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.     

Lack of systemic absorption of lidocaine from 5% patches placed on horses

OBJECTIVE: To measure concentrations of lidocaine serum after application of two 5% patches on horses. STUDY DESIGN: Prospective experimental trial ANIMALS: Six client-owned, systemically healthy horses. METHODS: The hair was clipped on the medial aspect above the carpus of both fore limbs and 2 patches of 5% lidocaine were applied within 30 minutes of jugular catheter placement and the area was then bandaged. Venous blood was drawn from a jugular vein catheter that was inserted using lidocaine as a local block. Samples were drawn immediately before and at 2, 4, 6, 8, and 12 hours after patch application. The presence of lidocaine in serum was determined using an ELISA test. RESULTS: Lidocaine was detected in the serum of three horses at 0 hours immediately following the local block for catheter placement. Lidocaine was not detected at any other time from 2 to 12 hours. There was mild erythema at the site of patch placement at 12 hours in one horse but this resolved within 1 hour of patch removal. There were no other apparent adverse effects from the patches on any other horse. CONCLUSION: Five percent lidocaine patches applied proximally to the carpus did not result in detectable systemic concentrations of lidocaine. CLINICAL RELEVANCE: Any analgesic effects that might be produced by application of 5% lidocaine patches on horses will not be due to systemic absorption of the drug.     

Pharmacokinetics of a lidocaine patch 5% in dogs

Lidocaine is increasingly used in transdermal drug delivery systems for different pain conditions in human medicine whereby several pharmacokinetic studies have demonstrated minimal systemic absorption in men. In the present study, the pharmacokinetics of a lidocaine patch 5% was studied in six dogs. In the first experiment, one single lidocaine patch was applied for 12 h to the lateral side of the thorax after removing the hair either by clipping or by the application of a depilatory agent, according to a two-way crossover design. No potential adverse effects induced by the patches were observed in either group. In dogs with clipped hair, a mean peak plasma lidocaine concentration of 62.94 ng/ml was obtained after 10.67 h. In the depilatory group, a mean peak plasma concentration of 103.55 ng/ml was reached after 9.27 h. Significant differences in the AUC(0 --> infinity), C(max), k(a) and T(1/2a) were noticed between the two groups. No significant differences were found for the elimination parameters and for T(max). In the second experiment, the patches were applied for 60 h to the clipped skin in order to study the absorption kinetics after a prolonged application period. There, the mean peak lidocaine plasma concentration was 45.18 ng/ml achieved after 24 h and a final concentration of 29.37 ng/ml was obtained at 60 h. In conclusion, all dogs tolerated the transdermal lidocaine patch well. The results of this study suggest that there is an overall minimal absorption from the lidocaine patch. However, the application of a depilatory agent leads to a more rapid and increased absorption of lidocaine.     

Evaluation of Plasma Detectable Concentrations of Two Lidocaine Transdermal Formulations and Their Analgesic Effect in the Horse

Transdermal absorption of four lidocaine (L) patches (5%) was compared with the transdermal absorption of L cream (5%) to evaluate the pharmacokinetics of the two formulations applied on the same anatomic region under dressing in eight horses. The animals were also assessed for antinociceptive effect after removal of the patches and cream, using a psychophysical method visual analog scale, by pricking the patient's skin to test the response to pain. Horses were randomly assigned to four treatment groups: in groups I and II, four L patches were applied for a period of 24 hours with and without alcohol precleaning, respectively; in group III, 5% L cream was applied every 2 hours over a 24-hour period on the same anatomic site. Group IV was the control. No clinical side effects were noted with either formulation. L was detectable in plasma 6 to 24 hours after application of the patches, and the highest plasma concentrations were reached between 12 and 18 hours. The use of alcohol to preclean the skin appeared to reduce the transdermal drug absorption over time. After L cream application, the peak plasma drug concentration occurred at 24 hours. Nociception assessment after L patch or L cream application showed a decreased response when the L cream was used. The results of this study showed that there was minimal absorption from the L patches compared with the L cream in horses. Also, the L cream treatment reduced significantly the intensity of nociception quality as measured by the visual analog scale.     

