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Local anaesthesia

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Mechanism of Action

Local anaesthetics reversibly inhibit impulse conduction along the nerve fibres by blocking sodium channels. Depending on their structure, the different nerves show varying susceptibility to the effects of anaesthesia. Thin, unmyelinated fibres are more susceptible than thick, myelinated ones.

 

Side effects

At their respective toxic plasma levels, all local anaesthetics can have side effects on the cardiovascular or central nervous systems. The higher the plasma levels and the quicker the rate of increase, the more pronounced are the symptoms. Allergic reactions are extremely rare with conventional local anaesthetics of the amide group. Some products, however, do contain the preservative methylparaben, which is an allergen. With prilocaine, in particular, metabolites can lead to a dose-dependent formation of methaemoglobin. This is hardly clinically relevant as long as the contraindications are observed (patients with impaired cardiac reserves or impaired pulmonary gas exchange, patient with glucose 6-phosphate-dehydrogenase deficiency).

Central nervous system complications

Preconvulsive hallmarks are restlessness, metallic taste, muscle twitches, slurred speech and tinnitus. These warning signs may be followed by a generalised seizure and/or central respiratory paralysis. If high toxic levels are reached very rapidly, e.g. by inadvertent intravascular injection, a primary generalised seizure or coma may occur without any warning.

Cardiovascular complications

Disturbances of pacemaker activity, excitability and conduction: bradycardia, signs of A-V block, arrhythmia, asystoles, negative inotropia, decreased cardiac output, and hypotension. Typically, when the blood levels of a local anaesthetic increase, central nervous system effects occur first, then cardiovascular complications. Bupivacaine is an exception because it can cause cardiac arrhythmias at subconvulsive doses. This bupivacaine cardiotoxicity is caused by a dose-dependent depression of ATP synthesis. Whilst most patients can survive central nervous system intoxications with bupivacaine without any sequelae when the appropriate measures are taken immediately, cardiovascular complications may take a lethal turn. Therefore, the chronological sequence of cardiovascular and central nervous system effects should be strictly monitored to ensure safe administration of local anaesthetics. Successful management may be crucially dependent on the time factor if central nervous system effects become manifest before cardiovascular complications.

 

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Evaluation of the Drugs

We prefer to use prilocaine for peripheral regional anaesthesia as our basic local anaesthetic because of its low toxicity and rapid onset of action. When a longer action is required, we combine prilocaine with ropivacaine or bupivacaine. We use mepivacaine for local anaesthesia of the puncture site or for infiltration of a stab incision. Mepivacaine can moreover be used in patients with contraindications for prilocaine. Its lipophilia lends bupivacaine a longer duration of action, which, conversely, is one reason for its higher toxicity. On bupivacaine, a dose-dependent reduction or, in come cases, complete cessation of ATP synthesis occurs in the mitochondria of the myocardial cells. This is the reason for the therapy-refractory asystoles associated with bupivacaine. Ropivacaine, a further development of bupivacaine, was launched in Germany in 1997. It differs chemically from its congener bupivacaine by just one propyl group. Ropivacaine presents as a pure S-enantiomer and not as a racemate. The motor blockade achievable with ropivacaine is dose-dependent. Motoric block adequate for surgical interventions is achieved with 0.5%-0.75% ropivacaine. When a 0.2% solution used for postoperative pain therapy is given, there is at the most a slight impairment of motor function. Just like bupivacaine, ropivacaine has a high protein binding, but is less lipophilic which makes it long acting, while its toxicity is comparatively reduced. On ropivacaine, ATP synthesis is impaired, but not completely abolished. Compared to bupivacaine, there is a much greater margin between the convulsive and lethal dose of ropivacaine. The arrhythmogenic risk associated with ropivacaine is considered to be twice as low as that of bupivacaine. Hence, we increasingly use ropivacaine instead of the conventional bupivacaine, especially for postoperative pain therapy. Because of its short duration of action, our department does not use lidocaine for regional anaesthesia. Neither do we see any clinical benefits to be derived from levobupivacaine, in terms of substance-specific and toxicological properties. We are unlikely to use special preparations (bicarbonate or added CO2 to accelerate the onset of action or added vasoconstrictor to prolong the action). Such parameters hardly pose problems in our daily clinical routine. Adding clonidine, particularly in combination with medium-acting local anaesthetics, appears to prolong the anaelgetic action and is therefore used in ambulatory patients occasionally.

 

drugs duration