A melhora na eficácia do bloqueio sensitivo induzida pela associação ou injeção prévia do opióide tramadol foi comprovada em animais e em humanos, sugerindo potencialização ou sinergismo de efeitos. No entanto, ainda não há estudos sobre a influência da associação da codeína ao anestésico local (AL) injetada concomitante ou previamente ao bloqueio funcional (sensitivo, motor e proprioceptivo) do nervo ciático. Dessa forma, o objetivo deste trabalho foi estudar a influência do analgésico opióide codeína na duração do bloqueio nervoso ciático de rato induzido por lidocaína, através de novos protocolos farmacológicos. Para isso, foi realizada uma análise da função sensitiva, proprioceptiva e motora desse nervo misto, comparando-se os efeitos da injeção prévia ou concomitante da codeína. Foram utilizados 80 ratos machos Wistar para serem avaliados funcionalmente após o recebimento na região do nervo ciático de soluções injetáveis dos diferentes fármacos: lidocaína com epinefrina (AL), AL sem vasoconstritor (AL SV), codeína (COD), tramadol (TRAM), AL + codeína (AL + COD), AL + tramadol (AL + TRAM), codeína 20 min antes do AL (COD 20 + AL) ou tramadol 20 min antes do AL (TRAM 20 + AL). O bloqueio sensitivo foi considerado o período de ausência do reflexo de retirada da pata após estímulo nociceptivo-pressórico (analgesímetro e pinça mosquito), já o bloqueio motor pela duração da claudicação (ausência do reflexo extensor postural) e o proprioceptivo, pela ausência de resposta do salto e tato (escore 0-3). A duração de ação do (AL + COD) foi maior (p<0.01) que a (COD) e que (COD20´+ AL) e os outros grupos (p<0.05). O COD isolado mostrou discreta atividade nociceptiva. Os resultados sugerem sinergismo de atividade entre opióide e AL. O uso concomitante de codeína ao AL melhora a eficácia do bloqueio sensitivo, motor e proprioceptivo, abrindo nova perspectiva no controle da dor a ser estudada em Odontologia. / The improvement in sensitive blockade induced by association or previous tramadol opioid injection was proved in animals and humans suggesting potencialization or sinergism in effects. Nevertheless, there are no experiments about the influence of codeine association to local anesthetics (LA) injected simultaneously or previously to block sciatic nerve functions (sensitive, motor and proprioceptive). The propose of this experiment was evaluate the influence of codeine analgesic opioid on duration of rat sciat nerve blockade induced by lidocaine using new pharmacological protocols. It was anallyzed the nociceptive, motor and proprioceptive functions of this mist nerve comparing the effects of previous or associated injection of codeine. Eighty (N=80) Wistar male rats were functional avaliated after they received differents injected drugs solutions, in sciat nerve region: lidocaine and epinephrine (LA), local anesthetics with no vasoconstrictor (LA NV), codeine (COD), tramadol (TRAM), LA + codeine (LA + COD), LA + tramadol (LA + tramadol), codeine 20 minutes previously to LA (COD 20+ LA) or tramadol 20 minutes previously to LA (TRAM 20 + LA). The sensitive blockade was considered the absence of withdraw reflex after nociceptive and pressoric stimulous (analgesimether and forceps), the motor was evaluated the duration of claudication and proprioceptive by de absence of hopping and tactile response (score 0-3). We concluded that the blockade duration of (LA + COD) was greater than (COD) (p<0.01) and than (COD 20 + LA) and than other groups (p<0.05). Codeine isolated showed discret nociceptive action. Our results suggested sinergism between opioid and LA. The associated use of codeine and LA improves de efficacy of sensitive, motor and proprioceptive blockade guiding to a new prospect in dentistrys pain control.

