The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Low-dose sugammadex reverses moderate rocuronium-induced neuromuscular block in horses.

BACKGROUND: Neuromuscular block (NMB) during general anaesthesia has an implicit risk of inadvertent residual NMB during recovery. Reversal of NMB is commonly encouraged to decrease this risk, and has historically been performed with neostigmine/atropine, two agents with important cardiac and gastrointestinal side effects. Sugammadex is a new selective relaxant binding agent that can reverse rocuronium-induced NMB efficiently and without these complications. Recommended doses are possibly cost-prohibitive. OBJECTIVES: To measure the recovery time from rocuronium-NMB after administration of low-dose sugammadex, compared with spontaneous recovery. STUDY DESIGN: Nonrandomised in vivo experiments. METHODS: Fourteen adult horses undergoing different research procedures were anaesthetised with detomidine and isoflurane. All horses received NMB with rocuronium 0.3 mg/kg IV. Neuromuscular function was measured with acceleromyographic train-of-four (TOF) ratio. Recovery occurred spontaneously in five horses weighing (median [range]) 548 (413-594) kg and was enhanced with sugammadex 200 mg (total dose) in nine horses (433 [362-515]) kg. Recovery time from moderate NMB to a TOF ratio 1.0, and total duration of NMB were compared between groups. Cases of recurarisation (decrease in the TOF ratio <0.9 after recovery) were identified within 30 min after sugammadex. RESULTS: The dose of sugammadex was 0.46 (0.39-0.55) mg/kg. The recovery period lasted 21 (17-39) minutes for spontaneous and 4 (3-7) minutes for sugammadex. Total duration of NMB was 58 (41-70) minutes for spontaneous and 36 (21-43) for sugammadex (both p ≤ 0.003). There were no instances of recurarisation. MAIN LIMITATIONS: Small sample size. CONCLUSIONS: A dose of sugammadex of approximately 0.5 mg/kg substantially shortened the recovery period from rocuronium-induced NMB from a median of 21 to 4 min, when given at a moderate depth of NMB. No recurarisation was observed within the next 30 min.

Evaluation of a rapid sequence induction technique in dogs with or without rocuronium.

OBJECTIVE: To determine, using a rapid sequence induction (RSI) technique, whether rocuronium improves the quality and speed of endotracheal intubation in healthy dogs. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six adult intact male Beagles (12.3 ± 0.4 kg). METHODS: Dogs were premedicated with intravenous acepromazine (0.03 mg kg-1) and hydromorphone (0.1 mg kg-1). Ten minutes later, anesthesia was induced with intravenous propofol (2 mg kg-1 over 5 seconds), followed by saline (0.06 mL kg-1, CT group) or rocuronium (0.6 mg kg-1, RT group), with orotracheal intubation attempted after 45 seconds. Intubation time (IT) and conditions (IC) were assessed. PaO2, PaCO2, arterial blood pH and serum cortisol were obtained before and after RSI. After endotracheal intubation, saline (0.04 mL kg-1) or sugammadex (4 mg kg-1) were administered intravenously in CT or RT groups, respectively. Spontaneous ventilation restoration was noted. RESULTS: The IT was 54.3 ± 6.9 (mean ± SD) and 57.8 ± 5.2 seconds for CT and RT, respectively (p = 0.385). All laryngoscopies indicated good IC in both treatment groups. Heart rate was lower in CT group than in RT group (66 ± 16 versus 103 ± 39 beats minute-1, p = 0.016). PaCO2, pH, PaO2 and cortisol did not differ between treatments. Compared with baseline, PaCO2 increased from 47.7 ± 6.2 to 58.8 ± 5.8 (p < 0.001) and pH decreased from 7.35 ± 0.04 to 7.28 ± 0.04 (p = 0.003), independent of treatment. Dogs in both treatment groups returned to spontaneous ventilation within 30 seconds of RSI. CONCLUSIONS AND CLINICAL RELEVANCE: RSI resulted in respiratory acidosis without hypoxemia or increased cortisol. Rocuronium did not improve IT or IC. Spontaneous ventilation was observed immediately after administering saline or sugammadex. The co-administration of rocuronium showed no clinical benefits over propofol alone in RSI in healthy dogs.

