Clinical Investigations Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: Mechanisms at the cellular and molecular levels Lars Larsson, MD, PhD; Xiaopeng Li, MD, PhD; Lars Edström, MD, PhD; Lars I. Eriksson, MD, PhD; Håkan Zackrisson, MD; Carla Argentini, BSc; Stefano Schiaffino, MD, PhD From Noll Physiological Research Center (Dr. Larsson), Pennsylvania State University, University Park, PA; Departments of Neurology (Drs. Larsson, Li, Edström, Zackrisson) and Anaesthesiology and Intensive Care (Drs. Eriksson, Zackrisson), Karolinska Hospital and Institute, Stockholm, Sweden; and Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche Center of Muscle Biology and Physiopathology (Drs. Argentini, Schiaffino), University of Padova, Padova, Italy. Supported, in part, by the Swedish Medical Research Council (Grant 8651), the European Union Commission (Biomed-2), the Swedish Work Environment Fund, and the General Clinical Research Center, University Park (Grant MO1-RR10732-03) (Dr. Larsson), and the Swedish Heart and Lung Foundation (Dr. Zackrisson). Address requests for reprints to: Lars Larsson, MD, PhD, Marie Underhill Noll Professor, Noll Physiological Research Center, Pennsylvania State University, University Park, PA 16802- 6900. E-mail: lgl5@psu.edu. Objective: Long-term treatment with nondepolarizing neuromuscular blocking agents and corticosteroids in the intensive care unit is not benign, and an increasing number of patients with acute quadriplegic myopathy have been reported with increased use of these drugs. The purpose of this study was to investigate the mechanisms underlying acute quadriplegic myopathy. Design: Percutaneous muscle biopsy samples were obtained, and electrophysiologic examinations were performed during the acute phase and during recovery in patients with acute quadriplegic myopathy. Regulation of muscle contraction and myofibrillar protein synthesis was studied using cell physiologic techniques, ultrasensitive electrophoresis, in situ hybridization, and histopathologic techniques. Setting: All patients were seen in the intensive care unit of different university hospitals. Patients: All patients were critically ill with sepsis. They had been given massive doses of corticosteroids in combination with variable doses of neuromuscular blocking agents. All patients developed paralysis of spinal nerve-innervated muscles. On the other hand, cranial nerve-innervated muscle and sensory and cognitive functions were well maintained after discontinuation of treatment with neuromuscular blocking agents. Intervention: Muscle biopsy samples were obtained and electrophysiologic examinations were performed in all patients.