Sugammadex and Neostigmine

Mechanism

🧪 Neostigmine

• Class: Reversible inhibitor of the enzyme acetylcholinesterase of the synaptic cleft.
• Indirect mechanism: Elevates the concentration of endogenous acetylcholine, competitively displacing the relaxant from nicotinic receptors.
• Requires mandatory coadministration of atropine or glycopyrrolate to mitigate serious systemic muscarinic-type side effects.

🧬 Sugammadex

• Class: Direct molecular encapsulation modified synthetic cyclodextrin.
• Selective mechanism: It encapsulates in a 1:1 stoichiometric manner the free rocuronium or vecuronium molecules present in the capillary blood plasma.
• Does not interfere with cholinergic neurotransmission, completely eliminating cardiovascular autonomic side effects of sorts.

Mechanism of action

Neostigmine: Binds reversibly covalently to the active site of the enzyme acetylcholinesterase, preventing the hydrolysis of the neurotransmitter acetylcholine into choline and acetate. The resulting increase in acetylcholine massively activates both motor plate nicotinic receptors and peripheral muscarinic receptors (causing extreme bradycardia, hypotension, bronchorrhea, severe bronchospasm, and colonic gastrointestinal hypermotility).

Sugammadex: It consists of a three-dimensionally modified cyclic oligosaccharide structure that has a hydrophobic central cavity and negatively charged branches. These negative charges electrostatically attract the positive quaternary ammonium charges of the aminosteroid relaxant (rocuronium or vecuronium), housing the molecule in its hydrophobic interior:

This entrapment quickly shifts the concentration balance of the relaxant from the motor plate space to the central intravascular compartment, immediately reducing the neuromuscular motor block.

Indicators and dose

Dosage and Use Guides

• Neostigmine: Standard dose of 0.03 - 0.07 mg/kg IV slowly, mandatory associated with atropine (0.015 - 0.02 mg/kg) in the same administration syringe.
• Sugammadex (Dosage according to TOF objective monitoring):
  • Reversal of Moderate Blockade (presence of T₂ or T₃ responses in TOF): 2.0 mg/kg direct IV.
  • Deep Block Reversal (TOF = 0, but PTC post-tetanic count 1): 4.0 mg/kg IV.
  • Immediate reversal after failed RSI rescue (3 minutes post-induction with rocuronium 1.2 mg/kg): 16.0 mg/kg IV.