A Comparison of Dobutamine, Norepinephrine, Vasopressin, and Hetastarch for the Treatment of Isoflurane-Induced Hypotension in Healthy, Normovolemic Dogs.

Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5-15 µg/kg/min; NEP, 0.1-2 µg/kg/min; VAS, 0.5-5 mU/kg/min; and HET, 6% 1-20 mL/kg/min. DOB improved CO, DO2, and VO2, but reduced SVR. VAS elevated SVR, but decreased CO, DO2, and VO2. HES minimally changed BP and mildly augmented CO, DO2, and VO2. These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 µg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.

Evaluation of Electrical Cardiometry for Measuring Cardiac Output and Derived Hemodynamic Variables in Comparison with Lithium Dilution in Anesthetized Dogs.

Numerous cardiac output (CO) technologies were developed to replace the 'gold standard' pulmonary artery thermodilution due to its invasiveness and the risks associated with it. Minimally invasive lithium dilution (LiD) shows excellent agreement with thermodilution and can be used as a reference standard in animals. This study evaluated CO via noninvasive electrical cardiometry (EC) and acquired hemodynamic variables against CO measured using LiD in six healthy, anesthetized dogs administered different treatments (dobutamine, esmolol, phenylephrine, and high-dose isoflurane) impacting CO values. These treatments were chosen to cause drastic variations in CO, so that fair comparisons between EC and LiD across a wide range of CO values (low, intermediate, and high) could be made. Statistical analysis included linear regression, Bland-Altman plots, Lin's concordance correlation coefficient (ρc), and polar plots. Values of p < 0.05 represented significance. Good agreement was observed between EC and LiD, but consistent underestimation was noted when the CO values were high. The good trending ability, ρc of 0.88, and low percentage error of ±31% signified EC's favorable performance. Other EC-acquired variables successfully tracked changes in CO measured using LiD. EC may be a pivotal hemodynamic tool for continuously monitoring circulatory changes, as well as guiding and treating cardiovascular anesthetic complications in clinical settings.

Pharmacokinetics and pharmacodynamics of intramuscular dexmedetomidine in dogs.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of dexmedetomidine after IM administration in dogs. ANIMALS: 6 healthy adult purpose-bred dogs (3 males, 3 females) with a mean ± SD body weight of 25.2 ± 1.8 kg. PROCEDURES: Each dog received 10 µg/kg dexmedetomidine, IM. Heart rate and respiratory rate were counted via cardiac auscultation and visual assessment of chest excursions. Sedation was assessed utilizing 2 sedation scoring systems. Plasma concentrations were determined using ultra performance liquid chromatography-mass spectrometry. Plasma concentrations versus time data after IM dexmedetomidine were analyzed using noncompartmental analysis for extravascular administration. RESULTS: Over the first 2 hours following IM injection of dexmedetomidine, plasma concentrations fluctuated in each dog. The geometric mean (range) maximum plasma concentration was 109.2 (22.4 to 211.5) ng/mL occurring at 20.5 (5 to 75) minutes, and the mean half-life was 25.5 (11.5 to 41.5) minutes. Heart rate was significantly lower than baseline from 30 minutes to 2 hours postdexmedetomidine administration, and respiratory rate was significantly lower than baseline from 45 minutes to 1.75 hours. Dogs were significantly more sedated from 30 minutes to 1.5 hours postdexmedetomidine administration. Median time to onset of sedation was 7.5 minutes (range, 2 to 10 minutes), and median time to peak sedation was 30 minutes (range, 15 to 60 minutes). CLINICAL RELEVANCE: Variations in plasma concentrations occurred in all dogs for the 2 hours postinjection of dexmedetomidine at 10 µg/kg, IM. This was likely due to alterations in absorption due to dexmedetomidine-induced local vasoconstriction. Despite variable plasma concentrations, all dogs were sedated following IM dexmedetomidine administration.

Risk of anesthesia-related complications in draft horses: a retrospective, single-center analysis.

OBJECTIVE: To report anesthetic-related complications and determine risks associated with anesthesia in draft horses. STUDY DESIGN: Retrospective study. ANIMALS: A total of 401 anesthetic records for draft horse breeds that underwent general anesthesia from January 2010 through December 2020 were reviewed; horses euthanized during general anesthesia were excluded. METHODS: Demographics, perioperative drugs used, procedure type and duration, time to extubation, number of attempts to stand, use of sling in recovery and perioperative morbidity and mortality were investigated. Morbidity and mortality statistical evaluation included univariable logistic regression analysis and ordinal regression analysis. RESULTS: American Society of Anesthesiologists (ASA) status I-II, ASA III-V and total mortality rate for all cases was 0.69% (2/288), 6.19% (7/113) and 2.24% (9/401), respectively, with Belgian horses being overrepresented (6/9). Cardiac arrest occurred in six out of nine horses that died without euthanasia, and five out of six of these horses underwent colic surgery. Factors associated with increased mortality risk included ASA status of III-V, increased body weight, emergency status and horses presenting for colic. Hypotension, hypercarbia and hypoxemia occurred in 56% (224/401), 46% (186/401) and 14% (58/401) of horses, respectively. During recovery from anesthesia, lighter horses and horses undergoing shorter anesthetic procedures were more likely to be successful on the first or second attempt to stand and were less likely to require a sling in recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Draft horses undergoing general anesthesia had a higher mortality rate than previously reported for all types and breeds of horses.

Evaluation of perfusion index as a noninvasive tool to determine epidural anesthesia effectiveness in dogs.

