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  Survivorship from critical illness may include substantial neuromuscular weakness that can persist for many years following the index hospitalization.

  
  
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  Immobility can commonly accompany supportive care. Understanding the effects of bed rest and immobility on muscle, heart, and nervous system is necessary to balance the risks and benefits of early mobilization.

  
  
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  Early physical therapy can be performed safely despite ongoing critical illness.

  
  
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  Alternative strategies for mobilization include cycle ergometry and neuromuscular stimulation.

  
  
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  Successful early mobility programs include criteria for safe mobilization, which focus on the neurologic, cardiovascular, and pulmonary criteria.

In the last quarter century, research developments have led to improvements in diagnosis and resuscitation of critically ill patients, particularly those undergoing mechanical ventilation (MV).^1-4 With these improvements, survival for many populations of critically ill patients has increased.^4-7 Accordingly, intensive care unit (ICU) outcomes research has expanded, documenting substantial morbidity in survivors. ICU-acquired weakness is a common problem following critical illness and is associated with prolonged hospitalization, delayed weaning, and increased mortality.^8-10 Up to 25% of patients requiring MV for greater than 7 days develop ICUAW,¹¹ and a systematic review of 24 studies including patients with sepsis, multiorgan failure, or prolonged MV identified neuromuscular dysfunction in 46% of patients.⁹ Furthermore, long-term follow-up studies of survivors of critical illness have demonstrated significantly impaired health-related quality of life and physical functioning up to 5 years after ICU discharge, with weakness being the most commonly reported physical limitation.^12,13

Factors such as systemic inflammation, medications (particularly corticosteroids), electrolyte disturbances, and immobility have been implicated in the pathogenesis of ICU-AW.^14,15 Although no one has systematically measured immobility during ICU care, clinicians acknowledge its presence during the earliest days of critical illness, particularly during deep sedation or neuromuscular blockade, specific MV strategies (eg, prone ventilation), and other advanced support (eg, continuous hemodialysis).

Rest is necessary for the natural repair of weakened or damaged tissue and remodeling of muscle. Bed rest is most often accompanied by sleep, a process necessary for normal neurologic, immune, and endocrine function. The average person rests for 6 to 9 hours per day during sleep and shorter periods of rest may occur at other times. When people are ill, they often sleep and rest for longer periods.¹⁶

Prolonging rest has the potential for several benefits during general illness. For the injured body part, rest may avoid pain. By avoiding unnecessary exertion, metabolic resources may be maximally utilized for healing. During critical illness, reducing oxygen consumption by muscles may help preferentially deliver oxygen to injured or hypoxic organ systems. Similarly, in patients with respiratory failure, oxygen requirements and minute ventilation needs may be reduced. For hypertensive patients, rest may lower blood pressure, potentially preventing myocardial ischemia and dysrhythmias. Finally—and perhaps the most common reason for prescribed bed rest in the hospital—confinement to bed reduces the risk of harmful falls in delirious and weak patients.

Investigations have only found a few select studies demonstrating benefits from bed rest. For example, women with preeclampsia had reduced fetal complications when prescribed bed rest.¹⁷ Additionally, bleeding complications after cardiac catheterization and liver biopsy were reduced with short-term bed rest following the procedure.^18-20 However, the therapeutic value of sustained bed rest is questionable. Trials of rheumatoid arthritis, low back pain, uncomplicated myocardial infarction, pulmonary tuberculosis, and deep venous thrombosis have demonstrated improved outcomes when bed rest was limited or avoided.²¹ Physical activity has beneficial effects on organ and system function; sustained rest prevents these benefits and risks serious complications.

Experimental models of prolonged physical inactivity include space flight, immobilization of a limb, lower limb suspension, and bed rest.²² Such experiments carefully controlling activity—modeled in both human and animal research—yield consistent results. Muscle mass, as assessed by computed tomography and magnetic resonance imaging, decreases by approximately 1.5% to 2.0% per day during the first 2 to 3 weeks of enforced rest. Although total numbers of muscle fibers seem to remain unchanged as a result of immobilization, reductions in the cross-sectional area of the individual muscle fibers, changes in the satellite cells, and alterations in the distribution and size of the capillaries and connective tissue occur. Antigravity muscles have been observed to lose contractile proteins, particularly the Type I fibers of myofilaments, with a corresponding increase in noncontractile tissue content, including collagen.

