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Lidocaine is the most commonly used local anesthetic in the United States. It is an amino amide with a pKa 7.7 and a commercial preparation pH in the range of 5.6 when prepared without epinephrine. It has a rapid onset of action with intermediate duration. Its toxicity is intermediate with metabolism occurring in the liver; the Alpha clearance half-life (redistribution) is thought to be 8 to 9 minutes and the Beta half-life (elimination) is 45 to 60 minutes. Clinical toxic dose associated with lidocaine is thought to be in the 400 mg. range without epinephrine and in excess of 500 mg. when used with epinephrine.
Clinical uses include topical use of lidocaine. It is associated with good topical anesthesia when used in the 4% concentration liquid. It is also prepared as a gelatin or a viscous solution for mucous membrane use. It is used for IV regional anesthesia at 1/2% concentration and is associated with an intravenous regional anesthetic of 45 to 60 minutes duration. It is used in 5% concentration combined with glucose for spinal anesthesia with 45 to 90 minutes duration depending on the age of the patient and the use of epinephrine in the solution. It is used for epidural anesthesia and analgesia in the 1% to 2% concentration and has a typical time to two segment regression of 45 to 60 minutes. Peripheral conduction block at all conduction sites is also performed with lidocaine and the duration of action is typically 1 to 3 hours and is accentuated with the use of exogenously applied epinephrine.
Controversy associated with lidocaine mainly resides in its use in obstetrics. In the late 1970s, Dr. Scanlon reported exaggerated effects of lidocaine on the fetus. His evaluation system was referred to as Early Neonatal, Neurobehavioral Scoring (ENNS) and he found there to be depression using this scale of the newborn behavior when lidocaine was used epidurally for analgesia or anesthesia for Cesarean-section. Subsequently work suggested the changes found in this system of scoring are very subtle, not clinically significant and, not reproducible from investigator to investigator. Subsequent studies have abolished lidocaine of morbidity associated with obstetric use. However, because of the low pKa of the agent and the propensity for ion trapping, lidocaine is not felt to be indicated in large doses for epidural anesthesia in mothers who have fetuses with any signs of fetal distress. This is because the fetal pH is already 1/10th of a pH unit lower than the mother in the normal state and any hypoxia or fetal stress may be associated with an even lower fetal pH and a higher propensity for ion trapping of lidocaine and hence higher toxicity of lidocaine in the newborn.
Mepivacaine is an amino amide with a pKa of 7.6 and in commercial preparation is typically pH 5.5. It is a rapid onset, intermediate duration, intermediate toxicity local anesthetic agent. Textbook suggests toxicity is higher than that of lidocaine, but the clinical experience suggests the opposite. One fact that must be kept in mind is that the fetal metabolism of mepivacaine is specifically limited and mepivacaine is not felt to be indicated for use in obstetrics. The toxic dose is 400 mg. without epinephrine and 500 to 600 mg. with the use of epinephrine, but the basis for this is anecdotal and many of the clinical studies with the use of mepivacaine the dose is considerably larger without reported signs of toxicity when used with epinephrine.
Clinical uses for mepivacaine include infiltration of the skin at the 1% concentration which is associated with 1-1/2 to three hour duration. Epidural anesthesia is with the 2% concentration with a 70 to 90 minute duration to two segment regression. Spinal anesthesia at the 4% concentration was used historically with a duration of 60 to 90 minutes, but is not currently used in the United States. Peripheral conduction block is performed at the 1% to 1-1/2% range and is associated with an approximate 3 hour duration of activity. Aside from the limited indications in obstetrics, there are no known controversies with the mepivacaine.
Bupivacaine is an amino amide local anesthetic with pKa of 8.1, a commercial preparation pH of 4.5 to 5.5. It is slow onset, long duration, highly toxic local anesthetic agent. The toxic dose is thought to be approximately 2-1/2 to 3 mg./kg., or 135 mg. The toxicity is probably also related to use of epinephrine.
Clinical uses include infiltration at the 1/4% concentration with the duration of action of 2 to 4 hours, or greater. Epidural analgesia and anesthesia are performed between a 1/4% and 3/4% concentration with 2 to 5 hour duration of action. At 1/4% the agent is uniquely suited to obstetric analgesia as it provides intense analgesia with minimal motor block, allowing the parturient to be active, in a motor sense, in the second stage of labor. Epidural anesthesia is performed at the 1/2% concentration as with all bupivacaine blocks, intensity of motor block is variable. Some practitioners use the 0.75% concentration to provide a more intense motor block for certain types of procedures. Spinal anesthesia is performed at the 0.75% concentration combined with 8.75% dextrose for hyperbaric spinal anesthesia and is also performed with isobaric or plain bupivacaine in concentrations ranging from 0.125% to 0.75% with satisfactory results. It should be noted that this agent is not approved in the United States for isobaric spinal anesthesia use. Peripheral conduction block is performed with the 0.25% to 0.50% concentrations, depending on the amount of motor block sought.
Considerable controversy surrounds the use of bupivacaine. Early reports of sudden cardiac arrest with bupivacaine injection are associated with considerable morbidity and mortality. The mortality is probably related to the high protein binding and lipid solubility of the agent. The results of this combination is a very limited prodrome with very short distance between very first signs of central nervous system disturbance and the massive cardiovascular collapse. This cardiovascular collapse is further complicated by the specific lipid solubility resulting in the tissue of the conduction system of the heart with a re-entrance type activation associated with intractable ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation. These arrhythmias are resistant to virtually all treatment, including the use of lidocaine and cardioversion. Some success has been obtained with the use bretylium. In many circumstances, prolonged cardio-pulmonary resuscitation is necessary and, at times, cardio-pulmonary bypass has been instituted to salvage the patient during the metabolism of the agent.
By consensus, the 0.75% concentration of bupivacaine is not used in obstetrics because of the associated mortality with the use. It is clear that the toxicity associated with bupivacaine is in fact magnified by respiratory acidosis, hypoxia, and in the parturient, probably because of the associated effects of progesterone.
Etidocaine is an amino amide with a pKa of 7.7 and a pH of 4.5 and virtually identical clinical profile to bupivacaine. The toxic dosis though to be in the 300 to 400 mg range with the higher range being associated with epinephrine.
Etidocaine is ideally suited for infiltration anesthesia at 1/2%, peripheral nerve block at 1/2% to 1% with duration in these cases from 3 to 12 hours and epidural anesthesia at 1% to l-1/2% with block associated with 3 to 5 hours of anesthesia. However, profound motor block is sometimes associated with a limited sensory block and this may make the agent less ideally suited to epidural anesthesia than bupivacaine with the similar toxicity profile.
Written by Dr John E Tetzlaff