Muscular weakness and muscle wasting in the critically ill

Background: Muscular weakness and/or muscle wasting is recognized as a key medical problem in critically ill patients on intensive care units (ICUs) worldwide.

Methods and results: Intensive care unit-acquired weakness (ICUAW) results from various diseases leading to critical illness and is observed in about 40% [1080/2686 patients, 95% confidence interval (CI): 38-42%] of mixed (medical-surgical) ICU patients. Muscle strength at ICU discharge is directly associated with mortality 5 years after discharge [hazard ratio 0.946, 95% CI: 0.928-0.968 per point increase in Medical Research Council (MRC) scores, P = 0.001]. ICUAW serves as umbrella term for the subgroups ‘critical illness myopathy’, ‘critical illness polyneuropathy’, and ‘critical illness polyneuromyopathy’, the latter distinguished using electrophysiology and/or biopsy studies. Diagnosing, studying, and developing treatments for ICUAW among the critically ill seems challenging due to the acuity and severity of the underlying heterogeneous diseases. Ventilator-induced diaphragmatic dysfunction occurs in up to 80% (n = 32/40) of ICUAW patients after mechanical ventilation and mostly results from distinct muscular pathologies, disuse, underlying critical illness, and/or effects imposed directly by mechanical ventilation. Swallowing disorders/dysphagia likely represent an additional (local) neuromuscular dysfunction/ICUAW sequelae and presents in 10.3% (n = 96/933) of mixed medical-surgical ICU survivors, with 60.4% (n = 58/96) of patients remaining dysphagia positive until hospital discharge. Key independent risk factors for dysphagia following mechanical ventilation are baseline neurological disease [odds ratio (OR) 4.45, 95% CI: 2.74-7.24, P < 0.01], emergency admission (OR 2.04, 95% CI: 1.15-3.59, P < 0.01), days on mechanical ventilation (OR 1.19, 95% CI: 1.06-1.34, P < 0.01), days on renal replacement therapy (OR 1.1, 95% CI: 1-1.23, P = 0.03), and disease severity (Acute Physiology and Chronic Health Evaluation II score within first 24 h; OR 1.03, 95% CI: 0.99-1.07, P < 0.01). Dysphagia positivity independently predicts 28-day and 90-day mortality (90-day univariate hazard ratio: 3.74; 95% CI, 2.01-6.95; P < 0.001) and is associated with a 9.2% excess (all-cause) mortality rate.

Conclusions: Neuromuscular weakness and muscle wasting is observed in many survivors of critical illness. ICUAW, ventilator-induced diaphragmatic dysfunction, and dysphagia are associated with complicated and prolonged ICU stay, impaired weaning from mechanical ventilation, impeded rehabilitative measures, and a considerable impact on morbidity and mortality is noted. Future research strategies should further explore underlying pathomechanisms and lead to development of causal treatment strategies.