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Local anesthetic update
Abstract
The development of new local anesthetics has not been an area of particularly active research for a number of years. However, as the use of regional anesthesia has expanded, additional anesthetic requirements and techniques have stimulated the search for newer drugs and ways of modifying existing ones. This article reviews some of the more recent developments in this field.
... For the management of postoperative pain after surgical procedure can be attained by usage of long acting local anaesthetic agents, cold ice therapy, opioid and NSAIDS. Bupivacaine and mepivacaine are long acting local anaesthetic agents used most commonly [3,4]. ...
... would at least in theory present a shorter latency than 2% lignocaine (pKa=7.9) [4,7]. Our results coincide with this assumption, as shorter latency or faster onset of anaesthesia was observed with 4% articaine group as compared to 2% lignocaine group respectively. ...
... Subjective evaluation of intraoperative pain experience using 4% articaine and 2% lignocaine was done by means of a visual analogue scale (V.A.S) in which the patients were instructed to score intraoperative pain intensity during the procedure [4,7]. The mean intraoperative pain scores for lignocaine group were 3.22 ± 1.67 cm and 2.13 ± 1.42 cm for articaine group respectively. ...
Background: The aim of the study was to evaluate the anaesthetic efficacy of 4% articaine hydrochloride with epinephrine/adrenaline 1:200000 versus 2% lignocaine hydrochloride with epinephrine/adrenaline 1:200000 in extractions of permanent mandibular posterior teeth.
Materials and methods: One hundred (100) patients were selected for the study in the Department of Oral and Maxillofacial Surgery and Implantology. Patients were equally but randomly divided into two different groups: i) Group 1-4% articaine solution; ii) Group 2-2% lignocaine solution, both with equal concentration of epinephrine (1:200000). Standardized clinical parameters included the Visual Analogue Scale (VAS) score for each, Pain on injection, Intraoperative Pain, Onset of anaesthesia, Duration of anaesthesia, Need of reanaesthesia.
Results: On statistical evaluation of the values obtained for each patient, it was observed that Group I (4% articaine with 1:200000 epinephrine) demonstrated low pain on injection, early onset of anaesthesia (shorter latency), low intraoperative pain and reasonable duration of soft tissue anaesthesia compared to Group II (2% lignocaine with 1:200000 epinephrine) that demonstrated slow onset, more intraoperative pain and minimally longer duration of soft tissue anaesthesia.
Conclusion: it can be stated that Septanest (4% articaine hydrochloride with 1:2000000 epinephrine) may be preferred to Xylocaine (2% lignocaine hydrochloride with 1:2000000 epinephrine) in simple minor oral surgical procedures.
... Levobupivacaine is a local anaesthetic that is relatively new to clinical practice. [8][9][10] Levobupivacaine is an S(À) enantiomer of bupivacaine and both agents have similar pharmacokinetic properties. [8][9][10] There are several studies that have reported that the cardiovascular and central nervous system-related side effects of levobupivacaine are less frequent than those experienced with bupivacaine. ...
... [8][9][10] Levobupivacaine is an S(À) enantiomer of bupivacaine and both agents have similar pharmacokinetic properties. [8][9][10] There are several studies that have reported that the cardiovascular and central nervous system-related side effects of levobupivacaine are less frequent than those experienced with bupivacaine. [8][9][10] Some toxic effects can be seen with high doses of bupivacaine and when it is used for a long duration. ...
... [8][9][10] There are several studies that have reported that the cardiovascular and central nervous system-related side effects of levobupivacaine are less frequent than those experienced with bupivacaine. [8][9][10] Some toxic effects can be seen with high doses of bupivacaine and when it is used for a long duration. [8][9][10] Based on these reports, [8][9][10] levobupivacaine is recommended as an alternative to bupivacaine for patients who experience cardiovascular system-related side effects. ...
To compare two intrathecal anaesthetics, bupivacaine and levobupivacaine, for their effects on motor and sensory blockade and haemodynamics in patients aged ≥65 years undergoing transurethral resection of the prostate (TUR-P) or transurethral resection of the urinary bladder (TUR-M).
Patients scheduled to undergo TUR-P or TUR-M were randomized to receive either 3 ml (15 mg) 0.5% isobaric levobupivacaine (group L) or 3 ml (15 mg) of 0.5% hyperbaric bupivacaine (group B) for spinal anaesthesia. The onset time, maximum level and time to reach the maximum level of sensory and motor blockade were recorded. Changes to haemodynamic parameters were also recorded.
The study randomized 100 patients: 57 to group L and 43 to group B. Levobupivacaine did not cause any significant changes in haemodynamic parameters, including systolic blood pressure, and showed a similar sensory block onset time compared with bupivacaine, but it had a significantly longer motor block onset time compared with bupivacaine.
These current findings suggest that levobupivacaine can be used as a substitute for bupivacaine for spinal anaesthesia in elderly patients ≥65 years of age undergoing elective TUR-P or TUR-M operations.
... Local anaesthetic suitable for spinal anaesthesia should provide effective anaesthesia and analgesia intraoperatively and should have no side effects. 6,7 Most commonly used local anaesthetic is hyperbaric bupivacaine in regional anaesthesia. It is a racemic mixture of two enantiomers, levobupivacaine, S (-) isomer and dexrobupivacaine, R (+) isomer. ...
BACKGROUND Isobaric levobupivacaine has minimal effect on positional variation of sensory and motor blockade given intrathecally. Also, it has lesser cardiotoxic and neurotoxic effects. Present study was done to compare efficacy, analgesia haemodynamic effects and any adverse effects after spinal anaesthesia with isobaric levobupivacaine with nalbuphine and fentanyl as adjuvants in transurethral endoscopic surgeries. METHODS 60 male adult patients of American Society of Anaesthesiologists (ASA class I-III) of age group 40 - 80 years were randomized into 2 groups (n = 30) in this prospective, double blinded study. 10 mg of 0.5 % levobupivacaine with 25 µg fentanyl in group LF and 10 mg of 0.5 % levobupivacaine with 0.8 mg nalbuphine in group LN. Parameters assessed were sensory and motor blockade characteristics and hemodynamic variables in both the groups. Adverse effects were recorded if any. RESULTS Onset of sensory and motor blockade were significantly faster in group LF compared to group LN. In both the groups, time for two segment regression was comparable. Statistically significant prolonged analgesic duration was noticed in group with nalbuphine than fentanyl as adjuvant to isobaric levobupivacaine. Difference in haemodynamic variation was not significant in both the groups. CONCLUSIONS Intrathecal nalbuphine 0.8 mg as an adjuvant with isobaric levobupivacaine 0.5 % 10 mg is as efficacious as fentanyl 25µg in transurethral endoscopic surgeries in elderly population with better hemodynamic stability. KEY WORDS Levobupivacaine; Fentanyl; Nalbuphine; Spinal anaesthesia.
