Intensive care unit-acquired weakness - preventive, and therapeutic aspects; future directions and special focus on lung transplantation.

In this editorial, comments are made on an interesting article in the recent issue of the World Journal of Clinical Cases by Wang and Long. The authors describe the use of neural network model to identify risk factors for the development of intensive care unit (ICU)-acquired weakness. This condition has now become common with an increasing number of patients treated in ICUs and continues to be a source of morbidity and mortality. Despite identification of certain risk factors and corrective measures thereof, lacunae still exist in our understanding of this clinical entity. Numerous possible pathogenetic mechanisms at a molecular level have been described and these continue to be increasing. The amount of retrievable data for analysis from the ICU patients for study can be huge and enormous. Machine learning techniques to identify patterns in vast amounts of data are well known and may well provide pointers to bridge the knowledge gap in this condition. This editorial discusses the current knowledge of the condition including pathogenesis, diagnosis, risk factors, preventive measures, and therapy. Furthermore, it looks specifically at ICU acquired weakness in recipients of lung transplantation, because - unlike other solid organ transplants- muscular strength plays a vital role in the preservation and survival of the transplanted lung. Lungs differ from other solid organ transplants in that the proper function of the allograft is dependent on muscle function. Muscular weakness especially diaphragmatic weakness may lead to prolonged ventilation which has deleterious effects on the transplanted lung - ranging from ventilator associated pneumonia to bronchial anastomotic complications due to prolonged positive pressure on the anastomosis.

Management of Polyneuromyopathy in a Critically Ill Patient with a Left Ventricular Assist Device.

Critical illness polyneuromyopathy after cardiac surgery is often unrecognized and is a rarely reported clinical condition. It is characterized by more proximal than distal symmetrical flaccid muscle weakness and difficulty in weaning from a respirator. When done in a timely manner, rehabilitation prevents early complications and reduces the length of hospitalization. Rehabilitation leads to better motor outcome, improves short-term and long-term functionality, and results in a better quality of life.

Encephaloradiculoneuropathy: A Rare Manifestation of COVID-19 Infection.

Neurological complications are being recognized as important outcomes of the coronavirus disease-2019 (COVID-19) pandemic. We report a rare case of both the central nervous system (CNS) and peripheral nervous system (PNS) involvement, encephalitis with polyradiculoneuropathy in a single patient of COVID infection. How to cite this article: Chakor RT, Barvalia PP, Nadaf S, Manjunath V. Encephaloradiculoneuropathy: A Rare Manifestation of COVID-19 Infection. Indian J Crit Care Med 2022;26(5):646-648.

Pathophysiology and management of critical illness polyneuropathy and myopathy.

Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Characteristics, treatments, and prognosis of a critical illness polyneuromyopathy patient with positive anti-GM1 after severe traumatic brain injury: A case report.

To investigate the clinical features, treatment and prognosis of critical illness polyneuromyopathy (CIPNM) in patients with severe traumatic brain injury (sTBI) who had positive anti-ganglioside GM1 (anti-GM1) antibody IgG. A case of CIPNM with positive anti-GM1 antibody IgG was retrospectively analysed and followed-up for 30 months. After 1 week of treatment with large dose of short-term glucocorticoid and human immunoglobulin, the muscle strength of both lower extremities was restored to grade 1. Three months later, the muscle strength and muscle tension of the patient's limbs returned to normal except for grade 3 of bilateral dorsal extensor muscle strength. In addition, the patient can walk alone with a waddling gait. After 30 months, there was no recurrence. The application of large dose of short-term glucocorticoid and human immunoglobulin to CIPNM that are positive for anti-GM1 antibodies may be an effective treatment.

Serum neurofilament light chain as outcome marker for intensive care unit patients.

OBJECTIVE: Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. METHODS: Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. RESULTS: NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). CONCLUSION: NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.

New Approaches to Critical Illness Polyneuromyopathy: High-Resolution Neuromuscular Ultrasound Characteristics and Cytokine Profiling.

BACKGROUND: Diagnosis of intensive care unit acquired weakness (ICUAW) is challenging. Pathogenesis of underlying critical illness polyneuromyopathy (CIPNM) remains incompletely understood. This exploratory study investigated whether longitudinal neuromuscular ultrasound examinations and cytokine analyses in correlation to classical clinical and electrophysiological assessment contribute to the understanding of CIPNM. METHODS: Intensive care unit patients were examined every 7 days until discharge from hospital. Clinical status, nerve conduction studies, electromyography as well as ultrasound of peripheral nerves and tibial anterior muscle were performed. Cytokine levels were analyzed by a bead-based multiplex assay system. RESULTS: Of 248 screened patients, 35 patients were included at median of 6 days (IQR: 8) after admission to intensive care unit. Axonal damage was the main feature of CIPNM. At the peak of CIPNM (7 days after inclusion), nerve ultrasound showed cross-sectional area increase of tibial nerve as a sign of inflammatory edema as well as hypoechoic nerves as a possible sign of inflammation. Cytokine analyses showed signs of monocyte and macrophage activation at this stage. Fourteen days after inclusion, cytokines indicated systemic immune response as well as profiles associated to neovascularization and regeneration. CONCLUSIONS: Exploratory neuromuscular ultrasound and cytokine analyses showed signs of inflammation like macrophage and monocyte activation at the peak of CIPNM followed by a systemic immune response parallel to axonal damage. This underlines the role of both axonal damage and inflammation in pathogenesis of CIPNM.

