Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs

Objective  To investigate the effects of a low-dose constant rate infusion (LCRI; 50 μg kg⁻¹ minute⁻¹) and high-dose CRI (HCRI; 200 μg kg⁻¹ minute⁻¹) lidocaine on arterial blood pressure and on the minimum alveolar concentration (MAC) of sevoflurane (Sevo), in dogs.
Study design  Prospective, randomized experimental design.
Animals  Eight healthy adult spayed female dogs, weighing 16.0 ± 2.1 kg.
Methods  Each dog was anesthetized with sevoflurane in oxygen and mechanically ventilated, on three separate occasions 7 days apart. Following a 40-minute equilibration period, a 0.1-mL kg⁻¹ saline loading dose or lidocaine (2 mg kg⁻¹ intravenously) was administered over 3 minutes, followed by saline CRI or lidocaine LCRI or HCRI. The sevoflurane MAC was determined using a tail clamp. Heart rate (HR), blood pressure and plasma concentration of lidocaine were measured. All values are expressed as mean ± SD.
Results  The MAC of Sevo was 2.30 ± 0.19%. The LCRI reduced MAC by 15% to 1.95 ± 0.23% and HCRI by 37% to 1.45 ± 0.21%. Diastolic and mean pressure increased with HCRI. Lidocaine plasma concentration was 0.84 ± 0.18 for LCRI and 1.89 ± 0.37 μg mL⁻¹ for HCRI. Seventy-five percent of HCRI dogs vomited during recovery.
Conclusion and clinical relevance  Lidocaine infusions dose dependently decreased the MAC of Sevo, did not induce clinically significant changes in HR or arterial blood pressure, but vomiting was common during recovery in HCRI.     

Serum concentrations of lidocaine and its metabolites after prolonged infusion in healthy horses

REASONS FOR PERFORMING STUDY: Continuous-rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. OBJECTIVE: To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. METHODS: Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance liquid chromatography during and after discontinuation of the infusion. RESULTS: Serum lidocaine concentrations reached steady state by 3 h and did not accumulate thereafter. Concentrations were above the target therapeutic concentration (980 ng/ml) only at 6 and 48 h, and did not reach the range described as potentially causing toxicity (>1850 ng/ml) at any time. MEGX did not accumulate over time, while the GX accumulated significantly up to 48 h and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 h of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. CONCLUSIONS: The metabolism of lidocaine was not significantly impaired by prolonged infusion and no adverse effects were observed. Prolonged infusions appear to be safe in normal horses but the accumulation of GX, a potentially toxic active metabolite, is cause for concern.     

Serum Concentrations of Lidocaine and Its Metabolites MEGX and GX During and After Prolonged Intravenous Infusion of Lidocaine in Horses after Colic Surgery

Lidocaine is the most commonly used prokinetic after gastrointestinal surgery in horses. Cardiovascular status, hepatic function, and duration of therapy are the primary determinants of lidocaine metabolism, and these factors could affect equine patients after colic surgery. This study examined the systemic concentrations of lidocaine and its active metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in horses that had undergone colic surgery and subsequently received prolonged postoperative lidocaine infusions. The mean lidocaine concentration increased over the course of treatment but did not exceed the therapeutic range. Concentrations of MEGX and GX increased progressively, and concentrations exceeding 1,000 ng/ml were observed frequently after 72 hours of infusion. None of the horses in the study developed severe signs of toxicity; however, the progressively increasing concentrations of lidocaine, MEGX, and GX are cause for concern in clinically ill patients receiving prolonged lidocaine therapy. The potential contribution of MEGX and GX should be considered when evaluating adverse reactions to prolonged lidocaine infusions.     

