Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration

Objective To measure the plasma fentanyl concentrations achieved over time with transdermal fentanyl patches in awake cats and cats undergoing anesthesia and ovariohysterectomy. Study design Randomized prospective experimental study. Animals Twenty‐four purpose‐bred cats. Methods Cats were randomly assigned to three groups for Part I of a larger concurrent study. Group P received only a 25 μg hour^?1 transdermal fentanyl patch. Group P/A received the patch and anesthesia. Group A received only anesthesia. After a minimum 1‐week washout period, the cats were randomly reassigned to two groups for Part II of the larger study. Group P/A/O received the patch, anesthesia and ovariohysterectomy. Group A/O received anesthesia and ovariohysterectomy. Patches were left in place for 72 hours and plasma samples were obtained for fentanyl analysis while the patches were in place, and for 8 hours after patch removal for cats in Group P, P/A, and P/A/O. Results The 25 μg hour^?1 transdermal fentanyl patches were well tolerated by the cats in this study (mean body weight of 3.0 kg) and no overt adverse effects were noted. Mean plasma fentanyl concentrations over time, mean plasma fentanyl concentrations at specific times (8, 25, 49, and 73 hours after patch placement), time to first detectable plasma fentanyl concentration, time to reach maximum plasma fentanyl concentration, maximum plasma fentanyl concentration, mean plasma fentanyl concentration from 8 to 73 hours, elimination half‐life, and total area under concentration (AUC) were not statistically different among the groups. Conclusions Halothane anesthesia and anesthesia/ovariohysterectomy did not significantly alter the plasma fentanyl concentrations achieved or pharmacokinetic parameters measured, when compared with awake cats. There was a high degree of individual variability observed both within and between groups of cats in parameters measured. Clinical significance The high degree of variability observed suggests that careful observation of cats with fentanyl patches in place is required to assess efficacy and any potential adverse effects. Anesthesia and anesthesia/ovariohysterectomy do not appear to alter plasma fentanyl concentrations achieved by placement of a 25 μg hour^?1 transdermal fentanyl patch when compared to cats not undergoing these procedures.     

Adverse reactions to fentanyl transdermal patches in calves: a preliminary clinical and pharmacokinetic study

Objective

To describe adverse reactions and measure plasma fentanyl concentrations in calves following administration of a fentanyl transdermal patch (FTP).

The disposition and behavioral effects of methadone in Greyhounds

ObjectiveTo determine the behavioral effects and pharmacokinetics of methadone in healthy Greyhounds.Study designProspective experimental study.AnimalsThree male and three female healthy Greyhounds.MethodsMethadone hydrochloride, 0.5 mg kg⁻¹ IV (equivalent to 0.45 mg kg⁻¹ methadone base), was administered as an IV bolus. Trained observers subjectively assessed the behavioral effects of methadone. Blood samples were obtained at predetermined time points and plasma methadone concentrations were measured by liquid chromatography with tandem mass spectrometry. Pharmacokinetic variables were estimated with computer software.ResultsMethadone was well tolerated by the dogs with panting and defecation observed as adverse effects. Mild sedation was present, but no vomiting, excitement, or dysphoria was observed. The elimination half-life, volume of distribution, and plasma clearance were 1.53 ± 0.18 hours, 7.79 ± 1.87 L kg⁻¹, and 56.04 ± 9.36 mL minute⁻¹ kg⁻¹, respectively.Conclusions and clinical relevanceMethadone was well tolerated by Greyhounds. The volume of distribution was larger than expected, with resultant lower plasma concentrations than expected. Higher doses may need to be administered to Greyhounds in comparison with non-Greyhound dogs in order to achieve similar plasma drug concentrations. A dosage of 1–1.5 mg kg⁻¹ every 3–4 hours is suggested for future studies of analgesic efficacy of methadone in Greyhounds.     

Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus)

Objective

To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine.

Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

ObjectiveTo investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs.Study designExperimental, balanced, block randomized, two-group design.AnimalsA group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old.MethodsDeltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg^–1 hour^–1 or fentanyl 5, 10, 20, 40, 80 and 160 μg kg^–1 hour^–1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%.ResultsNWR AUC increased at fentanyl 5 μg kg^–1 hour^–1 but decreased at fentanyl 40, 80 and 160 μg kg^–1 hour^–1 and dexmedetomidine 4.0 and 8.0 μg kg^–1 hour^–1. All pigs at fentanyl 80 μg kg^–1 hour^–1, and three pigs at dexmedetomidine 8.0 μg kg^–1 hour^–1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg^–1 hour^–1 but decreased at dexmedetomidine 2, 4 and 8 μg kg^–1 hour^–1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed.Conclusion and clinical relevanceIf anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.     

