Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain

OBJECTIVE: To compare three opioid agonist drugs for perioperative analgesia in cats. STUDY DESIGN: Prospective, blind, controlled, randomised trial. ANIMALS: Ninety client-owned cats, weighing 3.1 (2.1-4.5) kg, aged 14.6 (6.0-84.0) months, were studied. METHODS: Seventy-six cats, scheduled for ovariectomy, received either 0.6 mg kg(-1) racemic methadone, 0.3 mg kg(-1) levo-methadone, 0.05 mg kg(-1) dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single 'blinded' observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Fe'CO2 and SpO2 were recorded during anaesthesia. Post-operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time-dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time-dependent variables were analysed using chi2-tests. Significance was set at p < or = 0.05. RESULTS: There were no significant changes in appearance after pre-anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals' reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate-to-severe pain after surgery. In the levo-methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, 'rescue' analgesia was required more often in cats treated with dextromoramide or saline. CONCLUSION AND CLINICAL RELEVANCE: Dextromoramide (0.05 mg kg(-1)) was ineffective, while racemic methadone (0.6 mg kg(-1)) and levo-methadone (0.3 mg kg(-1)) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.     

Comparison between meloxicam and carprofen for postoperative analgesia after feline ovariohysterectomy

Eighty female cats presented for ovariohysterectomy were randomly allocated to one of two treatment groups in this assessor-blinded trial. After pre-anaesthetic assessment, the cats were premedicated with acepromazine (0.1 mg/kg). Anaesthesia was induced with thiopentone and maintained with halothane in oxygen. Forty cats received carprofen (4 mg/kg subcutaneously) and 40 received meloxicam (0.3 mg/kg subcutaneously) after anaesthetic induction. Following routine flank ovariohysterectomy the cats were assessed using visual analogue scale scores for pain and sedation over a 20-hour study period. Blood samples were taken before sedation and at 20 hours for serum biochemistry (urea, creatinine, alanine aminotransferase and aspartate aminotransferase). There were no significant differences between the groups for pain and sedation scores. Serum biochemistry values were similar between the groups, with some differences within groups between the pre-sedation and 20-hour values. One cat in the carprofen group and two cats in the meloxicam group required rescue analgesia with intramuscular morphine (0.2 mg/kg).     

Assessment of the influence of surgical technique on postoperative pain and wound tenderness in cats following ovariohysterectomy

Elective ovariohysterectomy was performed on 66 cats. Surgical approach was flank (group F) or midline (group M) allocated by block randomisation. Pre-anaesthetic medication was acepromazine (0.1 mg/kg) via intramuscular injection. Anaesthesia was induced with intravenous thiopentone, and maintained with halothane in 100% oxygen. Carprofen (4 mg/kg) was administered by the subcutaneous route immediately after induction of anaesthesia. Postoperative pain and wound tenderness were assessed at 1, 3, 6, 9, 11-12 and 20-24h after the end of surgery, and the assessment outcome marked on visual analogue scales (VAS). Intervention analgesia (if pain VAS was >40 mm) was pethidine 4 mg/kg via intramuscular injection. Area under the curve (AUC) for VAS for pain and VAS for wound tenderness for each cat were calculated. AUC for wound tenderness was significantly greater for group F (P = 0.007). There was no significant difference for AUC for pain between the groups. In conclusion, wounds after flank ovariohysterectomy are significantly more tender than after midline ovariohysterectomy in the cat. This indicates that interactive methods, including wound palpation, must be used to assess postoperative pain and the findings should be appropriately weighted in the overall assessment.     

Carprofen as an analgesic for postoperative pain in cats: Dose titration and assessment of efficacy in comparison to pethidine hydrochloride

The aim of this study was to titrate the optimal dose of carprofen for single dose usage, for alleviating postoperative pain, under a double-blind and randomised protocol, using both negative and positive controls. Renal tolerance was assessed by screening plasma urea and creatinine. Pre- and postoperative assessment of pain and sedation was made using a dynamic and interactive visual analogue scoring system in 60 cats undergoing ovariohysterectomy. The cats were randomly assigned to one of six groups: (1) carprofen at 1-0 mg/kg subcutaneously (sc); (2) carprofen at 2-0 mg/kg sc; (3) carprofen at 4-0 mg/kg sc; (4) pethidine at 5-0 mg/kg intramuscularly (im), (5) pethidine at 10-0 mg/kg im; and (6) no analgesics (injection of saline). All injections were given postoperatively on tracheal extuba-tion and administered in a double-blind manner. Assessments were made up to 20 hours post extubation. Prior to induction and at 20 hours post extubation, blood samples were taken for laboratory analysis of the urea and creatinine content to check for any adverse effect on renal function. Cats given pethidine did not appear more sedated than the groups receiving carprofen or saline. Cats receiving carprofen were in less pain postoperatively overall, with 4-0 mg/kg being the most effective dose rate (significantly better than the other doses of carprofen at four and eight hours post extubation). The highest dose of pethidine provided significantly better analgesia than the highest dose of carprofen up to two hours post extubation, but from two to 20 hours post extubation carprofen at 4-0 mg/kg provided significantly better analgesia than the pethidine. None of the analgesic regimens appeared to affect renal function adversely, as measured by urea and creatinine levels.     

