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Early ambulation in the ICU
Bedrest has historically been prescribed as an adjunct to the treatment of acute illness and to rehabilitation after surgery. Even as physicians and researchers began to realize the “evil sequelae of complete bed rest” in both medical and surgical patients, this therapy remained commonplace in the intensive care unit (ICU). Indeed, healthcare providers in the ICU have traditionally focused their attention on normalizing the physiologic derangements that threaten their patients’ survival. However, therapeutic advances and improvements in the management of critically ill patients have improved the outcomes in this patient population. As survival from critical illness has improved, the long-term complications and associated therapies have become more apparent. A large proportion of these patients experience long-term cognitive, psychological, and physical disability, with less than half of critical illness survivors returning to their prior functional status 1 year after discharge. Early mobilization and ambulation of critically ill patients are feasible, safe, and cost-effective interventions that improve physical, functional, and neuropsychiatric outcomes.
The physiology of bedrest
Bedrest has, at one time or another, been promoted as therapy for almost all ailments. Hippocrates suggested that all pain could be relieved by bedrest. However, as early as the 1940s, it was recommended that “the physician . . . always consider complete bed rest as a highly unphysiological and hazardous form of therapy.” Nonetheless, it was not until recently that the medical community began to acknowledge the ill effects of complete inactivity and immobility during critical illness.
Inactivity and immobility have profound effects on skeletal muscle. Disuse leads to reduced protein synthesis, accelerated proteolysis, and increased apoptosis, ultimately resulting in a catabolic state, atrophy, and physical weakness. , In a study of young, healthy volunteers, 28 days of bedrest resulted in a 0.4 ± 0.1 kg loss of lean leg mass and a 22.9 ± 3.5% reduction in leg extension strength. When healthy volunteers were subjected to 28 days of bedrest and hydrocortisone to achieve plasma cortisol levels mimicking trauma or critical illness, leg extension strength decreased even further (28.4 ± 4.4%, P = .012), and the loss of lean leg mass was increased threefold compared with bedrest alone (1.4 ± 0.1 kg, P = .004). Therefore it is apparent that both immobility and the systemic effects of critical illness contribute to the development of weakness in ICU patients.
ICU-acquired weakness
Neuromuscular weakness is a common complication of critical illness. Approximately half of ICU patients with sepsis, multiorgan failure, or prolonged mechanical ventilation have electrophysiologic evidence of neuromuscular dysfunction. In patients with both sepsis and multiorgan failure, the incidence can approach 100%. Electrophysiologic (EP) testing can detect weakness as early as 18–24 hours into the onset of critical illness. , Clinical evidence of weakness is present in a smaller, but significant, portion of ICU patients. The duration of bedrest is associated with worsening muscle weakness. Muscle strength has been estimated to decrease by 3%–11% with each additional day. , Many ICU survivors continue to have significantly impaired physical function and decreased quality of life for years after their hospitalization. ,
One of the many causes of generalized weakness in the critically ill population is intensive care unit–acquired weakness (ICUAW), a clinical syndrome of acquired neuromuscular dysfunction with no identifiable causative factors other than critical illness and its treatment. ICUAW is an umbrella term for different pathophysiologic entities, including muscle atrophy, critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or a combination of polyneuropathy and myopathy called critical illness neuromyopathy (CINM). , The pathophysiology of ICUAW is complex and not well-understood; it includes the sequelae of bedrest and the effects of critical illness–induced cytokine production such as impaired microcirculation, metabolic derangements, increased protein catabolism, and changes in nerve and muscle membrane excitability.
Diagnosis
The lack of a gold-standard diagnostic test has made it difficult to study ICUAW. Diagnosis of the pathophysiologic entities of CIP, CIM, and CINM requires advanced and/or invasive testing; EP evidence of axonal polyneuropathy confirms the diagnosis of CIP, whereas either EP and/or histologic findings of myopathy are used to diagnose CIM. The Medical Research Council (MRC) muscle strength score is one of the most commonly used clinical evaluations of ICUAW. It involves grading the strength of different muscle groups in each extremity on a scale from 0 to 5. The MRC sumscore, initially developed to assess muscle strength in patients with Guillain-Barré syndrome, involves testing strength in six different muscle groups bilaterally and adding these 12 scores together. The result can range from 0 (paralysis) to 60 (normal strength), and the diagnosis of ICUAW requires a score less than 48. The MRC sumscore is nonspecific for ICUAW; therefore other causes of weakness in critical illness must be excluded. In addition, the MRC sumscore has many limitations in the critically ill, most notably the need for an awake, cooperative patient who is able to maximally contract all extremities.
Routinely performing EP studies and muscle biopsies on all at-risk patients presents an obvious challenge, and using manual strength testing requires active participation. Developing a single diagnostic test that could be used even on comatose patients would facilitate uniformity in study design and help determine the incidence, risk factors, and outcomes of ICUAW. Limited nerve conduction studies (NCS) and quantitative neuromuscular ultrasound have both been evaluated, and limited NCS in particular shows promise as a sole diagnostic tool. Peripheral muscle ultrasound may be able to detect muscle weakness and assist with early diagnosis, but further studies are needed to help standardize this technique. Because of the current lack of an effective therapeutic option, making the early diagnosis of ICUAW does not affect outcomes, and as such, routine use of EP studies or quantitative muscle ultrasound in the ICU has not become standard practice.
Risk factors
A number of risk factors have been implicated in the development of ICUAW. Some of the earliest and most frequently identified factors are related to severity of illness and include the systemic inflammatory response syndrome, sepsis, and multiorgan failure. , , The relationship between ICUAW and other factors, such as age, gender, corticosteroids, hyperglycemia, aminoglycosides, or neuromuscular blocking agents, is inconsistent. , , , , Few, if any, studies have examined whether prehospital factors such as frailty or poor functional status are associated with developing ICUAW. The presence of multiorgan failure as one of the most consistently associated risks lends support to the hypothesis that ICUAW may be another manifestation of multiple organ dysfunction syndrome (MODS). , ,
Implications
ICUAW increases the duration of mechanical ventilation, ICU and hospital lengths of stay (LOSs), healthcare–related costs, and mortality. , In addition, ICUAW is associated with significant long-term sequelae. As treatment of critical illness has improved, many more patients are surviving their acute illness but continue to suffer serious long-term effects, a phenomenon called post–intensive care syndrome (PICS). PICS includes new or worsened impairments in many areas that affect quality of life, including physical, mental, and social health. ICUAW is an important contributor to PICS. Patients with respiratory failure requiring mechanical ventilation who were living independently before ICU admission rarely return to this level of functioning at 6-month follow-up. Survivors of acute respiratory distress syndrome report poor functional status at 1 year after discharge despite normalization of their pulmonary function tests. Only 49% of such previously employed patients are able to return to work within 1 year of their critical illness as a result of muscle loss, weakness, and fatigue. Five years after ICU discharge, 100% of survivors reported subjective weakness and decreased exercise capacity compared with their status before ICU admission. Similarly, survivors of severe sepsis with no functional limitations before ICU admission developed significant limitations in their ability to perform activities of daily living and continued to develop functional limitations at a more rapid rate after hospital discharge.
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