Table of Contents  
Year : 2014  |  Volume : 7  |  Issue : 2  |  Page : 81-87

Intensive care unit-acquired weakness

Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission13-Nov-2013
Date of Acceptance12-Dec-2014
Date of Web Publication31-May-2014

Correspondence Address:
Amr M El-Said
Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Abbassia, Cairo 11566
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.133301

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ICU-acquired weakness (ICU-AW) represents a severe and frequent complication of critical illness. It is believed that ICU-AW can affect more than half of all ICU patients. This major neuromuscular complication of critical illness is associated with increased rates of morbidity and mortality, markedly affecting both short-term and long-term clinical outcomes in critically ill patients. This article aimed to review all available data about this common problem.

Keywords: Weakness, paralysis, muscle atrophy, ICU neurological complications

How to cite this article:
El-Said AM. Intensive care unit-acquired weakness. Ain-Shams J Anaesthesiol 2014;7:81-7

How to cite this URL:
El-Said AM. Intensive care unit-acquired weakness. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Dec 7];7:81-7. Available from:

  Introduction Top

ICU-acquired weakness (ICU-AW) represents a severe and frequent complication of critical illness; thus, intensivists worldwide are faced with various difficulties. It is believed that ICU-AW can affect more than half of all ICU patients [1]. This major neuromuscular complication of critical illness is associated with increased rates of morbidity and mortality, markedly affecting both short-term and long-term clinical outcomes in critically ill patients. The importance of ICU-AW is supported by the observation that muscle wasting and weakness are among the most prominent long-term complications of survivors of acute respiratory distress syndrome (ARDS). In addition, a strong association appears to exist between acquired weakness and protracted ventilator dependence, an important determinant of ICU length of stay [2]. By causing prolongation of ICU stay and rehabilitation, ICU-AW leads to an increased risk of secondary complications and places a higher demand on already limited resources of healthcare systems. ICU-AW is further associated with decreases in health-related quality of life, which may be impaired for years after ICU discharge [2].

  Clinical presentation Top

Patients with ICU-AW are usually identified in two bedside contexts. Most commonly, the clinician struggling to liberate a patient from mechanical ventilation will entertain the diagnosis of weakness. The second bedside context involves patients with severe weakness and unexpected problems with mobilization, despite return of sensorium, so that causes of quadriplegia are considered.

Physical examination of patients for ICU-AW is dependent on the cooperation and maximal effort of the patient, an aspect of bedside assessment that can be confounded by sedation, delirium, encephalopathy, and other ICU influences on cortical brain function. When a reliable motor examination is possible, affected patients will generally show symmetrical weakness and decreased tone in all limbs, ranging from paresis to true quadriplegia [3]. This primarily affects the lower limbs, but may extend to quadriplegia in more severe cases, explaining its previous terminology of acute quadriplegic myopathy. Earlier detection of ICU-AW is possible and can be made by assessment of voluntary maximum strength in ICU patients, either by hand dynamometry or according to the Medical Research Council (MRC) score [4]. Values of less than 11-kg force for men and less than 7-kg force for women at dominant-hand dynamometry have been described to identify ICU-AW in previously healthy individuals [5]. The MRC score includes formal testing of three muscle groups in each limb on a scale from 1 to 5 [Table 1] [6]. This scoring has shown excellent inter-rater reliability, including evaluations of patients with Guillain-Barré syndrome receiving mechanical ventilation [7], and can be utilized to document the extent of disease and track serial changes over time (assuming intact cognition).
Table 1: Medical Research Council scale for muscle examination [6]

Click here to view

An early clue that may be noted by care providers is that painful stimulation (such as pressure on the nail bed) results in a limited to absent limb response, yet normal grimacing. This finding highlights the usual sparing of weakness in the muscles innervated by cranial nerves. Limited information is obtained from the assessment of reflexes and the sensory examination. Reflexes are usually diminished or absent, but normal reflexes do not rule out the diagnosis. Sensory examination is often curtailed by patient sensorium, interaction with the examiner, and edema.

Once a weakness syndrome is suspected, the clinician must clearly establish the absence of a neuromuscular condition that began before admission to the ICU, whereas the patients' history usually indicates exposure to ICU-AW-associated risk factors (see below). Careful review of the premorbid functional status must be performed [8].