The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats

The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol.     

Comparison of oral and subcutaneous administration of buprenorphine and meloxicam for preemptive analgesia in cats undergoing ovariohysterectomy

OBJECTIVE: To compare the effectiveness of preoperative PO and SC administration of buprenorphine and meloxicam for prevention of postoperative pain-associated behaviors in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled study. ANIMALS: 51 female cats (4 to 60 months old; weight range, 1.41 to 4.73 kg [3.1 to 10.4 lb]). PROCEDURE: Cats received 1 of 5 treatments at the time of anesthetic induction: buprenorphine PO (0.01 mg/kg [0.0045 mg/lb]; n = 10), buprenorphine SC (0.01 mg/kg; 10), meloxicam SC (0.3 mg/kg 10.14 mg/lb]; 10), meloxicam PO (0.3 mg/kg; 10), or 0.3 mL of sterile saline (0.9% NaCI) solution SC (control group; 11). Sedation scores and visual analog scale and interactive visual analog scale (IVAS) pain-associated behavior scores were assigned to each cat 2 hours before and at intervals until 20 hours after surgery. RESULTS: Cats receiving meloxicam PO or SC had significantly lower IVAS scores (2.91 and 2.02, respectively), compared with IVAS scores for cats receiving buprenorphine PO (755). Pain-associated behavior scores for cats administered buprenorphine or meloxicam PO or SC preoperatively did not differ significantly from control group scores. Rescue analgesia was not required by any of the cats receiving meloxicam, whereas 3 of 10 cats receiving buprenorphine PO, 2 of 10 cats receiving buprenorphine SC, and 1 of 11 cats receiving the control treatment required rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pain-associated behavior scores, cats receiving meloxicam PO or SC before ovariohysterectomy appeared to have less pain after surgery than those receiving buprenorphine PO preoperatively.     

Investigating medetomidine-buprenorphine as preanaesthetic medication in cats

O bjectives : The objective of this study was to investigate medetomidine-buprenorphine preanaesthetic medication in cats.
M ethods : Forty American Society of Anesthesiologists (ASA) I female cats were enrolled in this prospective, blinded, clinical study. Cats were randomised into one of four groups: group M30 were injected intramuscularly with 30 μg/kg medetomidine, groups M10+B, M30+B and M50+B received 10, 30 and 50 μg/kg of medetomidine, respectively, each in combination with 20 μg/kg buprenorphine. After 30 minutes, a sedation score was allocated. Anaesthesia was induced using intravenous propofol and maintained using isoflurane in oxygen, while cats underwent ovariohysterectomy. Heart rate, respiratory rate, end-tidal carbon dioxide tension and oxygen saturation of haemoglobin were recorded. Atipamezole was administered intramuscularly at volatile agent discontinuation. Time taken to lift their head, sit in sternal and stand were recorded along with quality of recovery.
R esults : M30+B cats required significantly less isoflurane compared with M30 cats. Heart rate and oxygen saturation of haemoglobin were significantly lower in M50+B cats than in M30 cats. All M+B groups experienced significantly better recoveries compared with the medetomidine only M30 control group.
C linical S ignificance : The addition of buprenorphine to medetomidine preanaesthetic medication in cats reduces volatile agent vaporiser setting and improves the quality of recovery from anaesthesia.     

Comparison of carprofen and pethidine as postoperative analgesics in the cat

The postoperative analgesia and sedation in cats given carprofen (4·0 mg/kg bodyweight by subcutaneous injection preoperatively) was compared to that in cats given pethidine (3·3 mg/kg bodyweight by intramuscular injection postoperatively) in a controlled, randomised, blinded, multicentre clinical trial. Further dosing with the particular analgesic was allowed if a cat was exhibiting unacceptable pain. In total, 57 carprofen cases and 59 pethidine cases were evaluated. Significantly fewer cats in the carprofen group required additional doses of analgesic, and mean pain scores were significantly lower from four hours after ovariohysterectomy, and at 18 to 24 hours after castration, compared to the pethidine group. In conclusion, carprofen provided as good a level of postoperative analgesia as pethidine, but of a longer duration (at least 24 hours) and was well tolerated. It thus provides an option for 'pre-emptive analgesia' in cats about to undergo surgery.     

