Modeling the anesthetic effect of ropivacaine after a femoral nerve block in orthopedic patients: a population pharmacokinetic-pharmacodynamic analysis

Anesthesiology
François GaudreaultFrance Varin

Abstract

Even though ropivacaine is frequently used during orthopedic surgery, the relationship between plasma concentrations and degree of sensory anesthesia after a peripheral nerve block is currently unknown. The aim of this study was to characterize this relation using population pharmacokinetic-pharmacodynamic modeling. Femoral nerve block was performed by the anterior approach using a single injection (20 ml) of 0.5% ropivacaine hydrochloride in 20 patients scheduled for total knee arthroplasty under spinal anesthesia. Sensory thresholds in response to a gradual increase in transcutaneous electrical stimulation (primary endpoints), loss and recovery of ice-cold sensation, as well as total ropivacaine plasma concentrations were determined up to 4 days after administration of the local anesthetic. Using NONMEM (ICON, USA), sensory block was modeled by assuming an equilibration delay (ke0) between amount in the depot and effect-site compartments. Mean effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 mg. At 2 × AE90, the sigmoid Emax model predicted a mean onset time of 23.4 min and mean duration of 22.9 h. Interindividual variability (IIV) for AE50 was 49%. Typical ke0 half-life was 34.7 mi...Continue Reading

References

Feb 1, 1980·Journal of Pharmacokinetics and Biopharmaceutics·D P Vaughan, M Dennis
Nov 1, 1995·British Journal of Anaesthesia·M CuratoloA M Zbinden
Jun 24, 2003·Best Practice & Research. Clinical Anaesthesiology·Mihai R Sadean, Peter S A Glass
Mar 15, 2005·Regional Anesthesia and Pain Medicine·Charles Pham DangMichel Pinaud
Aug 8, 2008·Journal of Pharmacokinetics and Pharmacodynamics·Jae Eun AhnThomas M Ludden
Sep 25, 2008·Anesthesiology·Erik OlofsenAlbert Dahan
Jan 14, 2011·The AAPS Journal·Kristin E KarlssonMats O Karlsson

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Citations

Feb 27, 2018·Anesthesia and Analgesia·Baptiste Duceau, Christian Jayr
Dec 14, 2017·Clinical Pharmacokinetics·Zoubir DjeradaJean-Marc Malinovsky
Apr 18, 2019·Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre·Xiao-Ying ZhaoJian-Xin Yang

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