Various measures of muscle strength demonstrate weakness that parallels the changes in muscle size. For example, maximal knee extensor contraction was reduced by approximately 15% after 14 days of bed rest.²³ Another measure, knee extensor strength, was reduced by 22% after 14 days and by 53% after 28 days of limb immobilization.^24,25 Limb casting models of immobilization suggest that the decline may be more significant, reaching as high as 5% to 6% per day.^28,29 For the recumbent critically ill patient, the antigravity muscle groups—located in the legs, trunk, and neck which function primarily to support the body—are particularly “rested.” Accordingly, muscle atrophy with protracted rest is more consistent and probably greatest in these muscles.

Loss of joint range of motion (ROM) occurs when the joints are not subjected to normal mobility and stress. Immobility leads to synovial fluid stasis and resultant increased intra-articular fluid volume and pressure. Heightened tension, pain, and decreased ROM ensue. Most ICUs are vigilant for this complication, and various measures to prevent contractures—such as ROM exercises and splinting—can prevent or reduce contractures. However, one study of survivors of a 2-week or longer critical illness found that joint contractures were identified in 61 of 155 patients.³⁰ At the time of discharge from intensive care, 34% of patients had at least one functionally significant contracture, and 23% of patients had functionally significant contractures persisting at the time of discharge home. The most commonly affected joints at the time of discharge home were the elbow (34%) and ankle (33%).

Skin ulcers are a well-recognized phenomenon of bed immobilization and can serve as a portal of entry for bacteria. Breakdown occurs at points of pressure between the skin and bed. Unrelieved pressure combines with impaired microcirculation, malnutrition, shear force, and humidity to result in skin ulcers. Furthermore, elevation of the head of the bed to reduce aspiration and ventilator-acquired pneumonia causes greater pressure at the skin-bed interface in the sacral region.^31,32 Frequent shifts of body position are preventive.

Lung compliance is reduced substantially during immobilization in the supine position. The diaphragm shifts cephalad and combines with the dorsal shift of the heart from the force of gravity, results in partial or complete atelectasis of the left lower lobe within 48 hours of recumbency in critically ill patients. Additional atelectasis in other dependent lung regions is frequently apparent on computed tomography. This atelectasis may predispose to pneumonia, raise pulmonary vascular resistance, and yield intrapulmonary shunt that may increase oxygen requirements.

Bed rest is an important risk factor for thromboembolic disease. Thrombosis culminates from impaired blood flow, vascular injury, and coagulopathy (Virchow triad). Blood flow through extremities varies with activity of muscles; therefore, inactivity may result in venous stasis. Furthermore, compression of veins from prolonged contact of limbs with the bed may also worsen stasis and potentially damage the vascular endothelium.

More indolent effects include endocrinopathy and vascular dysfunction. Studies of healthy volunteers undergoing 5 to 7 days of bed rest demonstrated that insulin resistance occurs within days of beginning bed rest.³³ The mechanism is unknown, but the effect is postulated to be limited to skeletal muscle.³⁴ Interestingly, insulin resistance occurs commonly in critically ill patients who have no prior history of diabetes and insulin therapy in critically ill patients has been correlated with improved neuromuscular outcomes.^35-37 Other metabolic derangements of bed rest measured in healthy subjects include increases in total cholesterol and triglycerides.³³

The cardiovascular effects of deconditioning occur on both heart tissue as well as the peripheral cardiovascular system. Orthostatic intolerance is commonplace and believed to be the result of a baroreceptor dysfunction. Studies implicate that systemic vascular resistance increases after bed rest. For example, hyperemic responses in normal subjects were significantly blunted after 3 to 5 days of bed rest, brachial artery diameter decreased significantly and was associated with significantly decreased brachial artery flow and increased systolic blood pressure. The significance of these findings to critically ill patients is unclear; however, critically ill patients frequently experience complications that may result from such vascular dysfunction.

