Background: A combination injection formulation containing 8.3 % w/v ketamine (K), 0.83 % w/v xylazine (X), and 0.083 % w/v butorphanol (B) is frequently used for sedation and anesthesia in New World Camelids. In this study, we aimed to evaluate the chemical and microbiological stability of this compounded formulation, providing scientific support for its use beyond the current 28-day beyond-use date (BUD) as outlined in the current USP < 797 > guidance. Methods: A sterile KXB formulation was aseptically prepared, consisting of 8.3 % w/v K, 0.83 % w/v X, and 0.083 % w/v B using the individual injections of each drug (K, X, B) filled into sterile 20 mL glass vials. A validated, stability-indicating HPLC method was developed to simultaneously quantify each drug in the injection formulation. The samples were stored at room temperature (similar to 23 degrees C) and at 40 degrees C and analyzed at 0.5, 1, 1.5, 2, and 3 months for physical and chemical stability. Microbiological stability was assessed to detect potential microbial growth over a 45-day period. Results: The developed HPLC assay was precise, accurate, and stability-indicating for each drug in the injection. The formulation remained clear and within pH 4.1-4.3 throughout the study. Drug assay values remained within 90-110 % after three months of storage at room temperature and at 40 degrees C. No microbial growth was observed up to and beyond 28 days, in compliance with USP guidelines. Conclusion: The validated HPLC method confirmed the KXB formulation demonstrated chemical stability for at least three months and maintained microbial stability up to and beyond a 28-day period, supporting an evidence-based beyond-use date of this multi-drug formulation.

OBJECTIVE:To determine if serum iron concentrations decrease acutely during and after general anesthesia in healthy horses. STUDY DESIGN:Prospective experimental study. ANIMALS:A convenience sample of 24 healthy adult horses (eight females, 16 geldings), weighing 545 ± 33 kg (mean ± standard deviation). METHODS:Horses were anesthetized for 120 minutes with isoflurane, after premedication with intravenous (IV) xylazine (0.8 mg kg-1) and induction with IV midazolam (0.1 mg kg-1) and ketamine (2.2 mg kg-1). Blood samples for serum iron analysis were obtained just before premedication (baseline), after 60 minutes of anesthesia (T60), after 120 minutes of anesthesia (T120), immediately after recovery (TREC) and 24 hours after induction (T24). Serum iron values are reported as mean ± standard deviation. RESULTS:Serum iron concentration was 152 ± 29 μg dL-1 at baseline, with reductions at other time points: 136 ± 25 μg dL-1 at T60, 133 ± 26 μg dL-1 at T120, 136 ± 26 μg dL-1 at TREC and 63 ± 19 μg dL-1 at T24. CONCLUSIONS AND CLINICAL RELEVANCE:Serum iron concentrations acutely decrease in healthy horses during and after general anesthesia for at least 24 hours. General anesthesia may interfere with the use of serum iron for detecting and monitoring systemic disease and inflammation in horses.

Objective The aim of this study was to describe the onset and duration of action of escalating doses of atracurium in healthy, anesthetized goats. Study design Randomized, blinded, triple crossover study. Animals A total of eight (five males and three females) healthy goats weighing 42.7-123.5 kg and aged from 11 months to 8 years. Methods Goats were anesthetized three times with propofol and anesthesia was maintained with isoflurane. One of three doses of atracurium was administered intravenously 30 minutes after induction: 0.25 mg kg(-1) (AT25), 0.5 mg kg(-1) (AT50) or 0.75 mg kg(-1) (AT75). Acceleromyographic train-of-four ratio (TOFR) followed by train-of-four counts (TOFC) were recorded at 30 second intervals after atracurium administration to determine blockade onset (TOFC = 0). The TOFR followed by TOFC were recorded at 5 minute intervals until return to pre-atracurium baseline (TOFR = 1.0). Normally distributed data were analyzed with repeated measures anova and a Tukey multiple comparison test. Data not normally distributed were analyzed with a Friedman test and a Dunn's multiple comparison test. Results For AT50 and AT75, 100% of goats achieved TOFC = 0 after atracurium administration. For AT25, however, 87.5% of goats achieved TOFC = 0 after atracurium administration. The onset time was shorter for AT75 [1.5 (0.5-1.5) minutes; median (range)] than for AT25 [2 (1-4) minutes] (p = 0.048). The duration of action [from onset time to complete reversal (TOFR = 1.0)] was significantly shorter for AT25 (52 +/- 12 minutes, mean +/- SD) than for AT50 (77 +/- 18 minutes) (p < 0.001) and AT75 (85 +/- 16 minutes) (p < 0.001). There was no significant difference in duration between AT50 and AT75 (p = 0.238). Conclusions and clinical relevance Doses of 0.5 and 0.75 mg kg(-1) atracurium may produce complete neuromuscular blockade in healthy, anesthetized goats.

