Beatriz P. Monteiro

Clinical effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in cats anesthetized with isoflurane

OBJECTIVE To evaluate the effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in healthy cats anesthetized with isoflurane. DESIGN Randomized, controlled, clinical trial. ANIMALS 23 cats undergoing elective ovariohysterectomy. PROCEDURES Cats were premedicated with acepromazine and morphine; anesthesia was induced with propofol and maintained with isoflurane. Cats were given constant rate infusions of remifentanil (20 μg/kg/h [9 μg/lb/h], IV; n = 8), remifentanil and ketamine (0.5 mg/kg [0.23 mg/lb], then 1.8 mg/kg/h [0.82 mg/lb/h], IV; 7), or crystalloid fluids (8). The anesthesiologist was blinded to treatment group, end-tidal isoflurane concentration, and vaporizer setting. Heart rate, systolic arterial blood pressure, respiratory rate, end-tidal partial pressure of CO2, temperature, and end-tidal isoflurane concentration were monitored; recovery scores were assigned. RESULTS There were no significant differences among treatment groups with respect to age, body weight, surgery time, anesthesia time, time to extubation, recovery score, or cardiorespiratory variables. End-tidal isoflurane concentration was significantly reduced in cats given remifentanil and ketamine (mean ± SD, 0.63 ± 0.4%), compared with concentration in cats given crystalloid fluids (1.22 ± 0.5%) but not compared with concentration in cats given remifentanil alone (1.03 ± 0.4%). Compared with cats given crystalloid fluids, mean isoflurane requirement was reduced by 48.3% in cats given remifentanil-ketamine and 15.6% in cats given remifentanil alone. CONCLUSIONS AND CLINICAL RELEVANCE At the dosages administered, a constant rate infusion of remifentanil-ketamine resulted in a significant decrease in the isoflurane requirement in healthy cats undergoing ovariohysterectomy. However, significant differences in cardiovascular variables were not observed among treatment groups.

Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.

Objectives This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Methods Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Results Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5–30)] than in OA cats [14 (8.5–28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Conclusion Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.

Analgesic efficacy of intraperitoneal administration of bupivacaine in cats.

Objectives The aim of this study was to evaluate the analgesic efficacy of intraperitoneal (IP) bupivacaine in cats undergoing ovariohysterectomy (OVH). Methods Forty-five cats were included in a randomized, prospective, blinded study after owners’ written consent was obtained. The anesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane. A ventral midline incision was made and cats (n = 15/group) were administered either IP saline 0.9% (negative and positive control groups; NG and PG, respectively) or IP bupivacaine (2 mg/kg; bupivacaine group; BG). Cats in the PG received meloxicam (0.2 mg/kg SC). An OVH was performed and postoperative pain was evaluated using a dynamic interactive visual analog scale (DIVAS), the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT) for up to 8 h after the end of surgery. Postoperative sedation was evaluated using DIVAS. Rescue analgesia was provided with buprenorphine and/or meloxicam. Repeated measures linear models and a Cochran–Mantel–Haenszel test were used for statistical analysis (P <0.05). Results There was a significant effect of treatment on the number of times rescue analgesia was administered (P = 0.002) (PG, n = 2, 13%; NG, n = 12, 80%; BG, n = 4, 27%) with the number of rescues being higher in the NG group than in the PG (P = 0.0004) and BG (P = 0.02) groups. The DIVAS, MCPS and MNT were significantly different when compared with baseline values at different time points; however, data were not significantly different among groups. Conclusions and relevance Treatments PG and BG produced similar analgesia in terms of pain scores, number of times rescue analgesia was administered and MNT. Based on rescue analgesia, IP administration of bupivacaine provides analgesia in cats after OVH.

A clinical comparison of remifentanil or alfentanil in propofol-anesthetized cats undergoing ovariohysterectomy

Sixteen cats were used to compare the cardiovascular and anesthetic effects of remifentanil (REMI) or alfentanil (ALF) in propofol-anesthetized cats undergoing ovariohysterectomy. After premedication with acepromazine, anesthesia was induced and maintained with a constant rate infusion of propofol (0.3 mg/kg/min). REMI or ALF infusions were administered simultaneously with propofol. Heart rate (HR), systolic arterial pressure (SAP), pulse oximetry (SpO2), rectal temperature (RT), and response to surgical stimulation were recorded at predefined time points during anesthesia. Data [mean ± standard deviation (SD)] were analyzed by analysis of variance (ANOVA) for repeated measures followed by a Dunnetts test and Student t-test (P < 0.05). SAP was significantly lower in ALF group than in REMI group. Extubation time was significantly shorter in REMI than in ALF group. Overall infusion rate of REMI and ALF was 0.24 ± 0.05 mg/kg/min and 0.97 ± 0.22 mg/kg/min, respectively. The combination of propofol and REMI or ALF provided satisfactory anesthesia in cats undergoing ovariohysterectomy.