Mobility has been recognized as a component of primary, secondary, and tertiary prevention of overall disease morbidity and mortality. Early ambulation was first introduced for inpatients during World War II in an effort to expedite the recovery of soldiers for return to the battlefield.³⁸ Since then, early mobilization has yielded improved outcomes in such varied conditions as community acquired pneumonia to orthopedic surgery. Given the known morbidity of ICU survivorship, clinical researchers have targeted the avoidance of bed rest as a potential opportunity to affect the quality of life for survivors. These trials highlight that early exercise and mobilization is possible to conduct despite ongoing critical illness. Although most investigations have focused selectively on patients undergoing MV, the results are likely generalizable to broader populations of critically ill patients.

The proposed goal of passive ROM exercise is to preserve of the range of the joint. Motion studies of the knee using radiolabeled tracers demonstrated that synovial fluid clearance rates can be increased under conditions of passive motion.³⁹ Simple joint motion creates fluctuations in intra-articular pressure and avoids fluid stasis. In critical care practice, periodic passive ROM exercises is an expectation of the bedside nurse, yet may be a necessary intervention by the physical therapist for the patient unable to engage in activity.

Technically, passive ROM differs from what is described as a prolonged muscle stretch. A prolonged muscle stretch usually implies holding a muscle or group of muscles in a lengthened position for a period. The purpose of “splinting” a joint follows from this notion that passive muscle stretch leads to maintenance of both the joint and muscle’s baseline range.

The evidence to support the use of passive movements as part of a program of early mobilization is weak. The limited evidence suggests that passive movements may prevent protein degradation, maintain muscle mass, and alter the inflammatory profile in humans. For example, in 20 subjects with severe sepsis or septic shock randomized to 30 minutes of predominantly passive exercise or no intervention, the passive exercise group preserved fat-free mass, decreased IL-6 and increased IL-10 levels compared with control patients who lost 7% of fat-free mass in the first 7 days following admission to the ICU.⁴⁰

One study examined whether muscle wasting in critically ill patients could be prevented with stretching alone. Continuous passive motion, administered by a machine, for 3-hour sessions was applied over 7 days to one leg of five separate critically ill adults.⁴¹ Both lower extremities received the usual passive ROM exercises from physiotherapists twice daily for up to 5 minutes. Percutaneous needle biopsies of both legs were obtained at baseline and after 7 days. In the muscles that received continuous passive stretch, there was less reduction in muscle fiber cross-sectional area and protein per gram of wet muscle weight over the 7 days compared with the muscles that did not receive continuous passive stretch. Clinical observation, however, suggests that more than simple passive movement should be done in order to help preserve muscle strength.

BARRIERS TO ACTIVE RANGE OF MOTION

The primary purpose of physical therapy in the ICU is to engage the alert patient, commence active ROM, and progress activity from bed exercises to transfers and early ambulation. However, early physical therapy—or early mobility—in critically ill patients is a complex and effort-intensive therapy, made more challenging by the presence of multiple barriers that impede broad uptake. These barriers include sedation and ventilation practices, concern regarding patient safety and physiological stability, inadequate staff to deliver physical therapy, and lack of equipment.

Physical therapy is feasible only if the patient is awake and cooperative. For the mechanically ventilated patient, the use of sedation and analgesia needs to be titrated to the least necessary dose to foster interaction while maintaining comfort. Studies of sedation and analgesia assessment tools, agents, and administration protocols have substantially changed clinical care. Patients are targeted for more awake levels and improved outcomes have been demonstrated with nurse-directed titration of drug, early transition to intermittent drug administration, and daily interruption of sedative infusions.⁴² As patients have become more interactive, the commonality of ICU delirium is exposed. Early physical therapy may help minimize such delirium, working through mechanisms of sedative minimization and fostering more sleep. The use of physical exertion to calm the agitated patient—in lieu of drug administration—may be an underlying mechanism; however, this inquiry remains incomplete.