Anesth Pain Med.  2018 Apr;13(2):122-127. 10.17085/apm.2018.13.2.122.

Updated review of resistance to neuromuscular blocking agents

• Jung KT
• An TH

• KMID: 2437417
• DOI: http://doi.org/10.17085/apm.2018.13.2.122

Abstract

Since neuromuscular blocking agents (NMBAs) were introduced to the surgical field, they have become almost mandatory for the induction and maintenance of anesthesia. However, resistance to NMBAs can develop in certain pathological states, such as central nerve injury, burns, and critical illnesses. During such pathological processes, quantitative and qualitative changes occur in the physiology of acetylcholine and the acetylcholine receptor (AChR) at the neuromuscular junction. Up-regulation of AChR leads to changes in the pharmacokinetics and pharmacodynamics of NMBA. As NMBA resistance may result in problems during anesthesia, it is of utmost importance to understand the mechanisms of NMBA resistance and their associations with pathological status to maintain adequate neuromuscular relaxation. This review presents the current knowledge of pharmacokinetic and pharmacodynamic changes and pathological status associated with NMBA resistance.

Keyword

Cholinergic receptors; Drug resistance; Neuromuscular blocking agents; Upregulation

MeSH Terms

Acetylcholine
Anesthesia
Burns
Critical Illness
Drug Resistance
Neuromuscular Blockade*
Neuromuscular Blocking Agents*
Neuromuscular Junction
Pathologic Processes
Pharmacokinetics
Physiology
Receptors, Cholinergic
Relaxation
Up-Regulation
Acetylcholine
Neuromuscular Blocking Agents
Receptors, Cholinergic

Figure

• 

  Fig. 1 Schematic drawing of the neuromuscular junction (NMJ) and the mechanism of resistance to neuromuscular blocking agents (NMBAs). (A) A normal NMJ and normal interaction between the acetylcholine (ACh) receptor and NMBA. NMBA resistance resulting from pharmacokinetic changes, such as increased volume of distribution (VD), increased protein binding, and increased clearance, is associated with a decrease in NMBA concentration at the receptor site. (B) NMBA resistance associated with increased volume of distribution. (C) NMBA resistance associated with increased protein binding. (D) NMBA resistance associated with increased clearance. Pharmacodynamic changes in NMBA resistance are mostly associated with changes in ACh receptor physiology, such as upregulation, which results in a change in the availability or reactivity of receptors. (E) NMBA resistance associated with upregulation.

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