Effect of intravenous lidocaine and ketamine on the minimum alveolar concentration of isoflurane in goats

OBJECTIVE: To evaluate the effects of i.v. lidocaine (L) and ketamine (K), alone and in combination (LK), on the minimum alveolar concentration (MAC) of isoflurane (ISO) in goats. STUDY DESIGN: Randomized crossover design. ANIMALS: Eight, adult mixed breed castrated male goats, aged 1-2 years weighing 24-51 kg. METHODS: Anesthesia was induced with ISO that was delivered via a mask. The tracheas were intubated and the animals ventilated to maintain an end-tidal carbon dioxide partial pressure between 25 and 30 mmHg (3.3-4 kPa). Baseline MAC (MAC(B)) that prevented purposeful movement in response to clamping a claw was determined in triplicate. After MAC(B) determination, each goat received one of the following treatments, which were administered as a loading (LD) dose followed by a constant rate infusion, IV: L (2.5 mg kg(-1); 100 microg kg(-1) minute(-1)), K (1.5 mg kg(-1); 50 microg kg(-1) minute(-1)), L and K combination or saline, and the MAC (MAC(T)) was re-determined in triplicate. Plasma concentrations of L and K were measured around each MAC point and the values averaged. RESULTS: The least-squares mean MAC(B) for all treatments was 1.13 +/- 0.03%. L, K, and LK reduced (p < 0.05) MAC(B) by 18.3%, 49.6% and 69.4%, respectively. Plasma concentrations for L, K, and LK were 1617 +/- 385, 1535 +/- 251 and 1865 +/- 317/1467 +/- 185 ng mL(-1), respectively. No change (p > 0.05) occurred with saline. CONCLUSION: Lidocaine and K caused significant decreases in the MAC of ISO. The combination (LK) had an additive effect. However, the plasma L concentrations were less than predicted, as was the MAC reduction with L. CLINICAL RELEVANCE: The use of L, K and the combination, at the doses studied, will allow a clinically important reduction in the concentration of ISO required to maintain general anesthesia in goats.     

The effects of ketamine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVES: To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg. METHODS: Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study. RESULTS: The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.     

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses

REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Results: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Conclusions and clinical relevance: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.     

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses

OBJECTIVE: To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease. ANIMALS: 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40 kg). PROCEDURE: Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded. RESULTS: Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean +/- SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 +/- 0.39 L/kg, 25 +/- 3 mL/kg/min, and 65 +/- 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 +/- 1 beats/min to 43 +/- 9 beats/min, and mean MAP ranged from 74 +/- 18 mm Hg to 89 +/- 10 mm Hg. Recovery quality ranged from poor to excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.     

Effect of intravenous lidocaine on isoflurane MAC in dogs

Lidocaine decreases minimum alveolar concentration (MAC) of inhalational anesthetics. This study determined the influence of a low dose, 50 µg kg^?1 minute^?1 (LDI) and high dose, 200 µg kg^?1 minute^?1 (HDI) constant rate infusion of lidocaine on the MAC of isoflurane (I) in dogs. Ten mongrel dogs were anesthetized with I in oxygen and mechanically ventilated. End‐tidal anesthetic (Fe ′A) and CO₂ (Pe ′CO₂) concentrations were monitored at the endotracheal tube adaptor with an infrared gas analyzer calibrated before each experiment with a standardized calibration gas mixture designed for the analyzer. Pe ′CO₂ and body temperature were maintained within normal limits. Noxious stimuli included clamping the hindlimb paw (HC) and electrical current (50 V at 50 cycles second^?1 for 10 milliseconds pulse^?1) applied subcutaneously to the forelimb (FE) at the level of the ulna. After an initial equilibration period of at least 40 minutes at an Fe ′A of 1.7%, the Fe ′A was decreased to a value close to the estimated MAC for dogs. MAC was defined as the Fe ′A mid‐way between the value permitting and preventing purposeful movement. Following baseline MAC, a loading dose of 2 mg kg^?1 of lidocaine IV was administered over 3 minutes followed by the LDI, and MAC determinations for the combination started after 30 minutes of infusion. Once determined, the lidocaine infusion was stopped for 30 minutes and the dog maintained at the ETC that prevented movement without the lidocaine. Following this period, a second loading dose of lidocaine was given (2 mg kg^?1) over 3 minutes followed by the HDI, and the MAC determination procedure repeated after 30 minutes of infusion. Data were analyzed using an anova for repeated measures. MAC of I was 1.34 ± 0.035% (mean ± SEM) for both the FE and HC stimuli. The LDI significantly decreased MAC to 1.09 ± 0.043% (18.7% reduction) and HDI to 0.76 ± 0.030% (43.3% reduction). In conclusion, lidocaine infusions decreased the MAC of isoflurane in a dose‐dependent manner.     

