Sugammadex: A Novel Agent for the Reversal of Neuromuscular Blockade

Abstract

To achieve spontaneous ventilation after completion of surgery, the nondepolarizing effects on skeletal muscle relaxation are often reversed by administration of an acetylcholinesterase inhibitor. However, these agents increase acetylcholine at both the neuromuscular junction and the muscarinic receptors. Therefore, coadministration of an anticholinergic agent is required to prevent parasympathetic adverse effects. In addition, a relative pharmacologic ceiling effect is seen with inhibition of acetylcholinesterase, necessitating some recovery of neuromuscular function before an acetylcholinesterase inhibitor is administered. Sugammadex is a new modified gamma-cyclodextrin compound under clinical investigation in the United States. It does not interact with cholinergic mechanisms to elicit reversal. Instead, it is a selective relaxant binding agent and acts by forming a 1:1 complex with steroidal nondepolarizing neuromuscular blockers in the plasma, lowering the effective concentration available at the receptor. Due to its selectivity, sugammadex does not inhibit the effects of nondepolarizing agents of the benzylisoquinolinium class. In contrast to acetylcholinesterase inhibition, sugammadex is effective even when administered during profound blockade, and it does not require coadministration of an anticholinergic agent. It provides a novel mechanism of action for reversal of the neuromuscular block induced by nondepolarizing aminosteroidal agents.

Sugammadex Efficacy for Rapid Reversal of Rocuronium Induced Neuromuscular Blockade in Pediatric Rigid Bronchoscopy Regardless the Depth of Anesthesia

“…Consistent with other studies [1,3,4,8,16], our findings revealed that the profound neuromuscular blockade can be rapidly and reliably reversed by sugammadex in young children aged 1-3 yrs undergoing rigid bronchoscopy. According to Epemolu et al [17] modified cyclodextrins like sugammadex form tightly bound 1:1 complexes with aminosteroid-based muscle relaxants and act as encapsulating drugs.…”

“…neostigmine) are injected to speed the rate of recovery from nondepolarizing NMBAs. However, such drugs remain as risk factors for complications such as respiratory depression and hypoxemia which are known as residual block [3]. In addition, muscarinic receptors may be activated by using these agents [3].…”

“…In contrast to acetylcholinesterase inhibitors, sugammadex achieves reversal by encapsulation of rocuronium, resulting in reduction of free rocuronium plasma concentration. This action leads to the removal of NMBDs from the neuromuscular joints to the central compartment through a gradient between the tissue compartment (including the NMJ) and plasma [3].…”

Osteotropic β-cyclodextrin for local bone regeneration

“…As another possibility, this ALN-mediated bone formation could be the direct result of tissues inflammation associated with ALN local administration [24] Since CDs are generally known as biologically inert, it is quiet a surprise to find that ALN-β-CD is bone anabolic. Further literature search found that the only known application of a CD derivative as an active therapeutic agent is sugammadex or Org 25969 (per-6-(2-carboxyethylthio)-per-6-deoxy-γ-cyclodextrin), which was developed as a lead compound for antagonism of prolonged rocuronium-induced neuromuscular block [25][26][27]. While highly water-soluble sugammadex does not have any direct or indirect action on any component of cholinergic transmission, it acts as a solubilized molecular host that complexes with rocuronium and facilitates its movement from the neuromuscular junction back into the plasma, which results in a fast recovery of neuromuscular function.…”

Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese patients

“…This substance is used in adults of normal weight at 2mg/kg to promote reversion of moderate NMB, measured by the train-of-four (TOF) stimulus sequence (T4/T1 ≥0.9); at 4mg/kg for reversal of deep NMB; and at a dose of 16mg/kg for immediate reversal of rocuronium-induced NMB [9][10][11][12][13] . Previous studies have suggested that reversal of NMB in morbidly obese patients could be achieved at 4mg/kg for deep blockade considering the ideal body weight, or 2mg/kg, regardless of which body weight is considered, ideal or actual 18,19 .…”