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ANESTHETIC PHARMACOLOGY

Sugammadex: Another Milestone in Clinical Neuromuscular Pharmacology

From the Department of Anesthesiology and Pain Medicine, Unit 409, Anderson Cancer Center, The University of Texas M. D., Houston, Texas.

Sugammadex is a revolutionary investigational reversal drug currently undergoing Phase III testing whose introduction into clinical practice may change the face of clinical neuromuscular pharmacology. A modified -cyclodextrin, sugammadex exerts its effect by forming very tight water-soluble complexes at a 1:1 ratio with steroidal neuromuscular blocking drugs (rocuronium > vecuronium >> pancuronium). During rocuronium-induced neuromuscular blockade, the IV administration of sugammadex creates a concentration gradient favoring the movement of rocuronium molecules from the neuromuscular junction back into the plasma, which results in a fast recovery of neuromuscular function. Sugammadex is biologically inactive, does not bind to plasma proteins, and appears to be safe and well tolerated. Additionally, it has no effect on acetylcholinesterase or any receptor system in the body. The compound's efficacy as an antagonist does not appear to rely on renal excretion of the cyclodextrin-relaxant complex. Human and animal studies have demonstrated that sugammadex can reverse very deep neuromuscular blockade induced by rocuronium without muscle weakness. Its future clinical use should decrease the incidence of postoperative muscle weakness, and thus contribute to increased patient safety. Sugammadex will also facilitate the use of rocuronium for rapid sequence induction of anesthesia by providing a faster onset-offset profile than that seen with 1.0 mg/kg succinylcholine. Furthermore, no additional anticholinesterase or anticholinergic drugs would be needed for antagonism of residual neuromuscular blockade, which would mean the end of the cardiovascular and other side effects of these compounds. The clinical use of sugammadex promises to eliminate many of the shortcomings in our current practice with regard to the antagonism of rocuronium and possibly other steroidal neuromuscular blockers.

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