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Canadian Journal of Anesthesia 51:851-852 (2004)
© Canadian Anesthesiologists' Society, 2004

Correspondence

REPLY

Joanne Guay, MD FRCPC

Montreal, Quebec

Dr. Blumenthal and colleagues disagree that at 12 mL·hr–1 ropivacaine accumulates and may result in potentially toxic blood concentrations. As one can see from the figureGo, steady state was never achieved since the highest blood concentrations were obtained on the last samples. When blood concentrations are increasing during a fixed infusion rate it is because the amount of drug administered is higher than the patient’s total elimination. So, yes, our patients were accumulating the drug.



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  		FIGURE Ropivacaine blood concentrations obtained after a bolus of 30 mL of ropivacaine 0.5% followed by an infusion of ropivacaine 0.2% at 12 mL·hr–1 for 48 hr. Logarithmic scale. FEM = continuous three-in-one block; PSOAS = continuous posterior lumbar plexus (psoas compartment) block. *P < 0.05.

 
After a major surgery, {alpha}1-glycoprotein increases as part of the inflammatory response to the surgical stress. It does not mean however that toxic concentrations of local anesthetics (free drug) will never be achieved. Patients with systemic signs of toxicity (preseizure) have been seen with infusion for continuous peripheral nerve blocks.1 This may be explained by several factors. To name a few: clearance may be reduced as part of a disease (for example the half-life of lidocaine may be increased from 1.5 to 5 hr with poor hepatic blood flow or liver insufficiency) or from inhibition of CYP1A2 (incidentally lowering the free fraction of a drug will in itself reduce the amount of drug available for metabolism and reduce clearance) or simply interindividual variability.2,3 The protein liaison may be displaced by other drugs (simple competition). Finally the amplitude of the inflammatory response may vary with the type of operation performed.

It does not mean, however, that continuous infusions of local anesthetics should be abandoned but simply that the infusion rate should be adjusted to the patient’s ability to handle it.

References

1 Bergman BD, Hebl JR, Kent J, Horlocker TT. Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg 2003; 96: 247–52.[Abstract/Free Full Text]

2 Jokinen MJ, Ahonen J, Neuvonen PJ, Olkkola KT. The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine. Anesth Analg 2000; 91: 1207–12.[Abstract/Free Full Text]

3 Emanuelsson BM, Persson J, Sandin S, Alm C, Gustafsson LL. Intraindividual and interindividual variability in the disposition of the local anesthetic ropivacaine in healthy subjects. Ther Drug Monit 1997; 19: 126–31.[Medline]


Related articles in CJA:

Ropivacaine plasma concentrations are similar during continuous lumbar plexus blockade using two techniques: pharmacokinetics or pharmacodynamics?
Stephan Blumenthal, Georgios Ekatodramis, and Alain Borgeat
CJA 2004 51: 851. [Full Text]  




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