Pharmacokinetics and tolerance of transdermal fentanyl administration in foals

ObjectiveTo characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS).Study designProspective experimental study.AnimalsSix (two male, four female) foals aged 4–8 days, weighing 56–74 kg.MethodsAfter placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 μg hour⁻¹, was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count and blood chemistry values were obtained. During the study, tolerance and safety were monitored by physical examination and assessment of behavior.ResultsFentanyl was detected as early as 20 minutes after FTS placement. Peak plasma concentrations were variable (0.1–28.7 ng mL⁻¹), were reached after 14.3 ± 7.6 hours (mean ± SD), and returned to baseline concentrations 12 hours after FTS removal. All foals satisfactorily tolerated the FTS application and no significant adverse effects were observed. Rectal temperature increased above 38.5 °C (max. 39.0 °C) in all foals, although this did not correlate with fentanyl plasma concentrations. Results of hematological and biochemical analyses were within reference ranges.Conclusion and clinical relevance Our data show that 100 μg hour⁻¹ fentanyl administered by an FTS results in time-related but variable plasma concentrations in foals. The FTS was easy to apply and was well tolerated.     

Development and optimization of a fentanyl pharmacokinetic model for target-controlled infusion in anaesthetized dogs

ObjectiveTo investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs.Study designProspective clinical study.AnimalsA group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic resonance imaging.MethodsFentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system incorporating a previously described fentanyl two-compartment PK. Arterial blood samples were collected at specific time points during the infusion and over 60 minutes post-infusion for measurement of fentanyl plasma concentrations. The predictive performance of the Sano PK model was assessed by comparing predicted and measured plasma concentrations. A population PK analysis was then performed using a nonlinear mixed-effect modelling approach, allowing inter- and intra-individual variability estimation. Finally, a quantitative stepwise evaluation of the influence of various covariates such as weight, body condition score, size, size-related age, sex and type of premedication on the PK model was considered.ResultsOverall predictive performance of the Sano PK set of variables was not clinically acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment model. Weight and sex were found to affect the volume of distribution of the central compartment. Addition of these two covariate/variable associations resulted in a reduction of the objective function value (OFV) from –340.18 to –448.34, and of the median population weighted residual and the median population absolute weighted residual from 16.1% and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations up to 5.4 ng mL^–1 in sevoflurane-anaesthetized dogs resulted in stable anaesthesia and smooth recoveries without complications.Conclusions and clinical relevanceA population three-compartment PK model for fentanyl TCI in anaesthetized dogs was developed. Weight and sex have been detected and incorporated as significant covariates.     

Effect of intravenous fentanyl on cough reflex and quality of endotracheal intubation in cats

ObjectiveTo assess the effects of intravenous (IV) fentanyl on cough reflex and quality of endotracheal intubation (ETI) in cats.Study designRandomized, blinded, negative controlled clinical trial.AnimalsA total of 30 client-owned cats undergoing general anaesthesia for diagnostic or surgical procedures.MethodsCats were sedated with dexmedetomidine (2 μg kg^–1 IV), and 5 minutes later either fentanyl (3 μg kg^–1, group F) or saline (group C) was administered IV. After alfaxalone (1.5 mg kg^–1 IV) administration and 2% lidocaine application to the larynx, ETI was attempted. If unsuccessful, alfaxalone (1 mg kg^–1 IV) was administered and ETI re-attempted. This process was repeated until successful ETI. Sedation scores, total number of ETI attempts, cough reflex, laryngeal response and quality of ETI were scored. Postinduction apnoea was recorded. Heart rate (HR) was continuously recorded and oscillometric arterial blood pressure (ABP) was measured every minute. Changes (Δ) in HR and ABP between pre-intubation and intubation were calculated. Groups were compared using univariate analysis. Statistical significance was set as p < 0.05.ResultsThe median and 95% confidence interval of alfaxalone dose was 1.5 (1.5–1.5) and 2.5 (1.5–2.5) mg kg^–1 in groups F and C, respectively (p = 0.001). The cough reflex was 2.10 (1.10–4.41) times more likely to occur in group C. The overall quality of ETI was superior in group F (p = 0.001), with lower laryngeal response to ETI (p < 0.0001) and ETI attempts (p = 0.045). No differences in HR, ABP and postinduction apnoea were found.Conclusions and clinical relevanceIn cats sedated with dexmedetomidine, fentanyl could be considered to reduce the alfaxalone induction dose, cough reflex and laryngeal response to ETI and to improve the overall quality of ETI.     

Accidental prehension and suspected transmucosal or oral absorption of fentanyl from a transdermal patch in a dog

A 100-microg hour(-1) transdermal fentanyl patch was applied to a 29-kg, 6-year-old, intact male mixed breed dog to help manage postoperative pain after total ear canal ablation and lateral bulla osteotomy. Two days later, the dog was found extremely sedated, and the reservoir of the transdermal patch was open. It was suspected that the dog ingested the contents of the reservoir of the transdermal patch and absorbed the fentanyl across its oral mucosa or through the gastrointestinal tract resulting in an overdose. The patch was removed, blood was drawn to determine serum fentanyl levels, and the dog recovered without incident. This clinical case documents the potential for neurologic sequelae, and bradycardia when fentanyl patches are used in animals to relieve postoperative pain.     

Context-sensitive half-time of fentanyl in dogs

Context-sensitive half-times (CSHTs) of fentanyl in dogs were determined using pharmacokinetic models reported by Murphy et al. and Sano et al., and compared with a human model. The CSHT was defined as the time required for a 50% decrease in drug concentration in the central compartment after the termination of infusion. Although CSHTs increased gradually as the infusion time increased, the CSHTs in dogs were shorter than those in humans. The CSHTs at steady-state were 31.3 and 69.2 min in dogs, and 306.5 min in humans. The CSHTs of fentanyl in dogs are apparently shorter than those in humans; therefore, a continuous infusion of fentanyl may be a rational regimen in dogs, even if duration of infusion is extended.     