Transdermal fentanyl patches in small animals

Fentanyl citrate is a potent opioid that can be delivered by the transdermal route in cats and dogs. Publications regarding transdermal fentanyl patches were obtained and systematically reviewed. Seven studies in cats and seven studies in dogs met the criteria for inclusion in this review. Dogs achieved effective plasma concentrations approximately 24 hours after patch application. Cats achieved effective plasma concentrations 7 hours after patch application. In dogs, transdermal fentanyl produced analgesia for up to 72 hours, except for the immediate 0- to 6-hour postoperative period. In cats, transdermal fentanyl produced analgesia equivalent to intermittent butorphanol administration for up to 72 hours following patch application.     

Comparison of Plasma Fentanyl Concentrations by Using Three Transdermal Fentanyl Patch Sizes in Dogs

Objective—To compare plasma fentanyl concentrations attained after the application of three transdermal fentanyl patch sizes (50, 75, and 100 μg/hour) in dogs. Design—Repeated Latin square controlled study. Animals—Six intact, mixed-breed adult dogs (2 males, 4 females) weighing 19.9 ± 3.4 kg. Methods—Each dog was randomly assigned to receive each of three treatments: 50 (P50), 75 (P75), or 100 (P100) μg/hour transdermal patches. Patches were left in place for 72 hours. Jugular venous blood was collected at 1,2, 4, 8, 12, 24, 36, 48, 60, and 72 hours after patch application and for 1, 2, 4, 8, and 12 hours after patch removal. Plasma fentanyl concentrations were measured using a radioimmunoassay technique. After a 96-hour washout period, each dog was moved to another treatment group and received a different patch size. Results—The following results were obtained (mean ± SD): average plasma fentanyl concentration from 24 to 72 hours, 0.7 ± 0.2 ng/mL (P50), 1.4 ± 0.5 ng/mL (P75), 1.2 ± 0.5 ng/mL (P100); the total area under the concentration versus time curve (0 hours to infinity), 46 ± 12.2 ng/h/mL (P50), 101.2 ± 41.4 ng/h/mL (P75), 80.4 ± 38.3 ng/h/mL (P100); and the apparent elimination half-life, 3.6 ± 1.2 hours (P50), 3.4 ± 2.7 hours (P75), and 2.5 ± 2.0 hours (P100). There was a high degree of variability in plasma fentanyl concentrations achieved. Plasma fentanyl concentrations declined rapidly after patch removal. Conclusions—The attainment of steady-state plasma concentrations takes up to 24 hours, and there is a great deal of variability in the final concentrations reached in different individuals. In this study, the 100 μg/hour patches did not provide statistically increased plasma concentrations when compared with the 50 μg/hour patches. Clinical Relevance—Because of the interindividual and intraindividual variation in plasma fentanyl concentrations, patches should be applied 24 hours before the anticipated time that analgesia will be required. Adequacy of analgesia and potentially deleterious side effects, such as sedation and respiratory depression, should be monitored while the patches are in place. Skin reactions may occur, and the patches should be removed if such skin irritation is seen. After the patch is removed, it is expected that analgesia will wane rapidly because of the brief elimination half-life.     

Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin

The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and C_MAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No‐Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated.     

Plasma fentanyl concentrations and analgesic effects during full or partial exposure to transdermal fentanyl patches in cats

OBJECTIVE: To compare plasma fentanyl concentrations and analgesic efficacy during full or partial exposure to 25-microg/h transdermal fentanyl patches (TFPs) in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 16 client-owned cats. PROCEDURE: Cats were randomly assigned to receive full or partial exposure to a TFP; patches were applied approximately 24 hours prior to ovariohysterectomy. Rectal temperature, heart rate, respiratory rate, blood glucose concentration, and blood pressure were measured and pain severity was assessed periodically for 72 hours after patch application. Venous blood samples were collected for determination of plasma fentanyl concentration 0, 6, 12, 18, 24, 36, 48, 60, and 72 hours after patch application. RESULTS: Mean +/- SD steady state plasma fentanyl concentration in cats in the full TFP exposure group (1.78 +/- 0.92 ng/mL) was significantly greater than concentration in cats in the partial exposure group (1.14 +/- 0.86 ng/mL). Steady state plasma fentanyl concentrations were evident between 18 and 72 hours after patch application. Subjective scores used to evaluate analgesic efficacy were not significantly different between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that delivery of fentanyl from TFPs can be reduced by decreasing the amount of exposed surface area. In cats weighing < 4 kg (9 lb), exposure to half a 25-microg/h TFP appears to provide adequate analgesia following ovariohysterectomy.     