Analgesic effects of epidurally administered levogyral ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy

OBJECTIVE: To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. ANIMALS: 30 dogs scheduled for ovariohysterectomy. PROCEDURE: Dogs were randomly allocated to 1 of 3 groups. Dogs in group 1 received S(+) ketamine (1 mg/kg), dogs in group 2 received S(+) ketamine (0.5 mg/kg) and morphine (0.05 mg/kg), and dogs in group 3 received S(+) ketamine (1 mg/kg) and morphine (0.025 mg/kg). The skin was incised 15 minutes after epidural administration of analgesics. Heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation as measured by pulse oximetry, and arterial blood gases were obtained before anesthesia, 15 minutes after epidural administration of analgesics, 15 and 30 minutes after initiation of surgery, and at the end of surgery. During the intraoperative period, an increase of > or =20% in baseline values for HR, RR, and SBP was considered a sign of intraoperative pain. Signs of pain and adverse effects were assessed at 2, 4, and 8 hours postoperatively. RESULTS: There were no significant differences in intraoperative or postoperative measurements among the 3 groups. No dogs had intraoperative signs of pain. Mean postoperative pain assessment scores were <3.5 in all 3 groups. Salivation was the most frequent adverse effect in dogs in groups 1 and 3, and sedation occurred more frequently in dogs in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: All 3 analgesic regimens provided good respiratory and cardiovascular stability intraoperatively and adequate postoperative analgesia with minimal adverse effects.     

Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid

The adequacy of postoperative analgesia was assessed in 40 cats following ovariohysterectomy. At extubation, cats were given one dose of carprofen, ketoprofen, meloxicam or tolfenamic acid. Postoperative analgesia was assessed using visual analogue scale (VAS) scoring for pain and sedation; measurement of mechanical nociceptive thresholds at the wound; recognition of the requirement for rescue intervention analgesia; and an overall clinical assessment score at 18 hours. VAS pain scores were low throughout the trial, with no significant differences found between the groups. Postoperative mechanical nociceptive thresholds decreased significantly from baseline in all four groups, with no significant differences between the groups. One cat in each of the tolfenamic acid, ketoprofen and meloxicam groups required rescue intervention analgesia. Nine out of 10 cats in all four groups were classified as having desirable overall clinical assessment scores. In summary, all four drugs provided good postoperative analgesia, although none was able to prevent postoperative wound tenderness.     

Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine and ketamine administered to telemetered cats

The quality and duration of anaesthesia, cardiorespiratory effects and recovery characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine hydrochloride intramuscularly. Atipamezole was administered intramuscularly at 120 min after MMK administration. Time to lateral recumbency, intubation, extubation and sternal recumbency were recorded. Cardiorespiratory variables and response to a noxious stimulus were recorded before and at 3 min and 10 min increments after drug administration until sternal recumbency. The time to lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively. Body temperature and haemoglobin saturation with oxygen remained unchanged compared to baseline values throughout anaesthesia. Respiratory rate, tidal volume, minute volume, heart rate, and blood pressure were significantly decreased during anaesthesia compared to baseline values. One cat met criteria for hypotension (systolic blood pressure <90 mmHg). End tidal carbon dioxide increased during anaesthesia compared to baseline values. All but one cat remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min, respectively. MMK drug combination produced excellent short-term anaesthesia and analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at least 120 min in all but one cat and was effectively reversed by atipamezole.     

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.     

Clinical use of dexmedetomidine as premedicant in cats undergoing propofol-sevoflurane anaesthesia

The purpose of this report was to evaluate the cardiorespiratory effects and efficacy of dexmedetomidine as a premedicant agent in cats undergoing ovariohysterectomy anaesthetized with propofol-sevoflurane. Cats were randomly divided into two groups of eight animals each. Dexmedetomidine (0.01 mg/kg) or 0.9% saline was administered intravenously (D and S, respectively). After 5 min, propofol was administered intravenously and anaesthesia was maintained with sevoflurane. Heart and respiratory rates, arterial blood pressure, oxygen saturation, rectal temperature and the amount of propofol needed for induction were measured. Premedication with dexmedetomidine reduced the requirement of propofol (6.7+/-3.8 mg/kg), but induced bradycardia, compared with the administration of saline (15.1+/-5.1 mg/kg). Recovery quality was significantly better in D but no significant difference in time to return of swallowing reflex was observed between groups (D=2.5+/-0.5 min; S=3.2+/-1.8 min). In conclusion, dexmedetomidine is a safe and effective agent for premedication in cats undergoing propofol-sevoflurane anaesthesia with minimal adverse effects.     