... Since its introduction in the late 1940s, lidocaine has become the most widely used anesthetic in medicine and dentistry due to its efficacy and clinical safety [1,2]. Articaine hydrochloride, a local anesthetic that contains an extra ester linkage, has been compared with this standard anesthetic [3,4] to ensure that it is reliable and safe to use. ...
PurposeThis study determined the frequency of adverse reactions related to the administration of local dental anesthesia with 4% articaine compared with 2% lidocaine, both associated with epinephrine 1:100,000. The null hypothesis was that there is no difference between the administrations of both dental local anesthesia.Methods
From a total of 727 patients in an emergency service, 338 and 389 patients were subjected to local anesthesia with lidocaine and articaine, respectively. A questionnaire was completed for each patient that contained patient data, the local anesthesia applied, and any reactions.ResultsThe overall frequency of adverse reactions was 3.71%, with sweating and pallor being the most frequently observed. There was an association between adverse reactions and the use of daily medication by patients anesthetized with articaine (p = 0.0266). In contrast, in patients anesthetized with lidocaine, there was an association among the duration of the procedure (p = 0.0423), the type of procedure (p = 0.0146), and first anesthesia exposure (p = 0.0448).Conclusions
The low frequency of adverse reactions with use of articaine and lidocaine led to the conclusion that both solutions are safe for use in dentistry.
... Ester local anesthetics are not available in dental cartridges essentially because of several reasons such as the lack of efficacy, the potential for allergenicity, and the advantages of amino amides [4][5][6][7]. ...
... Lidocaine, a cationic ion, is used to numb tissue in a specific area and to treat ventricular tachycardia. It can also be used for nerve blocks [26]. Etodolac and lidocaine might be good candidates for ionic liquid formation. ...
Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac patch alone, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine patch alone. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption.
... 7 A associação de vasoconstritores a anestésicos locais aumenta a duração e profundidade da anestesia, promove hemostasia e reduz a toxicidade sistêmica dos anestésicos. [8][9] A epinefrina, vasoconstritor adrenérgico associado à lidocaína neste estudo, apresenta seletividade para beta-1 (que aumenta a frequência cardíaca) e beta-2 (responsáveis pela vasodilatação das redes vasculares pulmonares) de 50%, e seletividade para receptores alfa de 100%, promovendo excelente vasoconstrição na circulação periférica local. [10][11] No entanto, a norepinefrina, neste estudo associada à mepivacaína, apresenta 25% da seletividade da epinefrina para receptores alfa, alta seletividade para beta-1 (85%) e muito pouca atividade beta-2 (15%), podendo por isto ocasionar um aumento na pressão sanguínea mais acentuado. ...
Resumo: As características farmacológicas de agentes anestésicos locais estão entre os diversos fatores que podem influenciar a percepção de dor pós-operatória. O objetivo deste estudo piloto foi avaliar a influência de dois agentes anestésicos na percepção de dor pós-operatória após cirurgia a retalho para raspagem e alisamento radicular (RAR). Neste ensaio clínico randomizado, paralelo, duplo-cego, foram realizadas 12 cirurgias para RAR em pacientes com doença periodontal que apresentassem sinais clínicos de inflamação após terapia periodontal básica em pelo menos um sextante. Os pacientes foram aleatoriamente alocados em um dos seguintes grupos: G1-mepivacaína 2% com norepinefrina 1:100.000; G2-lidocaína 2% com epinefrina 1:100.000. A intensidade da dor foi avaliada por meio de escala visual analógica (EVA) e escala numérica de 101 pontos (NRS-101), durante oito horas após a cirurgia. Os resultados demonstraram que a intensidade de dor pós-operatória foi estatisticamente inferior no grupo G2 em determinados períodos após a cirurgia, conforme indicam as respectivas medianas (Md). No período de uma hora: Md G1: 2,5; G2:18; p = 0,01; de duas horas: Md G1:2; G2:28,5; p = 0,009; de três horas: Md G1:6; G2:28; p = 0,01. Desta forma, os dados deste estudo piloto indicam que a utilização de mepivacaína 2% com norepinefrina 1:100.000 promove maior controle da dor no período pós-operatório imediato que a lidocaína 2% com epinefrina 1:100.000, após cirurgia de RAR a retalho. Palavras-chave: Solução anestésica; dor pós-operatória; lidocaína; mepivacaína. Abstract: Pharmacologic characteristics of local anesthetics agents are among several features that may influence postoperative pain intensity. The aim of this study was to evaluate the influence of two anesthetic agents on postoperative pain perception after open flap debridement surgeries. For this parallel-group, double-masked, placebo-controlled randomized clinical trial, 12 surgeries for open flap debridement were performed on patients who presented periodontal disease with clinical signs of inflammation after nonsurgical treatment on at least one sextant. Patients were allocated in one of the following groups: G1-2% mepivacaine with 1:100.000 norepinephrine; G2-2% lidocaine with 1:100.000 epinephrine. Pain intensity was assessed using visual analog scale (VAS) and 101-point numerical rate scale (NRS-101) during the first 8 hours after surgery. The results demonstrated that postoperative pain intensity was statistically lower in G2 at 1 (Median (Md) G1:2.5; G2:18; p = 0.01), 2 (Md G1:2; G2:28.5; p = 0.009) and 3 (Md G1:6; G2:28; p = 0.01) hours-period after surgery. Therefore, data from this pilot study indicate that 2% mepivacaine with 1:100.000 norepinephrine might promote more pain control at immediate postoperative period than does 2% lidocaine with 1:100.000 epinephrine after open flap debridement surgery.
... In 2000 the newest amide articaine was introduced .Infiltration with Lignocaine which is slightly painful procedure. Also Lignocaine when injected may be allergenic to some individuals (15).Use of electronic means which interfere with pain signal transmission are available but they require special gadgets (5.) Bupivacaine 5 % thermoreversible gel supplied by Rural College of Pharmacy,Loni was used in our study. Bupivacaine HCL (1-BUTYL-2,6pipecoloxylidide hydrochloride) is a long acting amide local anesthetic first synthesized in 1957 by Ekenstam at A.B.Bofors laboratories at Sweden (9).In the late 1970s Bupivacaine was introduced in the market. ...
Background: The efficacy of two intrapocket local anesthetics of amide group, Lignocaine 5% and Bupivacaine 5% were analyzed and compared to each other in the procedure of Scaling and root planing. Methods: Forty patients were divided in two equal groups of Lignocaine 5% and Bupivacaine 5% .Gels of each drug were obtained and used for the procedure of scaling and root planing (SRP). The gels were applied in the pocket with a 2mm diameter plastic canula attached to a syringe. Every 1 minute probing was done for anesthesia assessment and on 'no pain' of probing SRP done. Every 5 minutes probing was continued to find out the time for which the anesthetic drug effect lasted, SRP was done by an independent blind observer and pain assessment and gel application by another to eliminate the bias. Pain assessment was done on 100mm Visual analog scale (VAS), and Verbal Response Scale (VRS) on a four point scale having points labeled from none pain to severe pain, which was used at the end of the procedure. Results: The data analyzed showed that Bupivacaine 5% gel takes a longer time to start its action and similarly the peak effect is reached late when compared with Lignocaine 5% gel (p< 0.01).But the duration for which the anesthesia lasts is significantly higher for Bupivacaine (average 30.25 mins). And the overall pain experienced by patients is also significantly less than that by patients in Lignocaine group. Conclusion: Bupivacaine 5% is more effective topical intrapocket anesthetic for Scaling and Root Planing procedure and other time taking Periodontal procedures as compared to Lignocaine 5% ,and it may be a better alternative to Infiltration local anesthesia. anesthesia without the need of needles would be a major advancement in dentistry as needles play a role in fear and anxiety to the patient. Not only children but many adults also are at times afraid of needles. (1) Infiltration and nerve block provides sufficient anesthesia but main disadvantage is pain associated with needle insertion and long period of numbness of surrounding tissue such as lips and tongue. (2) It is a challenge to give local anesthesia without psychological as well as physical trauma. So with the emergence of topical anesthetic gels the problem seemed to be solved. There is less systemic absorption of the drug and reduction of dosage. They control pain perception and alter the pain reaction of an individual. They act by blocking the transmission of signals from terminal fibers of sensory nerve. (3) Chronic periodontitis is a progressive disease that affects gingiva, periodontal ligament and bone around the teeth .The main purpose of periodontal therapy is to eradicate the bacteria, reduce the inflammation, stop the disease process, maintain esthetics, give comfort to the patient and create a healthy environment for tooth .To achieve this, scaling and root planing (SRP) is the most commonly used procedure (4). Therefore there is need for long acting anesthetic preparation which is non invasive and which would be with easily and painlessly applied to pocket for scaling and root planing.(5) Multiple studies have documented the effectiveness of intraoral topical anesthetics with different formulation and concentration in reducing pain .(6) This article we explores some of the challenges in selecting the correct drug for pain reduction in scaling and root planing, and compares the efficacy of Bupivacaine 5% in comparison to Lignocaine 5%. Bupivacaine 5% gel was prepared with the help of Pravara Rural College of Pharmacy, Loni. It was decided to compare their efficacy in the non surgical dental procedure of scaling and root planing.
... Previous studies published after the market introduction of Oraqix® have proved the efficacy of the mixture of 5% lidocaine and prilocaine (EMLA®). This topical anesthetic has been mainly used to achieve pain control during sharp debridement of chronic leg ulcers of arterial, venous or arteriovenous aetiology in Dermatology as well as for soft tissues anesthesia in children (20-22). However, the effective duration of the topical anesthetic finished at 60 minutes (23). ...
Objectives: To evaluate the efficacy of Oraqix® during scaling and root planing (SRP) in comparison with 20% benzocaine and placebo.
Study Design: 15 patients requiring 4 sessions of SRP were enrolled. For each patient, Oraqix®, Hurricaine®, vaseline or no anesthetic product were randomly assigned each to a quadrant. Treatment pain was evaluated on a 100 mm Visual Analog Scale (VAS) and on a Verbal Rating Scale (VRS). The amount of product administered, the need to re-anesthetise, patient and operator satisfaction and the onset of side-effects were also recorded.
Results: Oraqix® was significantly better than nothing, with a reduction of VAS score to 13.3 units, but without significant differences with Vaseline or Hurricaine®. Oraqix® was better in VRS reduction than not using any anesthetic (p=0.001) or using vaseline (p=0.024), but similar to Hurricaine® (p=0.232).
Conclusions: Oraqix® effectively controls pain in SRP procedures, with few side-effects and a good acceptance on the part of patients and clinicians.
Key words:Controlled clinical trial, topical anesthetic, scaling and root planing.
... It was also shown that when compared to the solution with the lowest epinephrine concentration (1:400,000), the 1:100,000 solution has more than double therapeutic utilization time (mean 36 vs. 78 min). These results confirm the already known additional effect of the vasoconstrictor [32,34353637. Nevertheless, the extent of this effect has been discussed controversially. ...
Objectives
The aims of this study were to compare and evaluate the clinical anesthetic efficacy of five 4 % articaine solutions with and without epinephrine in pulpal anesthesia after infiltration.
Materials and methods
In a randomized, double-blinded, crossover study, ten volunteers received local anesthesia infiltration in the maxillary right central incisor with five different solutions (4 % articaine + epinephrine 1:100,000, + epinephrine 1:200,000, + epinephrine 1:300,000, + epinephrine 1:400,000, without epinephrine). Electronic pulp tester was used to calculate the onset, utilization time, time to recede, and the surface integral under the time–effect curve. Additionally, cardiovascular parameters and post-experimental soft tissue anesthesia were examined.
Results
Onset as well as time to recede was not influenced by the epinephrine concentration. When using the epinephrine-free agent, time to recede was significantly shorter. Upon decreasing epinephrine concentration, duration of pulpal anesthesia and total anesthetic efficacy declined. The shortest time of anesthesia and lowest anesthetic efficacy were seen for the solution without epinephrine. No association was found between the local anesthetic drug and cardiovascular parameters. Soft tissue anesthesia was significantly shorter without epinephrine.
Conclusions
This study shows the substantial benefits of vasoconstrictors in dental infiltration anesthesia. These findings were reflected by means of prolonged and deeper therapeutic effect in a dose-dependent manner.
Clinical relevance
Even when utilizing agents with reduced amount of epinephrine, a safe anesthesia is possible. The epinephrine-free solutions resulted in a distinct limitation of utilization time and efficacy.
... Since its introduction, lidocaine has been the most common dental local anaesthetic due to its clinical efficiency and safety. 1,2 Articaine, another amide type local anaesthetic, is also a widely used local anaesthetic and was compared to lidocaine in previous studies. 3,4 The vasodilator properties of amide justify the addition of a vasoconstrictor in order to increase the duration of action and decrease systemic toxicity. ...
The aim of this study was to evaluate the cardiovascular effects of maxillary infiltration using 2% lidocaine with 1:100,000 adrenaline, 4% articaine with 1:200,000 adrenaline, and 4% articaine with 1:100,000 adrenaline in different stages during restorative dental procedures.
Twenty healthy patients randomly received 1.8 mL of the three local anaesthetics. Systolic blood pressure, average blood pressure, diastolic blood pressure, and heart rate were evaluated by the oscillometric and photoplethysmograph methods in seven stages during the appointment.
Statistical analysis by ANOVA and Tukey tests of cardiovascular parameters did not show significant differences between the anaesthetic associations. There were significant differences for the parameters among different clinical stages.
The variation of cardiovascular parameters was similar for lidocaine and articaine with both adrenaline concentrations and showed no advantage of one drug over the other. Cardiovascular parameters were influenced by the stages of the dental procedures, which showed the effect of anxiety during restorative dental treatment.
... Its effectiveness is attributed to its bactericidal and bacteriostatic effects and its substantivity within the oral cavity. [6] Lidocaine is a local anesthetic with a long history used topically for a variety of indications [14] .Even though chlorhexidine/lidocaine sprays are marketed in several countries, there are no studies available on a combination product in sore throats. Lidocaine has been investigated in studies with sore throat or in the oral mucosa. ...
The aim of this trial was to assess the relative efficacy of a sage/echinacea spray and a chlorhexidine/lidocaine spray in the treatment of acute sore throats.
This was a multicenter, randomized, double-blind, double-dummy controlled trial carried out in eleven general practices in Switzerland. A total of 154 patients (133 analyzed in per protocol collective) at least 12 years old with acute sore throat present for not more than 72 hours prior to inclusion and with a throat score >/=6 participated in the study. They used either an echinacea/sage spray or a chlorhexidine/ lidocaine spray with two puffs every 2 hours, in a double-dummy blinded manner, up to 10 times daily until they were symptom-free, for a maximum of 5 days. The main outcome measures was the comparison of response rates during the first three days. A response was defined as a decrease of at least 50% of the total symptoms compared to baseline.
The echinacea/sage treatment exhibited similar efficacy to the chlorhexidine/lidocaine treatment in reducing sore throat symptoms during the first 3 days (P(x<Y) = .5083). Response rates after 3 days were 63.8% in the echinacea/sage group and 57.8% in the chlorhexidine/lidocaine group. For all secondary parameters, such as time to becoming symptom free, throat pain, and global assessments of efficacy by the physician and patient, no difference between the two treatments was seen. They were both very well tolerated.
An echinacea/sage preparation is as efficacious and well tolerated as a chlorhexidine/lidocaine spray in the treatment of acute sore throats.
Timely identification and management of problems at the immediate end of surgery may save lives. The likelihood of a patient developing complications depends on the nature of the procedure, anesthesia technique, coexisting diseases, and preoperative medical evaluation and optimization measures.
Local anesthetics are essential to the practice of dermatology and dermatologic surgery. By blocking the influx of sodium ions into peripheral nerve cells, local anesthetics prevent depolarization and temporarily interrupt nerve conduction. Local anesthesia is most commonly injected intradermally or subcutaneously. Infiltration of the papillary dermis yields more immediate onset with sustained duration of action, whereas subcutaneous infiltration is generally less painful and causes less tissue distortion. Topical anesthesia is particularly useful in children, although its role continues to increase with the evolution of dermatologic procedures. Mucosal surfaces have the highest absorption of local anesthetic, owing to the lack of a keratinized stratum corneum in the epidermis. Regional nerve blocks—the most common of which is the digital nerve block—are performed by injecting local anesthetic around the peripheral nerves located proximally to the cutaneous procedural sites. Regional blocks are beneficial for anesthetizing large areas of skin with minimal tissue distortion and needlesticks. Tumescent anesthesia is commonly employed for liposuction and results in longer-lasting analgesia by direct infiltration of large volumes of solution containing lidocaine, saline, and epinephrine. Adverse effects of local anesthesia are more frequently caused by the associated vasoconstrictors or the act of injecting, rather than as a result of the anesthetic itself. Moreover, allergic reactions to local anesthetics are exceedingly rare. Systemic toxicity is rare in routine dermatologic surgery, although it is important to minimize risk and identify its distinct clinical signs and symptoms.
Background:
Topical application, oral, and IV injection of tranexamic acid (TXA) have been used to reduce surgical bleeding.
Objective:
To evaluate the safety and efficacy of TXA injected subcutaneously to reduce bleeding during dermatologic surgery.
Methods:
In this double-blinded, placebo-controlled, randomized prospective study, 131 patients were randomized to subcutaneous injection of lidocaine 2% diluted 1:1 with either saline (placebo) or TXA 100 mg/1 mL before surgery. Before the second stage or closure, size measurements of bloodstain impregnation on Telfa and surgical wound size were recorded and analyzed using mixed-effects linear regression. Subjective evaluation of hemostasis was performed using 4-point scale grading and analyzed using Fischer's exact test.
Results:
One hundred twenty-seven patients completed the study. The bloodstain to surgical wound size ratio was smaller in the TXA group (1.77) compared with the placebo group (2.49) (p < .001). An improved effect of TXA on bleeding was observed in the subgroup of patients receiving anticoagulants (mean difference; 95% confidence interval; -0.83; -1.20 to -0.46 p < .001). The subjective hemostasis assessment was significantly better in the TXA group overall (p = .043) and anticoagulant subgroup (p = .001) compared with the placebo group.
Conclusion:
Subcutaneous injection of TXA was safe, reduced bleeding during dermatologic surgery, and particularly effective for patients receiving anticoagulation treatment.
This paper presents an exact three-dimensional analysis of the free vibration and natural frequencies
of an inhomogeneous pre-stressed hollow sphere filled with a compressible inviscid fluid. It is
assumed that the initial stresses in the hollow sphere are caused with the uniform compressible
radial forces acting on the outer surface as well as with the hydrostatic pressure acting on the inner
surface of that. Under these radial forces, initial stresses in the sphere are to be inhomogeneous.
These initial stresses in the sphere are determined analytically by using the concrete known
expressions.
The motion of the foregoing pre-stressed sphere is written within the scope of the three-dimensional
linearized theory of elastic waves in initially stressed elastic bodies [1,2]. However, the motion of
the fluid is written within the scope of the Navier-Stokes equations for compressible barotropic
inviscid fluids [3]. On interface surface between the sphere and fluid, the compatibility conditions
are satisfied.
For solution to the equations of motion related to the hollow sphere the discrete-analytical method
developed in the works [3, 4] is employed. According to this method, the hollow sphere is divided
into a certain number of sub-hollow spheres in each of them the initial stresses are taken as
homogeneous one. Namely, this statement allows using the analytical solution method for the
equations obtained for the potentials in the Helmholtz decomposition in the solution of the
equations of elastodynamics. The solution to the corresponding equations for fluid motion is found
analytically in the spherical coordinates through the spherical Bessel functions. Using the traction
free condition outer surface of the hollow sphere, the contact conditions between the sublayers and
compatibility conditions between the fluid and sphere on the inner surface of the sphere the
frequency equation is obtained for determination of the natural frequencies for the hydro-elastic
system under consideration.
The advent of novel drug delivery systems has allowed local anesthetics to become a popular and practical means of providing analgesia with minimal systemic effects. Through the complete and continuous blockade of pain transmission, these drugs can be effectively used to reduce or prevent the development of secondary hyperalgesia. Currently used novel drug delivery systems for local anesthetics include ambulatory electronic delivery, patient-controlled infusion, implantable local infusion, and ambulatory elastomeric infusion. Topical application products include transdermal creams and patches as well as iontophoretic delivery systems.
The aim of this study was to evaluate the influence of 2 anesthetic agents on patients' postoperative pain perception after periodontal surgery. For this parallel-group, double-blinded, randomized clinical trial, 36 open flap debridement surgeries were performed on patients who presented with periodontal disease with clinical signs of inflammation after nonsurgical treatment on at least 1 quadrant. Patients were allocated to 1 of the following groups: group 1, 2% lidocaine with 1 ∶ 100,000 epinephrine; group 2, 2% mepivacaine with 1 ∶ 100,000 norepinephrine. Pain intensity was assessed using the visual analog scale during the first 8 hours after surgery. All patients received 750-mg acetaminophen tablets, which they were instructed to take as a rescue medication if necessary. The results demonstrated that postoperative pain intensity was statistically lower in group 2 than in group 1 at the 1-, 2-, and 3-hour periods after surgery, although the pain intensity for all groups could be considered mild. In conclusion, patients in both groups reported similar mild pain after periodontal surgery.
The aim of this study was to compare the local anaesthetic efficacy of articaine HCl and prilocaine HCl during an operative procedure after their administration by either mandibular nerve block or maxillary infiltration.
Study design: The study was a double-blind clinical study which comprised 162 children (81 boys and 81 girls), who required a pulpotomy on their primary molars. Pain-related behaviours were used to assess the severity of pain during the injection of either prilocaine HCl or articaine HCl and the operative procedures following either a maxillary infiltration or mandibular nerve block of the two local anaesthetic agents. The frequencies of post-procedural adverse events in the prilocaine and articaine anaesthetised groups were also determined.
Significantly more discomfort (p<0.05) was observed following maxillary infiltration compared to mandibular nerve block. There were no significant differences in the pain-related behaviours scores between the two local anaesthetic agents administered during the dental operative procedures, except for the removal of the coronal pulp. For this latter procedure, the pain-related behaviour score was 1.5- times higher in the prilocain-anaesthetised children than in the articaine-anaesthetised children. The frequencies of post- procedural adverse events in the prilocaine-treated children were similar to those found in the articaine-treated children.
We concluded that local anaesthesia following mandibular nerve block is more effective than that following maxillary infiltration in 6-8-year-old children. However, the intensity of pain that was experienced by the children during administration of either prilocaine or articaine and some of the dental procedures after their administration were similar.
The primary purpose of this study was to review the standard prescribing practices of physicians providing local anaesthesia in a major abortion clinic in British Columbia.
We conducted a retrospective review of patients who underwent a first trimester surgical abortion at the Comprehensive Abortion and Reproductive Education (CARE) Program at BC Women's Hospital and Health Centre during 2004 (n = 1546). Patients' demographics and reproductive history including age, weight, gestational age, and gravidity were recorded. Main outcomes recorded were dosage of lidocaine administered and amount of conscious sedation (midazolam and fentanyl) administered for pain management. Incidence of toxicity was also recorded.
Almost one half (49.9%) of the patients received 20 mL of 0.5% lidocaine, and the remainder received 20 mL of 1.0% lidocaine. The volume of conscious sedation did not differ between groups. There was a positive correlation computed between midazolam and fentanyl dosages (r = 0.583, P < 0.01). Neither was significantly associated with gravidity. Gestational age was associated with both midazolam and fentanyl dose (r = 0.05, P = 0.047; r = 0.06, P = 0.024). There was no reported incidence of toxicity.
Similar doses of midazolam and fentanyl were administered to patients regardless of the amount of lidocaine given (20 mL of either 0.5% or 1.0%). Further investigation is required to assess whether fentanyl and midazolam doses used during procedures can be used as surrogate measurements of pain. Our findings suggest it would be reasonable to consider using a lower dose of local anaesthetic for first trimester abortions to further reduce the risk of toxicity.
Objectives: Meta-analysis was used to quantitatively synthesize results from clinical studies comparing four percent articaine hydrochloride to two percent lidocaine hydrochloride, both with epinephrine 1:100,000. The null hypothesis was that there is no statistically significant difference in efficacy of the two anesthetic agents. Methods: Potential studies for inclusion were identified using the MeSH database search terms carticaine (articaine MeSH term) and lidocaine in a PubMed search. Inclusion criteria included randomized clinical trials in humans with a clear determination of anesthetic efficacy with respect to initial administration of these two anesthetic agents in dental applications. Twelve randomized, clinical trials met the inclusion criteria. The overall approach of this meta-analysis emphasized the pulpal anesthetic success (by means of electric pulp test and/or visual analog scale for intra-operative pain); secondary analyses evaluated timelines of pulpal anesthesia. The combined results for percentage of teeth achieving pulpal anesthetic success were based on the reported data from ten suitable studies, using the Fisher meta-analytic method of combining significance probabilities. Results: Individually, two of these studies reported significantly superior performance of articaine hydrocholoride compared to lidocaine hydrochloride on the basis of achievement of pulpal anesthetic success; a third study reported a suggestive result (p=0.057). In four additional studies, the observed rate of anesthetic success was greater for articaine hydrocholoride, although not significantly so; the performance of the two anesthetic agents was identical in the remaining three studies. Differences in anesthetic success based upon tooth type/location and injection type were explored. Further results were obtained for pulpal anesthetic timelines. Conclusions: The overall result for anesthetic success based upon meta-analysis by the Fisher method was that articaine hydrochloride demonstrated statistically superior efficacy (p=0.004) relative to lidocaine hydrochloride. Supported by the University of Iowa Department of Endodontics.
A series of methyl N-(2-substituted aminopropanoyl)-3-cyanoanthranilates (4a-i), that are structurally-related to tocainide and lidocaine, was synthesized and was found to be active when evaluated for local anaesthetic activity using the frog-foot withdrawal reflex, the guinea pig wheal derm and the rabbit corneal reflex tests. A selected numbers of the series were preliminarily evaluated for antiarrhythmic activity using CaCl2-induced arrhythmia test. Compounds 4a, 4c and 4f at lower doses completely protected the animals against the induced arrhythmias.
Beside the already analysed bioanthropometric characteristics of the lower jaw, additional measurement of parameters insufficiently discussed in reference literature were performed in our study. On the basis of the obtained data it was possible to define relevant biometrical relations in the region of the lower jaw branch and anatomical regions that are especially important to the use of conduction anaesthesia. All measurements were defined on the basis of anteroposterior (horizontal) and vertical directions. The relation between different anatomical structures of the lower jaw interior branch and foramen mandibulae served as a focal point. When related to anteroposterior plane the mandibular foramen was located precisely in the middle of the distance between crista temporalis and posterior ramus ridge. Viewed in vertical direction the lowest point of mandibular opening was slightly closer to the mandibular angle than to incisure of mandible, meaning that in the majority of macerated skulls mandibular foramen had a relatively low position.
The aim of this study was to compare the onset and duration of pulpal anesthesia by maxillary infiltration using 2% lidocaine with 1:100,000 epinephrine, 4% articaine with 1:200,000 epinephrine, and 4% articaine with 1:100,000 epinephrine.
Twenty healthy patients randomly received 1.8 mL of one of the three local anesthetics during operative dentistry procedures of low complexity on three maxillary posterior teeth. Onset and duration were determined using an electric pulp tester.
The mean values for pulpal onset were 2.8, 1.6, and 1.4 minutes and for pulpal duration were 39.2, 56.7, and 66.3 minutes, respectively, for 2% lidocaine with 1:100,000 epinephrine, 4% articaine with 1:200,000 epinephrine, and 4% articaine with 1:100,000 epinephrine. Statistical analysis by the Kruskal-Wallis nonparametric test showed significant differences with better results (shorter onset and longer duration periods) for both articaine solutions compared with the lidocaine solution. Although 4% articaine with 1:100,000 epinephrine clinically presented the shortest onset and the longest duration periods, there was no statistically significant difference between the articaine solutions.
Both articaine solutions produced shorter onset and longer duration of pulpal anesthesia by maxillary infiltration than the lidocaine solution did. Statistical analysis did not confirm better clinical results of 4% articaine with 1:100,000 epinephrine than with 4% articaine with 1:200,000 epinephrine.
Using a randomized blind cross-over design, the comparative efficacy of clonidine in prolonging tetracaine spinal anaesthesia was studied in six mongrel dogs.
Lumbar subarachnoid injections (1 ml) of: tetracaine 4 mg with clonidine 150 µg, tetracaine 4 mg with epinephrine 200 µg, tetracaine 4 mg, clonidine 150 µg, epinephrine 200 µg, and five per cent dextrose in H2O (vehicle) were administered randomly to each animal at 5–7 day intervals.
Subarachnoid tetracaine produced a motor blockade of 186 ± 58 (mean ± SEM) min. Both clonidine and epinephrine produced a similar prolongation of tetracaine motor blockade, 135 percent(p < 0.01 ) and 116 per cent (p < 0.05) respectively, compared with tetracaine alone. No motor blockade was observed in dogs receiving clonidine, epinephrine or five per cent dextrose in H2O. The addition of clonidine to tetracaine spinal anaesthesia produced a significant increase in duration of sensory blockade, 56 per cent (p<0.01) and 107 per cent (p < 0.01) respectively, when compared to tetracaine with and without epinephrine. Subarachnoid clonidine alone produced a sensory blockade of 76 ± 17minutes, while only one animal receiving subarachnoid epinephrine had a sensory blockade (40 minutes). No neurologic deficits were observed in any of the animals.