Pharmacokinetics of intravenous and oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs

ObjectiveTo evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs.Study designProspective randomized experiment.AnimalsFive healthy Greyhound dogs (three males and two females) aged 2–4 years and weighing 32.5–39.7 kg.MethodsAfter jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg⁻¹). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed.ResultsOrally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (C_MAX) of amitriptyline was 27.4 ng mL⁻¹ at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean C_MAX of nortriptyline was 14.4 ng mL⁻¹ at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline.Conclusions and clinical relevanceAmitriptyline at 4 mg kg⁻¹ administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1–4 mg kg⁻¹) is appropriate in dogs.     

Effects of fentanyl–lidocaine–ketamine versus sufentanil–lidocaine–ketamine on the isoflurane requirements in dogs undergoing total ear canal ablation and lateral bulla osteotomy

ObjectiveTo compare the isoflurane-sparing effects of sufentanil–lidocaine–ketamine (SLK) and fentanyl–lidocaine–ketamine (FLK) infusions in dogs undergoing total ear canal ablation and lateral bulla osteotomy (TECA–LBO).Study designRandomized blinded clinical study.AnimalsA group of 20 client-owned dogs undergoing TECA–LBO.MethodsIntravenous (IV) administration of lidocaine (3 mg kg^–1) and ketamine (0.6 mg kg^–1) with fentanyl (5.4 μg kg^–1; n = 10; FLK group) or sufentanil (0.72 μg kg^–1; n = 10; SLK group) was immediately followed by the corresponding constant rate infusion (CRI) (lidocaine 3 mg kg^–1 hour^–1; ketamine 0.6 mg kg^–1 hour^–1; either fentanyl 5.4 μg kg^–1 hour^–1 or sufentanil 0.72 μg kg^–1 hour^–1). Anaesthesia was induced with propofol 3–5 mg kg^–1 IV and was maintained with isoflurane. End-tidal isoflurane concentration (Fe′Iso) was decreased in 0.2% steps every 15 minutes until spontaneous movements were observed (treated with propofol 1 mg kg^–1 IV) or an increase of > 30% in heart rate or mean arterial pressure from baseline occurred (treated with rescue fentanyl or sufentanil). Quality of recovery and pain were assessed at extubation using the short-form Glasgow Composite Pain Scale (SF-GCPS), Colorado State University Canine Acute Pain scale (CSU-CAP), and visual analogue scale (VAS). Data were analysed with analysis of variance, t tests, Fisher test and Spearman coefficient (p < 0.05).ResultsFe′Iso decreased significantly in SLK group (45%; p = 0.0006) but not in FLK (15%; p = 0.1135) (p = 0.0136). SLK group had lower scores for recovery quality (p = 0.0204), SF-GCPS (p = 0.0071) and CSU-CAP (p = 0.0273) than FLK at extubation. Intraoperative rescue analgesia and VAS were not significantly different between groups.Conclusions and clinical relevanceCompared with FLK infusion, CRI of SLK at these doses decreased isoflurane requirements, decreased pain scores and improved recovery quality at extubation in dogs undergoing TECA–LBO.     

Microcirculation assessment of dexmedetomidine constant rate infusion during anesthesia of dogs with sepsis from pyometra: a randomized clinical study

ObjectiveTo compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables.Study designRandomized clinical study.AnimalsA total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy.MethodsDogs were randomized into two groups: group DG, dexmedetomidine (3 μg kg^–1 hour^–1; 17 dogs) and group FG, fentanyl (5 μg kg^–1 hour^–1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used.ResultsMFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias).Conclusions and clinical relevanceDexmedetomidine (3 μg kg^–1 hour^–1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 μg kg^–1 hour^–1).     

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.

Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon)

ObjectiveTo assess the population pharmacokinetics of methadone in deer.Study designProspective non-randomized experimental trial.AnimalsTwelve healthy adult sika deer (nine males and three females).MethodsDeer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg⁻¹ or 1 mg kg⁻¹. Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM).ResultsA two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour⁻¹), metabolic clearance (34.6 L hour⁻¹), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour⁻¹), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour⁻¹, 121.0 L hour ⁻¹, 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration.Conclusions and Clinical relevanceFollowing intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer.     

Postoperative analgesic effects of either a constant rate infusion of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine after ovariohysterectomy in dogs

ObjectiveTo evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty-four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg⁻¹, infusion rate of saline 0.9% 2 mLkg⁻¹ hour⁻¹); FENT (5 μg kg⁻¹, 10 μg kg⁻¹hour⁻¹, then 2.5 μg kg⁻¹ hour⁻¹); KET (1 mgkg⁻¹, 40 μg kg⁻¹ minute⁻¹, then 10 μg kg⁻¹minute⁻¹); LIDO (2 mg kg⁻¹, 100 μg kg⁻¹ minute⁻¹, then 25 μg kg⁻¹ minute⁻¹); DEX (1 μgkg⁻¹, 3 μg kg⁻¹ hour⁻¹, then 1 μg kg⁻¹ hour⁻¹); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).ResultsAnimals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.Conclusions and clinical relevanceLKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.     