Analgesic effects of gabapentin and buprenorphine in cats undergoing ovariohysterectomy using two pain-scoring systems: a randomized clinical trial:

Objectives The aim of the study was to evaluate the analgesic efficacy of gabapentin–buprenorphine in comparison with meloxicam–buprenorphine or buprenorphine alone, and the correlation between two pain-scoring systems in cats. Methods Fifty-two adult cats were included in a randomized, controlled, blinded study. Anesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane. The gabapentin–buprenorphine group (GBG, n = 19) received gabapentin capsules (50 mg PO) and buprenorphine (0.02 mg/kg IM). The meloxicam–buprenorphine group (MBG, n = 15) received meloxicam (0.2 mg/kg SC), buprenorphine and placebo capsules (PO). The buprenorphine group (BG, n = 18) received buprenorphine and placebo capsules (PO). Gabapentin (GBG) and placebo (MBG and BG) capsules were administered 12 h and 1 h before surgery. Postoperative pain was evaluated up to 8 h after ovariohysterectomy using a multidimensional composite pain scale (MCPS) and the Glasgow pain scale (rCMPS-F). A dynamic interactive visual analog scale (DIVAS) was used to evaluate sedation. Rescue analgesia included buprenorphine and/or meloxicam if the MCPS ⩾6. A repeated measures linear model was used for statistical analysis (P <0.05). Spearman’s rank correlation between the MCPS and rCMPS-F was evaluated. Results The prevalence of rescue analgesia with a MCPS was not different (P = 0.08; GBG, n = 5 [26%]; MBG, n = 2 [13%]; BG, n = 9 [50%]), but it would have been significantly higher in the BG (n = 14 [78%]) than GBG (P = 0.003; n = 5 [26%]) and MBG (P = 0.005; n = 4 [27%]) if intervention was based on the rCMPS-F. DIVAS and MCPS/rCMPS-F scores were not different among treatments. A strong correlation was observed between scoring systems (P <0.0001). Conclusions and relevance Analgesia was not significantly different among treatments using an MCPS. Despite a strong correlation between scoring systems, GBG/MBG would have been superior to the BG with the rCMPS-F demonstrating a potential type II error with an MCPS due to small sample size.

Pharmacokinetics of bupivacaine after intraperitoneal administration to cats undergoing ovariohysterectomy

OBJECTIVE To evaluate pharmacokinetics of bupivacaine after IP administration to cats undergoing ovariohysterectomy. ANIMALS 8 healthy cats. PROCEDURES Anesthesia was induced with propofol and maintained with isoflurane. Buprenorphine (0.02 mg/kg, IV) and meloxicam (0.2 mg/kg, SC) were administered. A 20-gauge catheter was inserted into a jugular vein for blood sample collection. A ventral midline incision was made, and a solution of 0.5% bupivacaine (2 mg/kg) diluted with an equal volume of saline (0.9% NaCl) solution (final concentration, 0.25% bupivacaine) was injected into the peritoneal space over the right and left ovarian pedicles and caudal aspect of the uterus before ovariohysterectomy. Cats were monitored for signs of bupivacaine toxicosis. Venous blood samples (2 mL) were collected before (time 0) and 2, 5, 10, 15, 20, 30, 60, 120, and 240 minutes after bupivacaine administration. Plasma bupivacaine concentrations were determined with a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined by data plotting followed by analysis with a noncompartmental model. RESULTS No signs of bupivacaine toxicosis were observed. Maximum bupivacaine plasma concentration was 1,030 ± 497.5 ng/mL at a mean ± SD value of 30 ± 24 minutes after administration. Mean elimination half-life was 4.79 ± 2.7 hours. Mean clearance indexed by bioavailability and volume of distribution indexed by bioavailability were 0.35 ± 0.18 L•h/kg and 2.10 ± 0.84 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Intraperitoneal administration of bupivacaine resulted in concentrations that did not cause observable toxicosis. Studies to investigate analgesic effects for this technique in cats are warranted.

Preliminary investigation of the thermal antinociceptive effects of codeine in cats

Objectives The aim of this study was to evaluate the potential thermal antinociceptive effects of oral administration of a single dose of codeine in cats compared with positive (buprenorphine) and negative (saline 0.9%) controls. Methods Six adult healthy cats weighing 5.14 ± 0.6 kg were used. Skin temperature and thermal thresholds (TTs) were evaluated using a wireless device (Topcat Metrology) at baseline, 0.5, 1, 3, 6 and 10 h after treatment. In period 1, TTs were evaluated after subcutaneous administration of saline 0.9%. In period 2, cats were administered either oral codeine (10 mg total, 2.0 ± 0.2 mg/kg) or buccal buprenorphine (0.04 mg/kg) in a cross-over, blinded study design. Half of the volume of buprenorphine was administered into each cheek pouch. Δ TT (difference between TTs after and before treatment) was used for data comparison. Mean ± SD data were analyzed using one-way ANOVA followed by Dunnett’s or Tukey’s test when appropriate (P <0.05). Results Adverse effects did not occur in any group. Skin temperature was not different between groups nor over time. Temporal changes in TTs were not observed after saline or codeine. Buprenorphine increased Δ TT at 3 h (2.7 ± 3.3°C) when compared with baseline or saline (P <0.05). For buprenorphine, TTs were not >47.6°C at any time point in four cats. The mean highest temperature recorded in the two other cats in that group was 54.5 and 52.8°C at 3 h. Conclusions and clinical relevance At the dose administered, codeine did not produce thermal antinociception. Mild increases in TT after buccal buprenorphine might be related to the first-pass effect after drug swallowing, drug spillage during administration and/or individual variability. These factors should be taken in to consideration when administering buprenorphine by this route in the clinical setting.