Post-anesthetic CPS and EQUUS-FAP scores in surgical and non-surgical equine patients: an observational study.

Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs. Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures. Study design: Clinical observational study. Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected. Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2. Main limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results. Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively.

Evaluation of a three-axial acceleromyography monitor in dogs compared with mechanomyography.

OBJECTIVE: To compare the ratio of the train-of-four (TOF) and double burst stimulation (DBS) obtained with three-axial acceleromyography (AMG) and mechanomyography (MMG) in dogs during recovery from a rocuronium-induced neuromuscular block. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A total of six intact healthy adult male Beagle dogs, weighing 9.1 ± 1.9 kg and aged 3-5 years. METHODS: Dogs were anesthetized with intravenous (IV) dexmedetomidine and propofol, and isoflurane in oxygen. Neuromuscular function was measured with AMG and MMG in the contralateral thoracic limbs. Rocuronium (0.5 mg kg-1) was administered IV, and the TOF and DBS ratios measured. During neuromuscular block offset, MMG values were recorded when AMG first reached ratios of 0.9 and 1.0. True recovery from neuromuscular block was determined as MMG ratio ≥ 0.9. The false-positive (AMG ≥ 0.9 or 1.0, and MMG ratio < 0.9) rate was determined. Paired values were compared, and bias and limits of agreement were calculated. Receiver operating characteristic (ROC) curves were created. RESULTS: When AMG first reached 0.9 and 1.0 during recovery, MMG values were lower (p < 0.040). When AMG reached 0.9, the false-positive rate was 29% with TOF and 27% with DBS. It decreased to 12% (TOF) and 11% (DBS) when a ratio of 1.0 was used. AMG values were higher than paired MMG values (p < 0.001). The AMG overestimated MMG by 24% and 22% for TOF and DBS, respectively. Areas under the ROC curves (95% confidence interval) were 0.91 (0.89, 0.94) and 0.86 (0.81, 0.94) for TOF and DBS, respectively. CONCLUSIONS: and clinical relevance The three-axial AMG monitor overestimated neuromuscular function and, in some cases, indicated adequate recovery despite the MMG ratio being < 0.9. A TOF or DBS ratio of at least 1.0 should be considered when monitoring recovery of neuromuscular block with this AMG device.

Rocuronium-neuromuscular blockade does not influence the patient state index in anesthetized dogs.

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.

The effect of adding a heated humidified breathing circuit on body temperature in healthy anesthetized dogs.

OBJECTIVE: To compare the effect of a circulating warm water blanket (WWB) in combination with a heated humidified breathing circuit (HHBC) heated to 45 °C on rectal temperature (RT) in dogs undergoing general anesthesia for elective ovariohysterectomies. ANIMALS: 29 healthy dogs. PROCEDURES: Dogs in the experimental group (n = 8) and dogs in the control group (21) were connected to an HHBC and a conventional rebreathing circuit, respectively. All dogs were placed on a WWB in the operating room (OR). The RT was recorded at baseline, premedication, induction, transfer to OR, every 15 minutes during maintenance of anesthesia, and extubation. Incidence of hypothermia (RT < 37 °C) at extubation was recorded. Data were analyzed using unpaired t tests, the Fisher exact test, and mixed-effect ANOVA. Statistical significance was defined as P < .05. RESULTS: There was no difference in RT during baseline, premedication, induction, and transfer to OR. The overall RT was higher for the HHBC group during anesthesia (P = .005) and at extubation (37.7 ± 0.6 °C) compared with the control group (36.6 ± 1.0 °C; P = .006). The incidence of hypothermia at extubation was 12.5% for the HHBC group and 66.7% for the control group (P = .014). CLINICAL RELEVANCE: The combination of HHBC and WWB can reduce the incidence of postanesthetic hypothermia in dogs. Use of an HHBC should be considered in veterinary patients.

Evaluation of the electroencephalogram in awake, sedated, and anesthetized dogs.