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs.Study designProspective experimental study.MethodsA total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg^–1 hour^–1) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg^–1 hour^–1). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant.ResultsDexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline.Conclusions and clinical relevanceIV infusions of 90 and 180 μg kg^–1 hour^–1 of vatinoxan combined with 4.5 μg kg^–1 hour^–1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg^–1 hour^–1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.     

Effects of two continuous infusion doses of lidocaine on isoflurane minimum anesthetic concentration in chickens

ObjectiveTo assess the effect of two intravenous (IV) doses of lidocaine on the minimum anesthetic concentration (MAC) of isoflurane in chickens.Study designBlinded, prospective, randomized, experimental crossover study.AnimalsA total of six adult female chickens weighing 1.90 ± 0.15 kg.MethodsChickens were anesthetized with isoflurane and mechanically ventilated. Isoflurane MAC values were determined (T0) in duplicate using an electrical noxious stimulus and the bracketing method. After MAC determination, a low dose (LD; 3 mg kg^–1 followed by 3 mg kg^–1 hour^–1) or high dose (HD; 6 mg kg^?1 followed by 6 mg kg^?1 hour^–1) of lidocaine was administered IV. MAC determination was repeated at 1.5 (T1.5) and 3 (T3) hours of lidocaine administration and blood was collected for analysis of plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations. Pulse rate, peripheral hemoglobin oxygen saturation, noninvasive systolic arterial pressure and cloacal temperature were recorded at T0, T1.5 and T3. Treatments were separated by 1 week. Data were analyzed using mixed-effects model for repeated measures.ResultsMAC of isoflurane (mean ± standard deviation) at T0 was 1.47 ± 0.18%. MAC at T1.5 and T3 was 1.32 ± 0.27% and 1.26 ± 0.09% (treatment LD); and 1.28 ± 0.06% and 1.30 ± 0.06% (treatment HD). There were no significant differences between treatments or times. Maximum plasma lidocaine concentrations at T3 were 496 ± 98 and 1200 ± 286 ng mL^–1 for treatments LD and HD, respectively, and were not significantly different from T1.5. With treatment HD, plasma concentration of MEGX was significantly higher at T3 than at T1.5. Physiological variables were not significantly different among times with either treatment.Conclusions and clinical relevanceAdministration of lidocaine did not significantly change isoflurane MAC in chickens. Within treatments, plasma lidocaine concentrations were not significantly different at 1.5 and 3 hours.     

Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane‐anaesthetized sheep

ObjectiveTo determine the anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in sheep anaesthetized with isoflurane and undergoing orthopaedic surgery.Study designProspective, randomised, ‘blinded’ controlled study.AnimalsTwenty healthy sheep (weight mean 41.1 ± SD 4.5 kg).MethodsSheep were sedated with intravenous (IV) dexmedetomidine (4 μg kg⁻¹) and morphine (0.2 mg kg⁻¹). Anaesthesia was induced with propofol (1 mg kg⁻¹ minute⁻¹ to effect IV) and maintained with isoflurane in oxygen and a continuous rate infusion (CRI) of fentanyl 10 μg kg⁻¹ hour⁻¹ (group F) or saline (group P) for 100 minutes. The anaesthetic induction dose of propofol, isoflurane expiratory fraction (Fe’iso) required for maintenance and cardiorespiratory measurements were recorded and blood gases analyzed at predetermined intervals. The quality of recovery was assessed. Results were compared between groups using t-tests or Mann–Whitney as relevant.ResultsThe propofol induction dose was 4.7 ± 2.4 mg kg⁻¹. Fe’iso was significantly lower (by 22.6%) in group F sheep than group P (p = 0). Cardiac index (mean ± SD mL kg⁻¹ minute⁻¹) was significantly (p = 0.012) lower in group F (90 ± 15) than group P (102 ± 35). Other measured cardiorespiratory parameters did not differ statistically significantly between groups. Recovery times and recovery quality were statistically similar in both groups.Conclusions and clinical relevanceFentanyl reduced isoflurane requirements without clinically affecting the cardiorespiratory stability or post-operative recovery in anaesthetized sheep undergoing orthopaedic surgery.     

Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

ObjectiveTo assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs.Study designRandomized experimental trial.AnimalsSeven healthy male neutered Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg.MethodsThe study was a randomized Latin square block design. Dogs were randomly assigned to receive hydromorphone hydrochloride 0.1 mg kg⁻¹ or 0.5 mg kg⁻¹ IV (n = 4 dogs) or 0.1 mg kg⁻¹ (n = 6) or 0.5 mg kg⁻¹ (n = 5) SC on separate occasions with a minimum 14-day washout between experiments. Blood was sampled via a vascular access port at serial intervals after drug administration. Serum was analyzed by mass spectrometry. Pharmacokinetic parameters were determined with computer software.ResultsSerum concentrations of hydromorphone decreased quickly after both routes of administration of either dose. The serum half-life, clearance, and volume of distribution after IV hydromorphone at 0.1 mg kg⁻¹ were 0.57 hours (geometric mean), 106.28 mL minute⁻¹ kg⁻¹, and 5.35 L kg⁻¹, and at 0.5 mg kg⁻¹ were 1.00 hour, 60.30 mL minute⁻¹ kg⁻¹, and 5.23 L kg⁻¹, respectively. The serum half-life after SC hydromorphone at 0.1 mg kg⁻¹ and 0.5 mg kg⁻¹ was 0.66 hours and 1.11 hours, respectively.Conclusions and clinical relevanceHydromorphone has a short half-life, suggesting that frequent dosing intervals are needed. Based on pharmacokinetic parameters calculated in this study, 0.1 mg kg⁻¹ IV or SC q 2 hours or a constant rate infusion of hydromorphone at 0.03 mg kg⁻¹ hour⁻¹ are suggested for future studies to assess the analgesic effect of hydromorphone.     

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.     

Plasma histamine concentrations in horses administered sodium penicillin,guaifenesin–xylazine–ketamine and isoflurane with morphine or butorphanol

ObjectiveVarious drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions.Study designProspective studies with one randomized.AnimalsA total of 44 client-owned horses.MethodsIn one study, anesthesia was induced with xylazine followed by ketamine–diazepam. Anesthesia was maintained with guaifenesin–xylazine–ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg^–1 and 0.1 mg kg^–1 hour^–1; 15 horses) or butorphanol (group B: 0.05 mg kg^–1 and 0.01 mg kg^–1 hour^–1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05.ResultsWith histamine, differences occurred between baseline (3.2 ± 2.4 ng mL^–1) and GXK (5.2 ± 7.1 ng mL^–1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL^–1) and group M (11.1 ± 12.4 ng mL^–1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL^–1) than at 30 minutes (4.9 ± 3.1 ng mL^–1) and 60 minutes (4.0 ± 2.5 ng mL^–1). Histamine correlated with morphine at 2, 30 and 60 minutes.Conclusions and clinical relevanceGXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.     

Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats

ObjectiveTo compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.MethodsAfter premedication with medetomidine 0.01 mg kg⁻¹ intramuscularly and meloxicam 0.3 mg kg⁻¹ subcutaneously, the cats were assigned randomly into two groups: group A (n = 10) were administered alfaxalone 5 mg kg⁻¹ minute⁻¹ followed by 10 mg kg⁻¹ hour⁻¹ intravenously (IV) and group P (n = 10) were administered propofol 6 mg kg⁻¹ minute⁻¹ followed by 12 mg kg⁻¹hour⁻¹ IV for induction and maintenance of anaesthesia, respectively. After endotracheal intubation, the tube was connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (± 0.5 mg kg⁻¹ hour⁻¹) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs. If apnoea > 30 seconds, end-tidal carbon dioxide (Pe′CO₂) > 7.3 kPa (55 mmHg) or arterial haemoglobin oxygen saturation (SpO₂) < 90% occurred, manual ventilation was provided. Methadone was administered postoperatively. Data were analyzed using independent-samples t-tests, Fisher's exact test, linear mixed-effects models and binomial test.ResultsManual ventilation was required in two and eight of the cats in group A and P, respectively (p = 0.02). Two cats in both groups showed apnoea. Pe′CO₂ > 7.3 kPa was recorded in zero versus four and SpO₂ < 90% in zero versus six cats in groups A and P respectively. Induction and maintenance dose rates (mean ± SD) were 11.6 ± 0.3 mg kg⁻¹ and 10.7 ± 0.8 mg kg⁻¹ hour⁻¹ for alfaxalone and 11.7 ± 2.7 mg kg⁻¹ and 12.4 ± 0.5 mg kg⁻¹ hour⁻¹ for propofol.Conclusion and clinical relevanceAlfaxalone had less adverse influence on respiration than propofol in cats premedicated with medetomidine. Alfaxalone might be better than propofol for induction and maintenance of anaesthesia when artificial ventilation cannot be provided.     

Fatal overdose after ingestion of a transdermal fentanyl patch in two non‐human primates

Case history and presentationTwo non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour^?1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis.Management and follow-upAttempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L^?1) confirmed fentanyl overdose.ConclusionsThis report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach.