Methemoglobinemia Induced by Prilocaine in a Child With Noonan Syndrome.

Limited information is currently available on methemoglobinemia caused by the administration of prilocaine in children undergoing dental procedures in Japan. This case report presents the development of methemoglobinemia due to prilocaine overdose. The patient was a female aged 5 years 8 months with Noonan syndrome who also had pulmonary valve stenosis and hypertrophic cardiomyopathy. She presented with severe dental caries affecting 12 total teeth and required general anesthesia due to a lack of cooperation during dental treatment. General anesthesia was performed, during which 3% prilocaine with 0.03 IU/mL felypressin was administered intraoperatively via infiltration. Her SpO2 gradually decreased after 30 minutes, and cyanosis was observed postoperatively. Several assessments including a 12-lead electrocardiogram, an anteroposterior chest radiograph, and venous blood gas analysis were performed to identify potential causes. However, there were no indications of acute respiratory or cardiovascular abnormalities. It was noted that a total of 192 mg prilocaine was administered during the procedure, and methemoglobinemia was suspected to have developed because of overdose. Further testing revealed an elevated serum methemoglobin of 6.9%, supporting methemoglobinemia as the cause of her decreased SpO2. In dental procedures that require the use of prilocaine to treat multiple teeth, particularly for pediatric patients, it is important to carefully manage prilocaine dosing, as an overdose may lead to methemoglobinemia.

Patient Comfort with Various Local Infiltration Anesthetics for Minor Oculoplastic Surgery: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Although local anesthetics have been extensively studied, limited evidence is available regarding the optimal solution for maximizing patient comfort in minor oculoplastic procedures. OBJECTIVES: To determine the optimal anesthetic solution for local infiltration in minor oculoplastic surgeries to maximize patient comfort. METHODS: This systematic review with network meta-analysis of prospective studies was conducted to understand the efficacy of different local anesthetics in combination to maximize patient comfort. The study was designed according to the Cochrane Handbook for Systematic Reviews of Interventions. The population comprised patients receiving local infiltration anesthesia in minor oculoplastic surgeries. Various anesthetics with adjuvants were compared with respect to injection pain, operative bleeding, and complications. Random-effects model was performed. The primary outcome of injection pain was measured using the visual analog scale (VAS) or a preference question (which intervention was the least painful). Other outcomes were operative bleeding and complications, which were evaluated with a similar preference question. RESULTS: Eleven randomized controlled trials (RCTs) of 521 patients (917 eyes) were included. The network meta-analysis revealed that "bicarbonate-buffered lidocaine with epinephrine" led to a significant decrease in injection pain (preference question) compared to "prilocaine with felypressin" and "lidocaine with epinephrine," whereas no significant differences were detected in the analysis of injection pain measured using the VAS. CONCLUSIONS: "Bicarbonate-buffered lidocaine with epinephrine" may be the optimal anesthetic solution for local infiltration in minor oculoplastic surgeries due to reduced injection pain, operative bleeding, and postoperative swelling. However, this should be interpreted cautiously as the confidence in the evidence was very low. THE CLINICAL TRIAL REGISTRATION NUMBER: CRD42021260332 (PROSPERO).

An Octopus-Derived Peptide with Antidiuretic Activity in Rats.

Discovering new drug candidates with high efficacy and few side effects is a major challenge in new drug development. The two evolutionarily related peptides oxytocin (OXT) and arginine vasopressin (AVP) are known to be associated with a variety of physiological and psychological processes via the association of OXT with three types of AVP receptors. Over decades, many synthetic analogs of these peptides have been designed and tested for therapeutic applications; however, only a few studies of their natural analogs have been performed. In this study, we investigated the bioactivity and usefulness of two natural OXT/AVP analogs that originate from the marine invertebrate Octopus vulgaris, named octopressin (OTP) and cephalotocin (CPT). By measuring the intracellular Ca2+ or cyclic AMP increase in each OXT/AVP receptor subtype-overexpressing cell, we found that CPT, but not OTP, acts as a selective agonist of human AVP type 1b and 2 receptors. This behavior is reminiscent of desmopressin, the most widely prescribed antidiuretic drug in the world. Similar to the case for desmopressin, a single intravenous tail injection of CPT into Sprague-Dawley rats reduced urine output and increased urinary osmolality. In conclusion, we suggest that CPT has a significant antidiuretic effect and that CPT might be beneficial for treating urological conditions such as nocturia, enuresis, and diabetes insipidus.

Anesthetic Management of a Patient With Citrullinemia Type I During Dental Treatment.

We report a case involving intravenous sedation for third molar extractions in a 32-year-old man with citrullinemia type I (CTLN1), a genetic disorder that affects the urea cycle. The patient was diagnosed with CTLN1 after he exhibited seizures soon after birth and was intellectually disabled because of persistent hyperammonemia, although his recent serum ammonia levels were fairly well controlled. We planned to minimize his preoperative fasting, continue his routine oral medications, and monitor his serum ammonia levels at least twice. Sedation with midazolam and a propofol infusion was planned to suppress his gag reflex and reduce protein hypercatabolism due to stress. Epinephrine-containing local anesthetics, which enhance protein catabolism, were avoided, replaced by plain lidocaine for blocks and prilocaine with felypressin for infiltration anesthesia. No significant elevation in ammonia levels was observed. In patients with CTLN1, sedation can be useful for preventing hyperammonemia. Patients who develop symptomatic hyperammonemia may require urgent/emergent treatment involving other medical specialists. Therefore, preoperative endocrinology consultation, perioperative monitoring of serum ammonia levels, and preemptively coordinating for appropriate care in the event hyperammonemia occurs should all be considered.

Perfil de utilização de anestésicos locais de uma cidade brasileira com ênfase em diabéticos / Profile of use of local anesthetics in a Brazilian city with emphasis on diabetics

Objetivo: avaliar o conhecimento de cirurgiões-dentistas que trabalham em consultórios particulares de Palmas, Tocantins, quanto à utilização de anestésicos locais em pacientes portadores de diabetes mellitus. Materiais e método: trata-se de um estudo descritivo qualitativo, aprovado pelo Comitê de Ética em Pesquisa da FAMERP de São José do Rio Preto, sob o protocolo 032/2007 e CAAE: 0065.0.000.140-07, respeitando-se a Resolução 466/12, do Conselho Nacional de Saúde. A coleta de dados foi realizada por meio da aplicação de um questionário, utilizando um formulário estruturado. Resultados: de 113 participantes, 47 (41,6%) eram do sexo masculino e 66 (58,4%) do sexo feminino, com idade média de 35 anos. O anestésico mais utilizado pelos cirurgiões-dentistas avaliados foi a lidocaína 2% + adrenalina 1:100.000 (53,1%), o qual também é o mais utilizado para pacientes diabéticos controlados (64,6%). Quanto à variedade de anestésicos, 47,8% dos avaliados relataram possuir somente 3 tipos de anestésicos no consultório e que 83,2% nunca presenciaram nenhum problema decorrente do uso de anestésico. Além disso, 65,5% relataram não participar de cursos para atualização de conhecimentos, sendo que 53,1% mostraram-se insatisfeitos com o ensino de anestesiologia que receberam na graduação. Conclusão: observou-se que os cirurgiões-dentistas do atendimento odontológico particular de Palmas precisam de uma reciclagem profissional, a fim de atualizarem conhecimentos adquiridos na graduação sobre indicação e utilização de anestésicos locais em tratamentos odontológicos de pacientes com necessidades especiais, com ênfase em pacientes portadores de diabetes mellitus.(AU)

Objective: to evaluate the knowledge of dentists who work in private offices in Palmas, Tocantins, regarding the use of local anesthetics in patients with diabetes mellitus. Materials and method: this research is a qualitative descriptive study, approved by the Research Ethics Committee of FAMERP from São José do Rio Preto, under protocol number 032/2007 and CAAE: 0065.0.000.140-07 in compliance with the Resolution 466/12 of the National Health Council. Data collection was performed through the application of a questionnaire, using a structured form. Results: 47 (41.6%) out of 113 participants were male and 66 (58.4%) female, with an average age of 35 years old. The anesthetic most used by the dentists evaluated was lidocaine 2% + adrenaline 1: 100,000 (53.1%) which is also the most used for controlled diabetic patients (64.6%). As for the variety of anesthetics, 47.8% of those evaluated reported having only 3 types of anesthetics in the office and that 83.2% never saw any problems resulting from the use of anesthetics. Furthermore, 65.5% reported not participating in courses to update knowledge and 53.1% were dissatisfied with the teaching of anesthesiology they received during graduation. Conclusion: it was observed that dentists who work in private dental offices in Palmas need a professional retraining in order to update knowledge acquired during graduation on the indication and use of local anesthetics in dental treatments for patients with special needs, with an emphasis on patients with diabetes mellitus.(AU)

Comparison of two vasoconstrictors on glycemic levels in diabetic patients.

OBJECTIVES: The aim of this study was to evaluate glycemic levels in diabetic patients before, during, and after extractions using 2% lidocaine with 1:100,000 epinephrine (Lido/Epi) and 3% prilocaine with 0.03 IU/mL felypressin (Prilo/Fely). MATERIALS AND METHODS: A double-blind, randomized clinical trial was conducted to evaluate changes in body parameters and glycemic levels in diabetic patients undergoing two anesthetic protocols during dental extractions. During surgery, we evaluated blood pressure (BP), heart rate (HR), saturation (SpO2), and capillary glycemic levels (Gly). These parameters were measured at the following surgical moments: basal, 30 min after medication, incision, tooth removal, suture, and 30 and 60 min after anesthesia. RESULTS: Data analysis showed no differences between the groups considering age, weight, and time spent in surgery. Increased systolic BP and decreased diastolic BP were observed in the lido/epi group. No difference was observed in the prilo/fely group among the surgical moments or between the groups regarding BP. No difference was observed in HR and SpO2 between the groups at any surgical moment. However, differences were found when compared the differences in glycemic and basal levels in both groups with greater decreases in blood glucose values for the lido/epi group. In anxiety level evaluation, there was no difference between the different surgical moments. CONCLUSION: Thus, both lido/epi and prilo/fely (maximum 3.6 mL) can be safely used in controlled diabetic patients CLINICAL RELEVANCE: The use of lidocaine associated with epinephrine did not increase glycemic levels but leads to decrease over time when associated with an anxiety reduction protocol, offering some advantage over prilocaine plus felypressin for diabetic patients.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol.

BACKGROUND: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. OBJECTIVE: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. METHOD: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. RESULTS: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. CONCLUSIONS: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

Increase in pulse pressure on administration of a dental local anesthetic solution, prilocaine hydrochloride with felypressin in male diabetic patients with coronary heart disease.

OBJECTIVES: This study aimed to evaluate pulse pressure fluctuation on dental local anesthetic administration in diabetic patients with and without coronary heart disease undergoing tooth extraction. MATERIALS AND METHODS: This retrospective study in diabetic patients undergoing tooth extraction included 33 patients with coronary heart disease (mean age 79.3 ± 7.4, 64% male) and 49 patients without coronary heart disease (mean age 78.6 ± 6.5, 29% male). The increase in pulse pressure before and after administration of local anesthetics was compared between diabetic patients with and without coronary heart disease. RESULTS: Pulse pressure was increased in male diabetic patients with coronary heart disease compared with those without coronary heart disease following administration of 3% prilocaine hydrochloride with felypressin 0.03 IU/mL (prilocaine) (15.6 ± 15.4 mmHg in those with coronary heart disease (n = 11) versus 4.3 ± 10.9 mmHg in those without coronary heart disease (n = 13), p = 0.03). CONCLUSIONS: Prilocaine administration increased pulse pressure in male diabetic patients with coronary heart disease compared with those without coronary heart disease. Further study is needed to reveal the mechanisms involved in the increase in pulse pressure. CLINICAL RELEVANCE: This is the first study of pulse pressure fluctuation in diabetic patients with and without coronary heart disease following administration of local anesthetics. Our findings can help guide the choice of local anesthetics and serve as a predictor of coronary vascular condition in diabetic patients during dental treatment.

Difference in the Effects of Lidocaine With Epinephrine and Prilocaine With Felypressin on the Autonomic Nervous System During Extraction of the Impacted Mandibular Third Molar: A Randomized Controlled Trial.

PURPOSE: Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar. MATERIALS AND METHODS: In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P < .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P < .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P < .01). CONCLUSIONS: This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.

Cardiovascular Comparison of 2 Types of Local Anesthesia With Vasoconstrictor in Older Adults: A Crossover Study.

We assessed the effect of 2% lidocaine with 1:80,000 adrenaline (L + AD) and 3% prilocaine with 0.03 IU/mL felypressin (P + FP) on blood pressure and heart rate in older adults with systemic diseases undergoing dental extraction. This double-blind, randomized crossover study included 22 elderly participants, aged over 65 years. The participants were administered L + AD for one dental extraction and P + FP for the other. Blood pressure and heart rate were recorded immediately, 5, and 10 minutes after local anesthetic administration and the data were analyzed. The systolic and diastolic blood pressures in the P + FP group increased at all measurement points (p < .001). In the L + AD group, the diastolic blood pressure decreased at 5 and 10 minutes after local anesthetic administration (p < .05), whereas the heart rate increased at all measured time points (p < .001). There were statistically significant differences in systolic blood pressure at 5 and 10 minutes after local anesthetic administration and in diastolic blood pressure and heart rate at all time points between the 2 groups. In older adults, P + FP administration increased the systolic and diastolic blood pressures. L + AD administration increased the heart rate and decreased the diastolic blood pressure.

Casein-derived peptides as an alternative ingredient for low-phenylalanine diets / Péptidos derivados de la caseína como ingrediente alternativo para las dietas bajas en fenilalanina

Introduction: casein-derived peptides can be liberated both in vivo via normal digestion of casein, as well as in vitro via enzymatic hydrolysis. These peptides were suggested to have biological activity. Objectives: the aim of this study was to describe the production and characterization of casein peptides and to explore the potential of these peptides as an option for low-phenylalanine diets. Methods: peptides were produced by tryptic hydrolysis of sodium caseinate and acid precipitation with HCl, followed by precipitation with ethanol or aggregation of CaCl2 or ZnSO4. Results: the amino acid analysis revealed a significant reduction in the amount of phenylalanine from the original protein. Conclusion: casein-derived peptides could be a future alternative of short chain peptides to low-phenylalanine formulations

Introducción: los péptidos derivados de la caseína se pueden liberar tanto in vivo, a través de la digestión normal de la caseína, como in vitro a través de la hidrólisis enzimática. Se sugirió que estos péptidos tenían actividad biológica. Objetivos: el objetivo de este estudio fue describir la producción y caracterización de péptidos de caseína y explorar el potencial de estos péptidos como una opción para las dietas con bajo contenido de fenilalanina. Métodos: los péptidos se produjeron por hidrólisis tríptica de caseinato de sodio y precipitación ácida con HCl, seguido de precipitación con etanol o agregación de CaCl2 o ZnSO4. Resultados: el análisis de aminoácidos reveló una reducción significativa en la cantidad de fenilalanina de la proteína original. Conclusión: los péptidos derivados de la caseína podrían ser una alternativa futura de los péptidos de cadena corta a las formulaciones con bajo contenido de fenilalanina

Avaliação dos efeitos vasculares e expressão de mRNA de receptores de drogas vasoconstritoras em leito arterial mesentérico de ratos normotensos, diabéticos, hipertensos renais um-rim, um clip (1R-1C) e 1R-1C diabéticos / Vascular reactivity and vasoconstrictor drugs receptors RNAmexpression on mesenteric artery bed of normotensive, diabetic, 1K-1C hypertensive and 1K-1C hypertensive-diabetic rats

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.(AU)

The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.(AU)

Comparison of epinephrine and felypressin pressure effects in 1K1C hypertensive rats treated or not with atenolol.