Sedation and anesthesia alter the raw electroencephalogram (EEG). Interpretation of the EEG is facilitated by measuring the patient state index (PSI), visual inspection of density spectral arrays (DSA), and power density analysis of the delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta plus gamma (12-40 Hz) frequency bands. Baseline data were recorded in six male intact Beagles before sedation with intravenous acepromazine (0.03 mg/kg) and hydromorphone (0.1 mg/kg). Anesthesia was induced and maintained for five minutes with intravenous propofol (1.5 mg/kg over five seconds followed by 12 mg/kg/h). Additional propofol (0.5-1.0 mg/kg and up to 16.7 mg/kg/h) was administered within this time frame if the PSI was above 50. The effects of sedation and anesthesia were evaluated with a mixed-effect model followed by Dunnett's test (alpha = 0.05). The average baseline PSI (95% confidence interval) was 93.0 (91.4-94.6) and decreased on sedation [88.7 (86.0-91.3); p = 0.039] and anesthesia [44.5 (40.8-48.2); p < 0.001]. The awake DSA showed dense power in all bands. The power density decreased with sedation. During anesthesia, the power density was reduced in frequencies above 12 Hz. The baseline power density on the delta, theta, alpha, and beta plus gamma bands was higher than sedation (p < 0.007). Compared to baseline, anesthesia had lower power on delta, and beta plus gamma bands (p < 0.002). The interpretation in awake, sedated, and anesthetized dogs of the EEG can be facilitated by processing and generating PSI and DSA.

Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses.

OBJECTIVE: To evaluate a regional anesthetic technique for blocking the abdominal midline in horses. STUDY DESIGN: Anatomical description and prospective, crossover, placebo-controlled, blinded study. ANIMALS: Adult horses; two cadavers, six healthy animals. METHODS: In stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg-1) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg-1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded. RESULTS: The cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9-L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Antinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies.

A flexible endotracheal tube introducer improves first-attempt success of intubation in cats by novice anesthetists.

OBJECTIVE: To test whether the use of a flexible endotracheal tube introducer (ETI) facilitates intubation of cats by veterinary students with little or no experience. ANIMALS: 125 healthy cats. PROCEDURES: Cats were sedated with dexmedetomidine and morphine IM, and anesthesia was induced with propofol. They were randomly assigned to be intubated by supervised veterinary students using an ETI within a tracheal tube or an endotracheal tube alone (3.0, 3.5, or 4.0 internal diameter sizes). Success rate at first attempt, number of attempts to intubate (up to 3), and time to intubate were recorded. Multivariate logistic regression was used to test associations between several factors such as use of an ETI, cat's weight, endotracheal tube size, administration of ketamine for sedation, and first-attempt success. Significance was considered when P < 0.05. RESULTS: Success rate for the first attempt was higher with an ETI (79% [51/64) than without it (46% [28/61]), and attempts to intubate were fewer when an ETI was used (both P < 0.001). Time to intubate did not differ between groups (ETI, 30 seconds [4 to 143 seconds]; endotracheal tube, 28 seconds [5 to 180 seconds]). Use of an ETI was positively associated with improved first-attempt success, and the 3.0-mm internal diameter of the tube was negatively associated (both P ≤ 0.001). CLINICAL RELEVANCE: The use of a flexible ETI improved the success of first-attempt intubation of cats by veterinary students. This technique may help minimize the number of attempts during intubation and incidence of complications that could arise from multiple attempts.

A model of transient laryngeal hemiplegia in dogs through conduction blockade of the recurrent laryngeal nerve.

OBJECTIVE: To create a model of transient unilateral laryngeal paralysis (LP) that will allow the study of cricoarytenoideus dorsalis dysfunction and a method for quantification of varying degrees of LP in dogs. ANIMALS: 5 castrated male research Beagles. PROCEDURES: Between January and February 2018, dogs were anesthetized and instrumented with a laryngeal mask airway and a flexible endoscope to record the rima glottidis. The left or right recurrent laryngeal nerve (RLn) was localized using ultrasonography and electrical stimulation, then conduction blockade was induced with perineural lidocaine. The normalized glottal gap area (NGGA) was measured before and every 15 minutes after the block. Inspired 10% carbon dioxide (CO2) was administered for 1 minute at each sampling time. The inspiratory increase in NGGA (total and each side) was measured at peak inspiration. The change in hemi-NGGA for the control side versus the anesthetized side was evaluated with a mixed-effect model. RESULTS: During CO2 stimulation, the increase in inspiratory hemi-NGGA was consistently less (P < .001) for the treated side (-8% to 13%) versus the control side (49% to 82%). A compensatory increase (larger than at baseline) in the control hemi-NGGA was observed. The total NGGA remained unaffected. CLINICAL RELEVANCE: Unilateral local anesthesia of the RLn produced transient unilateral LP with a compensatory increase in the hemi-NGGA for the contralateral side. This model could facilitate the evaluation of respiratory dynamics, establishment of a grading system, and collection of other important information that is otherwise difficult to obtain in dogs with LP.