Transdermal absorption of a liposome-encapsulated formulation of lidocaine following topical administration in cats

OBJECTIVE: To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats. ANIMALS: 6 healthy adult cats with a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. PROCEDURE: CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay. Results-Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng.h/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats.     

Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration

Objective To measure the plasma fentanyl concentrations achieved over time with transdermal fentanyl patches in awake cats and cats undergoing anesthesia and ovariohysterectomy. Study design Randomized prospective experimental study. Animals Twenty‐four purpose‐bred cats. Methods Cats were randomly assigned to three groups for Part I of a larger concurrent study. Group P received only a 25 μg hour^?1 transdermal fentanyl patch. Group P/A received the patch and anesthesia. Group A received only anesthesia. After a minimum 1‐week washout period, the cats were randomly reassigned to two groups for Part II of the larger study. Group P/A/O received the patch, anesthesia and ovariohysterectomy. Group A/O received anesthesia and ovariohysterectomy. Patches were left in place for 72 hours and plasma samples were obtained for fentanyl analysis while the patches were in place, and for 8 hours after patch removal for cats in Group P, P/A, and P/A/O. Results The 25 μg hour^?1 transdermal fentanyl patches were well tolerated by the cats in this study (mean body weight of 3.0 kg) and no overt adverse effects were noted. Mean plasma fentanyl concentrations over time, mean plasma fentanyl concentrations at specific times (8, 25, 49, and 73 hours after patch placement), time to first detectable plasma fentanyl concentration, time to reach maximum plasma fentanyl concentration, maximum plasma fentanyl concentration, mean plasma fentanyl concentration from 8 to 73 hours, elimination half‐life, and total area under concentration (AUC) were not statistically different among the groups. Conclusions Halothane anesthesia and anesthesia/ovariohysterectomy did not significantly alter the plasma fentanyl concentrations achieved or pharmacokinetic parameters measured, when compared with awake cats. There was a high degree of individual variability observed both within and between groups of cats in parameters measured. Clinical significance The high degree of variability observed suggests that careful observation of cats with fentanyl patches in place is required to assess efficacy and any potential adverse effects. Anesthesia and anesthesia/ovariohysterectomy do not appear to alter plasma fentanyl concentrations achieved by placement of a 25 μg hour^?1 transdermal fentanyl patch when compared to cats not undergoing these procedures.     

Plasma lidocaine concentrations in conscious horses after cervicothoracic (stellate) ganglion block with 1% lidocaine HCl solution

Arterial and/or central venous plasma concentrations of lidocaine were determined in 12 nonmedicated adult horses (422 +/- 59 kg of body weight, mean +/- SD) after injecting a 1% lidocaine HCl solution into the cervicothoracic ganglion (CTG). A mean dosage of 2.9 +/- 0.5 mg of lidocaine/kg of body weight was used to induce unilateral CTG blockade in 8 horses and 4.8 +/- 0.8 mg was used to induce bilateral CTG blockade in 4 horses. Blood samples were collected before and at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after injection. The plasma lidocaine concentrations were determined by use of gas chromatography (sensitivity less than 0.01 microgram/ml). Cervicothoracic sympathetic blockade was characterized by Horner's syndrome and by profuse sweating over the face, neck, and thoracic limbs. Mean maximal venous concentrations of lidocaine were 0.86 +/- 0.33 microgram/ml at 26.3 +/- 6.9 minutes after unilateral CTG blockade, and 1.14 +/- 0.25 micrograms/ml at 31.2 +/- 18.9 minutes after bilateral CTG blockade. The mean venous and arterial concentrations of lidocaine were not significantly different at 45 and 120 minutes after injection. Venous concentrations of lidocaine were consistently higher than were concentrations in simultaneously collected arterial blood samples in 2 horses in which the right CTG and brachial plexus were temporarily anesthetized after repeated administration of 100 ml of lidocaine into the right CTG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous regional anesthesia in isoflurane anesthetized cats: lidocaine plasma concentrations and cardiovascular effects

Objective To determine if intravenous regional anesthesia (IVRA) can be used in cats without resulting in excessive plasma lidocaine concentrations or adverse cardiovascular effects. Study design Prospective, blinded crossover study. Animals Seven healthy male young adult cats weighing 3.96 ± 0.63 kg. Methods At 2.3% end‐tidal isoflurane concentration, lidocaine (L) 3 mg kg^?1 (1%) or saline (S) was injected in a distal cephalic venous catheter after application of two tourniquets to that forelimb which remained in place for 20 minutes. Heart and respiratory rates, arterial blood pressures and ECG were recorded every 5 minutes during tourniquet application and for 20 minutes following tourniquet removal. Lidocaine plasma concentrations were measured 5 minutes after injection and 0.5, 1, 2, 4, 8, 20 and 40 minutes after tourniquet removal. End tidal isoflurane concentrations were reduced to 1.5–2.0% to elicit a response to toe pinch (RTP) in the contralateral leg. The study was repeated similarly in the contralateral leg and RTP was graded for 40 minutes. Response was also tested in the leg previously injected, the differences between the two scores determined and those differences compared between the L and S treatments. The data were analyzed using anova for repeated measures comparing values to baseline. Significance was set at p < 0.005 using the Bonferroni method for multiple comparisons. Results There were no significant differences in physiologic parameters at either isoflurane concentration. Differences in RTP were significantly larger in the lidocaine treatment. The highest mean lidocaine concentrations were measured 0.5 minutes after tourniquet removal after both injections and were 2.79 ± 1.05 and 3.10 ± 1.11 µg mL^?1. The highest individual plasma concentration was 6.46 µg mL^?1. Conclusion No adverse hemodynamic effects were evident after IVRA lidocaine in any cat. The lidocaine dose studied inhibited a RTP until 20 minutes after tourniquet removal. Lidocaine concentrations varied and were measurable prior to tourniquet removal. Clinical relevance IVRA may be a suitable technique for cats undergoing surgery of the distal limbs.     

Assessment of serum concentrations and sedative effects of fentanyl after transdermal administration at three dosages in healthy llamas

OBJECTIVE: To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas. ANIMALS: 9 healthy adult female llamas (mean age, 8 +/- 3 years; mean weight, 150 +/- 18 kg). PROCEDURE: Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 microg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 microg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 microg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 microg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement. RESULTS: Following the placement of 4 patches, mean +/- SD serum fentanyl concentration in group 3 llamas reached 0.3 +/- 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that application of four 75 microg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known.     

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.     

The disposition of lidocaine during a 12-hour intravenous infusion to postoperative horses

Lidocaine is administered as an intravenous infusion to horses for a variety of reasons, but no study has assessed plasma lidocaine concentrations during a 12-h infusion to horses. The purpose of this study was to evaluate the plasma concentrations and pharmacokinetics of lidocaine during a 12-h infusion to postoperative horses. A second purpose of the study was to evaluate the in vitro plasma protein binding of lidocaine in equine plasma. Lidocaine hydrochloride was administered as a loading dose, 1.3 mg/kg over 15 min, then by a constant rate IV infusion, 50 microg/kg/min to six postoperative horses. Lidocaine plasma concentrations were measured by a validated high-pressure liquid chromatography method. One horse experienced tremors and collapsed 5.5 h into the study. The range of plasma concentrations during the infusion was 1.21-3.13 microg/mL. Lidocaine plasma concentrations were significantly increased at 0.5, 4, 6, 8, 10 and 12 h compared with 1, 2 and 3 h. The in vitro protein binding of lidocaine in equine plasma at 2 microg/mL was 53.06+/-10.28% and decreased to 27.33+/-9.72% and 29.52+/-6.44% when in combination with ceftiofur or the combination of ceftiofur and flunixin, respectively. In conclusion, a lower lidocaine infusion rate may need to be administered to horses on long-term lidocaine infusions. The in vitro protein binding of lidocaine is moderate in equine plasma, but highly protein bound drugs may displace lidocaine increasing unbound concentrations and the risk of lidocaine toxicity.     