The study concludes that during spinal anaesthesia with tetracaine in dogs, clonidine is as effective as epinephrine in prolonging motor blockade, but is more effective in prolonging sensory blockade.
In the nineteenth century, some natives of Peru noticed circumoral numbness, euphoria and analgesia after chewing the leaves of the Erythroxylen coca bush. By 1850, cocaine was isolated from the plant, marking the start of the local anesthetic era in clinical medicine. Over the past 50 years, many synthetic local anesthetics have been developed which have fewer side effects, increased specificity of action and a wider margin of safety than cocaine. Currently, local anesthetics are used topically, for local infiltration; and intravenously, for peripheral nerve blockade, for sympathetic blockade, as well as for epidural and intrathecal use. Although the route of administration may affect pharmacokinetics and pharmacodynamics, it is the purpose of this article to review the general pharmacology of this entire range of clinically useful compounds.
It has been claimed that anaesthesia of mandibular pulpal and lingual soft tissue, as well as maxillary palatal soft tissue, results following buccal infiltration of the local anaesthetic Ultracaine (articaine HC1). However, this has never been scientifically proven and the aim of this investigation was to test these claims by comparing articaine to a standard anaesthetic, Citanest (prilocaine HC1). In order to study this, a double blind, randomized trial was conducted in healthy adult volunteers. In these subjects, the ability to induce maxillary and mandibular anaesthesia following buccal infiltration with articaine (as compared to prilocaine given contralaterally), was determined by measuring sensation to electrical stimulation at the tooth, buccal and lingual soft tissue at each of the four non-carious, non-restored, second molars. Results showed that there were no statistically significant differences between articaine and prilocaine in their ability to induce anaesthesia for any tissue at any of the six sites (p greater than 0.05) as determined by chi-square analysis. Analysis of effect on sensation for 25 minutes post-administration also failed to demonstrate a difference between the two drugs. Therefore, these data are not consistent with superior anaesthesia efficacy by articaine at any site, including the mandibular pulpal, lingual or maxillary palatal tissues, in the second molars studied.
Claims that labial infiltration of the local anesthetic articaine HCl (Ultracaine DS) results in anesthesia of mandibular pulpal as well as maxillary and mandibular lingual soft tissue have never been scientifically substantiated. The aim of this investigation was to evaluate these claims, by comparing articaine to a standard anesthetic, prilocaine HCl (Citanest Forte). To investigate this, a double blind, randomized study was conducted in healthy adult volunteers. In each volunteer, the ability to induce maxillary and mandibular anesthesia following labial infiltration with articaine was compared to prilocaine given contralaterally. Anesthesia was determined by measuring sensation to electrical stimulation at the tooth, labial and lingual soft tissue for each of the 4 non-carious, non-restored, canines. Results showed that mandibular canine pulpal anesthesia had a success rate of 65% for articaine and 50% for prilocaine. Success rates for palatal and lingual anesthesia averaged 5% for each agent. As determined by chi-square analysis, no statistically significant differences were found between articaine and prilocaine for any tissue at any of the 6 sites (P greater than 0.05). A time-course assessment also failed to demonstrate a difference between the two drugs. Therefore these data are not consistent with superior anesthesia efficacy being produced by articaine at any site, including the mandibular pulpal, lingual or maxillary palatal tissues, in the canine teeth studied.
Sufentanil 25 micrograms plus clonidine 1 microgram/kg administered epidurally was compared with epidural sufentanil 50 micrograms alone in a double-blind fashion for pain relief in 40 patients after abdominal surgery. The duration of complete pain relief was significantly longer in those who received the mixture. Oxygen saturation was reduced 10 and 20 minutes after sufentanil alone, but remained stable after sufentanil and clonidine. There were significant decreases in arterial blood pressure in the latter group that were maximum between 20 and 120 minutes after administration.
The effects of local anesthetics in depressing myocardial contractility were studied in isolated guinea pig right ventricular papillary muscles. Bupivacaine and etidocaine, 4 and 10 microM, showed reverse frequency-dependent depression of contractility, that is, less significant depression of contractility at higher stimulation frequencies (2-3 Hz) than at lesser frequencies (less than 1 Hz). Lidocaine, 40 microM, demonstrated a similar trend. In contrast, the normal action potential maximum rate of depolarization (Vmax), a measure of sodium channel conductance, was significantly more depressed at 2-3 Hz by bupivacaine and etidocaine than by lidocaine. Consequently, contractile depression could be overcome only at higher stimulation frequencies, at which conduction was depressed. To explore the mechanism of the contractile depression, local anesthetic effects were studied on slow (calcium channel-mediated) action potentials in partially depolarized papillary muscles. Etidocaine and bupivacaine, 4 and 10 microM, and lidocaine, 40 and 100 microM, caused a marked depression of the late-peaking contractile responses, attributed to Ca2+ release from the sarcoplasmic reticulum. In contrast, only 10 microM bupivacaine caused any significant depression of the slow action potential rate of depolarization (to 89% of control), consistent with a possible small depression of Ca2+ entry.
Chemical compounds that demonstrate local anesthetic activity usually possess the following chemical arrangement: Aromatic portion — Intermediate chain — Amine Portion
To investigate the role of extracellular calcium in bupivacaine-induced muscle injury, the effects of the drug on creatine kinase (CK) release and muscle ultrastructure were studied in the isolated rat soleus in the presence and absence of calcium and of the Ca-channel blockers verapamil and nifedipine. Control muscles maintained a constant CK release rate and normal morphology for at least 3 hours. CK release rates increased markedly after exposure to 1.5 mM and 5 mM bupivacaine and electron microscopy showed evidence of damage to mitochondria, sarcoplasmic reticulum and the plasmalemma of muscle fibres with disruption of the Z-lines, I-bands and M-lines of myofibrils. When calcium was omitted from the incubation medium, there was a 3-fold reduction in CK release rates; the morphological changes were less severe initially but by 120 min were comparable to those in muscles incubated with bupivacaine and calcium. Neither 10(-6) M verapamil nor 10(-6) M nifedipine reduced CK release or muscle fibre damage. Verapamil (10(-5) M) reduced CK release but not the severity of muscle damage. The findings indicate that extracellular calcium plays a part in mediating the muscle damage caused by bupivacaine but that other factors must also be involved, and that Ca-channel blockers do not prevent muscle damage.