Quantitative assessment of progressive laryngeal hemiplegia in a 4-year-old beagle.

Progression of unilateral laryngeal paralysis (LP) was quantified in an asymptomatic 4-year-old beagle during spontaneous breathing stimulated with inhaled 10% CO2. Laryngeal evaluation was performed sequentially to track progression of LP over an 18-month period. Videos of the larynx during CO2-stimulated breathing were obtained under propofol anaesthesia. Maximal inspiratory normalised glottal gap area (NGGA) was determined on each occasion for left and right hemiglottis. Left NGGA was smaller than the right side throughout the period of follow-up. After 18 months, LP had progressed to such a degree that the left arytenoid was completely paralysed with no movement during inspiration. This case report demonstrates the possibility of early detection of LP, and quantification of progression. Early detection may allow regenerative surgical strategies for LP to maintain glottic area and reduce postoperative complication rates.

The effect of a ketamine constant rate infusion on cardiovascular variables in sheep anesthetized at the minimum alveolar concentration of sevoflurane that blunts adrenergic responses.

OBJECTIVE: To evaluate the effect of a constant rate infusion of ketamine on cardiac index (CI) in sheep, as estimated using noninvasive cardiac output (NICO) monitoring by partial carbon dioxide rebreathing, when anesthetized with sevoflurane at the previously determined minimum alveolar concentration that blunts adrenergic responses (MACBAR). ANIMALS: 12 healthy Dorset-crossbred adult sheep. PROCEDURES: Sheep were anesthetized 2 times in a balanced placebo-controlled crossover design. Anesthesia was induced with sevoflurane delivered via a tight-fitting face mask and maintained at MACBAR. Following induction, sheep received either ketamine (1.5 mg/kg IV, followed by a constant rate infusion of 1.5 mg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (placebo). After an 8-day washout period, each sheep received the alternate treatment. NICO measurements were performed in triplicate 20 minutes after treatment administration and were converted to CI. Blood samples were collected prior to the start of NICO measurements for analysis of ketamine plasma concentrations. The paired t test was used to compare CI values between groups and the ketamine plasma concentrations with those achieved during the previous study. RESULTS: Mean ± SD CI of the ketamine and placebo treatments were 2.69 ± 0.65 and 2.57 ± 0.53 L/min/m2, respectively. No significant difference was found between the 2 treatments. Mean ketamine plasma concentration achieved prior to the NICO measurement was 1.37 ± 0.58 µg/mL, with no significant difference observed between the current and prior study. CLINICAL RELEVANCE: Ketamine, at the dose administered, did not significantly increase the CI in sheep when determined by partial carbon dioxide rebreathing.

Implementation of a Low-Cost 3D-Printed Feline Larynx Model for Veterinary Students.

Endotracheal intubation (EI) in domestic cats is an important skill that veterinary students learn in order to perform anesthesia safely in this species. Implementing a 3D-printed larynx model (LaryngoCUBE) during the instruction process may improve student's learning of EI in felines. Twenty-two third-year students performed EI in cats with standard training (ST), and 16 students trained with the model (MT) the day before the laboratory. It was evaluated whether training with the model decreases the time and number of EI attempts, students' perceived difficulty performing EI using a visual analog score (VAS; 0 cm = very easy, 10 cm = extremely difficult; median [minimum-maximum]), and the incidence of failure to perform EI. The EI time on ST (58 [18-160] seconds) was longer, but not statistically different from MT (29 [13-120] seconds; p = .101). The number of EI attempts on ST (2 [1-3]) was higher than MT (1 [1-3]; p = .005). The VAS on the ST and MT were 4.5 (0.0-10.0) cm and 3.0 (0.2-10.0) cm, respectively (p = .029). The failure rate was 27% on the ST and 25% on the MT (p = 1.000). Students who practiced with a larynx model took fewer attempts to perform EI, tended to be faster, and found that EI was easier. However, the EI success rate in MT was not improved.