Investigation of the EEG effects of intravenous lidocaine during halothane anaesthesia in ponies

OBJECTIVE: To record the electroencephalographic changes during castration in ponies anaesthetized with halothane and given intravenous (IV) lidocaine by infusion. The hypothesis tested was that in ponies, IV lidocaine is antinociceptive and would therefore obtund EEG changes during castration. ANIMALS: Ten Welsh mountain ponies referred to the Department of Clinical Veterinary Medicine, Cambridge for castration under general anaesthesia. MATERIALS AND METHODS: Following pre-anaesthetic medication with intramuscular acepromazine (0.02 mg kg(-1)) anaesthesia was induced with IV guaiphenesin (60 mg kg(-1)) and thiopental (9 mg kg(-1)) and maintained with halothane at an end-tidal concentration (FE'HAL) of 1.2%. A constant rate infusion of IV lidocaine (100 microg kg(-1) minute(-1)) was administered throughout anaesthesia. The electroencephalogram (EEG) was recorded continuously using subcutaneous needle electrodes. All animals were castrated using a closed technique. The raw EEG signal was analysed after completion of each investigation, and the mean values of EEG variables (median frequency, spectral edge frequency, total amplitude) recorded during a baseline period (before surgery began) and the removal of each testicle were compared using anova for repeated measures. RESULTS: Spectral edge frequency (SEF) 95% decreased during removal of the second testicle compared with baseline recordings. No other significant EEG changes during castration were measured. CONCLUSIONS: Lidocaine obtunded the EEG changes identified during castration in a previous control study, providing indirect evidence that lidocaine administered peri-operatively was antinociceptive and contributed to anaesthesia during castration. CLINICAL RELEVANCE: The antinociceptive effect of lidocaine combined with its minimal cardiovascular effects indicate a potential use for systemic lidocaine in clinical anaesthetic techniques.     

Effects of morphine,lidocaine, ketamine,and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane

OBJECTIVE: To determine the effects of constant rate infusion of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine (MLK) combination on end-tidal isoflurane concentration (ET-Iso) and minimum alveolar concentration (MAC) in dogs anesthetized with isoflurane and monitor depth of anesthesia by use of the bispectral index (BIS). ANIMALS: 6 adult dogs. PROCEDURE: Each dog was anesthetized with isoflurane on 5 occasions, separated by a minimum of 7 to 10 days. Individual isoflurane MAC values were determined for each dog. Reduction in isoflurane MAC, induced by administration of morphine (3.3 microg/kg/min), lidocaine (50 microg/kg/min), ketamine (10 microg/kg/min), and MLK, was determined. Heart rate, mean arterial blood pressure, oxygen saturation as measured by pulse oximetry (Spo2), core body temperature, and BIS were monitored. RESULTS: Mean +/- SD isoflurane MAC was 1.38 +/- 0.08%. Morphine, lidocaine, ketamine, and MLK significantly lowered isoflurane MAC by 48, 29, 25, and 45%, respectively. The percentage reductions in isoflurane MAC for morphine and MLK were not significantly different but were significantly greater than for lidocaine and ketamine. The Spo2, mean arterial pressure, and core body temperature were not different among groups. Heart rate was significantly decreased at isoflurane MAC during infusion of morphine and MLK. The BIS was inversely related to the ET-Iso and was significantly increased at isoflurane MAC during infusions of morphine and ketamine, compared with isoflurane alone. CONCLUSIONS AND CLINICAL RELEVANCE: Low infusion doses of morphine, lidocaine, ketamine, and MLK decreased isoflurane MAC in dogs and were not associated with adverse hemodynamic effects. The BIS can be used to monitor depth of anesthesia.     

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC_B) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg⁻¹, CRI 50 μg kg⁻¹minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 100 μgkg⁻¹ minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 200 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mg kg⁻¹, CRI 50 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mgkg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹), or lidocaine (LD 2 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) + ketamine (LD 3 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) in combination. Post-treatment MAC (MAC_T) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MAC_B of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC_B by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.     