O Objetivo deste estudo controlado e duplo-cego foi avaliar os efeitos cardiovasculares induzidos pelo bloqueio pterigomandibular com o anestésico local cloridrato de lidocaína 2%, associado à epinefrina, seguido da administração de ansiolítico (midazolam 15mg) ou placebo, para realização de cirurgia de colocação de implantes dentários inferiores bilaterais, em 22 pacientes (13 mulheres 9 homens). Os parâmetros cardiovasculares Pressão Arterial Sistólica (PAS), Diastólica (PAD), Média (PAM) e Freqüência Cardíaca (FC) foram monitorados pelos métodos oscilométrico e fotopletismográfico. Os valores médios foram registrados a cada minuto e de forma contínua durante as etapas do experimento da seguinte forma: Fase 0 Período basal; Fase 1 Anestesia local; Fase 2 incisão; Fase 3 perfuração; Fase 4 colocação dos implantes; Fase 5 sutura; Fase 6 período final. Os indivíduos que receberam midazolam não apresentaram alterações de PAS, PAD, PAM e FC significativas (p>0,01) comparada ao placebo. Ocorreram alterações significantes dos valores para o grupo que recebeu placebo e dos valores médios do grupo que receberam midazolam na freqüência cardíaca / The purpose of this controlled and double-blind trial was to evaluate cardiovascular effects induced by pterigomandibular block of local anesthetic (LA) 2 % lidocaína hydrochloride with epinephrine, followed administration of benzodiazepine (midazolam 15mg on hour prior) or placebo during the surgical phase of placement of the lower bilateral dental implant in 22 normotensive outpatients (13 female and 9 male). The cardiovascular parameters systolic (SP), diastolic (DP) and mean (MP) pressures and heart rate (HR) were monitored by oscillometric and photopletismographic methods in 06 clinical phases during the procedure. The mean values were recorded every minute and in a continuous way during the phases of the experiment following the sequence: phase 0 basal period; phase 1 - anesthesia local; phase 2 mucoperiostal flap; phase 3 perforation; phase 4 placement of dental implants; phase 5 suture; phase 6 the end period. The group with received midazolam didnt induce significant SP, DP, MP and HR changes (p>0.01) compared to placebo. Significantly higher values in placebo group and mean values in midazolam group in heart-frequency were observed.

Dentre os adjuvantes para os anestésicos locais (AL), a enzima hialuronidase tem seu uso consagrado na anestesia oftalmológica como difusor do AL. É utilizada para melhorar a eficácia clínica e prolongar a anestesia como alternativa aos anestésicos locais de longa duração em pacientes com comprometimento sistêmico. Este estudo duplo-cego e controlado avaliou os efeitos cardiovasculares induzidos por 3,6 ml de anestésico local (AL) cloridrato de mepivacaína 2% com epinefrina 1:100.000 concomitantemente à hialuronidase 75 UTR/ml ou placebo (veiculo), em bloqueio do nervo alveolar inferior para realização de cirurgia de terceiros molares inferiores bilaterais e simétricos, em 20 pacientes. Foi realizada apenas uma cirurgia por consulta, no mesmo horário e operador. Os parâmetros cardiovasculares pressão sistólica (PS), diastólica (PD), média (PM) e freqüência cardíaca (FC) foram monitorados através de método oscilométrico e fotopletismográfico, em 10 etapas clínicas. Os registros eletrocardiográficos (ECG) das 12 derivações foram obtidos em 4 etapas: (T1) basal; (T2) anestésico local; (T3), 5 min. do AL; (T4) após a cirurgia. Foram avaliadas no ECG as seguintes variáveis: frequência cardíaca, duração do intervalo PR , duração do complexo QRS, duração do segmento QT corrigido. A hialuronidase injetada concomitantemente com o anestésico local (AL) não induziu alterações nas PS, PD, PM e FC (p>0,01, n=20) comparada ao placebo, mas houve alteração (p>0,01) na PS e FC na interação tempo x fármacos. Não foram observadas alterações eletrocardiográficas (n=18) consideradas de importância clínica como: infradesnivelamento do segmento ST, supradesnivelamento do segmento ST, extrassístoles de complexo QRS largo e extrassístoles de complexo QRS estreito. O uso do anestésico local injetado concomitante à hialuronidase 75 UTR/ml mostrou-se seguro para esta dose e via de administração. / Among the adjuvants to local anesthetics (LA), the enzyme hyaluronidase has its consecrated in ophthalmic anesthesia as a diffuser (spread) of the LA. It is used to improve the clinical efficacy and prolong anesthesia as an alternative to long lasting local anesthetics in patients with systemic involvement. This double-blind, controlled trial evaluated the cardiovascular effects induced by 3.6 ml of local anesthetic (LA) 2% mepivacaine hydrochloride with epinephrine 1:100,000 concomitantly with hyaluronidase 75 TRU/ml or placebo (vehicle) in blocking inferior alveolar nerve for performing third molar surgery bilateral and symmetrical in 20 patients. Surgery was performed only one by appointment, at the same time and operator. The cardiovascular parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were monitored using the oscillometric method and photoplethysmography in 10 clinical stages. Records electrocardiographic (ECG) of 12 leads were obtained in four steps: (T1) baseline, (T2) local anesthetic, (T3), 5 mim AL, (T4) after surgery. ECG were evaluated in the following variables: heart rate, duration of PR segment, duration of the complex QRS, duration of the corrected QT interval. Hyaluronidase injected concomitantly with local anesthetic did not induce changes in the SBP, DBP, MBP, and HR (p> 0.01, n = 20) compared to placebo, except in the interaction between steps and drugs (p<0.01) for SBP and HR. There were no ECG changes (n = 18) considered of clinical importance as ST segment depression, ST segment elevation, extrasystoles wide QRS complex and extrasystoles of narrow QRS complex. The use of local anesthetic injected concomitantly with hyaluronidase 75 TRU/ml was safe at this dose and route of administration.