Influence of doxapram and intermittent 10% carbon dioxide inspiration on cardiovascular and laryngeal functions in anesthetized dogs.

OBJECTIVE: To compare the effects of two doses of doxapram intravenous injection and carbon dioxide inhalation on the cardiovascular and laryngeal functions of anesthetized hounds. STUDY DESIGN: Experimental study. ANIMALS: Six healthy adult dogs. METHODS: In a Latin-square design, the mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously. The inspiratory normalized glottic gap areas (iNGGA) were measured before and after each stimulation with 0.55 mg/kg of doxapram (L-DOX), 2.2 mg/kg of doxapram (H-DOX), or 90 s of inhalation of 10% carbon dioxide in oxygen (I-CO2 ). The stimulations were tested in duplicate or triplicate. Video clips of the laryngeal movement were scored by board-certified surgeons masked to the treatment. RESULTS: The MABP increased with L-DOX and H-DOX up to 81% (both p < .001 compared to I-CO2 ), and persisted during the other stimulations (both p < .001). An intermittent tachycardic effect of up to 79% increase in HR was observed with doxapram. The HR following H-DOX was higher than L-DOX and I-CO2 (both p < .016). Neither hypertension nor tachycardia was observed with I-CO2 . The iNGGA increased with all treatments (p < .001). The iNGGA was greater with H-DOX than L-DOX and I-CO2 (both p < .007). All treatments received higher scores (all p < .001) with acceptable inter- and intra-observers Krippendorff's alphas. CONCLUSION: All treatments were effective respiratory stimulants in anesthetized dogs; however, doxapram caused hypertension and tachycardia. CLINICAL SIGNIFICANCE: Carbon dioxide inhalation might improve arytenoid motion without cardiovascular effects in dogs during clinical airway examinations.

Pharmacokinetics and pharmacodynamics of methadone administered intravenously and intramuscularly to isoflurane-anesthetized chickens.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of methadone after IV or IM administration to isoflurane-anesthetized chickens. ANIMALS: 6 healthy adult Hy-Line hens. PROCEDURES: In a randomized crossover-design study, methadone (6 mg/kg) was administered IV and IM to isoflurane-anesthetized chickens with a 1-week washout period between experiments. Blood samples were collected immediately before and at predetermined time points up to 480 minutes after methadone administration. Plasma concentrations were determined by liquid chromatography-mass spectrometry, and appropriate compartmental models were fit to the plasma concentration-versus-time data. Cardiorespiratory variables were compared between treatments and over time with mixed-effect repeated-measures analysis. RESULTS: A 3-compartment model best described the changes in plasma methadone concentration after IV or IM administration. Estimated typical values for volumes of distribution were 692 mL/kg for the central compartment and 2,439 and 2,293 mL/kg for the first and second peripheral compartments, respectively, with metabolic clearance of 23.3 mL/kg/min and first and second distributional clearances of 556.4 and 51.8 mL/kg/min, respectively. Typical bioavailability after IM administration was 79%. Elimination half-life was 177 minutes, and maximum plasma concentration after IM administration was 950 ng/mL. Heart rate was mildly decreased at most time points beginning 5 minutes after IV or IM drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Disposition of methadone in isoflurane-anesthetized chickens was characterized by a large volume of distribution and moderate clearance, with high bioavailability after IM administration. Additional studies are warranted to assess pharmacokinetics and pharmacodynamics of methadone in awake chickens.

Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.

OBJECTIVE: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. STUDY DESIGN: prospective, randomized, blinded, crossover trial. ANIMALS: Six adult horses weighing 494 ± 33 kg. METHODS: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. RESULTS: Meperidine terminal half-life (T1/2 ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). CONCLUSION: Maximum meperidine concentrations were achieved quickly with a short T1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. CLINICAL SIGNIFICANCE: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses.

