Muscle Relaxants in Burns, Trauma, and Critical Illness

Martyn, J. A. J.; Fukushima, Yukinobu; Chon, JinYoung; Yang, Hong Seuk

doi:10.1097/00004311-200604420-00008

Cited by 41 publications

(3 citation statements)

References 69 publications

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“…Although there is no evidence that steroidal neuromuscular blocking agents have steroidal effects on muscle (110), all neuromuscular blocking agents cause a denervation-like state in the muscle (111). It might be possible to address or even eliminate some of the risk factors if patients are diagnosed with muscle weakness early in the disease.…”

Section: Clinical Implications Of Muscle Strength Measurementsmentioning

confidence: 99%

Measurement of muscle strength in the intensive care unit

Bittner

Martyn

George

et al. 2009

Critical Care Medicine

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Traditional (indirect) techniques, such as electromyography and nerve conduction velocity measurement, do not reliably predict intensive care unit-acquired muscle weakness and its clinical consequences. Therefore, quantitative assessment of skeletal muscle force is important for diagnosis of intensive care unit-acquired motor dysfunction. There are a number of ways for assessing objectively muscle strength, which can be categorized as techniques that quantify maximum voluntary contraction force and those that assess evoked (stimulated) muscle force. Important factors that limit the repetitive evaluation of maximum voluntary contraction force in intensive care unit patients are learning effects, pain during muscular contraction, and alteration of consciousness.The selection of the appropriate muscle is crucial for making adequate predictions of a patient's outcome. The upper airway dilators are much more susceptible to a decrease in muscle strength than the diaphragm, and impairment of upper airway patency is a key mechanism of extubation failure in intensive care unit patients. Data suggest that the adductor pollicis muscle is an appropriate reference muscle to predict weakness of muscles that are typically affected by intensive care unit-acquired weakness, i.e., upper airway as well as extremity muscles. Stimulated (evoked) force of skeletal muscles, such as the adductor pollicis, can be assessed repetitively, independent of brain function, even in heavily sedated patients during high acuity of their disease.

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Section: Clinical Implications Of Muscle Strength Measurementsmentioning

confidence: 99%

Measurement of muscle strength in the intensive care unit

Bittner

Martyn

George

et al. 2009

Critical Care Medicine

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“…The expression of γ-AChR has clinical significance, because the two subtypes have different electrophysiological and drug-binding properties (Martyn et al, 1992). Upregulation and spreading of nAChRs, especially the immature form, can induce resistance to NDMRs, as documented in burns, denervation and immobilization (Martyn et al, 1992;Martyn and Richtsfeld, 2006;Jeevendra et al, 2006). Thus, Dex-induced upregulation of functional nAChRs can lead to resistance to NMBRs (Maestrone et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

Chen¹,

Yang²,

Huang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the influence of chronic dexamethasone (Dex) administration on rat diaphragm sensitivity to non-depolarizing muscle relaxants (NDMRs) and muscular nicotinic acetylcholine receptor (nAChR) expression, which may help direct future administration of NDMRs. Adult male SpragueDawley rats were randomized to receive a daily intraperitoneal injection of Dex (600 μg/kg body mass) or an equivalent volume of saline (N = 20 in each group) for 14 days. We evaluated isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect supramaximal stimulation at 0.1 Hz. Real-time quantitative PCR was performed to determine the mRNA expression of two nAChR subunits (ε-subunit and γ-subunit) in the diaphragm. Dex administration markedly (P < 0.01) increased the 50% twitch depression (IC 50 ) of the three NDMRs. The IC 50 ratio, which standardized the magnitudes of the resistance, was the Differential Dex-induced resistance to muscle relaxants largest for atracurium, with the second largest for vecuronium and the smallest for rocuronium (P < 0.01). The ε-and γ-subunit mRNAs were both upregulated with an increased γ/ε ratio in rats exposed to Dex. The results indicated that chronic Dex administration induces hyposensitivity to NDMRs, the degree of which depends on the kind of neuromuscular blocker, and is associated with increased nAChR expression.

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“…Nicotinic acetylcholine receptors (AChRs) are involved in mediating fast excitatory neurotransmission at the neuromuscular junction and at synapses in the central and peripheral nervous systems and are important therapeutic targets (e.g., Gotti et al ., 2006 ; Jeevandra Martyn et al ., 2006 ). The gene family of AChR subunits is a member of the Cys‐loop superfamily of ligand‐gated ion channel subunits, which also includes subunits of glycine, GABA A and 5‐HT 3 receptors.…”

Section: Introductionmentioning

confidence: 99%

The role of the amino acid residue at α1:189 in the binding of neuromuscular blocking agents to mouse and human muscle nicotinic acetylcholine receptors

Purohit¹,

Tate²,

Pow³

et al. 2007

British J Pharmacology

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Background and Purpose: Nicotinic acetylcholine receptors (AChRs) are valuable therapeutic targets. To exploit them fully requires rapid assays for the evaluation of potentially therapeutic ligands and improved understanding of the interaction of such ligands with their receptor binding sites. Experimental Approach: A variety of neuromuscular blocking agents (NMBAs) were tested for their ability to inhibit the binding of [125 I]a-bungarotoxin to TE671 cells expressing human muscle AChRs. Association and dissociation rate constants for vecuronium inhibition of functional agonist responses were then estimated by electrophysiological studies on mouse muscle AChRs expressed in Xenopus oocytes containing either wild type or mutant a1 subunits. Key results: The TE671 inhibition binding assay allowed for the rapid detection of competitive nicotinic AChR ligands and the relative IC 50 results obtained for NMBAs agreed well with clinical data. Electrophysiological studies revealed that acetylcholine EC 50 values of muscle AChRs were not substantially altered by non-conservative mutagenesis of phenylalanine at a1:189 and proline at a1:194 to serine. However the a1:Phe189Ser mutation did result in a 3-4 fold increase in the rate of dissociation of vecuronium from mouse muscle AChRs. Conclusions and implications:The TE671 binding assay is a useful tool for the evaluation of potential therapeutic agents. The a1:Phe189Ser substitution, but not a1:Pro194Ser, significantly increases the rate of dissociation of vecuronium from mouse muscle AChRs. In contrast, these non-conservative mutations had little effect on EC 50 values. This suggests that the AChR agonist binding site has a robust functional architecture, possibly as a result of evolutionary 'reinforcement'.

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Muscle Relaxants in Burns, Trauma, and Critical Illness

Cited by 41 publications

References 69 publications

Measurement of muscle strength in the intensive care unit

Measurement of muscle strength in the intensive care unit

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

The role of the amino acid residue at α1:189 in the binding of neuromuscular blocking agents to mouse and human muscle nicotinic acetylcholine receptors

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