Updated review of resistance to neuromuscular blocking agents

Ki Tae Jung, Tae Hun An
2018 Anesthesia and Pain Medicine  
Since neuromuscular blocking agents (NMBAs) were introduced into the surgical field, they have become indispensable for surgery. However, there are many reports of resistance to NMBAs, which are commonly referred to as tachyphylaxis or hyposensitivity [1, 2] . Resistance to NMBAs is identified based on increases in the NMBA dosage required to inhibit the muscular twitch response, the time to maximum response, and decreases in the degree of twitch depression or the duration of neuromuscular
more » ... ade after a bolus [1]. Approximately 1% of all patients administered general anesthesia exhibit inadequate relaxation, interrupting the procedure [3]. Thus, it is of great importance to understand the mechanisms of NMBA resistance associated with different pathological states to maintain adequate neuromuscular relaxation. Certain pathological states, such as central nerve injury [4], burns [5], and critical illnesses [6], are associated with resistance to NMBAs. This resistance can be explained by up-regulation of acetylcholine receptors (AChRs) in skeletal muscle [2]. In addition, quantitative and qualitative changes in the physiology of acetylcholine (ACh) and AChR at the neuromuscular junction (NMJ) develop during pathological processes, which lead to changes in the pharmacokinetics and pharmacodynamics of NMBAs [1,2]. PHARMACOKINETIC CHANGES IN NMBA RESISTANCE Pharmacokinetic changes in NMBA resistance are associated with changes in the volume of distribution (VD), protein binding, and clearance of NMBAs (Table 1 ). These changes result in a decrease in the effective NMBA concentration at This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. Review 122 the receptor site (Fig. 1) , and are observed in patients with hepatic dysfunction, thermal injury, oncological diseases, and acid-base disturbances.
doi:10.17085/apm.2018.13.2.122 fatcat:3ehdqpmburferpierjoqzgwmze