Jeff C. Ko

Pharmacokinetics of lidocaine following the application of 5% lidocaine patches to cats.

Lidocaine patches have been used to provide local analgesia in dogs and cats. We conducted this study to assess the systemic and local absorption of lidocaine from topical patches in cats. Eight 2-year-old cats received either intravenous lidocaine at 2 mg/kg or one 700 mg lidocaine patch placed on the lateral thorax for 72 h, in a cross-over randomized repeated measures design. Plasma was collected at specific times and the skin was biopsied at the time of patch removal for the quantitative analysis of lidocaine and its major metabolite, monoethylglycinexylidide (MEGX), by gas chromatography with mass spectrometry. Percent absorption time plots for systemic lidocaine appearance were constructed using the Loo-Riegelman method. Approximately, constant rate absorption was observed from 12-72 h after patch application at a mean +/- SD rate of 109 +/- 49 microg/kg/h, resulting in steady-state lidocaine plasma concentrations of 0.083 +/- 0.032 microg/mL and MEGX concentrations of 0.012 +/- 0.009 microg/mL. Overall bioavailability of transdermal lidocaine was 6.3 +/- 2.7%, and only 56 +/- 29% of the total lidocaine dose delivered by the patch reached systemic circulation. Skin lidocaine concentrations were much higher than plasma concentrations, at 211 +/- 113 microg/g in the thoracic skin beneath the patch and 2.2 +/- 0.6 microg/g in the contralateral thoracic skin without the patch. As both lidocaine and MEGX were recovered from contralateral skin, it is likely that lidocaine accumulated in the skin from low systemic concentrations of circulating lidocaine over the 72-h period of patch application. Plasma lidocaine concentrations remained well below systemically toxic concentrations, and no obvious clinical side effects were observed in any of the cats. The low systemic absorption rate coupled with high local lidocaine concentrations on the skin support the safe use of lidocaine patches in cats.

Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats

OBJECTIVE To compare the efficacy and cardiorespiratory effects of dexmedetomidine-ketamine in combination with butorphanol, hydromorphone, or buprenorphine with or without reversal by atipamezole in cats undergoing castration. DESIGN Prospective, randomized, split-plot, blinded study. ANIMALS 30 healthy male cats. PROCEDURES Cats were assigned to receive dexmedetomidine (25 ?g/kg [11.4 ?g/lb]) and ketamine (3 mg/kg [1.4 mg/lb]) with butorphanol (0.2 mg/kg [0.09 mg/lb]; DKBut; n = 10), hydromorphone (0.05 mg/kg [0.023 mg/lb]; DKH; 10), or buprenorphine (30 ?g/kg [13.6 ?g/lb]; DKBup; 10). Drugs were administered as a single IM injection. Supplemental isoflurane was administered to cats if the level of anesthesia was inadequate for surgery. At the conclusion of surgery, half the cats (5 cats in each treatment group) received atipamezole (250 ?g/kg [113.6 ?g/lb], IM) and the remainder received saline (0.9% NaCl) solution IM. All cats received meloxicam (0.2 mg/kg, SC) immediately prior to the conclusion of surgery. RESULTS All drug combinations induced lateral recumbency, and intubation was achievable in 13 of 30 (43%) cats at 10 minutes after injection. Supplemental isoflurane was needed for the surgery in 1 of 10 of the DKBut-, 2 of 10 of the DKH-, and 7 of 10 of the DKBup-treated cats. Cats that received atipamezole had a significantly shorter recovery time. CONCLUSIONS AND CLINICAL RELEVANCE DKBut and DKH combinations were suitable injectable anesthetic protocols for castration in cats commencing at 10 minutes after injection, but cats receiving DKBup may require additional time or anesthetics for adequate anesthesia.

Anesthesia in shelter medicine.

Shelter medicine presents a unique challenge that is different from veterinary medicine in a hospital setting. The shelter and/or mobile unit environment requires special anesthetic considerations to support high-volume spay-neuter and feral animal programs with high quality of anesthesia/immobilization for surgery and diagnostic procedures. The anesthetic protocols can be tailored to the needs of each specific shelter setting. An ideal shelter anesthesia protocol will have a wide safety margin for animals of all ages. The protocol must also be effective, economical, and easy to use with a small volume for injection, have rapid on- and off-set with a reasonable surgical duration after a single administration, be predictable, and possess perioperative analgesic properties. An anesthesia protocol with a combination of tiletamine-zolazepam and dexmedetomidine in combination with an opioid fits the criteria of the shelter anesthesia protocols. These combinations possess rapid induction of immobilization, unconsciousness, and muscle relaxation with an anesthesia duration of 30 to 45 minutes. Specific and nonspecific reversal agents are also available to facilitate recovery. This article describes the use of these anesthetic protocols as well as monitoring support for these protocols.

