Sugammadex, an Antagonist of Neuromuscular Blocking Agents, Reverses Immediate Postoperative Neurologic Depression by a Central Pro-Cholinergic Mechanism
Carlos L. Errando, Oscar Díaz-Cambronero
Med Sci Hypotheses 2016; 3:1-11
Available online: 2016-03-11
Neuromuscular blocking agents are commonly used to allow surgery and airway management. However, there have been few studies of the effects of these drugs on the central nervous system. Sugammadex is a recently introduced cyclodextrin that reverses neuromuscular block, chelating the neuromuscular blocking agent molecule, making it unable to bind to the acetylcholine receptor in the nerve-muscle endplate. In addition to this pharmacodynamic effect, clinicians perceive that patients administered sugammadex recover from general anesthesia qualitatively better than those with spontaneous reversal or those reversed with neostigmine.
Recent theories on the mechanisms of action of general anesthetic drugs and on the blood-brain barrier anatomy and function permits speculating how sugammadex might improve recovery from general anesthesia. These findings can be summarized in 3 main points. First, acetylcholine and the nicotinic acetylcholine receptors are critically located in central nervous system anatomical structures and centers, explaining the “common final effects” of most anesthetics. Second, blood-brain barrier disruptions are more frequent than expected, both in pathological and physiological circumstances, such as aging or an inflammatory background such as that occurring during and after surgical procedures. Thereby, some substances usually not found in the cerebrospinal fluid could easily pass through the blood-brain barrier. Third, we hypothesize that sugammadex, by linking to the muscle relaxants (that also putatively blocked the acetylcholine receptors in the central nervous system), increases acetylcholine molecules availability, thus improving neuronal conduction in key areas and prompting better and quicker recovery from general anesthesia. If this can be proven, a significant improvement in some postoperative complaints and complications might be ameliorated, such as postoperative cognitive dysfunction syndrome. Moreover, due to the huge number of operations per year worldwide, this improvement can translate into considerable economic savings.
Keywords: Nondepolarizing Neuromuscular Blocking Agents, Postoperative Complications, Receptors, Nicotinic