ESMOLOL BLUNTS TACHYCARDIA DUE TO TOPICAL COCAINE AND LIDOCAINE WITH EPINEPHRINE INFILTRATION
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Esmolol
Infiltration (HVAC)
In Brief The effects of tumescent solutions consisting of lidocaine and epinephrine on skin flap survival in rats were studied. Dorsal skin flaps of rats were infiltrated using lidocaine (1%) with epinephrine in concentrations of 1:100,000, 1:200,000, 1:400,000, and 1:800,000 prior to elevating flaps of the different experimental groups. The solutions were applied intradermally or subcutaneously, and the flaps were raised “immediately” or “delayed” after injection in the different groups. Control flaps were infiltrated by lidocaine (1%) only. The survival of the flaps was assessed on the seventh day after the operation. As a result, the flaps showed higher necrosis rates in the groups injected by lidocaine with epinephrine in concentration of 1:100,000 and 1:200,000 than of the other experimental or all control groups (P < 0.01). In conclusion, lidocaine with epinephrine in concentrations of 1:400,000 and 1:800,000 was found safe on skin flap survival for tumescent technique in rats. In a rat dorsal skin flap model, pre-infiltration of the flaps with epinephrine solutions of 1:100,000 or 1:200,000 showed higher necrosis rates than controls. Concentrations of 1:400,000 and 1:800,000 were no different from controls.
Skin flap
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Abstract Objective We investigated the role of epinephrine in prolonging the localization of a topical anesthetic on oral mucosa and inhibiting its absorption in blood. Methods We used 7–8-week-old specific-pathogen-free Wistar male rats (n = 128) for our study. We divided them into lidocaine and lidocaine with epinephrine groups and applied 5 µL of 14 C-labeled lidocaine hydrochloride gel and 10 µg/mL 14 C-labeled lidocaine hydrochloride gel with added epinephrine to the palatal mucosae of the rats, respectively. The amount of lidocaine was measured by radioactivity and was observed using autoradiograms. Results After 4 min, the values were significantly lower in the lidocaine with epinephrine group (1040.0 ± 142.8 vs. 701.2 ± 109.0 ng/mg [20 min]). After 40 min, the lidocaine level became significantly higher in the lidocaine with epinephrine group (586.8 ± 112.4 vs. 1131.3 ± 155.2 ng/mg [40 min]). Similar results were observed in the palatine bone and mucosa and serum. Conclusion Epinephrine prolonged the localization of lidocaine applied to the mucosa and inhibited its absorption into the bloodstream. Clinical studies are required to evaluate the use of epinephrine-containing topical anesthetics on the oral mucosa.
Oral mucosa
Lidocaine Hydrochloride
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The effects of topical application of local anesthetics on peripheral nerve blood flow (NBF) were studied in the rat sciatic nerve. Sciatic NBF was measured by laser doppler in 45 adult female Sprague-Dawley rats (90 nerves) after topical application of 25 microliter lidocaine and epinephrine, alone and in combination (lidocaine plus epinephrine), as well as bupivacaine, tetracaine, and normal saline, and studied in a randomized, blinded experimental design. NBF changes produced by lidocaine were dose-dependent. Compared with that for saline, blood flow reduction for lidocaine 0.5% was not significant, but it was significant for lidocaine 1.0% at 2-5 min and for lidocaine 2.0% at all time periods after 1 min (P less than 0.05). Maximum reduction was seen at all concentrations by 5 min after application. Average blood flow reduction at 5 min was 7% for lidocaine 0.5%, 12% for lidocaine 1.0% and 18% for lidocaine 2.0%. Epinephrine also produced dose-dependent changes in NBF. Epinephrine 2.5 micrograms/ml produced a transient 20% increase in NBF lasting 2-3 min (P less than 0.05), followed by a return to baseline. Epinephrine 5.0 micrograms/ml and epinephrine 10.0 micrograms/ml produced reductions of 20% and 35%, respectively (P less than 0.05), which lasted throughout the study. The effects of each of the three concentrations were significantly different from the others. The combination of lidocaine plus epinephrine resulted in synergistic reduction of NBF for all drug concentrations (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Tetracaine
