38. LOCAL ANAESTHETIC TOXICITY

Local anaesthetics are drugs that produce reversible blockade of nerve impulse conduction. They act directly on specific receptors on sodium channels inhibiting sodium ion influx. The first local anaesthetic discovered was cocaine. This local anaesthetic is present in large amounts in the leaves of a tree growing in the Andes Mountains and was first used by Koller in 1884 to produce local anaesthesia of the eye.

Different nerves have different sensitivity to local anaesthetics. Usually a patient will develop a sympathetic block with peripheral vasodilatation and increased skin temperature followed by loss of pain and temperature sensation. This is followed by loss of proprioception, then loss of touch and pressure sensation and finally motor paralysis.

Local anaesthetics may cause systemic toxicity involving mainly the cardiovascular and central nervous system, local tissue damage, allergy, addiction and methaemaglobinaemia.

The amount of local anaesthetic absorbed depends on the dose given, the blood supply to the area injected, the presence of adrenaline (epinephrine) in the solution, and the physical and chemical properties of the drug. There is more absorption of local anaesthetic from intercostal nerve blocks than from brachial plexus nerve blocks. The addition of adrenaline (1:200,000) will reduce absorption by about 50%.

Different local anaesthetics are more likely to cause systemic toxicity. The safest local anaesthetics are the esters, chlorprocaine and procaine. From least toxic too most toxic the local anaesthetics can be ranked: chlorprocaine, procaine, prilocaine, lignocaine, mepivacaine (carbocaine), etidocaine, bupivacaine, tetracaine (amethocaine), dibucaine (cinchocaine) and cocaine.

Central Nervous System Toxicity

The stronger the local anaesthetic, the greater the central nervous system toxicity. Lignocaine, procaine and prilocaine cause central nervous system toxicity when plasma concentrations reach about 5 to 10 microgram/ml. Bupivacaine and etidocaine cause central nervous system toxicity at about 1.5 microgram/ml. The severity of signs and symptoms of central nervous system toxicity increase with the severity of toxicity. Early signs include numbness of the tongue and light-headedness. Increasing toxicity will cause visual and auditory disturbances, muscular twitching and tremors of the face, hands and feet. Severe toxicity will cause unconsciousness, convulsions (tonic-clonic) and coma. At lower levels of toxicity, the local anaesthetics cause blockade of inhibitory pathways in the cerebral cortex causing the initial excitatory signs and symptoms. With higher levels of toxicity both inhibitory and excitatory pathways are blocked.

The acid-base status of the patient can change the central nervous system toxicity of the local anaesthetic agent. The higher the PCO2, the lower the dose needed to cause convulsions. If the PCO2 is elevated from 25 to 40 mmHg to 65 to 80 mmHg then the dose required to produce convulsions is halved for various local anaesthetics.

Cardiovascular Toxicity

The cardiovascular system is more resistant than the central nervous system to local anaesthetic toxicity. Experimentally, sheep need seven times more lignocaine to cause cardiovascular collapse compared to that needed to cause convulsions.

Toxicity can occur though altered cardiac conduction, reduced force of contraction of the ventricles and peripheral vascular smooth muscle relaxation.

Local anaesthetics block conduction of nerve impulses by a direct action on sodium channels. At low concentrations of local anaesthetics, the blockade of cardiac sodium channels may prevent or treat cardiac arrhythmias. (Lignocaine is used to treat ventricular arrhythmias). However, higher doses of local anaesthetics will cause cardiac arrest. The cardiovascular toxicity of bupivacaine appears to differ from lignocaine. Rapid intravenous administration of bupivacaine will cause fatal ventricular fibrillation. Pregnant patients are more sensitive to bupivacaine toxicity. Cardiac resuscitation is more difficult with bupivacaine toxicity, and acidosis and hypoxia potentiate the cardiotoxicity of bupivacaine.

The mechanism by which local anaesthetics reduce the force of contraction of the heart (contractility) is unknown.

Low doses of local anaesthetics can cause vasoconstriction but as the dose increases they cause vasodilatation. Cocaine is the only local anaesthetic to cause vasoconstriction at all blood concentrations.

Low blood levels of local anaesthetics produce no change in blood pressure or heart rate. Higher blood levels will cause an increase in cardiac output, blood pressure and heart rate directly related to the convulsions of central nervous system toxicity. Higher doses will cause a transient and reversible fall in blood pressure. A further increase in dosage and blood levels will cause marked vasodilatation; depressed heart contractility and severe bradycardia that will lead to cardiac arrest. Some local anaesthetics (bupivacaine and to a lesser extent ropivacaine) can also cause ventricular fibrillation.

Treatment of Systemic Toxicity

At the first sign of local anaesthetic toxicity the anaesthetist must stop giving the local anaesthetic. They must monitor the patient’s conscious state, blood pressure and heart rate. Oxygen should be administered. If convulsions occur, an anticonvulsant should be given (diazepam 5 to 10 mg or midazolam 1 to 2 mg or thiopentone 50 to 100 mg). The anaesthetist must ensure that the patient has a patent airway and is breathing. If required, the anaesthetist may need to “bag and mask” or intubate the patient. The anaesthetist must prevent a rise in arterial carbon dioxide levels (hypercarbia) as this will increase the local anaesthetic toxicity. If cardiac arrest occurs, the patient will need cardiopulmonary resuscitation.

Allergic Reactions

Allergic reactions to local anaesthetics are rare. Ester local anaesthetics (chlorprocaine, procaine, tetracaine and cocaine) are more likely to cause an allergic reaction. Allergic reactions to amide local anaesthetics are extremely rare. The preservative in some local anaesthetics may also cause allergic reactions.

Methaemoglobinaemia

Methaemoglobinaemia is a side-effect of large dosages of prilocaine. Usually in excess of 600 mg. The formation of methaemoglobinaemia is due to a breakdown product of prilocaine, O-toludine. O-toludine oxidises haemoglobin to methaemoglobin. Usually the methaemoglobinaemia is not of clinical significance and spontaneously resolves. It may be treated with methylene blue.

Addiction - Cocaine can become a drug of addiction.

LOCAL ANAESTHETICS