Search Results (31)

Intensive Care Unit-Acquired Weakness (ICU-AW) is a secondary neuromuscular disorder diagnosed during a critical illness and related to ICU stay and intensive treatments, once other possible etiologies have been excluded. Micronutrients are essential components of human nutrition that are needed in small amounts to maintain pivotal organ functions, but their role in critical care nutrition and in prevention and treatment of ICU-AW is unclear. This narrative review aimed to provide a synthesis of the current evidence on the potential role of micronutrients in ICU-AW, with a glance at what is known in medical settings outside the ICU. Available evidence is fragmented, showing controversial results. Studies on vitamin K1 and vitamin D suggest potential benefits on handgrip strength, skeletal muscle mass and mobility, while Coenzyme Q10 may have a role in improving skeletal muscle composition. Moreover, zinc homeostasis may influence muscle degradation, whereas copper levels may represent a risk factor. Evidence on iron and carnitine showed uncertain results. Conversely, more robust evidence on muscle weakness is available for medical settings outside the ICU. Larger observational studies and RCTs are needed to further evaluate the possible efficacy of micronutrient supplementation in the critical care setting. Full article

ICU-acquired weakness (ICUAW) is a clinical condition characterized by muscle weakness in critically ill patients that is not directly attributable to the underlying illness. It affects approximately 40% of intensive care unit patients, primarily impairing the limbs and respiratory muscles, and can compromise motor and respiratory function even after recovery from acute illness. ICUAW exhibits heterogeneous phenotypes. In addition, diverse risk factors influence its occurrence. Although this condition is recognized, the underlying mechanisms contributing to critical illness-associated muscle dysfunction remain poorly understood and are likely interrelated. This review summarizes the current experimental evidence from translational studies involving diverse muscle biopsies under various conditions, providing insights into normal skeletal muscle physiology and its alterations in critical illness-associated muscle dysfunction. Here, we focus on muscle ultrastructure, mitochondrial function, atrophy, protein breakdown, inflammation, and key molecular pathways, with consideration of the proposed role of NLRP3 inflammasome signalling, for which direct experimental evidence in human skeletal muscle during critical illness remains limited and constitutes a priority area for future mechanistic research. Full article

Critical illness myopathy (CIM) is linked to mechanical ventilation and complete mechanical muscle silencing in intensive care unit (ICU) patients. Limb muscles show atrophy and declined specific single fibre force through altered protein turnover and diminished myosin-to-actin ratios. A rat ICU model reproducing preferential myosin loss and specific force decline in limb muscle was used to assess myofibrillar remodelling. After 5 or 10 days of ICU intervention, single extensor digitorum longus (EDL) and soleus muscle fibres were imaged using label-free, Second Harmonic Generation (SHG) microscopy, followed by quantitative 3D morphometry. The degree and severity of deranged myofibrillar architecture was assessed through (i) 2D and 3D Cosine Angle Sums (CAS2D/CAS3D) and (ii), Vernier Densities (VD) parameters. A progressively declining myofibrillar order was seen by dropping CAS2D/3D and increasing VD values during ICU intervention, reflecting angular and axial register deviations. Effects of chaperone co-inducer BGP-15, dissociative glucocorticoid Vamorolone (VBP-15) or its parent compound Prednisolone on myofibrillar architecture were explored. Both BGP-15 and VBP-15 modulated the progression of myofibrillar disorder seen during ICU intervention alone: For soleus fibres, BGP-15 maintained structural integrity at day 5 but not at day 10, while even worsening myofibrillar order in the EDL. VBP-15 reversed atrophy at day 10 in soleus but not in EDL fibres. Our study is the first to quantify myofibrillar remodelling in limb muscle fibres during ICU intervention in 3D and provides exploratory assessment of BGP-15 and VBP-15 treatments on aberrant remodelling in CIM. Full article

Intensive care unit-acquired weakness (ICUAW) is a common and devastating complication in critically ill patients admitted to the intensive care unit (ICU). ICUAW is characterized by profound skeletal and respiratory muscle weakness and degeneration, as well as peripheral nerve dysfunction. The condition is further categorized into three primary diagnoses: critical illness myopathy (CIM), which affects skeletal muscles, critical illness polyneuropathy (CIP), which affects peripheral nerves, and critical illness polyneuromyopathy (CIPNM), which exhibits features of both CIM and CIP. Although the pathophysiology of ICUAW remains poorly understood, several risk factors have been identified, including female sex, advanced age, prolonged mechanical ventilation, extended ICU stay, prolonged immobilization, multiorgan failure, shock, infection, and other factors related to critical illness and its treatment. Currently, ICUAW is diagnosed after the onset of critical illness, and only once all other possible causes of generalized weakness have been excluded. The most commonly used assessments for suspected ICUAW are the Medical Research Council sum score (MRC-SS) and handgrip dynamometry. However, these tools require active patient participation and are, therefore, impractical for many ICU patients. Non-volitional testing methods, including electromyography (EMG) and nerve conduction studies, can be used to evaluate ICUAW, but these tests are invasive and require specialized training and resources. Due to the lack of effective diagnostic tools and an incomplete understanding of disease mechanisms, management of ICUAW is largely restricted to physical rehabilitation. ICUAW is associated with high morbidity and mortality, and survivors often experience long-term disability and reduced quality of life following hospital discharge. Future areas of research, including biomarker analysis and risk prediction modeling, may enable earlier diagnosis and intervention in critically ill patients. This review summarizes potential diagnostic tools, current management strategies, and short- and long-term prognosis and identifies emerging areas of research aimed at improving outcomes for critically ill patients with suspected ICUAW. Full article

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is an important but under-recognised complication in neuromuscular diseases. In adults, emerging epidemiological data suggests increased VTE occurrence in conditions such as Amyotrophic Lateral Sclerosis, myotonic dystrophy, myasthenia gravis, inflammatory neuropathies, inflammatory myopathies, and POEMS syndrome. This heightened risk reflects not only disease-related immobility but also disorder-specific biological mechanisms, including inflammation, endothelial dysfunction and cardiomyopathy-related stasis. Therapies such as corticosteroids, IVIG-related hyperviscosity, long-term central venous access, perioperative immobility, critical illness, and complex orthopaedic procedures have prothrombotic effects. Despite this multifactorial risk profile, disease-specific guidance for thromboprophylaxis is lacking, and current practice relies heavily on extrapolation from general medical and surgical recommendations rather than data derived from neuromuscular cohorts. In children and adolescents, the VTE burden is less well-characterised, but events have been reported in Duchenne and Becker muscular dystrophy, congenital myopathies, and spinal muscular atrophy particularly with advanced motor impairment, severe cardiomyopathy, ventilatory insufficiency, and prolonged hospitalisation. Beyond venous events, selected neuromuscular disorders also exhibit increased arterial thrombosis risk. Myotonic dystrophy and dystrophinopathies are associated with cardiomyopathy and arrhythmia that predispose to systemic embolism and stroke, while inflammatory myopathies may demonstrate arterial events related to vasculitic or endothelial processes, although overall evidence remains limited. This review summarises available empirical and epidemiological evidence on venous and arterial thrombosis across adult and paediatric neuromuscular disorders, outlines disease-specific mechanistic pathways, examines treatment-related contributors, and highlights key evidence gaps that must be addressed to guide rational and targeted prophylaxis strategies in this complex, heterogeneous population. Full article

Intensive Care Unit Acquired Weakness (ICUAW) is a highly prevalent neuromuscular complication affecting around 40% of critically ill patients, rising to over 80% in high-risk cohorts. It is independently associated with prolonged mechanical ventilation, increased intensive care unit (ICU) and hospital length of stay, elevated mortality (in-hospital, 1-year, and 5-year), higher healthcare costs, and long-term functional impairment. ICUAW is clinically defined by symmetric flaccid tetraparesis, frequently involving respiratory muscles, and exhibits significant pathobiological heterogeneity. Further subclassification is based on neurotopographic patterns: Critical Illness Polyneuropathy (CIP), Myopathy (CIM), and Polyneuromyopathy (CIPNM). Diagnosis typically relies on the Medical Research Council (MRC) Sum Score, with a threshold of <48 indicating clinically relevant weakness. While adjunct modalities such as electromyography/nerve conduction studies support assessment, their utility may be limited by patient cooperation and availability. Preventive strategies center on modifiable metabolic factors. Caloric and protein deficits exacerbate catabolism, while overfeeding—linked to anabolic resistance and stress hyperglycemia—also impairs recovery. To date, pharmacologic interventions remain inconclusive. However, early mobilization and neuromuscular electrical stimulation are promising non-pharmacologic strategies. The multifactorial and heterogeneous pathophysiology of ICUAW highlights the need for a biologically refined definition that can guide future targeted therapeutic interventions. Comprehensive multimodal strategies, together with structured long-term follow-up in Post-Intensive Care Syndrome (PICS) clinics, are essential for improving outcomes in this prevalent complication of critical care. Full article

Loss of muscle mass and strength is a common condition associated with adverse outcomes in critically ill patients. Here, we determined the correlation between non-thyroidal illness (NTIS) and molecular alterations in the muscle of critically ill individuals. We evaluated deiodinase expression, intramuscular triiodothyronine (T3) levels, and mitochondria and sarcoplasmic reticulum components. The cellular colocalization of the enzymes and its influence on myocytes and genes regulated by T3 were shown, including those of mitochondria. A prospective cohort of 96 patients. Blood and muscular samples were collected on admission to the intensive care unit (ICU), as well as clinical data and ultrasonographic measurements. Patients with NTIS showed increased oxidative stress markers associated with critical illness in muscle biopsy, such as carbonyl content and low sulfhydryl and GSH. The distribution pattern of deiodinases in muscle and its biochemical properties showed significant pathophysiological linkage between NTIS and muscle loss, as type 3-deiodinase (D3) was highly expressed in stem cells, preventing their differentiation in mature myocytes. Despite the high type 2-deiodinase (D2) expression in muscle tissue in the acute phase of critical illness, T3 was unmeasurable in the samples. In this scenario, we also demonstrated impaired expression of glucose transporters GLUT4, IRS1, and 2, which are involved in muscle illness. Here, we provide evidence that altered thyroid hormone metabolism contributes to stem cell dysfunction and further explain the mechanisms underlying critical illness-induced myopathy. Full article

Intensive Care Unit-Acquired Weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by profound and often prolonged muscle weakness. The complexity of its diagnosis and management requires a multidimensional approach that integrates clinical, electrophysiological, and imaging tools. This review focuses on the challenges in diagnosing ICU-AW, emphasizing the limitations of traditional methods such as manual muscle testing and electrophysiological studies, and highlights the emerging role of neuromuscular ultrasound (NMUS) as a promising, non-invasive diagnostic aid. Despite its utility, no gold standard exists for NMUS, making it an evolving area of research. The pathophysiological basis of ICU-AW involves multiple mechanisms, including critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and muscle atrophy due to disuse. Understanding these underlying mechanisms is crucial for advancing diagnostic strategies and informing therapeutic interventions. Recent insights into the molecular and cellular pathways involved, such as the role of oxidative stress, mitochondrial dysfunction, and the ubiquitin-proteasome system, have opened new avenues for targeted therapies. Management of ICU-AW remains challenging as no specific treatment has been proven fully effective. Current strategies focus on early mobilization, minimizing sedation, and optimizing nutritional support. Emerging therapies targeting molecular pathways involved in muscle degradation are under investigation, highlighting the potential to translate pathophysiological understanding into therapeutic innovations. This review underscores the need for ongoing research to establish standardized diagnostic protocols and develop targeted treatments for ICU-AW. Full article

Millions of critically ill patients are discharged from intensive care units (ICUs) every year. These ICU survivors may suffer from a condition known as post-intensive care syndrome (PICS) which includes a wide range of cognitive, psychological, and physical impairments. This article will provide an extensive review of PICS. ICU survivors may experience cognitive deficits in memory and attention, with a slow-down of mental processing and problem-solving. From psychological perspectives, depression, anxiety, and post-traumatic stress disorder are the most common issues suffered after ICU discharge. These psycho-cognitive impairments might be coupled with ICU-acquired weakness (polyneuropathy and/or myopathy), further reducing the quality of life, the ability to return to work, and other daily activities. The burden of ICU survivors extends to families too, leading to the so-called PICS-family (or PICS-F), which entails the psychological impairments suffered by the family and, in particular, by the caregiver of the ICU survivor. The development of PICS (and PICS-F) is likely multifactorial, and both patient- and ICU-related factors may influence it. Whilst the prevention of PICS is complex, it is important to identify the patients at higher risk of PICS, and clinicians should be aware of the tools available for diagnosis. Stakeholders should implement strategies to achieve PICS prevention and to support its effective treatment during the recovery phase with dedicated pathways and supporting care. Full article

Background/Objectives: This study aimed to evaluate and establish the incidence of all types of neurological complications at our high-volume reference center for open TAAA repair in the Netherlands and Germany. Additionally, we sought to identify predictors for various neurological complications. Methods: This retrospective study was conducted in accordance with the STROBE guidelines, with the aim of reporting neurological outcomes for all patients who underwent open thoracoabdominal aortic aneurysm repair at two centers (Maastricht-Aachen) from 2000 to 2023, and to examine the association between these outcomes and pre- and perioperative parameters. The primary endpoints of the study were all-cause mortality, spinal cord ischemia (SCI), stroke, intracerebral bleeding (ICB), critical illness polyneuropathy/myopathy (CIP/CIM), and recurrent laryngeal nerve paralysis. Results: A total of 577 patients were operated on for open TAAA repair in two centers. The total in-hospital mortality rate was 20.6%, while the elective cases in-hospital mortality rate was 14.6%. In all, 28.2% of patients experienced neurological complications. The spinal cord ischemia rate was 7.5%, intracerebral bleeding 3.6%, stroke 5.9%, critical illness polyneuropathy 3.5%, and laryngeal nerve paresis 5.7%. Crawford extent II was significantly associated with increased neurological complications (OR 2.05, 95% CI 1.39–3.03, p = 0.003), while Crawford extent III and IV were significantly associated with fewer postoperative neurological complications (OR 0.61 (0.38–0.98) p = 0.04) (OR 0.52 (0.30–0.92) p = 0.02). Preoperative ASA score > 3 (OR 1.76, 95% CI 1.16–2.67, p = 0.007), COPD (OR 1.82, 95% CI 1.19–2.78, p = 0.006), massive intraoperative transfusion (OR 1.48, 95% CI 1.01–2.17, p = 0.04), and reinterventions during hospital stay (OR 1.98, 95% CI 1.36–2.89, p < 0.001) and surgery time (p =< 0.001) were significantly associated with neurological complications. Patients with neurological complications had higher rates of other postoperative morbidities. Conclusions: Neurological complications after open TAAA repair remain a significant concern, with identified risk factors associated with increased morbidity, mortality, and resource utilization. Identifying at-risk patients could potentially lead to a reduction in neurological complications. Full article

