Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts. Anesth Analg Comparison of effects of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, refractoriness, and wavelength: an epicardial mapping study. Anesthesiology ; 3 Moggi L. Cardiotoxicity of ropivacaine-a new amide local anesthetic agent.

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SUMMARY Local anesthetics LA are drugs widely used in the practice of anesthesia, with low incidence of adverse events; however, in case of toxicity , mortality is very high.

Currently, the systemic toxicity rates have dropped from 0. In view of the high risk of latent mortality, studies in humans are not feasible and hence the available sources of information are extrapolated animal studies or case reports. Severe LA toxicity manifestations occur mainly as a result of intravascular administration rather than due to tissue absorption; hence, bupivacaine is the LA that exhibits the highest risk.

Clinically there are awareness disorders and tonic-clonic seizures followed by cardiovascular involvement resulting from conduction blocks and difficult to manage cardiovascular collapse. With regards to management, prevention is the key, followed by an adequate anesthetic technique; rapid identification and diagnosis and early application of ACLS rescue measures.

Recibido: febrero12 de Enviado para modificaciones: abril 27 de Aceptado: agosto 28 de Local anesthetics LA are drugs widely used in the practice of anesthesia, with low incidence of adverse events; however, in case of toxicity, mortality is very high. With regards to management, prevention is the key, followed by an adequate anesthetic technique; rapid identification and diagnosis and. Fat Emulsions, Intravenous. Local anesthetics LA are drugs commonly used in anesthesia, particularly in hospitals doing procedures under regional techniques.

They are a tool for the treatment or the prevention of acute or chronic pain and for pain management when making a diagnosis or establishing a prognosis 1. Although the occurrence of adverse events due to LA is infrequent, their study is extremely important because the severity of the toxicity -resulting from the risk of inadequate administration, i.

Moreover, different molecules may express isomers of varying properties of their racemic molecule potency, receptor affinity, toxic effects, among others 3. The available data to this date are supported by low-grade evidence studies since for ethical and obvious reasons, trials with exposure to high levels of toxicity are not allowed in humans. Thus, most of the information comes from extrapolating the results in animal models 4,5.

The rates of systemic toxicity due to LA have dropped significantly in the last three decades, from 0. Tabla 1. No se observaron eventos de colapso cardiovascular. El bloqueo de los canales de sodio voltaje dependientes con mayor afinidad por los canales abiertos, es la forma como realiza su efecto axo-.

The highest toxicity rates have been reported as secondary to the peripheral nerve block 7. The mortality rate was 0.

Table 1. In the study by Barrington et al 11 , the incidence of LA toxicity was 0. Minor complications were agitation and signs of mild CNS involvement. There were no events from cardiovascular collapse. Depending on the type of LA, the incidence was higher with ropivacaine and there was one case associated to the use of lidocaine.

Voltage-dependent calcium channel blockers, with greater affinity for open channels, is the mode of action for axonal effect that produces. Tabla 2. The presence of these blockers in the central, cardiac and peripheral spaces explains the symptomatology of AL toxicity 12, The existing information about LAs dosing is mostly not evidence-based; usually it is shown as the maximum total dose for preventing excessive administration and thus toxicity Table 2.

Official recommendations about maximum doses of local anesthetics in Finland, Germany, Japan, Sweden and the United States. A pesar de su baja incidencia, su desenlace puede ser fatal. Con presencia de compromiso, principalmente, de SNC inicial-.

In this case, the recommendation is to individualize the dose according to the patient's characteristics age, comorbidities , procedure to be performed, type of LA pharmacokinetics, pharmacodynamics , etc.

In the case of amino esters LAs, these are matabolized by plasma estearases and reduce the risk of acute toxicity; however, the opposite is true with regards to their metabolites that are responsible for anaphylactic reactions 5. In any case, it is important to keep in mind the potential occurrence of LA-related toxicity, regardless of the dose or resulting from drug interactions. Originally described by Mayer in , who published 40 cases of deaths following the administration of local anesthetic techniques 17 ; recently, Dr.