General anesthesia in farm animals, like cattle, small ruminants, camelids, and pigs, requires special attention due to anatomic and physiologic differences from dogs, cats, and horses. There are many anatomic and physiologic characteristics of pigs that make anesthetic management challenging. Oral administration of a tranquilizer or sedative is sometimes needed to facilitate capture and/or reduce stress associated with restraint. In ruminants and camelids, oral medication is absorbed primarily via the rumen into the circulation. Neuromyopathy has been associated with improper positioning and inadequate padding of the surgery table. Positional changes required for anesthesia and surgery can result in significant mismatching of ventilation and perfusion. Ruminal tympany, regurgitation, and aspiration pneumonia are common problems associated with general anesthesia in ruminants. Tracheal intubation is often difficult to accomplish in farm animals. Decreased heat production as well as increased heat loss are the primary causes of significant decreases in body temperature and hypothermia observed during anesthesia and surgery.

OBJECTIVE To compare image quality and acquisition time of corneal and retinal spectral domain optical coherence tomography (SD-OCT) under 3 different sedation-anesthesia conditions in horses. ANIMALS 6 middle-aged geldings free of ocular disease. PROCEDURES 1 randomly selected eye of each horse was evaluated via SD-OCT under the following 3 conditions: standing sedation without retrobulbar anesthetic block (RB), standing sedation with RB, and general anesthesia with RB. Five regions of interest were evaluated in the cornea (axial and 12, 3, 6, and 9 o’clock positions) and fundus (optic nerve head). Three diagnostic scans of predetermined quality were obtained per anatomical region. Image acquisition times and total scans per site were recorded. Corneal and retinal SD-OCT image quality was graded on a subjective scale from 0 (nondiagnostic) to 4 (excellent). RESULTS Mean values for the standing sedation without RB, standing sedation with RB, and general anesthesia conditions were 24, 23, and 17, respectively, for total cornea scan attempts; 23, 19, and 19 for total retina-scan attempts; 14.6, 13.2, and 9.2 minutes for total cornea scan time; 19.1, 9.2, and 13.0 for total retina scan time; 2.0, 2.3, and 2.5 for cornea grade; and 2.7, 2.9, and 2.5 for retina grade. CONCLUSIONS AND CLINICAL RELEVANCE The RB facilitated globe akinesia and improved the percentage of scans in frame and region of interest accuracy for retinal imaging via OCT in horses. Retrobulbar blocks improved clinical image acquisition while minimizing motion artifact.

When general anesthesia is considered in farm animal species, factors that affect the decision between injectable and inhalation anesthesia include the type of procedure to be performed, anticipated duration of the procedure, inhalation anesthetic equipment availability, familiarity of the veterinarians with the anesthetic technique, and anesthetic costs. Successful general anesthesia with inhalation anesthetics requires experience with successful tracheal intubation and sophisticated anesthetic machines and accessories. A small animal anesthesia machine is usually adequate for newborn calves, small ruminants, potbellied pigs, and young camelids weighing less than 150kg. A large animal machine will be required for adult cattle, camelids, and agricultural commercial pigs. The most commonly used ventilators in veterinary anesthesia machines are classified into two types, volume-limited and pressure-limited. Respiratory depression is a common complication in anesthetized animals and is often a result of anesthetic-induced respiratory depression and the abnormal position (e.g. lateral or dorsal recumbency) required for surgical procedures.