Differences in need for hemodynamic support in horses anesthetized with sevoflurane as compared to isoflurane

OBJECTIVE: To study whether hemodynamic function in horses, particularly mean arterial blood pressure (MAP), is better maintained with sevoflurane than isoflurane, thus requiring less pharmacological support. STUDY DESIGN: Prospective randomized clinical investigation. Animals Thirty-nine racehorses undergoing arthroscopy in lateral recumbency. METHODS: Horses were assigned to receive either isoflurane (n = 20) or sevoflurane (n = 19) at 0.9-1.0 minimum alveolar concentration (MAC) for maintenance of anesthesia. Besides routine clinical monitoring, cardiac output (CO) was measured by lithium dilution. Hemodynamic support was prescribed as follows: when MAP decreased to <70 mmHg, patients were to receive infusion of 0.1% dobutamine, which was to be discontinued at MAP >85 mmHg or heart rate >60 beats minute(-1). Statistical analysis of results, given as mean +/- SD, included a clustered regression approach. RESULTS: Average inhalant anesthetic time [91 +/- 35 (isoflurane group) versus 97 +/- 26 minutes (sevoflurane group)] and dose (in MAC multiples), volume of crystalloid solution infused, and cardiopulmonary parameters including CO were similar in the two groups, except heart rate was 8% higher in isoflurane than sevoflurane horses (p < 0.05). To maintain MAP >70 mmHg, isoflurane horses received dobutamine over a significantly longer period (55 +/- 26 versus 28 +/- 21% of total anesthetic time, p < 0.01) and at a 51% higher dose than sevoflurane horses (41 +/- 19 versus 27 +/- 23 microg kg(-1) MAC hour(-1); p = 0.058), with 14/20 isoflurane animals and only 9/19 sevoflurane horses being infused with dobutamine at >30 microg kg(-1) MAC hour(-1) (p < 0.05). Dobutamine infusion rates were consistently lower in the sevoflurane as compared to the isoflurane group, with differences reaching significance level during the 0-30 minutes (p < 0.01) and 61-90 minutes periods (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Horses under sevoflurane anesthesia may require less pharmacological support in the form of dobutamine than isoflurane-anesthetized horses. This could be due to less suppression of vasomotor tone.     

Use of intravenous lidocaine to treat dexmedetomidine-induced bradycardia in sedated and anesthetized dogs

ObjectiveTo assess cardiopulmonary function in sedated and anesthetized dogs administered intravenous (IV) dexmedetomidine and subsequently administered IV lidocaine to treat dexmedetomidine-induced bradycardia.Study designProspective, randomized, crossover experimental trial.AnimalsA total of six purpose-bred female Beagle dogs, weighing 9.1 ± 0.6 kg (mean ± standard deviation).MethodsDogs were randomly assigned to one of three treatments: dexmedetomidine (10 μg kg^–1 IV) administered to conscious (treatments SED1 and SED2) or isoflurane-anesthetized dogs (end-tidal isoflurane concentration 1.19 ± 0.04%; treatment ISO). After 30 minutes, a lidocaine bolus (2 mg kg^–1) IV was administered in treatments SED1 and ISO, followed 20 minutes later by a second bolus (2 mg kg^–1) and a 30 minute lidocaine constant rate infusion (L-CRI) at 50 (SED1) or 100 μg kg^–1 minute^–1 (ISO). In SED2, lidocaine bolus and L-CRI (50 μg kg^–1 minute^–1) were administered 5 minutes after dexmedetomidine. Cardiopulmonary measurements were obtained after dexmedetomidine, after lidocaine bolus, during L-CRI and 30 minutes after discontinuing L-CRI. A mixed linear model was used for comparisons within treatments (p < 0.05).ResultsWhen administered after a bolus of dexmedetomidine, lidocaine bolus and L-CRI significantly increased heart rate and cardiac index, decreased mean blood pressure, systemic vascular resistance index and oxygen extraction ratio, and did not affect stroke volume index in all treatments.Conclusion and clinical relevanceLidocaine was an effective treatment for dexmedetomidine-induced bradycardia in healthy research dogs.     

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.     