Albright reported the risk of the new LAs in Later, increasing importance has been given to the pathophysi-ological and therapeutic description of acute toxicity caused by LA agents. LA systemic reactions are rare and their incidence tends to decrease due to the positive affect of established procedures and safer LAs.

Despite its low incidence, the outcomes can be fatal. Systemic reactions usually present themselves with mild manifestations and are frequently unnoticed, leading to a probable under-registration of such events 6.

The acute toxic effects following the intravas-cular administration of LAs tend to be more severe and short lasting than those arising from the slow systemic absorption of perineu-ral administration. This is due to the by-pass of the body's clearance systems 1.

Usually these effects occur as a result of the inadvertent intravascular or intrathecal injection, secondary to high doses. There is mainly ini-. Three types can be differentiated, depending on the reaction Table 3. Long lasting LAs, despite the current availability of isomers developed levobupivacaine, ropivacaine , with a view to reduce the toxic effects of bupivacaine, are still particularly important, due to the presence of severe acute toxicity events Miotoxicity: LAs may cause tissue necrosis at the site of administration and two of the causes for this complication are trauma and bleeding resulting from the adminsitration of the anesthetic agent.

A condrotoxic effect has been experimentally described with the intraarticular administration of bupivacaine Neurotoxicity: neurotoxicity has been shown at high concentrations in laboratory models; however, it may not be attributed exclusively to LAs, since other types of substances should be considered as well; i. Likewise, transient neurological signs have been described disesthesias, parestesias, decreased or temporary loss of motor function, incontinence, Cauda Equina syndrome, etc.

Experimental studies have shown a greater tendency. De los diferentes AL, y sobre modelos. Central Nervous System Toxicity: with the progressive increase in LAs serum concentration following their administration, there is an increased risk of central toxicity due to its greater sensitivity.

Initially there is a depressor effect on the inhibitory pathways mediated by the GABA receptors 22 , and a stimulating effect over the NMDA receptors 22 , with clinical manifestations such as agitation, dizziness, myoclonic responses, nistag-mus, disartria, muscle contractures, perioral parestesias, taste disorders metallic taste , hearing disorders tinnitus , poor response to verbal instructions, speech disorders and finally, tonic-clonic seizures 22, At higher serum concentrations, the depressor effect of the inhibitory pathways continues and blocks the excitatory pathways, causing respiratory depression hypoxia, acidosis and coma 22, Cardiovascular Toxicity: Acute hemodynamic changes are the result of a systemic response to acute toxicity that generates changes in the cardiovascular direct effect and central nervous system indirect effect mediated by the stimulus to the autonomic nervous system 6.

Cardiac toxicity is expressed through two mechanisms: one, associated with autonomic ganglion dysfunction and second, as an effect over the miocardial conduction systems. Ventricular arrhythmias are a rare occurrence, except with bupivacaine, that has shown tachycardia and ventricular fibrilation Among the various LAs and based on animal models, bupi-vacaine has shown the greatest cardiotoxicity due to the strong attraction and dissociation.

The serum concentrations required for AL severe toxicity to occur except for bupivacaine in the heart, exceed those required to produce tonic-clonic seizures; the clinical manifestations are tachicardia, hypertension initially , hypotension and bradycardia severe toxicity , miocardial depression and low cardiac output associated with arrhythmias delayed conduction, branch blocks, PR prolongation, ventricular ectopia, ventricular tachycardia, ventricular fibrilation, torsade de pointes, sinus arrest, asystole 22,30, Likewise, the ischemic cardiac disease and conduction disorders encourage LA related toxicity Table 4 shows the serum concentrations of various LAs at the time of cardiovascular collapse, in accordance with an animal model study.

Tabla 4. Table 4. Cumulative dose and plasma concentration of local anesthetics in cardiovascular collapse. It must be said that every procedure with regional techniques should be performed under the appropriate conditions to prevent the occurrence of complications. Consequently, basic, non-invasive monitoring should be provided pulse oximetry, continuous electro-cardiographic monitoring and non-invasive arterial pressure control, keeping in mind the cardiovascular complications and the need to identify them early on to start corrective actions.