Gabapentin has been used to treat chronic pain in people and small animals. To date, no study has reported its use in horses for the treatment of chronic painful conditions. The clinical effectiveness of gabapentin as an analgesic in horses with chronic lameness was evaluated in a double-blinded crossover study. Six horses with chronic lameness referable to musculoskeletal pathology were randomly assigned to one of three treatments: 5 and 10 mg/kg body weight of gabapentin, and placebo administered PO three times daily for 14 days. All horses received each treatment separated by a 2-week interval. Complete blood count and serum biochemistry were performed before and after each treatment. Lameness was evaluated subjectively by blinded observers before, during, and after each treatment period. The data were analyzed using the general linear model for repeated-measures analysis of variance. A P value of < .05 was considered significant. No significant reduction in lameness level was observed while receiving either gabapentin dose when compared with the placebo group. Further studies are necessary to determine effective plasma concentration and length of treatment period after PO administered gabapentin for analgesia in horses with chronic lameness. (C) 2015 Elsevier Inc. All rights reserved.

Anesthetized animals should be monitored closely and continuously throughout the anesthesia period. Accurate assessment of the physical condition of an anesthetized patient and the depth of anesthesia of that patient are best accomplished using a combination of several parameters rather than relying on a single parameter. Intravenous catheterization for perioperative fluid therapy in pigs is difficult and often impossible, particularly in potbellied pigs, because of the lack of visible superficial veins. Improper positioning of the patient can result in postanesthetic neuromyopathy in cattle and camelids, similar to that seen in horses. The chapter describes positioning of an anesthetized ruminant and camelid to elevate the neck to avoid pooling of saliva and regurgitated materials. Treatment of impending cardiovascular failure should begin with correction of the causative disease status, rapid administration of supportive fluid, and reduction or even cessation of anesthesia. Severe cardiac arrhythmias rarely occur in anesthetized farm animals.

Standing sedation and chemical restraint with or without local or regional anesthesia are common techniques used to perform diagnostic and/or surgical procedures in farm animal species. In adult cattle, intramuscular or IV administration of xylazine at 0.015–0.025mg/kg produces standing sedation without recumbency; increasing the dose to 0.1–0.2mg/kg causes recumbency and light anesthesia to occur. Intratesticular injection of xylazine and midazolam has been used successfully for castration in small ruminants. Diazepam and butorphanol are effective in producing short-duration sedation with recumbency in camelids. Azaperone is the only tranquilizer approved by the Food and Drug Administration for use in swine. It can be used to control aggression when mixing commercial pigs. Standing sedation in farm animal species presents more of a challenge than in other domestic species. Ruminants and camelids have a tendency to assume sternal recumbency when they are sedated.

Pain experienced by farm animal is often difficult to recognize due to their stoic temperament and the natural instinct of prey animals not to attract the attention of predators when injured. Awareness of the need for proper pain management of farm animals has prompted several research groups worldwide, including some in the US, to promote the study of objective methods to recognize and evaluate pain and develop effective and safe analgesics. A combination of local or regional anesthesia, nonsteroidal anti-inflammatory drugs (NSAIDs), and low doses of an opioid and/or an alpha-2 agonist is the most commonly practiced multimodal treatment for intraand postoperative pain management in farm animals. This chapter discusses the local or regional anesthetic techniques commonly involved in pain management such as caudal epidural analgesia, lumbosacral epidural analgesia, and intra-articular analgesia.