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD. Full article

The study aimed to show the potential clinical application of supplements used among sportsmen for patients suffering from Intensive Care Unit-acquired Weakness (ICUAW) treatment. ICUAW is a common complication affecting approximately 40% of critically ill patients, often leading to long-term functional disability. ICUAW comprises critical illness polyneuropathy, critical illness myopathy, or a combination of both, such as critical illness polyneuromyopathy. Muscle degeneration begins shortly after the initiation of mechanical ventilation and persists post-ICU discharge until proteolysis and autophagy processes normalize. Several factors, including prolonged bedrest and muscle electrical silencing, contribute to muscle weakness, resulting from an imbalance between protein degradation and synthesis. ICUAW is associated with tissue hypoxia, oxidative stress, insulin resistance, reduced glucose uptake, lower adenosine triphosphate (ATP) formation, mitochondrial dysfunction, and increased free-radical production. Several well-studied dietary supplements and pharmaceuticals commonly used by athletes are proven to prevent the aforementioned mechanisms or aid in muscle building, regeneration, and maintenance. While there is no standardized treatment to prevent the occurrence of ICUAW, nutritional interventions have demonstrated the potential for its mitigation. The use of ergogenic substances, popular among muscle-building sociates, may offer potential benefits in preventing muscle loss and aiding recovery based on their work mechanisms. Full article

Background: Foot drop syndrome (FDS), characterized by severe weakness and atrophy of the dorsiflexion muscles of the feet, is commonly found in patients with severe acquired brain injury (ABI). If the syndrome is unilateral, the cause is often a peroneal neuropathy (PN), due to compression of the nervous trunk on the neck of the fibula at the knee level; less frequently, the cause is a previous or concomitant lumbar radiculopathy. Bilateral syndromes are caused by polyneuropathies and myopathies. Central causes, due to brain or spinal injury, mimic this syndrome but are usually accompanied by other symptoms, such as spasticity. Critical illness polyneuropathy (CIP) and myopathy (CIM), isolated or in combination (critical illness polyneuromyopathy, CIPNM), have been shown to constitute an important cause of FDS in patients with ABI. Assessing the causes of FDS in the intensive rehabilitation unit (IRU) has several limitations, which include the complexity of the electrophysiological tests, limited availability of neurophysiology consultants, and the severe disturbance in consciousness and lack of cooperation from patients. Objectives: We sought to propose a simplified electrophysiological screening that identifies FDS causes, particularly PN and CIPNM, to help clinicians to recognize the significant clinical predictors of poor outcomes in severe ABI at admission to IRU. Methods: This prospective, single-center study included 20 severe ABI patients with FDS (11 females/9 males, mean age 55.10 + 16.26; CRS-R= 11.90 + 6.32; LCF: 3.30 + 1.30; DRS: 21.45 + 3.33), with prolonged rehabilitation treatment (≥2 months). We applied direct tibialis anterior muscle stimulation (DMS) associated with peroneal nerve motor conduction evaluation, across the fibular head (NCS), to identify CIP and/or CIM and to exclude demyelinating or compressive unilateral PN. Results: At admission to IRU, simplified electrophysiological screening reported four unilateral PN, four CIP and six CIM with a CIPNM overall prevalence estimate of about 50%. After 2 months, the CIPNM group showed significantly poorer outcomes compared to other ABI patients without CIPNM, as demonstrated by the lower probability of achieving endotracheal-tube weaning (20% versus 90%) and lower CRS-R and DRS scores. Due to the subacute rehabilitation setting of our study, it was not possible to evaluate the motor results of recovery of the standing position, functional walking and balance, impaired by the presence of unilateral PN. Conclusions: The implementation of the proposed simplified electrophysiological screening may enable the early identification of unilateral PN or CIPNM in severe ABI patients, thereby contributing to better functional prognosis in rehabilitative settings. Full article

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient–ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient–ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient–ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease. Full article

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW. Full article