantly greater than B10 (260 ± 11.4), D20 (250 ± 7.9) and D40 (255 ± 11.4). The AUC for B10/D20 (273 ± 12.2) was significantly greater than D20 but not the other treatments. No sedation was seen after administration of B10 or B20 and maximal sedation was seen for all animals in the D40 and B10/D20 groups and most animals in the D20 group.ConclusionsD20 alone had the smallest analgesic effect; B10 alone provided no sedation but their combination gave good sedation with analgesia comparable with B20.Clinical relevanceThis combination could be a useful multimodal sedative/analgesic regimen in cats.     

Effects of ketamine constant rate infusions on cardiac biomarkers and cardiac function in dogs

Objective

To evaluate the effects of ketamine continuous rate infusions (CRI) at two dose rates on cardiovascular function and serum creatine kinase MB isoenzyme (CK-MB) and troponin I in healthy conscious dogs.

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.     

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats

Objective

To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L^–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.

Opioid-sparing effect of a medetomidine constant rate infusion during thoraco-lumbar hemilaminectomy in dogs administered a ketamine infusion

ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg^–1 MED loading dose, followed by a 1.7 μg kg^–1 hour^–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg^–1 hour^–1 compared to SAL 3 (1.8–5.3) μg kg^–1 hour^–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.     

Pharmacokinetics of buprenorphine and its metabolite norbuprenorphine in neutered male cats anesthetized with isoflurane

ObjectiveTo characterize the pharmacokinetics of buprenorphine and norbuprenorphine in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsA group of six healthy adult male neutered cats.MethodsCats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for buprenorphine and lactated Ringer’s solution administration. Buprenorphine hydrochloride (40 μg kg^–1 over 5 minutes) was administered intravenously. Blood samples were collected before buprenorphine administration and at various times up to 12 hours after administration. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed effect (population) modeling.ResultsA five-compartment model (three compartments for buprenorphine and two compartments for norbuprenorphine) best fitted the data. Typical value (% interindividual variability) for the three buprenorphine volumes of distribution, and the metabolic clearance to norbuprenorphine, the remaining metabolic clearance and the two distribution clearances were 157 (33), 759 (34) and 1432 (43) mL kg^–1, and 5.3 (33), 16.4 (11), 58.7 (27) and 6.0 (not estimated) mL minute^–1 kg^–1, respectively. Typical values (% interindividual variability) for the two norbuprenorphine volumes of distribution, and the norbuprenorphine metabolic and distribution clearances were 1437 (30) and 8428 (not estimated) mL kg^–1 and 48.4 (68) and 235.9 (not estimated) mL minute^–1 kg^–1, respectively.Conclusions and clinical relevanceThe pharmacokinetics of buprenorphine in isoflurane-anesthetized cats were characterized by a medium clearance.     

Anaesthetic and cardiorespiratory effects of romifidine/ketamine combinations in cats

ObjectiveTo study the anaesthetic and cardiorespiratory effects of intramuscular (IM) administration of different combinations of romifidine and ketamine in cats.Study designProspective, randomized, cross-over experiment.AnimalsSeven healthy adult cats weighing (mean ± SD) 3.4 ± 0.7 kg and aged 4.6 ± 3.2 years.MethodsAnimals received romifidine 100 μg kg^?1 with ketamine 7.5 (R100/K7.5) and 10 mg kg^?1 (R100/K10), romifidine 200 μg kg^?1 with ketamine 5 (R200/K5), 7.5 (R200/K7.5) and 10 mg kg^?1 (R200/K10) by IM injection. The time required to perform orotracheal intubation (IT) was measured and the ease of intubation assessed. The onset of anaesthesia (OA), duration of anaesthesia (DA) and anaesthesia recovery times (AR) were measured. Analgesia and muscle relaxation scores were recorded every 5 minutes for 60 minutes after OA. Heart rate, systolic arterial pressure, arterial haemoglobin saturation, respiratory rate, end-tidal carbon dioxide and oesophageal temperature were also measured.ResultsThe IT, OA and DA were not significantly different between the treatments. The analgesia and muscle relaxation scores were similar between all treatments at most time points. The cardiorespiratory variables were not significantly different between the treatments in most cases. The adverse effects were dose dependent and similar to those previously described for other combinations of α₂-agonists and ketamine.Conclusions and clinical relevanceAnaesthesia produced by the studied combinations of romifidine and ketamine may only be reliable when conducting brief and noninvasive procedures in cats. The OA times were slower and the DA shorter than those reported for other alpha-2 agonists combined with ketamine. A dose-related increase in the intensity of the anaesthetic effects could not be demonstrated in this study.     

Comparison of preoperative carprofen and postoperative butorphanol as postsurgical analgesics in cats undergoing ovariohysterectomy

OBJECTIVE: To compare carprofen to butorphanol, with regard to postsurgical analgesic effects, duration of analgesia, and adverse side effects. STUDY DESIGN: Blinded, randomized clinical study. ANIMALS: Seventy-one cats, 0.5-5 years of age, weighing 3.24 +/- 0.61 kg, undergoing ovariohysterectomy (OHE). METHODS: Cats were premedicated with subcutaneous atropine (0.04 mg kg(-1)), acepromazine (0.02 mg kg(-1)), and ketamine (5 mg kg(-1)). Anesthesia was induced with ketamine (5 mg kg(-1)) and diazepam (0.25 mg kg(-1)) given intravenously, and maintained with isoflurane. There were three treatment groups: group C (4 mg kg(-1) carprofen SC at induction), group B (0.4 mg kg(-1) butorphanol SC at end of surgery), and group S (0.08 mL kg(-1) of sterile saline SC at induction and end of surgery). Behavioral data were collected using a composite pain scale (CPS), prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post-surgery. Interaction scores were analyzed separately. Cats with CPS scores >12 received rescue analgesia (meperidine, 4 mg kg(-1), intramuscular). RESULTS: Sixty cats completed the study. The CPS scores did not differ significantly between groups C and B at any time period. CPS scores for groups B and C were significantly increased for 12 hours post-surgery, and in group S for 20 hours. Both group C and B CPS scores were significantly lower than group S in this 20-hour postoperative period, except at 4 hours (B and C) and at 3 and 8 hours (B alone). Interaction scores for group C returned to preoperative baseline 4 hours after surgery, while both groups B and S remained increased for at least 24 hours post-surgery. Nine cats required meperidine. CONCLUSION: In this study, carprofen provided better postsurgical analgesia than butorphanol. Clinical relevance Neither drug completely abolished pain, however preoperative carprofen provided better pain control compared with postoperative butorphanol in the 24-hour period following OHE surgery in cats.     

Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs

ObjectiveTo evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsSix healthy adult Beagles.MethodsDogs were randomly given three treatments: dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with ketamine at 1 and 2 mg kg^–1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran’s Q tests; p < 0.050.ResultsIncreased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3–12 minutes) and duration of recumbency (29–51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively.Conclusions and clinical relevanceThe addition of 1 or 2 mg kg^–1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected.