Local anesthetics: systemic toxicity
Local anesthetic toxicity can be seen in organs of the body that depend upon sodium channels for proper functioning. These include the central nervous system and heart. The CNS is more sensitive to the effects of local anesthetics than the cardiac system and will generally manifest signs/symptoms of toxicity first.
Pharmacologic Data (see image for tables)
Effects on Organ Systems
Central nervous system
The initial CNS symptoms are tinnitus, blurred vision, dizziness, tongue parathesias, and circumoral numbness. Excitatory signs such as nervousness, agitation, restlessness, and muscle twitching are the result of blockade of inhibitory pathways. Muscle twitching heralds the onset on tonic-clonic seizures. The early signs/symptoms advance to CNS depression with slurred speech, drowsiness, unconsciousness, and then respiratory arrest. Patients who have received CNS depressant drugs may present with only CNS depression without any preceding excitatory signs.
The effects on the CNS depend on various clinical factors including:
Hypercarbia – Increased PaCO2 lowers the seizure threshold with local anesthetic administration. There is a concomitant increase in cerebral blood flow which allows more local anesthetic to be delivered to the CNS. An increase in intracellular pH leads to ion-trapping of the local anesthetic. The acidosis caused by hypercarbia decreases the protein binding of local anesthetics making more drug available to the CNS.
CNS Depression – Conscious patients receiving CNS depressant drugs such as benzodiazepines or IV anesthetic drugs will have higher seizure threshold, and may not manifest seizure activity before complete CNS depression results.
Local anesthetics have directs effects on the heart and peripheral blood vessels. They block the fast sodium channels in the fast-conducting tissue of Purkinje fibers and ventricles resulting in a decrease rate of depolarization. The effective refractory period and action potential duration are also reduced by local anesthetics. High concentrations can decrease conduction times leading to prolonged PR intervals and widened QRS complexes, and even sinus brady/arrest. Ventricular arrhythmias, including fibrillation, are more likely to occur with bupivacaine than lidocaine. Local anesthetics have a dose-dependent negative inotropic effect. This depressant effect is directly proportional to the drugs relative potency (see chart). Patients with acidosis and/or hypoxia are at a greater risk for the cardiac depressant effects of local anesthetics. Cardiotoxicity of local anesthetics can be compared using the CC/CNS dose ratio that is the ratio of the dose causing cardiac collapse (CC) to the dose causing seizure/convulsions. The lower the number the more cardiotoxic the drug (ex. The CC/CNS for bupivacaine is approximately 3 versus 7 for lidocaine). It is important to note that patients under general anesthesia will typically present with cardiotoxicity as the first sign of local anesthetic toxicity.
Local Anesthetic Relative Potency Procaine 1 Chloroprocaine 1 Cocaine 2 Lidocaine 2 Prilocaine 2 Mepivacaine 2 Etidocaine 6 Bupivacaine 8 Tetracaine 8
Peripheral vascular effects
Low doses of local anesthetics may cause vasoconstriction, where as, moderate or high doses result in vasodilation and decreased SVR. Cocaine is the only local anesthetic that causes vasoconstriction at all doses.
Different nerve blocks
Generally speaking, after a given injection with the same amount of local anesthetic, serum levels are highest following intercostal blocks followed by epidural/caudal blocks, followed by brachial plexus and femoral/sciatic nerve blocks, followed by subcutaneous injections. This order parallels the vascular supply of each tissue. See Keyword below.
Absorption of Local Anesthetics (most to least)
- Caudal epidural
- Lumbar epidural
- Brachial plexus
Bupivacaine has been shown to have increased cardiotoxicity in pregnant women resulting in a decreased CC/CNS dose ration.
A side effect unique to prilocaine is methemoglobinemia at doses of at least 600mg. The liver metabolizes prilocaine to O-toluidine which oxidizes hemoglobin to methemoglobin. Methemoglobinemia is readily treated with methylene blue
Lidocaine: A Focus