O Objetivo deste estudo controlado e duplo-cego foi avaliar os efeitos cardiovasculares induzidos pelo bloqueio pterigomandibular com o anestésico local cloridrato de mepivacaína 2%, associado à epinefrina, seguido da injeção de hialuronidase 75 UTR ou placebo, antes da regressão do efeito anestésico, para realização de cirurgia de terceiros molares inferiores bilaterais e simétricos, em 20 pacientes. Os parâmetros cardiovasculares Pressão Arterial Sistólica (PS), Diastólica (PD), Média (PM) e Freqüência Cardíaca (FC) foram monitorados pelos métodos oscilométrico e fotopletismográfico, em 12 etapas. A hialuronidase injetada isoladamente depois do anestésico local (AL) não induziu alterações de PS, PD, PM e FC significativas (p>0,01) comparada ao placebo. O uso do AL seguido de hialuronidase injetada isoladamente antes da regressão do efeito anestésico mostrou-se segura para esta dose e via de administração. / The purpose of this controlled and double-blind trial was to evaluate cardiovascular effects induced by pterigomandibular block of local anesthetic (LA) 2 % mepivacaine with epinephrine, followed by injection of hyaluronidase 75 IU or placebo (solvent) before the regression of the anesthetic effect, on symmetric bilateral lower third molar surgery in 20 outpatients. The cardiovascular parameters systolic (SP), diastolic (DP) and mean (MP) pressures and heart rate (HR) were monitored by oscillometric and photopletismographic methods in 12 clinical steps during the procedure. The plain hyaluronidase injected after LA didn\'t induce significant SP, DP, MP and HR changes (p>0.01) compared to placebo. The use of LA followed by plain hyaluronidase injected before the regression of anesthetic effects showed to be safe for this dose and route of administration.

Bupivacaine ((R, S)-1-butyl-2-piperidylformo-2', 6'-xylidide), an anilide type local anaesthetic is manufactured in the standard racemic form and is widely used in the practice of regional anaesthesia. Despite its popularity as a local anesthetic, it has the potential to produce severe cardiotoxicity. Enantiomers, which are a pair of chiral isomers that are direct, nonsuperimposable mirror images of each other, vary in their chemical, pharmacological and toxicological profiles due to different stereospecific recognition in the body. Single enantiomeric drugs, when compared to racemic drugs, exert similar clinical effects but produce decreased risks of cardiac and neurotoxicity. This has led to the development of the single enantiomeric drugs ropivacaine ((S)-1-propyl-2-piperidylformo-2', 6'-xylidide) and levobupivacaine ((S)-1-butyl-2-piperidylformo-2', 6'-xylidide). Since local anaesthetics are extensively bound (>90%) to plasma protein in blood such as album and alpha1-acid-glycoprotein, it is only the free form of the flowing drug that can exert its pharmacological effects and are believed to be closely related to systemic toxicity. Although the safety and efficacy of these newer local anaesthetics have been ascertained in the literatures, but there are limited data on their pharmacokinetic profiles; thus it is envisioned that further pharmacokinetic trials would be required to elucidate their pharmacological and clinical effects. The aim of this thesis was to develop sensitive, reproducible and reliable methods of local anaesthetic assays to support such clinical trials. / The assays described in the thesis have been applied to numerous clinical research projects. Out of the various studies, the following will be discussed: Ropivacaine undergoes slower systemic absorption from the caudal epidural space in children than bupivacaine; Arterial and venous pharmacokinetics of ropivacaine with and without epinephrine after thoracic paravertebral block; Pharmacokinetics of levobupivacaine after thoracic paravertebral block. / The first method developed is the simultaneous determination of ropivacaine and bupivacaine in human plasma using high performance chromatography (HPLC). Most published methods of determining ropivacaine in human plasma use gas chromatography and a review of literature to date shows no data describing the use of HPLC to simultaneously determine both drugs. This is the first report describing a simple, isocratic, reversed-phase, liquid-liquid extraction procedure of high-performance liquid chromatographic method that allows the simultaneous detection of both local anaesthetics in one single injection. The chromatography was achieved using a reversed-phase chromatographic system with a Waters Novapak C18 column. 