Hemodynamic influence of acepromazine or dexmedetomidine premedication in isoflurane-anesthetized dogs.

OBJECTIVE To investigate hemodynamic effects of acepromazine and dexmedetomidine premedication in dogs undergoing general anesthesia induced with propofol and maintained with isoflurane in oxygen and assess the influence of these drugs on oxygen-carrying capacity and PCV. DESIGN Prospective, randomized crossover study. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received acepromazine (0.05 mg/kg [0.023 mg/lb]) or dexmedetomidine (15.0 μg/kg [6.82 μg/lb]) IM. Fifteen minutes later, anesthesia was induced with propofol and maintained at end-tidal isoflurane concentration of 1.28% (1 minimum alveolar concentration) for 30 minutes. Hemodynamic variables were recorded at predetermined times. The experiment was repeated 48 hours later with the alternate premedication. Results were analyzed by repeated-measures ANOVA with a mixed-models procedure. RESULTS Bradycardia, hypertension, and significant cardiac output (CO) reduction developed after dexmedetomidine premedication but improved during isoflurane anesthesia. Hypotension developed after acepromazine administration and persisted throughout the isoflurane maintenance period, but CO was maintained throughout the anesthetic period when dogs received this treatment. Oxygen delivery and consumption were not different between treatments at most time points, whereas arterial oxygen content was lower with acepromazine premedication owing to lower PCV during isoflurane anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE Acepromazine exacerbated hypotension, but CO did not change in dogs anesthetized with propofol and isoflurane. Dexmedetomidine reduced CO but prevented propofol-isoflurane-induced hypotension. In general, oxygen-carrying capacity and PCV were higher in dexmedetomidine-treated than in acepromazine-treated dogs anesthetized with propofol and isoflurane.

Hemodynamic effects in dogs after intramuscular administration of a combination of dexmedetomidine-butorphanol-tiletamine-zolazepam or dexmedetomidine-butorphanol-ketamine

OBJECTIVE To evaluate hemodynamic effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg, butorphanol (0.15 mg/kg), and tiletamine-zolazepam (3 mg/kg [DBTZ]) or dexmedetomidine (15 μg/kg), butorphanol (0.3 mg/kg), and ketamine (3 mg/kg [DBK]). ANIMALS 5 healthy adult mixed-breed dogs. PROCEDURES Each dog received DBTZ and DBK in a randomized crossover study with a 48-hour interval between treatments. Anesthesia was induced and maintained with sevoflurane in 100% oxygen while instrumentation with Swan-Ganz and arterial catheters was performed. Following instrumentation, hemodynamic measurements were recorded at 3.54% (1.5 times the minimum alveolar concentration) sevoflurane; then sevoflurane administration was discontinued, and dogs were allowed to recover. Six hours after cessation of sevoflurane administration, baseline hemodynamic measurements were recorded, each dog was given an IM injection of DBTZ or DBK, and hemodynamic measurements were obtained at predetermined intervals for 70 minutes. RESULTS DBTZ and DBK induced hypoventilation (Paco2, approx 60 to 70 mm Hg), respiratory acidosis (pH, approx 7.2), hypertension (mean arterial blood pressure, approx 115 to 174 mm Hg), increases in systemic vascular resistance, and reflex bradycardia. Cardiac output, oxygen delivery, and oxygen consumption following DBTZ or DBK administration were similar to those following sevoflurane administration to achieve a surgical plane of anesthesia. Blood l-lactate concentrations remained within the reference range at all times for all protocols. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs, both DBTZ and DBK maintained oxygen delivery and oxygen consumption to tissues and blood lactate concentrations within the reference range. However, ventilation should be carefully monitored and assisted when necessary to prevent hypoventilation.

Analgesic Effect of Bupivacaine Eluting Porcine Small Intestinal Submucosa (SIS) in Ferrets Undergoing Acute Abdominal Hernia Defect Surgery

BACKGROUND Porcine small intestinal submucosa (SIS) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. This prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to SIS for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets. MATERIALS AND METHODS Eighteen healthy ferrets were randomly and equally assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS with no bupivacaine subjected to surgery, and (3) anesthesia only control group. Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for the surgery. Control ferrets were anesthetized in the same fashion for the same duration without surgery. Behavior and pain were evaluated in all ferrets by behavioral observation, algometer, and palpometer measurements, and heart and respiratory rates each obtained before surgery and at various intervals for 96 h after surgery. When pain reached a predetermined threshold, buprenorphine was used as a rescue analgesic. The serum and combined tissue concentrations of bupivacaine were analyzed. RESULTS Overall, the palpometer testing was better tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P = 0.04). There was an observed physiologically significant difference in algometer and other palpometer readings as well as heart and respiratory rates. All ferrets in the untreated SIS group were rescued while 33% of the SIS-bupivacaine groups were rescued (P < 0.01). Peak serum concentrations of bupivacaine were in the range of 0.7 μg/mL with tissue level below detection levels and no clinical signs of toxicity were observed. CONCLUSIONS Bupivacaine adsorbed to SIS provided some degree of pain relief over 2-4 days with no clinical adverse effects observed in the ferrets.