PURPOSE: Epinephrine is considered the gold standard vasoconstrictor for hypertensive patients, but few studies report felypressin's effects. The present study aimed to analyze and compare the effects of these two vasoconstrictors, injected by the intravenous route, on the arterial pressure of normotensive, hypertensive and atenolol-treated hypertensive rats. METHOD: The hypertension model was one-kidney-one-clip (1K1C): the main left renal artery was partially constricted and the right kidney was surgically removed in 45-day-old male Wistar rats. 1K1C hypertensive rats received atenolol (90 mg/kg/day) by gavage for 2 weeks. 28-35 days after hypertension induction, a catheter was inserted into the left carotid artery to record direct blood pressure values. The following parameters were recorded: minimal hypotensive response, maximal hypertensive response, response duration and heart rate. RESULTS: Epinephrine, but not felypressin, exerted an important hypotensive action; non-treated hypertensive rats showed more pronounced vasodilation. Treated and non-treated rats showed hypertensive responses of the same magnitudes in all groups; 1K1C atenolol rats showed reduced hypertensive responses to both vasoconstrictors. Felypressin's response duration was longer than that of epinephrine in all groups. Epinephrine increased heart rate while felypressin reduced this parameter only in the normotensive group. CONCLUSIONS: Our results suggest that felypressin has equipotent pressure responses when compared with epinephrine, showing a greater extent of action. Atenolol's reduction of hypertensive effects surprisingly suggests that atenolol ß-blockade may also be important for felypressin's cardiovascular effect, as is widely known for epinephrine. Our data suggest that felypressin is safe for hypertensive subjects, in particular those receiving atenolol.

Advantages of anterior inferior alveolar nerve block with felypressin-propitocaine over conventional epinephrine-lidocaine: an efficacy and safety study

BACKGROUND: Conventional anesthetic nerve block injections into the mandibular foramen risk causing nerve damage. This study aimed to compare the efficacy and safety of the anterior technique (AT) of inferior alveolar nerve block using felypressin-propitocaine with a conventional nerve block technique (CT) using epinephrine and lidocaine for anesthesia via the mandibular foramen. METHODS: Forty healthy university students with no recent dental work were recruited as subjects and assigned to two groups: right side CT or right side AT. Anesthesia was evaluated in terms of success rate, duration of action, and injection pain. These parameters were assessed at the first incisor, premolar, and molar, 60 min after injection. Chi-square and unpaired t-tests were used for statistical comparisons, with a P value of < 0.05 designating significance. RESULTS: The two nerve block techniques generated comparable success rates for the right mandible, with rates of 65% (CT) and 60% (AT) at both the first molar and premolar, and rates of 60% (CT) and 50% (AT) at the lateral incisor. The duration of anesthesia using the CT was 233 ± 37 min, which was approximately 40 min shorter than using the AT. This difference was statistically significant (P < 0.05). Injection pain using the AT was rated as milder compared with the CT. This difference was also statistically significant (P < 0.05). CONCLUSIONS: The AT is no less successful than the CT for inducing anesthesia, and has the added benefits of a significantly longer duration of action and significantly less pain.

Intraoperative local anaesthesia for reduction of postoperative pain following general anaesthesia for dental treatment in children and adolescents.