0.5 ml plasma was used for the sample preparation procedures. Bupivacaine and ropivacaine concentrations ranging from 10ng/ml to 3000 ng/ml and fixed amounts of pentycaine (internal standard) were spiked into the plasma samples for calculating the calibration graphs. Calibration graphs were linear over the range 10-3000 ng/ml (r=0.9978 for bupivacaine and r=0.9986 for ropivacaine). The within-day (intra-assay) coefficient of variation of the assay varied between 13.84% at 100 ng/ml, 1.84% at 500 ng/ml and 3.34% at 2000 ng/ml for bupivacaine; and 5.29% at 100 ng/ml, 1.38% at 500 ng/ml and 3.93% at 2000 ng/ml for ropivacaine. The between-day (inter-assay) coefficient of variation was 8.43% at 100 ng/ml, 4.06% at 500 ng/ml and 9.15% at 2000 ng/ml for bupivacaine, and 5.66% at 100 ng/ml, 4.40% at 500 ng/ml and 8.14% at 2000 ng/ml for ropivacaine. The limit of detection for both drugs was 10 ng/ml. / The fourth analytical technique describes the successful development of an ultrafiltration protein binding procedure to detect the free levels of the local anaesthetics in human plasma. Sample plasma was deposited in the ultrafiltration apparatus and ultrafiltrate containing the free local anaesthetics was forced thru a membrane under a fixed-angle rotor centrifugal force. Experiments were done to establish the optimum parameters for the ultrafiltration apparatus' binding capacities. The validated procedures use 0.5 ml plasma as the starting volume and it was deposited into the ultrafiltration apparatus. It was then subjected to 1750g centrifugal force for 20 minutes at centrifugal temperature of 37&deg;C. The resultant ultrafiltrate was processed according to the described LC-MS/MS method to detect the free local anaesthetic levels. / The second analytical methodology describes the assay of levobupivacaine in human plasma using HPLC. Calibration graphs relating peak height ratios and concentrations were linear over the range 10-3000 ng/ml (r=0.9995). The chromatography was achieved with an XTerra MS C18 column with the ultraviolet monitor set at 210 nm. The sample preparation steps were similar to the first analytical method, but with a different internal standard used. Precision and accuracy were assessed by performing analysis on replicate control plasma samples. The within-day (intra-assay) coefficient of variation of the assay varied between 4.25% at 50 ng/ml, 3.38% at 500 ng/ml, 3.76% at 1000 ng/ml and 3.14% at 2000 ng/ml. The between-day (inter-assay) coefficient of variation of the assay varied between 4.68% at 50 ng/ml, 4.94% at 500 ng/ml, 4.25% at 1000 ng/ml and 2.94% at 2000 ng/ml. The limit of detection was 10 ng/ml. / The third analytical methodology details the development and validation of a chiral analytical technique. This is the first report describing the development of a simple, isocratic, reversed-phase, liquid-liquid extraction procedure of a direct chiral method that allows the simultaneous detection of either free or total concentrations of bupivacaine enantiomers and ropivacaine in one single injection. It is also a novel technique to assay bupivacaine enantiomers with the use of vancomycin CSP column and liquid chromatography-mass spectrometry (LC-MS/MS) analysis, which achieved the lowest published detection limit with the lowest volume of plasma used. Calibration graphs were linear over the range 0.1-2000 ng/ml. Precision and accuracy were assessed by performing analysis on replicate control plasma samples. The within-day (intrassay) coefficient of variations of the assay for the drugs ropivacaine, levobupivacaine, dextrobupivacaine varied from 2.20% to 5.78%, 1.96% to 9.64%, 1.78% to 6.34%, respectively, for concentrations between 0.5 ng/ml to 2000 ng/ml. The between-day (interassay) coefficient of variations of the assay for the drugs ropivaciane, levobupivacaine, dextrobupivacaine varied from 3.66% to 9.61%, 3.18% to 8.34%, 2.22% to 10.59%, respectively, for concentrations between 0.5 ng/ml to 2000 ng/ml. The limit of detection was 0.05 ng/ml. / Wong Sum Yee April. / "November 2005." / Advisers: Manoj Karmakar; Tony Gin. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6370. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 207-217). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

