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Dexamethsone and sugammadex ..avoid this mix

Sugammadex binds and inactivates the aminosteroid nondepolarizing muscle relaxants rocuronium and vecuronium. Sugammadex is available in 50 countries, but the United States is not one of them.  The US Food and Drug Administration turned down approval for the drug in 2008 because it sought more information concerning allergic reactions and bleeding events.  Approval was also denied in the 3rd quarter last year due to concerns about a hypersensitivity study.  Hopefully sugammadex will be available here soon.

In clinical situations, three drugs have been shown to displace rocuronium from sugammadex: toremifene, a selective estrogen receptor modulator used to treat patients with breast cancer, fusidic acid, an antibiotic that inhibits translocation during protein synthesis, and flucloxacillin, an antibiotic analog of cloxacillin.  None of these are commonly used in anesthesia or postoperative care, and so it seems unlikely that this could be an important clinical problem with sugammadex.

In a recent preclinical study of functional innervation and IL-6 secretion, the authors saw an interaction between dexamethasone and sugammadex.  Dr. Tomaz Mars, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, and colleagues hypothesized, therefore, that in an in vitromodel, dexamethasone and sugammadex would interact.  The results of their analysis are published in this month’s issue of Anesthesia and Analgesia in the article titled “Dexamethasone Produces Dose-Dependent Inhibition of Sugammadex Reversal in In Vitro Innervated Primary Human Muscle Cells.”

Muscle tissue obtained from patients who underwent orthopedic surgery was cultured with rat dissected spinal cord explants to form contracting units in the proximity of the spinal cord explant.  Rocuronium treatment increased neuromuscular blockade in a dose-dependent fashion: 10 µM rocuronium significantly increased neuromuscular blockade. Blockade was reversed with equimolar concentrations of sugammadex.  Dexamethasone, in a dose-dependent manner, decreased the effectiveness of the reversal of rocuronium-induced neuromuscular blockade by sugammadex, with a peak effect seen at 10 µM dexamethasone.  Micromolar rather than nanomolar concentrations of dexamethasone affected the efficiency of sugammadex.

Whether these effects would match those observed in vivo is unclear.  Plasma levels typically peak after injection and then quickly dissipate with rapid distribution to other compartments, though the actual concentrations used in this study match in vivo conditions. However, it may be wise to avoid using dexamethasone in the PACU in patients who have recently received sugammadex until the clinical relevance of this bench study is fully understood.

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