A clinical comparison of two anaesthetic protocols using lidocaine or medetomidine in horses

OBJECTIVE: To compare the effects of two balanced anaesthetic protocols on end-tidal isoflurane (Fe'ISO), cardiopulmonary performance and quality of recovery in horses. DESIGN: Prospective blinded randomized clinical study. ANIMALS: Sixty-nine client-owned horses, American Society of Anesthesiologists category I and II, undergoing elective surgery. METHODS: The horses were premedicated with acepromazine (0.03 mg kg(-1)) IM 30-60 minutes before induction of anaesthesia and were randomly assigned to one of two treatments: in group L (37 horses) xylazine (1 mg kg(-1)) and in group M (31 horses) medetomidine (7 microg kg(-1)) was administered IV for sedation. Anaesthesia was induced 5 minutes later with ketamine (2.2 mg kg(-1)) and diazepam (0.02 mg kg(-1)) IV and maintained with isoflurane in oxygen/air (initial FIO2 0.40-0.50) and a constant rate infusion (CRI) of either lidocaine (2 mg kg(-1)/15 minutes loading dose followed by 50 microg kg(-1) minute(-1)) (group L) or medetomidine (3.5 microg kg(-1) hour(-1)) (group M). If horses showed movement or nystagmus, additional thiopental or ketamine was administered. Heart rate, mean arterial pressure (MAP), Fe'ISO and arterial blood gases were measured. Cardiac output was measured with the lithium dilution method in 10 (group L) and 11 (group M) horses every 45 minutes. Recovery was scored. RESULTS: Heart rate and the cardiac index (CI) were significantly higher in group L with changes over time. In group M, MAP was significantly higher during the first 50 minutes. Group L needed more additional ketamine and thiopental to maintain a surgical plane of anaesthesia and Fe'ISO was significantly higher from 70 minutes. Recovery was longer in group M and of better quality. The significance level was set at p < 0.05. CONCLUSIONS AND CLINICAL RELEVANCE: In group M, maintenance of stable anaesthetic depth was easier and lower Fe'ISO was required to maintain a surgical plane of anaesthesia. Recoveries were longer but of better quality. The CI was higher in group L but cardiovascular function was generally well maintained in both groups.     

Evaluation of an anaesthetic technique used in dogs undergoing craniectomy for tumour resection

ObjeCTIVE: To evaluate a total intravenous anaesthetic technique in dogs undergoing craniectomy. STUDY DESIGN: Prospective clinical study. ANIMALS: Ten dogs admitted for elective surgical resection of rostro-tentorial tumours. METHODS: All dogs were premedicated with methadone, 0.2 mg kg(-1) intramuscularly 30 minutes prior to induction of anaesthesia. Anaesthesia was induced with propofol administered intravenously (IV) to effect, following administration of lidocaine 1 mg kg(-1) IV and maintained with a continuous infusion of propofol at < or =0.4 mg kg(-1) minute(-1) during instrumentation and preparation and during movement of the animals to recovery. During surgery, anaesthesia was maintained using a continuous infusion of propofol at 相似文献   

Effects of two continuous infusion doses of lidocaine on isoflurane minimum anesthetic concentration in chickens

ObjectiveTo assess the effect of two intravenous (IV) doses of lidocaine on the minimum anesthetic concentration (MAC) of isoflurane in chickens.Study designBlinded, prospective, randomized, experimental crossover study.AnimalsA total of six adult female chickens weighing 1.90 ± 0.15 kg.MethodsChickens were anesthetized with isoflurane and mechanically ventilated. Isoflurane MAC values were determined (T0) in duplicate using an electrical noxious stimulus and the bracketing method. After MAC determination, a low dose (LD; 3 mg kg^–1 followed by 3 mg kg^–1 hour^–1) or high dose (HD; 6 mg kg^?1 followed by 6 mg kg^?1 hour^–1) of lidocaine was administered IV. MAC determination was repeated at 1.5 (T1.5) and 3 (T3) hours of lidocaine administration and blood was collected for analysis of plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations. Pulse rate, peripheral hemoglobin oxygen saturation, noninvasive systolic arterial pressure and cloacal temperature were recorded at T0, T1.5 and T3. Treatments were separated by 1 week. Data were analyzed using mixed-effects model for repeated measures.ResultsMAC of isoflurane (mean ± standard deviation) at T0 was 1.47 ± 0.18%. MAC at T1.5 and T3 was 1.32 ± 0.27% and 1.26 ± 0.09% (treatment LD); and 1.28 ± 0.06% and 1.30 ± 0.06% (treatment HD). There were no significant differences between treatments or times. Maximum plasma lidocaine concentrations at T3 were 496 ± 98 and 1200 ± 286 ng mL^–1 for treatments LD and HD, respectively, and were not significantly different from T1.5. With treatment HD, plasma concentration of MEGX was significantly higher at T3 than at T1.5. Physiological variables were not significantly different among times with either treatment.Conclusions and clinical relevanceAdministration of lidocaine did not significantly change isoflurane MAC in chickens. Within treatments, plasma lidocaine concentrations were not significantly different at 1.5 and 3 hours.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

Pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide, after intravenous administration of lidocaine to awake and isoflurane-anesthetized cats

OBJECTIVE: To describe the pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide (MEGX), after i.v. administration of a single bolus of lidocaine in cats that were awake in phase 1 and anesthetized with isoflurane in phase 2 of the study. ANIMALS: 8 healthy adult cats. PROCEDURE: During phase 1, cats were administered lidocaine (2 mg/kg, i.v.) as a bolus injection (time 0). During phase 2, cats were anesthetized with isoflurane and maintained at 0.75 times the minimum alveolar concentration of isoflurane for each specific cat. After a 15-minute equilibration period, lidocaine (2 mg/kg, i.v.) was administered as a bolus injection to each cat (time 0). In both phases, plasma concentrations of lidocaine and MEGX were measured at various time points by use of liquid chromatography-mass spectrometry. RESULTS: Anesthesia with isoflurane significantly decreased the volume of the central compartment, clearance, and elimination half-life of lidocaine and significantly increased the extrapolated plasma drug concentration at time 0, compared with values for awake cats. Pharmacokinetics of MEGX were also changed by isoflurane-induced anesthesia because the maximum observed plasma concentration (C(max)), area under the concentration-time curve extrapolated to infinity, and time to C(max) were significantly higher in anesthetized cats, compared with values for awake cats. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of lidocaine and MEGX were substantially altered in cats anesthetized by use of isoflurane. When pharmacokinetic variables are used to determine loading and infusion doses in awake or anesthetized cats, they should be measured in cats that are awake or anesthetized, respectively.     

Comparison of cardiovascular function and quality of recovery in isoflurane‐anaesthetised horses administered a constant rate infusion of lidocaine or lidocaine and medetomidine during elective surgery

Reasons for performing study: The effects of lidocaine combined with medetomidine or lidocaine alone on cardiovascular function during anaesthesia and their effects on recovery have not been thoroughly investigated in isoflurane‐anaesthetised horses. Objectives: To determine the effects of an intraoperative i.v. constant rate infusion of lidocaine combined with medetomidine (Group 1) or lidocaine (Group 2) alone on cardiovascular function and on the quality of recovery in 12 isoflurane‐anaesthetised horses undergoing arthroscopy. Hypothesis: The combination would depress cardiovascular function but improve the quality of recovery when compared to lidocaine alone in isoflurane‐anaesthetised horses. Methods: Lidocaine (2 mg/kg bwt i.v. bolus followed by 50 µg/kg bwt/min i.v.) or lidocaine (same dose) and medetomidine (5 µg/kg bwt/h i.v.) was started 30 min after induction of anaesthesia. Lidocaine administration was discontinued 30 min before the end of surgery in both groups, whereas medetomidine administration was continued until the end of surgery. Cardiovascular function and quality of recovery were assessed. Results: Horses in Group 1 had longer recoveries, which were of better quality due to better strength and overall attitude during the recovery phase than those in Group 2. Arterial blood pressure was significantly higher in Group 1 than in Group 2 and this effect was associated with medetomidine. No significant differences in cardiac output, arterial blood gases, electrolytes and acid‐base status were detected between the 2 groups. Conclusions and potential relevance: The combination of an intraoperative constant rate infusion of lidocaine and medetomidine did not adversely affect cardiovascular function in isoflurane‐anaesthetised horses and improved the quality of recovery when compared to an intraoperative infusion of lidocaine alone.