O Objetivo deste estudo controlado e duplo-cego foi avaliar os efeitos cardiovasculares induzidos pelo bloqueio pterigomandibular com o anestésico local cloridrato de lidocaína 2%, associado à epinefrina, seguido da administração de ansiolítico (midazolam 15mg) ou placebo, para realização de cirurgia de colocação de implantes dentários inferiores bilaterais, em 22 pacientes (13 mulheres 9 homens). Os parâmetros cardiovasculares Pressão Arterial Sistólica (PAS), Diastólica (PAD), Média (PAM) e Freqüência Cardíaca (FC) foram monitorados pelos métodos oscilométrico e fotopletismográfico. Os valores médios foram registrados a cada minuto e de forma contínua durante as etapas do experimento da seguinte forma: Fase 0 Período basal; Fase 1 Anestesia local; Fase 2 incisão; Fase 3 perfuração; Fase 4 colocação dos implantes; Fase 5 sutura; Fase 6 período final. Os indivíduos que receberam midazolam não apresentaram alterações de PAS, PAD, PAM e FC significativas (p>0,01) comparada ao placebo. Ocorreram alterações significantes dos valores para o grupo que recebeu placebo e dos valores médios do grupo que receberam midazolam na freqüência cardíaca / The purpose of this controlled and double-blind trial was to evaluate cardiovascular effects induced by pterigomandibular block of local anesthetic (LA) 2 % lidocaína hydrochloride with epinephrine, followed administration of benzodiazepine (midazolam 15mg on hour prior) or placebo during the surgical phase of placement of the lower bilateral dental implant in 22 normotensive outpatients (13 female and 9 male). The cardiovascular parameters systolic (SP), diastolic (DP) and mean (MP) pressures and heart rate (HR) were monitored by oscillometric and photopletismographic methods in 06 clinical phases during the procedure. The mean values were recorded every minute and in a continuous way during the phases of the experiment following the sequence: phase 0 basal period; phase 1 - anesthesia local; phase 2 mucoperiostal flap; phase 3 perforation; phase 4 placement of dental implants; phase 5 suture; phase 6 the end period. The group with received midazolam didnt induce significant SP, DP, MP and HR changes (p>0.01) compared to placebo. Significantly higher values in placebo group and mean values in midazolam group in heart-frequency were observed.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

O Objetivo deste estudo controlado e duplo-cego foi avaliar os efeitos cardiovasculares induzidos pelo bloqueio pterigomandibular com o anestésico local cloridrato de mepivacaína 2%, associado à epinefrina, seguido da injeção de hialuronidase 75 UTR ou placebo, antes da regressão do efeito anestésico, para realização de cirurgia de terceiros molares inferiores bilaterais e simétricos, em 20 pacientes. Os parâmetros cardiovasculares Pressão Arterial Sistólica (PS), Diastólica (PD), Média (PM) e Freqüência Cardíaca (FC) foram monitorados pelos métodos oscilométrico e fotopletismográfico, em 12 etapas. A hialuronidase injetada isoladamente depois do anestésico local (AL) não induziu alterações de PS, PD, PM e FC significativas (p>0,01) comparada ao placebo. O uso do AL seguido de hialuronidase injetada isoladamente antes da regressão do efeito anestésico mostrou-se segura para esta dose e via de administração. / The purpose of this controlled and double-blind trial was to evaluate cardiovascular effects induced by pterigomandibular block of local anesthetic (LA) 2 % mepivacaine with epinephrine, followed by injection of hyaluronidase 75 IU or placebo (solvent) before the regression of the anesthetic effect, on symmetric bilateral lower third molar surgery in 20 outpatients. The cardiovascular parameters systolic (SP), diastolic (DP) and mean (MP) pressures and heart rate (HR) were monitored by oscillometric and photopletismographic methods in 12 clinical steps during the procedure. The plain hyaluronidase injected after LA didn\'t induce significant SP, DP, MP and HR changes (p>0.01) compared to placebo. The use of LA followed by plain hyaluronidase injected before the regression of anesthetic effects showed to be safe for this dose and route of administration.