Ketamine is a dissociative anesthetic commonly used for short-term and induction of anesthesia in bovine species. Ketamine has recently become popular for use as a constant-rate infusion for continuous pain relief. Lidocaine, a local anesthetic, is frequently used for local infiltration and epidural nerve blocks. Two of the most common local blocks in adult cattle are the inverted-L local infiltration and caudal epidural nerve blocks. These blocks are utilized for numerous standing surgical procedures such as cesarean sections, obstetric manipulations, correction of a displaced abomasum and perineal surgery. These animals may occasionally be sent for slaughter following a surgical procedure, and the Food and Drug Administration (FDA) has a zero-tolerance policy for drug residues in meat and milk. There is limited information and no published data on meat and milk withdrawal times for ketamine anesthesia or lidocaine administration via these two different techniques. The objectives of this study were to investigate the pharmacokinetics of ketamine following administration of a single intravenous dose and lidocaine administered via inverted-Land caudal epidural nerve blocks, and to establish the withdrawal times for meat and milk of these two anesthetics in mature Holstein cows.

OBJECTIVE:To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses.DESIGN:Prospective study.ANIMALS:6 adult horses.PROCEDURES:Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration.RESULTS:After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration.CONCLUSIONS AND CLINICAL RELEVANCE:Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.

Yohimbine (0.25 mg/kg i.v.), tolazoline (2.2 μg/kg i.v.) or atipamezole (60 μg/kg i.v.) were given to 6 healthy, Holstein calves (156.8-241.1 kg) 30 min after anaesthesia with a combination (MK) of medetomidine (20 μg/kg i.v.) and ketamine (2.2 mg/kg i.v.) with an interval of 1 week between treatments. Heart and respiratory rates, indirect arterial blood pressures (systolic (SAP), mean (MAP), diastolic (DAP)), and arterial blood gases were measured. Calves became sternally recumbent in 2±14 s for a duration of 94±25 min after administration of MK. Respiratory rate, PaCO2 and arterial blood pressure were significantly increased while PaO2, pHa and SaO2 were significantly decreased during anaesthesia. The values for most of the blood gas variables returned to normal after administration of tolazoline and atipamezole. The duration of recumbency following administration of yohimbine, tolazoline, or atipamezole was 80±22, 46±9 and 34±3 min, respectively. Calves stood in 48±20, 16±9 and 4±3 min, respectively, after the injection of yohimbine, tolazoline and atipamezole. It was concluded that medetomidine and ketamine combination can be used effectively to induce anaesthesia in dairy calves. Either tolazoline or atipamezole can be administered to antagonize the anaesthetic effects and induce rapid recovery.

OBJECTIVE:To study the combined effects of intra-abdominal CO2 insufflation with changes in body position during laparoscopy in xylazine-ketamine-halothane anesthetized llamas.STUDY DESIGN:Prospective, controlled study.ANIMALS:Nine castrated, male llamas weighing 114 +/- 23 kg, 3 to 13 years old.METHODS:Three llamas (preliminary study [PS] group) were used to study the effect of right, lateral, dorsal, and left lateral recumbency on gas exchange and acid-base status. The other six (experimental study [ES] group) were used to study the combined effects of changes in body position and CO2 insufflation to an intraabdominal pressure of 10 to 12 mm Hg. Heart rate, respiratory rate, and indirect arterial blood pressures (systolic [SAP], mean [MAP], and diastolic [DAP]) were recorded every 5 minutes during anesthesia. Arterial blood gases (PaO2 and PaCO2) and acid-base status (pHa and HCO3-) were measured immediately after induction of anesthesia and before each change of position.RESULTS:In the PS group, significant decreases in SAP, MAP and PaCO2 and increases in PaO2 and pHa were observed when the llamas were turned from right lateral to dorsal recumbency. Values for HCO3- were lower than the postinduction values, but they remained unaffected by the changes in position. In the ES group, values for MAP were significantly lower when the llamas were placed in dorsal and left lateral recumbency than those observed during right lateral recumbency. Arterial O2 tension during right lateral recumbency was lower but returned to preinsufflation values when the llamas were placed in the dorsal position. All llamas recovered uneventfully within 30 minutes after termination of anesthesia.CONCLUSIONS:Insufflation of CO2 and changing body position induce minor and transient changes in cardiovascular and respiratory function.CLINICAL RELEVANCE:Laparoscopy with mild intra-abdominal CO2 insufflation (10 to 12 mm Hg) can be used safely in spontaneously breathing llamas anesthetized with xylazine, ketamine, and halothane.