Effects of intravenous administration of lidocaine on the thermal threshold in cats

OBJECTIVE: To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. ANIMALS: 6 cats. PROCEDURE: 2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination. RESULTS: In experiment 2, actual plasma lidocaine concentrations were 0.00 +/- 0.00 microg/mL, 0.25 +/- 0.18 microg/mL, 0.57 +/- 0.20 microg/mL, 1.39 +/- 0.13 microg/mL, 2.33 +/- 0.45 microg/mL, and 4.32 +/- 0.66 microg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.     

Assessment of the hemodynamic effects of lidocaine administered IV in isoflurane-anesthetized cats

OBJECTIVE:To determine the hemodynamic effects of lidocaine (administered IV to achieve 6 plasma concentrations) in isoflurane-anesthetized cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with isoflurane in oxygen (end-tidal isoflurane concentration set at 1.25 times the predetermined individual minimum alveolar concentration). Lidocaine was administered IV to each cat to achieve target pseudo-steady-state plasma concentrations of 0, 3, 5, 7 9, and 11 microg/mL, and isoflurane concentration was reduced to an equipotent concentration. At each plasma lidocaine concentration, cardiovascular and blood gas variables; PCV; and plasma total protein, lactate, lidocaine, and monoethylglycinexylidide concentrations were measured in cats before and during noxious stimulation. Derived variables were calculated. RESULTS: n isoflurane-anesthetized cats, heart rate, cardiac index, stroke index, right ventricular stroke work index, plasma total protein concentration, mixed-venous PO2 and hemoglobin oxygen saturation, arterial and mixed-venous bicarbonate concentrations, and oxygen delivery were significantly lower during lidocaine administration, compared with values determined without lidocaine administration. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed-venous hemoglobin concentrations, plasma lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine, compared with values determined without lidocaine administration. Noxious stimulation did not significantly affect most variables. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized cats, although IV administration of lidocaine significantly decreased inhalant requirements, it appeared to be associated with greater cardiovascular depression than an equipotent dose of isoflurane alone. Administration of lidocaine to reduce isoflurane requirements is not recommended in cats.     

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.     

Hemodynamic effects of intravenous lidocaine in isoflurane anesthetized cats

Lidocaine dose‐dependently decreases the minimum alveolar concentration (MAC) of isoflurane in cats. The purpose of this study was to determine the hemodynamic effects of six lidocaine plasma concentrations in isoflurane anesthetized cats. Six cats were studied. After instrumentation, end‐tidal isoflurane concentration was set at 1.25 times the individual minimum alveolar concentration (MAC), which was determined in a previous study. Lidocaine was administered intravenously to target pseudo‐steady state plasma concentrations of 0, 3, 5, 7, 9, and 11 μg ml^–1, and isoflurane concentration was reduced to an equipotent concentration, determined in a previous study. Cardiovascular variables; blood gases; PCV; total protein and lactate concentrations; and lidocaine and monoethylglycinexylidide concentrations were measured at each lidocaine target concentration, before and during noxious stimulation. Derived variables were calculated. Data were analyzed using a repeated measures anova , followed by a Tukey test for pairwise comparisons where appropriate. One cat was excluded from analysis because the study was aborted at 7 μg ml^–1 due to severe cardiorespiratory depression. Heart rate, cardiac index, stroke index, right ventricular stroke work index, total protein concentration, mixed‐venous PO₂ and hemoglobin oxygen saturation, arterial and mixed‐venous bicarbonate concentrations, and oxygen delivery were significantly lower during lidocaine administration than when no lidocaine was administered. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed‐venous hemoglobin concentrations, lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine than when no lidocaine was administered. Most changes were significant at lidocaine target plasma concentrations of 7 μg ml^–1 and above. Noxious stimulation did not significantly affect most variables. Despite significantly decreasing in inhalant requirements, when combined with isoflurane, lidocaine produces greater cardiovascular depression than an equipotent dose of isoflurane alone. The use of lidocaine to reduce isoflurane requirements is not recommended in cats.