Convulsion bupivacaine

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

The earliest signs of CNS toxicity are circumoral and tongue numbness, tinnitus, tremor, and dizziness. These appear at plasma lidocaine (lignocaine) concentrations of about 5 pg-mL-1. The value for prilocaine is similar to lidocaine but bupivacaine toxicity appears at about half those of lidocaine. Further progression is evidenced by drowsiness, visual disturbances, or muscle twitching (plasma lidocaine of 5-10 pg-mL-1). Over 10 p-mL-1 grand mal convulsions, coma and respiratory arrest are likely. Serious CNS toxicity is indicative of imminent and potentially fatal cardiac toxicity since lidocaine is associated with direct cardiac depression at plasma concentrations in excess of 20 pg-mL-1. 

The racemic compound bupivacaine, which was first synthesized by Ekenstam et al. in 1957, is an amide-type LA with a high lipophilicity, protein binding and pKa giving rise to an intermediate onset and a long duration of action. At the same time, bupivacaine has a high toxicity potential relatively often associated with convulsions and life-threatening cardivascular collapse (Moore et al., 1978). Levobupivacaine, the (S)-enantiomer of bupivacaine, has recently been developed for clinical use addressing the enantioselectivity of side-effects of bupivacaine (see below). 

With local infiltration, toxic side-effects like convulsions and cardiovascular collaps occur in the dose range of 2.5 to 3 mg/kg body weight. Because of its systemic toxicity, bupivacaine is contraindicated for intravenous regional anesthesia. 

Toxicity. Bupivacaine is several times more toxic than lignocaine. Muscular rigidity has been reported in 2 subjects having blood concentrations of 9 and 12 ig/ml following the administration of approximately 210 mg, and convulsions have been reported at plasma concentrations greater than 4 pg/ml. 

During a study of 104 adults to compare the efficacy and safety of 40 ml of 0.75% ropivacaine (300 mg) and 40 ml of 0.5% bupivacaine (200 mg) for axillary plexus block, significantly more patients reported postoperative dizziness in the ropivacaine group (5 versus 0) (63). However, this occurred 4-5 hours after the injection in two patients and the day after in the other three, and was therefore unlikely to have been due to high serum concentrations. One patient developed dizziness, dysarthria, and unconsciousness, with convulsions shortly after an injection of ropivacaine, indicating an intravenous injection. 

In about 10% of cases, obstetric use of epidural anesthesia will cause some bradycardia in the fetus, but this is not always a clinical problem (SEDA-15, 119). However, accidental intravenous injection of bupivacaine can lead to both maternal convulsions and severe fetal bradycardia (156). 

Brooker CD, Lawson AD. Convulsions following bupivacaine infiltration for excision of carotid body tumour. Anaesth Intensive Care I993 2I(6) 877-8. 

Convulsions have occurred after inadvertent intravenous injection of ropivacaine during regional anesthesia (4,5). CNS adverse effects from ropivacaine occur before or without severe cardiovascular toxicity, as there have been several similar reports of CNS toxicity, but not yet one with severe or fatal cardiotoxicity. This reinforces the claim of increased safety from cardiovascular toxicity with this enantiomeric local anesthetic compared with racemic bupivacaine. 

Treatment of toxicity Severe toxicity is best treated symptomatically. Convulsions are often treated with intravenous diazepam or a short-acting barbiturate such as thiopental. Hyperventilation with oxygen is helpful. Occasionally, a neuromuscular blocking drug may be used to control violent convulsive activity. The cardiovascular toxicity of bupivacaine overdose is difficult to treat and has caused fatalities in healthy young adults. 

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