Additionally, the steps to prevent overdosing, aspiration prior to infiltration, test dose and dose fragmentation should be implemented. All these measures have decreased the occurrence of adverse events during the last few decades Therefore, all the necessary inputs should be at hand for an adequate management of the airway; i. It must also be kept in mind that the use of bupivacaine results in a higher depressor effect over the cardiac conduction, especially in the ventricular space.

Likewise, the association of bupivacaine-lidocaine is related with a higher increase in the number of cardiac conduction disorders due to the additive effect of lidocaine 24, Trial dose: The objective of a trial dose is the early identification of intravascular injection 17 , taking into account several factors that may alter the result age, gestation, use of drugs such as benzodiazepines, b-blockers, opiates, clonidine, general anesthesia 17,32, Igualmente, se debe considerar la posibilidad de bypass cardiopulmonar o el uso de EL 18 , ante el evento de toxicidad refractaria al tratamiento 30, Dose Fractioning: fractioning the dose administered slow dose 5 mL, with frequent aspirations and non-invasive monitoring 34 , will reduce the maximum arterial concentration, although there is no experimental evidence yet as to the impact of the result.

Early detection of any toxic effects to stop the administration of the LA in case of suggestive symptoms, although is not enough to prevent an acute LA toxicity, does provide the time required to reduce the blood concentrations and allow for distribution and removal 6.

Early Response: Early response to the identification of mild symptoms of toxicity increases the probability of success with treatment 30, In the presence of suggestive symptoms, the necessary therapeutic measures should be initiated securing the airway and adequate ventilation; administration of resuscitation maneuvers in accordance with ACLS protocols, prevention and early treatment of seizures, correcting arrhythmias and myocar-dial depression 30, The administration of epinephrine at high doses animal models during the resuscitation maneuvers, together with Lipid Emulsions LE for managing cardiovascular toxicity due to bupivacaine, showed no benefits in recovery and suggests that this combination will prevent the reversal of bupivacaine toxicity Cardiopulmonary bypass or the use of LE 18 should also be considered in case of toxicity refractory to treatment 30, It must be emphasized that propofol does not replace this type of drugs because of its low lipid content and cardiodepressant effect.

Zausig y cols. There are different theories about the mechanism of action of the intravenous administration of LEs. Among the most widely accepted theory is the serum extraction from the LAs through a lipid interface; others treat the metabolic effect by reestablishing the delivery of fatty acids to the mitochondria in order to restore the energy output. The activation of the calcium and potassium channels has also been shown, as well as the decrease of tissue acidosis and in the production of CO2 during ischemic episodes associated with cardiovascular collapse The solubility of long lasting LAs in Lipid Emulsions and their high binding potential, probably explains their clinical efficacy in the management of LA toxicity.

Among these LEs, long chain triglycerides are more effective than the medium chain triglycerides, as shown by Mazoit et al Moreover, the pharmacokinetic properties of the LAs hydrophobicity , favor this effect, while acidosis reduces the binding potential. Zausig et al 37 suggest that the effects of LEs on cardiovascular tox-icity cardiac arrest induced by the LAs, is strongly dependent on lipophilicity of each particular type of anesthetic and the best effects are from bupivacaine induced toxicity.

However, additional studies are required to validate these results. Cave et al 40 did a study to assess the guidelines published by AAGBI for the management of LA toxicity with a view to assess their efficacy. This protocol showed a trend towards the spontaneous and faster recovery of the circulation versus the control group. Although these findings are encouraging, additional experimental evidence is required.


2005, NĂºmero 4

A dose perineal de 20 mg foi realizada em todas as pacientes dos 2 grupos. Aos 15 minutos, no grupo I todas as pacientes apresentavam dor igual ou inferior a 3. No grupo II, neste momento, uma paciente apresentava intensidade 5 e todas as outras apresentavam inferior a 3. Aos 30 minutos somente uma paciente do grupo II apresentava dor de intensidade 4.


Toggle navigation. Der Arzneistoff wird als Racemat eingesetzt. Es hat einen relativ langsamen Wirkungseintritt und eine lange Wirkungsdauer, die bis zu 12 Stunden andauert. It is used by injecting it into the area, around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of epinephrine to make it last longer.



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