OBJECTIVE: To evaluate perfusion index (PI) as a noninvasive tool to determine effectiveness and onset of epidural anesthesia in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 21 adult dogs, aged 6.5 ± 3 years and weighing 34.9 ± 6.4 kg, undergoing a tibial plateau leveling osteotomy. METHODS: Dogs were premedicated intramuscularly with acepromazine (0.03 mg kg-1) and hydromorphone (0.1 mg kg-1) and anesthetized with intravenous propofol (to effect) and isoflurane in oxygen. A surface transflectance probe was secured to the tail base to monitor PI and a dorsal pedal artery catheter was placed for invasive blood pressure monitoring. A lumbosacral epidural was performed with the dog in sternal recumbency. Dogs were randomly assigned for inclusion of epidural morphine (0.1 mg kg-1) or morphine (0.1 mg kg-1) and lidocaine (4 mg kg-1). PI was recorded following instrumentation of each dog just prior to the epidural (baseline), at 10 minute intervals for 30 minutes, before and after the surgical skin incision and before and after completion of the osteotomy. Physiological variables and end-tidal isoflurane were recorded at the same time points. RESULTS: There was no significant difference in PI between the groups at any time point. There was a significant change in end-tidal isoflurane before and after the skin incision in the epidural morphine and epidural morphine-lidocaine groups (p = 0.04, p = 0.05, respectively) and before and after the osteotomy in each group for heart rate (p = 0.001, p = 0.04), diastolic (p = 0.01, p = 0.01) and mean arterial blood pressure (p = 0.03, p = 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: PI did not provide an objective means for determining the onset or effectiveness of epidural anesthesia in anesthetized dogs and alternate methods of noninvasive assessment should be investigated.

Effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats.

OBJECTIVE: To investigate the effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats. ANIMALS: 8 healthy adult cats. PROCEDURES: For this crossover study, cats were sedated with dexmedetomidine and methadone administered IM. Cats next received a priming induction dose of alfaxalone (0.25 mg/kg, IV) or saline (0.9% NaCl) solution (0.025 mL/kg, IV) over 60 seconds and then an induction dose of alfaxalone (0.5 mg/kg/min, IV) until orotracheal intubation was achieved. Cardiorespiratory variables were recorded at baseline (immediately prior to priming agent administration), immediately after priming agent administration, after orotracheal intubation, and every 2 minutes until extubation. The total induction dose of alfaxalone was compared between the 2 priming agents. RESULTS: Mean ± SD total anesthetic induction dose of alfaxalone was significantly lower when cats received a priming dose of alfaxalone (0.98 ± 0.28 mg/kg), compared with when cats received a priming dose of saline solution (1.41 ± 0.17 mg/kg). Mean arterial blood pressure was significantly higher when alfaxalone was used as the priming dose. No cats became apneic or had a hemoglobin oxygen saturation of < 90%. Expired volume per minute was not significantly different between the 2 priming agents. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a priming dose of alfaxalone to healthy sedated cats reduced the total dose of alfaxalone needed to achieve orotracheal intubation, maintained mean arterial blood pressure, and did not adversely impact the measured respiratory variables.

Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.

OBJECTIVE: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs. ANIMALS: 6 young healthy mixed-breed hounds. PROCEDURES: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments. RESULTS: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection. CONCLUSIONS AND CLINICAL RELEVANCE: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.

Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). PROCEDURES: Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. RESULTS: Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.

Pharmacokinetics and pharmacodynamic effects of oral transmucosal and intravenous administration of dexmedetomidine in dogs.

OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs. ANIMALS: 6 healthy dogs. PROCEDURES: Injectable dexmedetomidine was administered IV (5 µg/kg) or via the OTM route (20 µg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry. RESULTS: For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.

Pharmacokinetics and pharmacodynamics of intranasal and intravenous naloxone hydrochloride administration in healthy dogs.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. ANIMALS: 6 healthy adult mixed-breed dogs. PROCEDURES: In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. RESULTS: Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs. STUDY DESIGN: Prospective blinded, single-observer, randomized crossover experimental study. ANIMALS: Six adult (age 6.8 ± 1.6 months) healthy dogs (three males and three females), weighing 24.8 ± 3.4 kg (mean ± standard deviation). METHODS: Each dog was anesthetized twice with a minimum of 7 days between anesthetic episodes. Dogs were randomly assigned to be administered two treatments in a crossover design: premedication with trazodone (8 mg kg-1; TRAZ-ISO) orally 2 hours prior to an anesthetic episode or no (ISO). Dogs were anesthetized with intravenous propofol (6 mg kg-1) and isoflurane in >95% oxygen. Isoflurane MAC was determined using an iterative bracketing technique with electrodes placed in the buccal mucosa. Hemodynamic variables were compared at the lowest end-tidal isoflurane concentration at which each dog did not respond. A paired t test was used to assess the effect of treatment on outcome variables with significance set to a value of p < 0.05. RESULTS: The MAC concentration (mean ± standard deviation) in dogs administered TRAZ-ISO was 0.85 ± 0.17% compared with 1.02 ± 0.11% in those administered ISO (p = 0.01, 95% confidence interval -0.25 to -0.05), resulting in a mean MAC reduction of 17 ± 12%. There were no differences in hemodynamic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication of dogs with oral trazodone (8 mg kg-1) 2 hours prior to anesthetic induction has a significant isoflurane MAC sparing effect with no significant observed hemodynamic benefit.