OBJECTIVE: To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. STUDY DESIGN: Randomized, masked, crossover design. ANIMALS: A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. METHODS: Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (fR), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant. RESULTS: The mean ± SD hydromorphone terminal half-life (t1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute⁻1 kg⁻1 and 1125 ± 309 mL kg⁻1. The t1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: IM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration. IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.

Effect of Meperidine on Equine Blood Histamine, Tryptase, and Immunoglobulin-E Concentrations.

Objectives: To evaluate changes in immunological parameters following subcutaneous (SC) and intramuscular (IM) administration of meperidine in horses through quantitative analysis of plasma tryptase, histamine, and IgE levels. Methods: Six adult horses were enrolled in a prospective randomized crossover design. Horses were administered one treatment per day, with a seven day washout period: (a) meperidine 1 mg/kg IM, saline 6 mL SC; (b) saline 6 mL IM, meperidine 1 mg/kg SC; (c) saline 6 mL SC, saline 6 mL IM. Blood samples were obtained for plasmatic histamine (baseline, 5, 10, 15, 30, and 60 min) via LC-MS/MS and plasmatic tryptase (baseline, 15, 30, 60, 120, and 240 min) quantification with enzyme-linked immunoabsorbent assays. Serum immunoglobulin E (IgE) concentrations prior to any meperidine treatment and 7-14 days following the first meperidine treatment were evaluated with enzyme-linked immunoabsorbent assays. Histamine and tryptase concentrations were evaluated with a mixed-effect analysis of variance. The levels of IgE at baseline (before the administration of the first dose of meperidine) were compared with the IgE values at 60 min following the second meperidine administration with the Paired t test. Biopsies of localized injection site reactions from subcutaneous meperidine administration were collected from two horses. Results: No statistically significant elevations from baseline in histamine (p = 0.595), tryptase (p = 0.836), or IgE (p = 0.844) were found in any of the horses in this study. There were no differences between treatment groups. Administration of SC meperidine caused a localized vasculitis and thrombosis with regional edema and hemorrhage. Conclusion: No evidence of anaphylactoid or anaphylactic type reactions occurred following IM or SC meperidine administration.

A retrospective analysis of the epidural use of bupivacaine 0.0625-0.125% with opioids in bitches undergoing cesarean section.

Epidural anesthesia, often used during cesarean surgery, can exacerbate hypotension from general anesthesia and delay discharge due to motor block. Decreasing the local anesthetic dose might reduce those complications. Cases of dogs undergoing cesarean section that were anesthetized without epidural (n = 29) (control) and dogs with low-dose epidural bupivacaine with fentanyl or buprenorphine (n = 37) were reviewed. The incidence of hypotension was equal between groups. Intraoperative opioids were administered more to control (93%) than to treated dogs (18%; P < 0.0001). Epidural bupivacaine 0.0625-0.125% combined with an opioid reduced the use of intraoperative opioids and did not exacerbate arterial hypotension during cesarean section in anesthetized dogs.

Analyse rétrospective de l'utilisation de bupivacaine 0,0625­0,125 % avec des opioïdes lors d'épidurale chez des chiennes soumises à une césarienne. L'anesthésie épidurale, souvent utilisée lors d'une césarienne, peut exacerber l'hypotension due à l'anesthésie générale et retarder le congé à cause d'un bloc moteur. Une diminution de la dose d'anesthésique local pourrait réduire ces complications. Une revue fut effectuée des cas de chiennes soumises à une césarienne et anesthésiées sans épidurale (n = 29) (témoin) et des chiennes avec une épidurale en utilisant une faible dose de bupivacaine avec du fentanyl ou de la buprenorphine (n = 37). L'incidence d'hypotension était égale entre les groupes. Des opioïdes intra-opératoires furent administrés plus fréquemment chez les témoins (93 %) que chez les animaux traités (18 %; P < 0,001). De la bupivacaine 0,0625­0,125 % en épidurale combinée à un opioïde réduisit l'utilisation d'opioïdes intra-opératoires et n'a pas exacerbé l'hypotension artérielle durant la césarienne chez des chiennes anesthésiées.(Traduit par Dr Serge Messier).