BACKGROUND: Whilst carrying out dental procedures under general anaesthesia (GA), practitioners routinely give local anaesthetics (LA) intraoperatively to children. Local anaesthetics are used to help manage postoperative pain and reduce bleeding and the physiological response to procedures. Studies of effectiveness of intraoperative LA to date have reported contradictory results. OBJECTIVES: To assess the effects of intraoperative local anaesthesia for reducing postoperative pain following general anaesthesia for dental treatment in children and young people aged 17 years or younger. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 12), MEDLINE via OVID (1946 to 02 January 2014), EMBASE via OVID (1980 to 02 January 2014) and Web of Science Conference Proceedings (1990 to 02 January 2014). We searched for ongoing trials in the US National Institutes of Health Register, the metaRegister of Controlled Trials (mRCT) and the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) Clinical Trials Portal. We did not place any restrictions on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials in which local anaesthetic was given intraoperatively under general anaesthesia for dental treatment of children and young people aged 17 years or younger. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We performed data extraction and assessment of risk of bias independently and in duplicate. We contacted authors to clarify omissions in trial reports. In the 'Summary of findings' tables, we elected to report the outcomes pain, distress, postoperative bleeding, and physiological parameters related to the general anaesthetic, as we considered these to be the outcomes of greatest importance to readers of the review. MAIN RESULTS: We included 14 trials in this review, with 1152 randomised participants. The studies were published between 1990 and 2009 and were conducted in the United Kingdom, Egypt, Saudi Arabia, and the United States. The age of participants ranged from 2 to 40 years. Three studies were at an overall high risk of bias, seven studies were at an unclear risk of bias, and we judged four studies to be at low risk of bias. The clinical heterogeneity of the included studies precluded pooling of studies in terms of method of administration of LA (e.g., intraligamental injection, infiltration injection, or topical delivery) and variation in the use of supplementary analgesics and follow-up time.Of the seven studies where administration of LA was by infiltration injection, six studies (very low-quality body of evidence, 542 participants analysed, 1 study had overall high risk of bias, 4 studies had overall unclear risk of bias, 1 study had overall low risk of bias) measured postoperative pain. The results were equivocal. There was a decrease in bleeding and increase in soft tissue damage in the LA groups, but we did not judge this to be clinically significant.In the 2 studies where administration of LA was by intraligamental injection, there was no difference in mean pain scores, and they did not report any soft tissue damage (very low-quality body of evidence, 115 participants analysed, 1 study had overall high risk of bias, 1 study had overall unclear risk of bias).One 3-armed study (very low-quality body of evidence, 54 participants analysed, overall high risk of bias) compared the effects of intraligamental and infiltration LA injection with no treatment. There was no evidence of a mean difference in pain, distress, or postoperative anxiety among the three groups.Four studies (very low-quality body of evidence, 343 participants analysed, 2 studies had overall low risk of bias, 2 studies had overall unclear risk of bias) evaluated the effects of topical LA compared with no treatment or placebo. One study (overall unclear risk of bias) with a no-treatment comparator reported lower mean pain in the LA group; all other studies reported no difference in mean pain scores. Two studies reported on bleeding (overall unclear risk of bias): One study reported a clinically insignificant increase in bleeding with no treatment; the other reported no difference.None of the studies reported on participant or child satisfaction. AUTHORS' CONCLUSIONS: In this review, it was difficult to reach firm conclusions as to the benefit of using local anaesthetic for dental treatment under general anaesthesia. The information reported in the included studies was comprehensive and applicable to the review question, but ultimately it was not sufficient to address the objective of the review. We were unable to pool the included studies in a meta-analysis because of substantial variation in outcome measures, interventions, and treatment types. The use of supplementary analgesia further obscured the effect of local anaesthetics.Based on the literature review and the results of this review, we recommend further randomised controlled trials that minimise bias through adequate allocation concealment and blinding of participants and assessors, and assess the effect of intraoperative local anaesthetic on the volume and type of anaesthetic used and on the cardiovascular system in participants receiving supplementary analgesics as well. Researchers should give consideration to the impact of any changes on the health and well-being of the participant and report baseline measures of pain or distress, or both, and preoperative anxiety.