Effects of morphine and fentanyl constant rate infusion on urine output in healthy and traumatized dogs

ObjectiveTo determine whether healthy and traumatized dogs receiving a constant rate infusion (CRI) of either morphine or fentanyl have decreased urine production.Study designProspective randomized controlled study.Animal populationEighteen privately owned previously healthy dogs that had undergone trauma were included. Twenty-three privately owned healthy dogs were used as the controls.MethodsTraumatized dogs were randomized into one of two groups. Group Tmorphine received a CRI of morphine (0.12 mg kg⁻¹ hour⁻¹) and group Tfentanyl received a CRI of fentanyl (3 μg kg⁻¹ hour⁻¹) both administered in lactated Ringer’s solution (LRS) at a rate of 60 mL kg⁻¹ day⁻¹. Control healthy dogs were randomized into one of three groups. The LRS control group (CLRS) (n = 8) received LRS at a rate of 60 mL kg⁻¹ day⁻¹. Group Cmorphine (n = 8) and group Cfentanyl (n = 7) received the same infusions as Tmorphine and Tfentanyl, respectively. Collected data were identical for all groups and consisted of measuring total fluid administered, urine output, and urine specific gravity (USG) for a 24-hour period. An analysis of variance (anova) was used for statistical analysis and a p < 0.05 was considered statistically significant.ResultsUrine output was significantly decreased (p < 0.05) in all groups compared with the LRS control group. The end mean USG was significantly lower (p = 0.003) in the LRS control group compared with all other groups.ConclusionsThere was a decrease in urine output with a CRI of morphine or fentanyl in both healthy and traumatized dogs.Clinical relevanceDecreased urine output caused by an opioid effect might lead to improper assessments of renal function and urine production.     

Analgesic management of an eight-year-old Springer Spaniel after amputation of a thoracic limb

Analgesic agents were administered perioperatively to an eight-year-old Springer Spaniel undergoing amputation of its right thoracic limb. The amputation was carried out due to a painful, infiltrative and poorly differentiated sarcoma involving the nerves of the brachial plexus. A combination of pre-emptive and multimodal perioperative analgesic strategies was used; including intravenous (IV) infusions of fentanyl, morphine, lidocaine and ketamine.     

Total intravenous anaesthesia (TIVA) with propofol-fentanyl and propofol-midazolam combinations in spontaneously-breathing goats

ObjectiveTo compare the efficacy and cardiopulmonary effects of propofol and fentanyl, with propofol and midazolam for total intravenous anaesthesia.Study designProspective, randomized, crossover experimental study.AnimalsSix goats; three does and three wethers.MethodsGoats received either fentanyl 0.02 mg kg^?1 (treatment FP) or midazolam 0.3 mg kg^?1 (treatment MP) intravenously. One minute later anaesthesia was induced with propofol, then maintained by constant rate infusion of propofol 12.0 mg kg^?1 hour^?1 and fentanyl 0.02 mg kg^?1 hour^?1 (treatment FP) or propofol 12.0 mg kg^?1 hour^?1 and midazolam 0.3 mg kg^?1 hour^?1 (treatment MP) for 90 minutes. Response to noxious stimulus was tested every 10 minutes and propofol dose adjusted to prevent purposeful movement. Cardiopulmonary parameters were measured continuously, and arterial blood-gas analysis performed intermittently. Recovery was timed and quality scored. Results are presented as median (IQR).ResultsDifferences in the propofol induction dose [4.00 (3.96-4.01) and 3.97 (3.91-4.00) mg kg^?1 for treatments FP and MP, respectively] were not significant. Quality of induction in both groups was smooth. The median propofol dose for maintenance was less (p = 0.004) with treatment FP (12.0 mg kg^?1 hour^?1) than MP (18.0 mg kg^?1 hour^?1). Cardiopulmonary function was well maintained with both treatments. Recovery times in minutes from the end of anaesthetic infusion for treatments FP and MP respectively were; to extubation 3.0 (3.0-3.0) and 4.5 (3.3-5.0); to sternal position, 4.5 (3.3-5.0) and 5.0 (5.0-6.5) and to standing 13.0 (10.3-15.0) and 15.0 (11.3-17.3). Quality of recovery was acceptable in both groups, but abnormal behavioural signs were observed after treatment FP.Conclusions and clinical relevanceTotal intravenous anaesthesia with propofol and fentanyl or propofol and midazolam, at the doses studied, in spontaneously-breathing, oxygen-supplemented goats is practicable. Recovery from the fentanyl-propofol combination is not always smooth.     

芬太尼联合异丙酚在食管静脉曲张套扎中的有效性和安全性分析

目的探讨芬太尼联合异丙酚用于食管静脉曲张套扎治疗的疗效和安全性。方法73例肝硬化患者分为芬太尼联合异丙酚组（Ⅰ组）、镇静剂组（Ⅱ组）和普通胃镜组（Ⅲ组）,共进行114例次内镜下套扎术,比较各组胃镜操作时间、视野清晰度、术中不适反应和呼吸、心率、血压、血氧饱和度变化。结果Ⅰ组胃镜操作时间明显短于Ⅲ组（P〈0．05）,Ⅰ组及Ⅱ组视野清晰度明显高于Ⅲ组（P〈0．05）。除Ⅰ组患者术中血压有一过性下降外（P〈0．01）,各组的呼吸、心率、血氧饱和度无明显变化,但Ⅰ、Ⅱ组术中不适反应少。结论芬太尼联合异丙酚实行食管静脉曲张套扎术疗效良好,不适反应少。