critical illness polyneuropathy; critical illness myopathy; nerve membrane; muscle membrane; nerve excitability testing; muscle fiber velocity recovery cycles; intensive care; electrophysiology; nerve membrane potential; muscle membrane potential; membrane depolarization
Ackermann Karin, Bostock Hugh, Brander Lukas, Schröder Ralph, Djafarzadeh Siamak, Tuchscherer Daniel, Jakob Stephan, Takala Jukka, Z'Graggen Werner (2014), Early changes of muscle membrane properties in porcine faecal peritonitis, in Critcal Care
, 18, 484.
Boërio Delphine, Bostock Hugh, Spescha Romana, Z'Graggen Werner (2014), Potassium and the excitability properties of normal human motor axons in vivo, in PLoS One
, 9(6), e98262.
Bostock Hugh, Tan Veronica, Boërio Delphine, Z'Graggen Werner (2013), Validity of multi-fiber muscle velocity recovery cycles recorded at a single site using submaximal stimuli, in Clin Neurophysiol
, 123(11), 2296-2305.
Boerio Delphine, Z'Graggen Werner J, Tan Veronica S, Guetg Andri, Ackermann Karin, Bostock Hugh (2012), Muscle velocity recovery cycles: Effects of repetitive stimulation on two muscles, in Muscle & Nerve
, 46(1), 102-111.
Bostock Hugh, Baumann Corina, Humm Andrea M, Z'Graggen Werner J (2012), Temperature dependency of human muscle velocity recovery cycles, in Muscle & Nerve
, 46(2), 264-266.
Bostock Hugh, Tan Veronica S, Boerio Delphine, Z'Graggen Werner J (2012), Velocity recovery cycles of human muscle action potentials: Repeatability and variability, in Clinical Neurophysiology
, 123(11), 2296-2305.
Z'Graggen Werner, Bostock Hugh (2011), Die Methode der Nervenexzitabilitätsmessung, in Klin Neurophysiol
, 42, 149-155.
In this project, recently developed nerve and muscle excitability tests sensitive to membrane potential will be combined with conventional methods to investigate the pathogenesis of critical illness polyneuropathy (CIP) and critical illness myopathy (CIM). CIP and CIM are frequent and serious complications of intensive care, which both result in weakness that delays weaning from mechanical ventilation and increases mortality. CIP and CIM are strongly associated with the systemic inflammatory response syndrome (SIRS), but the mechanisms leading to nerve and muscle damage are not well understood. However, in preliminary nerve and muscle excitability studies we have found evidence of chronic membrane depolarization in patients with CIP and CIM. Membrane depolarization has been implicated as a causative factor in other axonal neuropathies and myopathies. To test the hypothesis that CIP and CIM are caused by depolarization of nerve and muscle fibres respectively, this study will follow 80 patients longitudinally through their stay in the intensive care unit at Inselspital, Bern. They will be investigated clinically, by the new nerve and muscle excitability tests, and by conventional nerve conduction and electromyographic studies, within two days of admission and at day 4, 7 and 14 of their stay on intensive care. To assess involvement of C-fibers in the course of CIP, skin biopsies will be performed within two days of admission and at day 14. Diagnosis of CIP and CIM will be made according to the criteria proposed by Bolten (2005). For firm diagnosis of CIM muscle biopsy is needed, which will be performed on day 14. The study will be complemented by an animal study to investigate changes in nerve and muscle excitability within the first 24 hours of sepsis. The nerve excitability testing involves measurement of strength-duration behaviour, recovery cycle after a single action potential (refractoriness, superexcitability and late subexcitability), threshold electrotonus and a current-threshold relationship. The muscle excitability testing measures the velocity recovery cycle of fibres at rest. About 50% of the patients are expected to develop CIP or CIM, so that we will be able to assess the contribution of membrane depolarization in the pathophysiology of these disorders. The results will improve understanding of the pathophysiology of CIP and CIM, and should enable us to suggest new strategies to reduce the incidence of these expensive and sometimes fatal complications of intensive care.