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LETTERS TO THE EDITOR

Safety of Levobupivacaine?

Department of Anesthesia, Mid-Western Regional Hospital, Dooradoyle, Limerick, Ireland

To the Editor:

We read with interest Crews and Rothmans’ deduction that levobupivacaine is significantly safer than bupivacaine (1).

There is no reference to the ease of interscalene blockade (obesity frequently producing anatomical difficulties) or if blood was aspirated at any time (obviously a vessel was entered at some point allowing intravascular absorption).

If levobupivacaine enters the arterial system, seizures can occur with as little as 2 mL of local anesthetic, not enough to cause cardiovascular collapse. The rapidity of seizures with absolutely no prodrome may suggest intraarterial administration, supported perhaps by the patient’s prolonged coma.

If the drug was indeed injected intravenously, it is impossible to estimate (without plasma drug levels) exactly how much drug became intravascular or remained in the plexus sheath (to result in shoulder analgesia).

The local anesthetic cumulative convulsive dose is 2.4 times lower than the cumulative lethal (cardiovascular collapse) dose (2), and as little as 17.5 mg of levobupivacaine may have caused seizures (a dose too small to cause cardiovascular collapse?) (3).

Finally, epinephrine 1/200,000 may provide vasopressor and chronotropic support, preventing severe decreases in blood pressure.

In conclusion, this case does not prove that levobupivacaine if administered in larger doses has significantly fewer cardiovascular risks than bupivacaine.

References

1. Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg 2003; 96: 1188–90.[Abstract/Free Full Text]
2. Lofstrom JB, Bengtesson M. Physiology of nerve conduction and local anesthetic drugs. In: Healy TEJ, Cohen PJ, eds. Practice of anaesthesiology. 6th ed. London: Edwards Arnold, 1995: 172–88.
3. Bradsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998; 46: 245–9.[Web of Science][Medline]

Response

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC

In Response:

We appreciate the opportunity to respond to the comments of Drs. Mustafa and Coleman. Their view of our case report as a "deduction that levobupivacaine is significantly safer than bupivacaine" is inaccurate. Our report (1) presented a case and reviewed several other published cases of central nervous system toxicity developing without cardiovascular toxicity following neural blockade procedures with either ropivacaine or levobupivacaine. We stated in our report that, "Whereas serious cardiotoxicity with either of these single isomer local anesthetics is possible, these cases of local anesthetic-induced seizures without serious cardiac toxicity with ropivacaine and levobupivacaine support the claim that these drugs may be a safer alternative to racemic bupivacaine." The claim referred to in this case is that of the safety studies conducted in vitro and in animal models as referenced in our report.

We can further clarify that the interscalene block in our case was not associated with any difficulties or significant anatomic anomalies and was in no way "atypical," with the obvious exception of the seizure following the block. We presumed that the seizure activity following the injection of levobupivacaine was likely the result of an intravascular injection, and did not speculate on whether the injection was intravenous or intraarterial. Incidentally, we do clearly state in our report that, "No blood or fluid could be aspirated at any time before or during the injection."

We agree that this case does not prove that levobupivacaine has significantly fewer cardiovascular risks than bupivacaine. We also are, in no way, suggesting that any potential safety advantages that may be associated with levobupivacaine support the administration of levobupivacaine in "larger doses" than bupivacaine, as implied in the letter of Mustafa and Coleman. We did not write or intend our case report to be read as "proof" that levobupivacaine is safer than bupivacaine. However, we do contend that based on current data, if an unintentional intravascular injection of local anesthetic can occur, despite adherence to common clinical regional anesthetic practices developed to reduce this occurrence, then we prefer the use of a potentially safer alternative to racemic bupivacaine, such as levobupivacaine.

Reference

1. Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Anal 2003; 96: 1188–90.

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