The dose-dependent actions of bupivacaine on the microvasculature were evaluated by television microscopy in an in vivo rat cremaster muscle preparation. Animals were anesthetized with chloralose and urethane. Mean arterial pressure was measured via a carotid artery cannula; heart rate was calculated from the phasic pressure trace. The cremaster muscle was suffused with a balanced electrolyte solution that was controlled for temperature, pH, PO2, PCO2, and osmolarity to provide a physiologic environment. Internal diameters of fourth-order arterioles were measured with an electronic vernier displayed on the video monitor. Arteriolar diameters were measured every 30 s during a 10-min control period, a 10-min period of topical application of bupivacaine hydrochloride, and a 30-min recovery period. Bupivacaine 10(-1), 10(0), 10(1), and 10(2) micrograms X ml-1 produced progressive vasoconstriction to 82.7 +/- 2.9%, 75.0 +/- 5.6%, 71.0 +/- 7.0%, and 65.7 +/- 9.4% of control (P less than 0.05 for each), respectively. Bupivacaine, 10(3) and 2.5 X 10(3) micrograms X ml-1, did not alter arteriolar diameters significantly, although there was a tendency for vasodilation. In a second group of animals, arteriolar diameters were measured during intravenous bupivacaine infusion that produced stable plasma concentrations of 2.3 +/- 0.2 micrograms X ml-1. Vasoconstriction of 91.4 +/- 2.2%, of control (P less than 0.01) was observed. These results demonstrate that dose-dependent arteriolar constriction occurs even with blood bupivacaine levels that are at the upper limits of those expected to occur during regional anesthesia.
This study was designed to evaluate a new drug delivery system. The authors undertook to determine if microdroplets prepared by encapsulating volatile anesthetics with a membrane of lecithin could be used for local anesthesia. Local anesthesia was determined by monitoring the response of the rat to tail clamping and electrical stimulation of the skin following the intradermal injection of the microdroplets. Microdroplets were prepared from isoflurane, enflurane, halothane, methoxyflurane, diethyl ether, chloroform, and heptane. Although all microdroplet preparations produced local anesthesia, only methoxyflurane microdroplets produced an ultra-long duration of local anesthesia (approximately 24 h). Further characterization of the methoxyflurane microdroplets revealed two important differences from conventional local anesthetics. First, the local anesthetic effect of methoxyflurane reached a plateau that did not change significantly for 20 h while the injection of lidocaine and bupivacaine resulted in a peak effect that returned to baseline within 1 and 3 h, respectively. Second, the anesthetic effect of methoxyflurane remained essentially localized to the site of injection, while the anesthetic effect of lidocaine and bupivacaine migrated 15 cm in less than 1 h. The toxicity and safety of methoxyflurane were evaluated. When administered over the dosage range 1-16% (v/v) intradermally, or by injections into muscle, or by repeat injections every 4 days for 16 days, all animals regained their pretreatment response to painful stimulations, and there was no evidence of gross injury to tissue. Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect. The present study demonstrates that methoxyflurane microdroplets produce an anesthetic effect that is highly localized, stable in intensity, ultra-long in duration, and reversible.
The effects of the cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine in their base form)
were studied in volunteers. When tested by pin-prick, EMLA cream 2.5% and 5% produced analgesia of the area tested, the cream
being most effective if left in contact with the skin for 60 min. The pain produced by the insertion of an i. v. cannula was
successfully blocked by the application of this formulation, especially if applied to the antecubital area. Temporary blanching
of the skin areas was frequently observed on removal of the occlusive tape bandages, but prolonged, or repeated, application
of 5% EMLA cream did not produce local skin reactions. Tests for delayed hypersensitivity reactions were negative. Plasma
concentrations of lignocaine and prilocaine were low after a standard application.
A 5% eutectic mixture of the two local anaesthetics lidocaine and prilocaine (EMLA, Astra Läkemedel AB) has been tested for application to the skin in the removal of split skin grafts. EMLA is an oil-in-water emulsion cream, containing 50 mg of active substances per ml (25 mg lidocaine, 25 mg prilocaine). The cream has been used on the donor sites of 146 patients and was applied a minimum of 1 h 30 min before surgery. 123 patients (84.3%) experienced adequate analgesia, feeling only the pressure of the dermatome or slight pain without objection to the skin graft being cut. 20 patients (13.7%) described the pain as being moderate, but the operation could be completed without further local or general anaesthesia. Three patients (2.0%) needed additional anaesthesia. Six patients complained of slight transient irritation immediately after application. After removal of the cream, erythema was present in 42 patients, pallor in 62 and oedema in 14. The concentrations of lidocaine and prilocaine in the blood were measured in 106 patients and did not exceed 1100 ng ml-1 for lidocaine and 200 ng ml-1 for prilocaine. There were no systemic side-effects.
Levels of epidural analgesia were studied in 23 women in early pregnancy scheduled for abortion, and compar ed with a non-pregnant control group (n = 12) scheduled for elective surgical procedures:levels for pin-scratch and cold always coincided. The lower level of analgesia included all sacral segments in every patient. In early pregnant patients the average upper level included the 4th thoracic dermatome (range Th2-Th7). This corresponded to a mean dose of 21.3 mg lidocaine per segment. In the control group the mean upper level was Th8 (range Th6-Th11) which corresponded to a mean dose of 27.1 mg lidocaine per segment. Thus, the pregnant group demonstrated a 28.8% higher spread, or a lower dose requirement per segment than the control group; the differences were significant (p<0.001). The mean time to reach maximal spread was 28.3 minutes (range 20-40) in the pregnant group whereas in the control group maximal spread was complete after 20.5 minutes (range 15-30). The time difference was also significant (p<0.001). The average rate of epidural spread, i.e. segments blocked per unit time, was similar in both groups and amounted to 0.67 and 0.68 segments per minute in pregnant and non-pregnant patients, respectively.
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