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Bupivacaine and lidocaine are often used concurrently, in theory, to combine the more rapid onset of lidocaine and the longer duration of bupivacaine. The purpose of this study was to evaluate this concept.Twenty-five subjects were enrolled in a double-blinded, randomized block design study to evaluate the onset and duration of four different mixtures of lidocaine and bupivacaine with epinephrine. The study was designed to achieve 80% power to detect an effect size of 0.37 at 5% overall significance. The four mixtures tested were: 0.25% bupivacaine with epinephrine (1:200,000); 1% lidocaine with epinephrine (1:100,000); 0.125% bupivacaine and 0.5% lidocaine with epinephrine (1:150,000); and 0.25% bupivacaine and 1% lidocaine with epinephrine (1:150,000). Four intradermal injections were made in the volar forearms of each participant. Time to effect and duration were measured by sensation of a sharp skin prick.Mean time to onset ranged from 12 s to 29 s without statistical significance across all tested solutions (P=0.891). Mean duration of effect ranged from 6 h 38 min to 7 h 25 min with a statistically significant difference across the tested solutions (P=0.036).No statistical benefit was measured when comparing lidocaine with epinephrine, bupivacaine with epinephrine, and mixtures of these local anesthetics with regard to onset of action. While a statistical difference was observed in duration of effect, the clinical benefit measured was narrow.La bupivacaïne et la lidocaïne sont souvent utilisées conjointement, en théorie, pour associer le délai d’action plus rapide de la lidocaïne à la durée d’action plus longue de la bupivacaïne. La présente étude visait à évaluer ce concept.Vingt-cinq sujets ont participé à une étude aléatoire par bloc à double insu conçue pour évaluer le délai et la durée d’action de quatre mélanges différents de lidocaïne et de bupivacaïne associés à l’adrénaline. L’étude était conçue pour atteindre une puissance de 80 % afin de déceler une ampleur de l’effet de 0,37, selon une signification globale de 5 %. Les quatre mélanges à l’essai étaient la bupivacaïne 0,25 % associée à l’adrénaline (1 sur 200 000); la lidocaïne 1 % associée à l’adrénaline (1 sur 100 000); la bupivacaïne 0,125 % et la lidocaïne 0,5 % associées à l’adrénaline (1 sur 150 000); et la bupivacaïne 0,25 % et la lidocaïne 1 % associées à l’adrénaline (1 sur 150 000). Chaque participant a reçu quatre injections intradermiques dans l’avant-bras palmaire. Les chercheurs ont mesuré le délai et la durée d’action au moyen de la sensation d’une piqûre épidermique.Le délai d’action moyen variait de 12 secondes à 29 secondes, sans signification statistique entre les diverses solutions à l’essai (P=0,891). La durée d’action moyenne variait de 6 h 38 min à 7 h 25 min et s’associait à une différence statistiquement significative entre les solutions à l’essai (P=0,036).Les auteurs n’ont mesuré aucun avantage statistique lorsqu’ils ont comparé le délai d’action de la lidocaïne associée à l’adrénaline, de la bupivacaïne associée à l’adrénaline et des mélanges de ces anesthésiques locaux. Ils ont constaté une différence statistique quant à la durée d’action, mais l’avantage clinique mesuré était minime.
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Buffered lidocaine has been recently recommended for local anesthesia, as there is less pain on injection of the buffered solution. Reduced pain on injection of lidocaine and epinephrine buffered to a neutral pH was confirmed in 20 subjects ( P < .01). Concentrations of buffered lidocaine and epinephrine were performed in order to evaluate their stability. Buffered lidocaine dropped to 66.1% of initial concentrations after 4 weeks when stored at 25°C. Buffered epinephrine fell to 1.34% of its initial concentration under similar conditions. Buffered lidocaine and epinephrine maintained 94.54% and 82.04%, respectively, of their initial concentrations after 4 weeks when refrigerated at 0–4°C. Both lidocaine and epinephrine maintained greater than 90% concentration 2 weeks after buffering when stored at 0–4°C. This permits batch buffering of lidocaine with epinephrine and storage for periods up to 2 weeks when properly refrigerated.