Holter ECG assessment of the effects of three different local anesthetic solutions on cardiovascular system in the sedated dental patients with coronary artery disease.

OBJECTIVE: The purpose of the study is to compare the effects of lidocaine alone, epinephrine-combined lidocaine and prilocaine with octapressin on the cardiovascular system during minor oral surgery of sedated cardiac dental patients under local anesthesia. METHODS: Connected to a Holter electrocardiogram (ECG) monitor for a total of 5 hours starting 1 hour before the procedure, twenty patients with high risk of coronary artery disease were included in the prospective cohort study. All the patients had three operations at 3 different appointments with at least one-week intervals and each operation was performed under local anesthesia achieved by 3.6 mL of 3% prilocaine with octapressin, 3.6 mL of 2% lidocaine with 1:80.000 epinephrine and 3.6 mL of 2% lidocaine without a vasoconstrictor. Data of the Holter ECG device assessed at the end of every hour and evaluated statistically. Repeated measures ANOVA, Friedman test, and Wilcoxon signed ranks test were used to perform statistical analysis. RESULTS: Heart-rate showed significant differences between lidocaine with epinephrine and pure lidocaine in an hour following the injection (p<0.05 for all). Cardiac rhythm showed significant differences between prilocaine with octapressin and pure lidocaine at the second hour after its administration (p<0.05 for all). There were no significant differences between 3 local anesthetics in terms of ST segment deviation. CONCLUSION: In minor oral operation on the sedated patients with cardiac disease, the use of 3.6 mL or a less amount of local anesthetic injection containing epinephrine appears to be a predictable and safe method.

Felipressina aumenta pressão arterial durante procedimento odontológico em pacientes hipertensos / Felypressin increases blood pressure during dental procedures in hypertensive patients

FUNDAMENTO: A felipressina foi adicionada ao anestésico local para aumentar a duração do efeito anestésico e reduzir a toxicidade nos procedimentos dentários. No entanto, o efeito sobre a pressão arterial é incerta, e isso pode ser altamente relevante no tratamento dentário de pacientes hipertensos. OBJETIVO: Investigar o efeito da felipressina sobre a pressão arterial em pacientes hipertensos com pressão arterial controlada. MÉTODOS: Foram estudados 71 indivíduos com essas características e com necessidade de tratamento periodontal. Após 10 minutos de repouso, a anestesia local (prilocaína) foi infiltrada com e sem adição de felipressina. Em seguida, uma raspagem subgengival profunda foi realizada. A pressão arterial foi medida por um equipamento oscilométrico automático (DIXTAL DX2010). Dez minutos após a administração do anestésico, o pico de ação anestésica foi gravado. O Inventário de Ansiedade Traço-Estado (IDATE) foi utilizado para avaliar o traço de ansiedade nos pacientes. RESULTADOS: A pressão arterial sistólica aumentou após a anestesia, independentemente da associação com felipressina, durante todo o procedimento dentário (p < 0,05), e essa resposta pode ser explicada, pelo menos em parte, pelos níveis de traço de ansiedade dos indivíduos. No entanto, um aumento adicional na pressão arterial diastólica foi observado quando a prilocaína foi associada a felipressina (p < 0,05), mas essa resposta não se alterou com os níveis de traço de ansiedade. CONCLUSÃO: A felipressina aumentou a pressão arterial diastólica de pacientes hipertensos com pressão arterial controlada. Pacientes com traço de ansiedade elevado apresentaram aumento na pressão arterial sistólica em alguns procedimentos, sugerindo que um aumento da pressão arterial também pode estar relacionado ao medo ou à ansiedade.

BACKGROUND: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. OBJECTIVE: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. METHODS: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. RESULTS: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p<0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p<0.05), but this response did not change with trait anxiety levels. CONCLUSION: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety.