Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: Mechanisms at the cellular and molecular levels

Abstract

Acute quadriplegic myopathy is associated with a specific decrease in thick-filament proteins related to an altered transcription rate. Although the decreased content of thick-filament proteins is important for prolonged muscle weakness, it is not the primary cause of muscle paralysis in the acute stage, during which impaired muscle membrane excitability probably plays a more significant role. Several factors contribute to this condition, but the action of corticosteroids seems to be the predominant one, along with potentiation by neuromuscular blocking agents, immobilization, and probably also concurrent sepsis.

Skeletal muscle contractile protein function is preserved in human heart failure

“…4A, a decrease in MHC protein content would reduce muscle force production. A similar relationship of MHC protein content to muscle force production has been demonstrated in human single muscle fibers (6,14). In this context, and in light of the current results, we put forth the hypothesis that skeletal muscle contractile dysfunction in heart failure (26) patients is caused by reduced MHC protein content rather than by alterations in the function of individual contractile proteins.…”

Acute quadriplegic myopathy following autologous peripheral blood stem cell transplantation for breast cancer

“…The loss of thick filament proteins appears to be caused by a block in protein synthesis at the transcriptional level and enhanced myofibrillar protein degradation. 10 High-dose corticosteroid treatment in combination with non-depolarizing neuromuscular blocking agents and severe systemic illness appear to be the main risk factors associated with AQM. 5 It should be pointed out that, except for one dose of succinylcholine chloride before intubation, our patient did not receive therapy with muscle relaxants, demonstrating that steroid treatment and severe illness alone can induce AQM.…”

Mechanisms of Neuromuscular Dysfunction in Critical Illness

“…Early reports of patients with CIM noted an association with exposure to either neuromuscular blocking agents or to systemic corticosteroids, leading investigators to postulate that these agents may be involved in the pathogenesis of this syndrome [2][3][4]. These studies, however, did not adjust for confounding variables that might associate with the development of NMD and, in fact, many of these same patients with ICU weakness had sepsis, multi-organ dysfunction (MOD), or organ rejection.…”

“…There are at least three factors that contribute to weakness in patients with CIM -atrophy of muscle fibers,loss of myosin, and muscle inexcitability [3,38]. Atrophy and loss of myosin both cause weakness due to loss of force generation following muscle fiber action potentials.…”

“…In the first case report, myopathy developed in a patient treated for status asthmaticus [1]. Since that time there have been many reports of debilitating myopathy that develop in various ICU settings [2][3][4]. The acquired myopathy has been identified as a cause of prolonged weakness and is termed critical illness myopathy (CIM), among which there are several variants including acute quadriplegic myopathy, thick filament myopathy, or acute myopathy of critical illness [5].…”