Plasma fentanyl concentrations and analgesic effects during full or partial exposure to transdermal fentanyl patches in cats

OBJECTIVE: To compare plasma fentanyl concentrations and analgesic efficacy during full or partial exposure to 25-microg/h transdermal fentanyl patches (TFPs) in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 16 client-owned cats. PROCEDURE: Cats were randomly assigned to receive full or partial exposure to a TFP; patches were applied approximately 24 hours prior to ovariohysterectomy. Rectal temperature, heart rate, respiratory rate, blood glucose concentration, and blood pressure were measured and pain severity was assessed periodically for 72 hours after patch application. Venous blood samples were collected for determination of plasma fentanyl concentration 0, 6, 12, 18, 24, 36, 48, 60, and 72 hours after patch application. RESULTS: Mean +/- SD steady state plasma fentanyl concentration in cats in the full TFP exposure group (1.78 +/- 0.92 ng/mL) was significantly greater than concentration in cats in the partial exposure group (1.14 +/- 0.86 ng/mL). Steady state plasma fentanyl concentrations were evident between 18 and 72 hours after patch application. Subjective scores used to evaluate analgesic efficacy were not significantly different between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that delivery of fentanyl from TFPs can be reduced by decreasing the amount of exposed surface area. In cats weighing < 4 kg (9 lb), exposure to half a 25-microg/h TFP appears to provide adequate analgesia following ovariohysterectomy.     

The optimal intravenous dose of midazolam after intravenous ketamine in healthy awake cats

The effects of intravenous administration of variable-dose midazolam (0, 0.05, 0.075, 0.1, 0.3 and 0.5 mg/kg) and ketamine (3 mg/kg) were studied in twenty-four healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine the optimal dose to allow a short period of restraint without noxious stimuli, a short period of restraint with noxious stimuli and endotracheal intubation. Recovery characteristics, as well as undesirable behaviours observed during recovery, were also recorded. The dose of midazolam to achieve lateral recumbency with head down was found to be 0.016 mg/kg in 50% of the population (ED₅₀) and 0.054 mg/kg in 95% (ED₉₅) of the population. A midazolam dose of 0.286 mg/kg was required to prevent conscious perception of a stimulus to the ulnar nerve in 50% of the population and 0.652 mg/kg in 95% of the population. The ED₅₀ and ED₉₅ of midazolam required to prevent swallowing in response to a laryngoscope placed on the back of the tongue were found to be 0.265 mg/kg and 0.583 mg/kg, respectively. The ED₅₀ doses of 0.265 mg/kg for intubation and 0.286 mg/kg for restraint with noxious stimulation were close to the tested dose of 0.3 mg/kg. At that dose, the lack of responses lasted 3.67 ± 2.27 min for laryngoscope and 2.50 ± 2.20 min for ulnar nerve stimulation, with recovery to walking with ataxia taking 41.50 ± 15.18 min and complete recovery taking 3.6 ± 1.3 h. The predominant behavioural pattern during recovery was found to be normal, but some cats also exhibited abnormal behavioural patterns. Nine of the twelve cats exhibited an abnormal arousal state, with 4 being restless and 5 being sedated. Seven of the twelve cats exhibited an abnormal behaviour when approached, with three of the cats being more difficult to approach and four of the cats being easier to approach. Eight of the twelve cats exhibited an abnormal behavioural pattern when restrained, with the cats equally divided between more difficult and easier to restrain. Five of the twelve cats vocalized more during the recovery. The ED₅₀ of 0.042 mg/kg to induce chemical restraint without a noxious stimulus is close to the tested dose of 0.05 mg/kg. At that dose, cats remained lateral with head down for 5.49 ± 4.02 min, took 25.96 ± 5.77 min to walk with ataxia and 1.7 ± 0.4 h for complete recovery. The predominant behavioural patterns during recovery were normal, with several cats exhibiting some abnormal patterns. Two cats were sedated, one cat was more difficult to approach, one cat was easier to restrain and three cats were more vocal.