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

Background The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. Methods Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett’s test and treatment comparisons using two-way ANOVA with Bonferroni’s correction (P < 0.05). Results Thermal thresholds were significantly increased after SC, IV and OTM from 1–24 hours (except 2 hours), 0.5–8 hours (except 6 hours), and 1–8 hours (except 6 hours), respectively, when compared with baseline. Thermal thresholds were significantly increased after SC (1–30 hours), IV (1–8 hours) and OTM (1–12 hours) when compared with SAL, but not different among buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake. Conclusion The SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes.

Evaluation of interobserver agreement for postoperative pain and sedation assessment in cats

OBJECTIVE To evaluate agreement between observers with different training and experience for assessment of postoperative pain and sedation in cats by use of a dynamic and interactive visual analog scale (DIVAS) and for assessment of postoperative pain in the same cats with a multidimensional composite pain scale (MCPS). DESIGN Randomized, controlled, blinded study. ANIMALS 45 adult cats undergoing ovariohysterectomy. PROCEDURES Cats received 1 of 3 preoperative treatments: bupivacaine, IP; meloxicam, SC with saline (0.9% NaCl) solution, IP, (positive control); or saline solution only, IP (negative control). All cats received premedication with buprenorphine prior to general anesthesia. An experienced observer (observer 1; male; native language, Spanish) used scales in English, and an inexperienced observer (observer 2; female; native language, French) used scales in French to assess signs of sedation and pain. Rescue analgesia was administered according to MCPS scoring by observer 1. Mean pain and sedation scores per treatment and time point, proportions of cats in each group with MCPS scores necessitating rescue analgesia, and mean MCPS scores assigned at the time of rescue analgesia were compared between observers. Agreement was assessed by intraclass correlation coefficient determination. Percentage disagreement between observers on the need for rescue analgesia was calculated. RESULTS Interobserver agreements for pain scores were good, and that for sedation scores was fair. On the basis of observer 1s MCPS scores, a greater proportion of cats in the negative control group received rescue analgesia than in the bupivacaine or positive control groups. Scores from observer 2 indicated a greater proportion of cats in the negative control group than in the positive control group required rescue analgesia but identified no significant difference between the negative control and bupivacaine groups for this variable. Overall, disagreement regarding need for rescue analgesia was identified for 22 of 360 (6.1%) paired observations. CONCLUSIONS AND CLINICAL RELEVANCE Interobserver differences in assessing pain can lead to different conclusions regarding treatment effectiveness.

Refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians: detection of naturally occurring osteoarthritis in laboratory cats:

Objectives Feline osteoarthritis causes pain and disability. Detection and measurement is challenging, relying heavily on owner report. This study describes refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians. Methods A video analysis of osteoarthritic (n = 6) and non-osteoarthritic (n = 4) cats facilitated expansion of scale items. Three successive therapeutic trials (using gabapentin, tramadol and oral transmucosal meloxicam spray) in laboratory cats with and without natural osteoarthritis (n = 12–20) permitted construct validation (assessments of disease status sensitivity and therapeutic responsiveness) and further scale refinements based on performance. Results Scale osteoarthritic sensitivity improved from phase I to phase III; phase III scale total score (P = 0.0001) and 4/5 subcategories – body posture (P = 0.0006), gait (P = 0.0031), jumping (0.0824) and global distance examination (P = 0.0001) – detected osteoarthritic cats. Total score inter-rater (intra-class correlation coefficients [ICC] = 0.64–0.75), intra-rater (ICC = 0.90–0.91) and overall internal consistency (Cronbach’s alpha = 0.85) reliability were good to excellent. von Frey anesthesiometer-induced paw withdrawal threshold increased with gabapentin in phase I, in osteoarthritic cats (P <0.001) but not in non-osteoarthritic cats (P = 0.075). Night-time activity increased during gabapentin treatment. Objective measures also detected tramadol and/or meloxicam treatment effects in osteoarthritic cats in phases II and III. There was some treatment responsiveness: in phase I, 3/10 subcategory scores improved (P <0.09) in treated osteoarthritic cats; in phase II, 3/8 subcategories improved; and in phase III, 1/5 subcategories improved (P <0.096). Conclusions and relevance The revised scale detected naturally occurring osteoarthritis, but not treatment effects, in laboratory cats, suggesting future potential for screening of at-risk cats. Further study is needed to confirm reliability, validity (disease sensitivity and treatment responsiveness) and clinical feasibility, as well as cut-off scores for osteoarthritic vs non-osteoarthritic status, in client-owned cats.