Influence of ketamine on the cardiopulmonary effects of intramuscular administration of dexmedetomidine-buprenorphine with subsequent reversal with atipamezole in dogs

OBJECTIVE To compare the cardiorespiratory effects of IM administration of dexmedetomidine-buprenorphine (DB) and dexmedetomidine-buprenorphine-ketamine (DBK) in dogs with subsequent reversal with atipamezole. DESIGN Prospective, randomized crossover study. ANIMALS 5 healthy dogs. PROCEDURES Dogs were instrumented for cardiac output (CO) measurement and received DB (15 μg of dexmedetomidine/kg [6.8 μg/lb] and 40 μg of buprenorphine/kg [18.2 μg/lb]) or DBK (DB plus 3 mg of ketamine/kg [1.36 mg/lb]) in randomized order while breathing room air. Atipamezole (150 μg/kg [68.2 μg/lb], IM) was administered 1 hour later. Hemodynamic data were collected in the conscious dogs and then at 5, 10, 15, 20, 30, 45, and 60 minutes after drug administration. Lactate concentration was measured in mixed venous blood samples. Oxygen delivery (Do(2)) and oxygen consumption ([Formula: see text]o(2)) were calculated. RESULTS Heart rate (HR), CO, and Do(2) decreased after DB and DBK administration. The [Formula: see text]o(2) did not change in the DB group but decreased in the DBK group. The HR was higher in the DBK group than in the DB group throughout the study, but the CO, Do(2), and [Formula: see text]o(2) values were similar for the 2 groups. Blood lactate concentrations remained low (< 1 mmol/L) throughout the study. Arterial hypoxemia and hypercapnea occurred in both groups. Mean arterial blood pressure and pulmonary artery wedge pressure were markedly increased in both groups, but to a greater extent in the DBK group. After atipamezole administration, HR, CO, and Do(2) returned to the baseline values. CONCLUSIONS AND CLINICAL RELEVANCE Adding ketamine to the DB combination allowed dogs to maintain a higher HR and delayed the onset of sinus arrhythmias but failed to provide a significantly higher CO because of a reduction in stroke volume.

Evaluation of anesthetic, analgesic, and cardiorespiratory effects in dogs after intramuscular administration of dexmedetomidine–butorphanol–tiletamine-zolazepam or dexmedetomidine-tramadol-ketamine drug combinations

OBJECTIVE To compare anesthetic, analgesic, and cardiorespiratory effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg)-butorphanol (0.15 mg/kg)-tiletamine-zolazepam (3.0 mg/kg; DBTZ) or dexmedetomidine (15.0 μg/kg)-tramadol (3.0 mg/kg)-ketamine (3.0 mg/kg; DTrK) combinations. ANIMALS 6 healthy adult mixed-breed dogs. PROCEDURES Each dog received DBTZ and DTrK in a randomized, crossover-design study with a 5-day interval between treatments. Cardiorespiratory variables and duration and quality of sedation-anesthesia (assessed via auditory stimulation and sedation-anesthesia scoring) and analgesia (assessed via algometry and electrical nerve stimulation) were evaluated at predetermined intervals. RESULTS DBTZ or DTrK induced general anesthesia sufficient for endotracheal intubation ≤ 7 minutes after injection. Anesthetic quality and time from drug administration to standing recovery (131.5 vs 109.5 minutes after injection of DBTZ and DTrK, respectively) were similar between treatments. Duration of analgesia was significantly longer with DBTZ treatment, compared with DTrK treatment. Analgesic effects were significantly greater with DBTZ treatment than with DTrK treatment at several time points. Transient hypertension (mean arterial blood pressure > 135 mm Hg), bradycardia (heart rate < 60 beats/min), and hypoxemia (oxygen saturation < 90% via pulse oximetry) were detected during both treatments. Tidal volume decreased significantly from baseline with both treatments and was significantly lower after DBTZ administration, compared with DTrK, at several time points. CONCLUSIONS AND CLINICAL RELEVANCE DBTZ or DTrK rapidly induced short-term anesthesia and analgesia in healthy dogs. Further research is needed to assess efficacy of these drug combinations for surgical anesthesia. Supplemental 100% oxygen should be provided when DBTZ or DTrK are used.

Evaluation of 25% Poloxamer As a Slow Release Carrier for Morphine in a Rat Model

The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous poloxamer–morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats’ flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the Culex™ unit for 48 h. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t1/2) was significantly longer in the PM (5.5 ± 7.2 h) than M (0.7 ± 0.8 h) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 min and Cmax was approximately three times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M versus PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t1/2 of morphine, without a significant tissue irritation.