Critical Illness Polyneuromyopathy and the Diagnostic Dilemma.

Critical illness polyneuromyopathy is a growing concern in intensive care units, but its presentation within 24-48 hours of admission is very unusual. Such presentations should be carefully scrutinized, especially in the presence of severe hypokalemia. HOW TO CITE THIS ARTICLE: Sulakshana S, Naik BK. Critical Illness Polyneuromyopathy and the Diagnostic Dilemma. Indian J Crit Care Med 2020;24(7):603.

Reply to the Letter to Editor Regarding "An Unusual Case of Critical Illness Polyneuromyopathy".

Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and critical illness polyneuromyopathy (CIPNM) are the group of disorders that are commonly presented as neuromuscular weakness in intensive care unit (ICU) settings. They are responsible for prolonged ICU stay and failure to wean off from mechanical ventilation.1 We report one such case of young female who was admitted with undiagnosed type I diabetes mellitus with diabetic ketoacidosis with severe hypokalemia with sepsis developed acute-onset quadriplegia and diaphragmatic palsy within 72 hours of ICU admission. Detailed investigation led to the diagnosis of critical illness polyneuromyopathy. In view of high morbidity, mortality, and poor prognosis, a guided approach to diagnoses and treatment in earliest possible duration might give better improvement and outcome of the illness. Despite all the odds, our patient showed good clinical improvement and finally got discharged. HOW TO CITE THIS ARTICLE: Mahashabde M, Chaudhary GA, Kanchi G, Rohatgi S, Rao P, Patil R, et al. Reply to the Letter to Editor Regarding "An Unusual Case of Critical Illness Polyneuromyopathy". Indian J Crit Care Med 2020;24(7):604-605.

Intensive care unit-acquired weakness: unanswered questions and targets for future research.

Intensive care unit-acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient's ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW). ICU-AW can be caused by a critical illness polyneuropathy, a critical illness myopathy, or muscle disuse atrophy, alone or in combination. Its diagnosis requires both clinical assessment of muscle strength and complete electrophysiological evaluation of peripheral nerves and muscles. The peroneal nerve test (PENT) is a quick simplified electrophysiological test with high sensitivity and good specificity that can be used instead of complete electrophysiological evaluation as a screening test in non-cooperative patients. DW, assessed by bilateral phrenic nerve magnetic stimulation or diaphragm ultrasound, can be an isolated event without concurrent limb muscle involvement. Therefore, it remains uncertain whether DW and limb weakness are different manifestations of the same syndrome or are two distinct entities. Delirium is often associated with ICU-AW but a clear correlation between these two entities requires further studies. Artificial nutrition may have an impact on ICU-AW, but no study has assessed the impact of nutrition on ICU-AW as the primary outcome. Early mobilization improves activity limitation at hospital discharge if it is started early in the ICU, but beneficial long-term effects are not established. Determinants of ICU-AW can be many and can interact with each other. Therefore, future studies assessing early mobilization should consider a holistic patient approach with consideration of all components that may lead to muscle weakness.

Measurement of muscle strength with handheld dynamometer in Intensive Care Unit.

BACKGROUND: Intensive Care Unit (ICU) acquired weakness is a common complication in critically ill patients affecting their prognosis. The handheld dynamometry is an objective method in detecting minimum muscle strength change, which has an impact on the physical function of ICU survivors. The minimal change in the force can be measured in units of weight such as pounds or kilograms. AIM OF THE STUDY: To detect the changes in peripheral muscle strength with handheld dynamometer in the early stage of ICU stay and to observe the progression of muscle weakness. METHODOLOGY: Three upper and three lower limb muscles force measured with handheld dynamometer during ICU stay. Data were analyzed using repeated measures ANOVA to detect changes in force generated by muscle on alternate days of ICU stay. RESULTS: There was a reduction in peripheral muscle strength from day 3 to day 5 as well from day 5 to day 7 of ICU stay (P < 0.01). The average reduction in peripheral muscle strength was 11.8% during ICU stay. CONCLUSION: This study showed a progressive reduction in peripheral muscle strength as measured by handheld dynamometer during early period of ICU stay.