Dentre os adjuvantes para os anestésicos locais (AL), a enzima hialuronidase tem seu uso consagrado na anestesia oftalmológica como difusor do AL. É utilizada para melhorar a eficácia clínica e prolongar a anestesia como alternativa aos anestésicos locais de longa duração em pacientes com comprometimento sistêmico. Este estudo duplo-cego e controlado avaliou os efeitos cardiovasculares induzidos por 3,6 ml de anestésico local (AL) cloridrato de mepivacaína 2% com epinefrina 1:100.000 concomitantemente à hialuronidase 75 UTR/ml ou placebo (veiculo), em bloqueio do nervo alveolar inferior para realização de cirurgia de terceiros molares inferiores bilaterais e simétricos, em 20 pacientes. Foi realizada apenas uma cirurgia por consulta, no mesmo horário e operador. Os parâmetros cardiovasculares pressão sistólica (PS), diastólica (PD), média (PM) e freqüência cardíaca (FC) foram monitorados através de método oscilométrico e fotopletismográfico, em 10 etapas clínicas. Os registros eletrocardiográficos (ECG) das 12 derivações foram obtidos em 4 etapas: (T1) basal; (T2) anestésico local; (T3), 5 min. do AL; (T4) após a cirurgia. Foram avaliadas no ECG as seguintes variáveis: frequência cardíaca, duração do intervalo PR , duração do complexo QRS, duração do segmento QT corrigido. A hialuronidase injetada concomitantemente com o anestésico local (AL) não induziu alterações nas PS, PD, PM e FC (p>0,01, n=20) comparada ao placebo, mas houve alteração (p>0,01) na PS e FC na interação tempo x fármacos. Não foram observadas alterações eletrocardiográficas (n=18) consideradas de importância clínica como: infradesnivelamento do segmento ST, supradesnivelamento do segmento ST, extrassístoles de complexo QRS largo e extrassístoles de complexo QRS estreito. O uso do anestésico local injetado concomitante à hialuronidase 75 UTR/ml mostrou-se seguro para esta dose e via de administração. / Among the adjuvants to local anesthetics (LA), the enzyme hyaluronidase has its consecrated in ophthalmic anesthesia as a diffuser (spread) of the LA. It is used to improve the clinical efficacy and prolong anesthesia as an alternative to long lasting local anesthetics in patients with systemic involvement. This double-blind, controlled trial evaluated the cardiovascular effects induced by 3.6 ml of local anesthetic (LA) 2% mepivacaine hydrochloride with epinephrine 1:100,000 concomitantly with hyaluronidase 75 TRU/ml or placebo (vehicle) in blocking inferior alveolar nerve for performing third molar surgery bilateral and symmetrical in 20 patients. Surgery was performed only one by appointment, at the same time and operator. The cardiovascular parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were monitored using the oscillometric method and photoplethysmography in 10 clinical stages. Records electrocardiographic (ECG) of 12 leads were obtained in four steps: (T1) baseline, (T2) local anesthetic, (T3), 5 mim AL, (T4) after surgery. ECG were evaluated in the following variables: heart rate, duration of PR segment, duration of the complex QRS, duration of the corrected QT interval. Hyaluronidase injected concomitantly with local anesthetic did not induce changes in the SBP, DBP, MBP, and HR (p> 0.01, n = 20) compared to placebo, except in the interaction between steps and drugs (p<0.01) for SBP and HR. There were no ECG changes (n = 18) considered of clinical importance as ST segment depression, ST segment elevation, extrasystoles wide QRS complex and extrasystoles of narrow QRS complex. The use of local anesthetic injected concomitantly with hyaluronidase 75 TRU/ml was safe at this dose and route of administration.