| Project Detail |
Background and rationale: Critical illness myopathy is an acute and acquired primary myopathy, and is one of the most frequent neuromuscular complications following intensive care treatment. So far, attempts to prevent the development of critical illness myopathy have mostly been unsuccessful. The main reasons for this are the lack of validated early diagnostic and monitoring methods, and the insufficient understanding of the aetiology of critical illness myopathy. Therefore, there is an evident clinical need to better understand the pathophysiology underlying critical illness myopathy and to develop a validated technique for early diagnosis and monitoring of the disease. In a recent study in patients with COVID-19, we showed that muscle excitability measurements can serve as a method for early diagnosis and monitoring the development of critical illness myopathy, and we found an association of altered potassium homeostasis and acute kidney injury with the development of critical illness myopathy. Overall objectives: The proposed project is based on the findings of our previous study and aims at a comprehensive investigation of critical illness myopathy, including the introduction and validation of a new method for early and confirmatory diagnosis, and the investigation of specific aetiological factors. Specific aims: Diagnosis: To validate muscle excitability measurements as a technique for early and confirmatory diagnosis of critical illness myopathy. Aetiology: To further examine the aetiology of critical illness myopathy with special note to the role of acute kidney injury, potassium homeostasis, and inflammation-induced tryptophan degradation. Diagnostic programme: To create a software application for automated recording, analysing and interpretation of muscle excitability measurements designated for diagnosis of critical illness myopathy. Methods: This is a prospective cohort study investigating patients admitted to the intensive care unit who are in need of mechanical ventilation. Patients will be examined on Days 1, 2, 5 and 10 after intubation. Clinical examination, muscle excitability measurements, conventional neurophysiological examination, muscle ultrasound, medication record and laboratory analyses including analysis of inflammation-induced tryptophan degradation and kynurenines, will be performed on all study visits, and additional muscle biopsy on Day 10. Expected results and their impact: The proposed project will provide a validated diagnostic method for early diagnosis and monitoring of critical illness myopathy and expand our understanding of the kidney-muscle axis, which in turn could open up new preventive and therapeutic options for critical illness myopathy. In addition, a diagnostic programme specifically for early and confirmatory diagnosis of critical illness myopathy will be provided, which is user-friendly and facilitates application in intensive care units. This forms the basis for the conduction of future interventional trials. Critical illness myopathy is a frequent sequela in critical illness survivors and is associated with high mortality and morbidity rates, long rehabilitation, and reduced re-integration into former life. Intensive care is one of the most expensive disciplines in modern health care and for patients with critical illness myopathy the costs are threefold, excluding the costs for rehabilitation. Furthermore, the long-term socioeconomic impact on affected patients and their family members is enormous. |