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This study investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. Eighty rats were divided into 4 groups to receive an intrathecal injection of normal saline containing 5% lidocaine, 5% lidocaine with 0.2 mg/mL of epinephrine, 0.2 mg/mL of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail‐flick test administered 4 to 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. Conclude the neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine. Comment by Octavio Calvillo, M.D., Ph.D. The authors studied the neurotoxicity of epinephrine added to lidocaine injected intrathecally in rats. The animals were allocated to four groups of 20 rats each, receiving: normal saline alone, normal saline and 5% lidocaine, 5% lidocaine with epinephrine [0.2 mg/ml] in saline or epinephrine 0.2 mgml in saline. The animals were assessed for sensory deficits 4 and 7 days after infusion and then sacrificed. The spinal cords and nerve roots were prepared for neuropathological evaluation. Sections obtained from animals treated with lidocaine, lidocaine with epinephrine. Rats given 5% lidocaine developed persistent sensory impairment and histological evidence of damage, the addition of epinephrine, resulted in further damage. Histological changes in animals treated with epinephrine alone did not differ significantly from saline controls. The authors concluded that the neurotoxicity of intrathecally‐administered lidocaine is increased by the addition of epinephrine. They raised the possibility that the neurotoxicity of commercially available epinephrine may be due to the bisulfite contained therein, this chemical has been associated with neurotoxicity.
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Abstract Plastic surgeons commonly administer subcutaneous epinephrine to reduce intraoperative blood loss. The authors hypothesized that there are safe and effective concentration of epinephrine for vasoconstriction and their durations. The aim of this study is to summarize the existing literatures for the usage of epinephrine mixed with lidocaine in plastic surgical field. In 1903, Braun reported that adrenaline prolonged the local anesthetic effects of cocaine. The Parke-Davis Company began selling cocaine with adrenaline, as well as combining adrenaline with new synthetic local anesthetics. Based on a review of the literature, concentrations between 1:50,000 and 1:400,000 are equally effective and provide superior vasoconstriction compared with more dilute solutions. If epinephrine is further diluted, its onset and time to peak serum concentration are delayed, and its duration of action is shortened. When lidocaine is used without epinephrine, duration of anesthesia is shortened reverse proportionally to the lidocaine concentration. When lidocaine is used with epinephrine, duration of anesthesia is prolonged proportionally to the lidocaine concentration. With slow injection rate in the soft tissue, the maximum safe dose of lidocaine is approximately 3 mg/kg plain and 7 mg/kg when mixed with epinephrine. Lidocaine may protect the myocardium because of its antiarrhythmic activity, which is the rationale for infiltrating lidocaine mixed with epinephrine in general anesthesia. In plastic surgery, subcutaneous infiltration of epinephrine-lidocaine solution is performed to reduce intraoperative blood loss. Even in general anesthesia, infiltrating lidocaine mixed with epinephrine may protect the myocardium because of its antiarrhythmic activity.
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Sodium bicarbonate
Infiltration (HVAC)
Local anesthesia
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We have observed 5 patients with hypertrophic scarring at the lateral boundaries of the chemically peeled area when circumoral peel was combined with facial rhytidectomy. Some of the potential contributory factors include flap elevation, epinephrine, and lidocaine hydrochloride. To discover whether any one of these three factors or a combination played a role, a rat model study was designed. Initially, 40, 400-gm Sprague-Dawley rats were divided into 4 groups, each comprised by 10 rats. Injections with lidocaine or lidocaine with epinephrine, and chemical peel were done in 2 groups. The same injections were used in the remaining 2 groups together with simultaneous preliminary flap elevations and chemical peeling. After the review of the initial study results, another 40 Sprague-Dawley rats were used to repeat the study and compare on a larger scale the effects of lidocaine with and without epinephrine on the depth of chemical peel. The findings of the rat model studies indicate that preliminary injections with lidocaine containing solution (with or without epinephrine) result in a major delay in healing time. Flap elevation and chemical peeling were associated with major morbidity and mortality in the test rats. The presence of epinephrine in lidocaine solution had no significant role in increasing the delay in the healing process.
Lidocaine Hydrochloride
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Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat.Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation.Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls.The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.
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