- To understand the mechanism of action of local anaesthetics
- To understand their contribution to the management of acute pain
- To be aware of the inherent risks of using such drugs and to implement strategies reduce such risk
Koller introduced the ester cocaine into clinical practice for eye surgery in 1884 because the conditions provided by general anaesthesia were poor. It is interesting that the use of local anaesthesia for eye surgery has once more become very popular, although much safer drugs than cocaine are now employed. In 1948 Gordh was the first to use the amide drug, lignocaine; the amide local anaesthetics are used now in preference to the esters in the U.K. as they have fewer undesirable effects. Local anaesthetics are either aminoesters (e.g. procaine) or aminoamides (e.g. lignocaine) which reversibly inhibit nerve conduction.
Mechanisms of action
Local anaesthetics inhibit nerve conduction by interfering with the physiological changes in ionic permeability during an action potential. Nerve cells are selective in their permeability to ions and consequently have an electrical potential across their membrane; at rest this is of the order of minus 50 to minus 80 mV, with the inside being negative. Cell membranes are composed mainly of lipids and do not permit ions to pass through them, but they are crossed by specialised protein ion channels, which allow potassium, sodium and other ions to pass through.
At rest, the potassium channels in nerve cell membranes are open and the sodium gates are closed; when a nerve cell is excited, the membrane suddenly becomes transiently permeable to sodium as that ionic channel opens. The membrane potential is reversed so that it has a positive charge inside, and a propagated action potential is passed along the fibre. Local anaesthetics block sodium channels, prevent the evolution of the action potential and so prevent or decrease sensation arising in the affected area. It is thought that most local anaesthetics work by blocking the sodium channel from the inside of the cell into which they must first diffuse before they can act. In infected tissues, acidic conditions prevent this diffusion and thus local anaesthetics then tend to be less effective.
Local anaesthetics are used on their own and combination with opioids for epidural and spinal blocks. Local anaesthetics are also used for local blocks and are used extensively for day case surgery, limb surgery and hand surgery. Local anaesthetics can also be used systemically for pain management. Sodium channel blockers can be used to reduce pain due to nerve damage and intravenous lignocaine and oral mexiletine (an oral analogue) can both reduce neuropathic pain in nonmalignant and cancer pain .
Adverse effects to local anaesthetics can be due to the use of excessive doses, abnormal reactions to normal doses, or to toxicity or depression of vital centres after inadvertent injection into the bloodstream or the cerebrospinal fluid. Toxic reactions to local anaesthetics can be reduced by slow administration, and intravenous access should always be secured before a block is performed in case of untoward events occurring. Resuscitation equipment and drugs should be immediately available. The effects of local anaesthetics are as follows:
Central nervous system – is particularly sensitive to the effects of local anaesthetics and with increasing blood concentrations predictable consequences present. Early signs of toxicity are shivering, confusion, and twitching and tremors followed by generalised seizures. Eventually, with large doses, generalised central nervous system depression ensues with cessation of seizures, respiratory arrest and hypoxia. Treatment comprises the administration of anticonvulsants (thiopentone or diazepam) and oxygenation, with tracheal intubation and respiratory support if necessary.
Cardiovascular system – is more resistant to local anaesthetics, but vasodilatation, myocardial depression and disorders of rhythm occur and can lead to cardiac arrest and circulatory collapse. Cardiovascular toxicity may be precipitated and worsened by hypoxia, hypercarbia and acidosis consequent to inadequate treatment of the convulsions and respiratory arrest described above. In particular, hypoxia and acidosis potentiate the cardiodepressant effects and arrhythmias associated with bupivacaine toxicity. Cardiac massage, ventricular defibrillation, intravenous fluids and inotropic support are indicated and resuscitation may be prolonged, especially with bupivacaine.
Allergic reactions – to local anaesthetics are rare and most involve the aminoesters. There is also cross-sensitivity between the para-aminobenzoic acid derivatives and methylparaben, a preservative commonly used in local anaesthetic preparations. Allergy to amide local anaesthetics is rare, and almost all have been related to methylparaben.
Methaemoglobin – The administration of large doses of prilocaine (10 mg/kg) may lead to the accumulation of an oxidising agent, which converts haemoglobin to methaemoglobin. Patients may appear cyanosed at a methaemoglobin concentration of 3 – 5 g/100 ml of blood, but in healthy individuals this should not present a problem. In patients who have other cardiorespiratory abnormalities, immediate treatment for methaemoglobinaemia may be required and the reducing agent methylene blue, 1 – 5 mg/kg, should be given intravenously. Lignocaine also produces methaemoglobin, but a clinical problem rarely presents. Prilocaine may be a problem if EMLA is used in large quantities on premature babies.
This is the most commonly used agent in the U.K.; it is available in solutions of 0.5 – 2%. The effect of lignocaine is prolonged considerably by the addition of the vasoconstrictor adrenaline.
Bupivacaine is more potent than lignocaine; 0.5% bupivacaine is as effective as 2% lignocaine. It is available in 0.25 – 0.75% concentrations. It is more cardiotoxic than other local anaesthetics and is not recommended for intravenous regional analgesia. The duration of action is from 4 to 16 hours, and bupivacaine produces more sensory than motor block. Levo-bupivacaine is also available and while the concentrations and usage are the same as bupivacaine, evidence suggests that it may be less cardiotoxic.
The potency of prilocaine is similar to lignocaine but as it is metabolised in the lung as well as the liver it is cleared from the body more quickly than the other amides (this makes it particularly useful for intravenous regional analgesia). Methaemoglobinaemia is associated with the use of high doses and it is unsuitable for use in obstetrics because of this risk to the unborn child.
You may like to examine some of the protocols or guidelines you have in practice that deal with problems associated with epidurals and spinals. Are they valid, reliable and evidence based? Refer to the NPSA Alert notice ‘Safer practice with epidural injection and infusions’ Alert No 0396.
Ropivacaine is a long acting local anaesthetics like bupivacaine but is associated with less cardiovascular toxicity. It is one of the newer local anaesthetics .
- Kalso, E., ,, McQuay, H.J., Moore, R.A., 1998. Systemic local-anaesthetic-type drugs in chronic pain: a systematic review.. Eur J Pain, Eur J Pain 2, 3-14.
- Erichsen, C.J., ,, Kehlet, H., Hedlund, C., Arvidsson, T., 1996. Pharmacokinetics and analgesic effect of ropivacaine during continuous epidural infusion for postoperative pain relief.. Anesthesiology, Anesthesiology 84, 834-42.