  Distinction between polyneuropathy and myopathy Top

As delirium and sedation are frequent in ICU patients, reliable bedside examination of neuromuscular function can be difficult. Given these obstacles, (early) studies of seemingly weak patients have relied on electrophysiologic testing to provide a rigorous description of underlying neuromuscular dysfunction. Comprehensive electrophysiologic studies including motor and sensory nerve conduction studies as well as needle electromyography in the upper and lower limbs defined two broad categories of ICU-AW: critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) [8].

In CIP, electrophysiologic testing usually shows sensorimotor axonopathy with decreased compound muscle action potential (CMAP) and sensory nerve action potential, yet normal nerve conduction velocities (assuming the absence of persistent neuromuscular blockade) [8]. Abnormalities may be detected as early as 48 h into critical illness [9]. Spontaneous muscle activity with fibrillation potentials can be detected in severe axonal disease.

An accompanying prolongation of the CMAP duration suggests an associated myopathy [10]. CIM is an acute primary myopathy (not secondary to muscle denervation) and is diagnosed by abnormalities of the electromyographic tracing during a voluntary contraction (requiring patient cooperation). The affected muscle shows a characteristic pattern of abundant low-amplitude, short-duration polyphasic units with early recruitment.

The definitive diagnosis of muscle involvement requires examination of muscle tissue by biopsy. The reported light-microscopic findings in specimens from CIM patients include muscle fiber atrophy (preferentially type II fibers), occasional fiber necrosis, regeneration, and decreased or absent reactivity in myofibrillar ATP staining, corresponding to a selective loss of myosin filaments. This selective loss of myosin is practically pathognomonic for CIM [11].

To overcome the challenges of patient cooperation and completely avoid muscle biopsy, the method of direct muscle stimulation has been evaluated and was intended to differentiate between CIM and CIP. Both conditions show reduced nerve-evoked CMAP amplitude, and yet, denervated muscle (as in CIP) should retain electrical excitability and the direct muscle stimulation CMAP amplitude should be normal. CIM patients should show loss of electrical excitability, and both nerve-stimulated and direct muscle-stimulated CMAPs should be reduced [12].

Significant overlap of CIP and CIM was noted, leading to the use of a new descriptive term critical illness polyneuromyopathy or critical illness myoneuropathy (CIPNM, CIMN), which is more frequent than previously considered and applies to ICU-AW patients with both neuropathy and myopathy [4]. Myopathy is likely to present the predominant feature of ICU-AW and has been shown to precede neuropathy in patients with CIMN, whereas additional polyneuropathy develops later and less frequently.

As critical care practice has evolved to a 'least sedation' model, it has been advocated using physical examination as the primary determinant of ICU-AW. Careful implementation of the structured MRC examination should be performed and documented serially as a matter of routine. Patients showing the characteristic examination combined with any evidence of recovery on serial examination usually require no further investigation. Patients with fixed or focal motor defects or persistent altered sensorium despite adequate sedation washout should undergo more advanced diagnostics (i.e. CNS imaging, electrophysiologic studies, and/or muscle biopsy) [Figure 1] [3].
Figure 1:

Click here to view

  Epidemiology Top

The occurrence of ICU-AW varies considerably depending on the patient case mix, diagnostic method used, and the timing of examination. De Jonghe et al. [13] found clinically significant ICU-AW in 25% of patients who received mechanical ventilation for at least 7 days. Of note, a considerable number of patients could not be evaluated by muscle strength testing, most commonly the result of death before regaining consciousness. Electrophysiologic testing to delineate CIP does not share similar limitations in the unresponsive patient, and has resulted in reports of higher incidences of acquired neuromuscular disease in similar cohorts. For example, a prospective study [14] of 50 patients receiving mechanical ventilation for more than 7 days documented CIP in 58%. Studies [15],[16] using cohorts restricted to sepsis and multiorgan failure have found even higher incidences of neuromuscular disease, ranging from 50 to 100%.

[TAG:2]Risk factors involved in intensive care

unit-acquired weakness[/TAG:2]

Although the exact molecular mechanisms contributing toward ICU-AW remain to be elucidated, five central risk factors of ICU-AW have been repeatedly reported [17]. Possibly, the most important risk factor complex comprises conditions leading to multiple organ failure, particularly severe sepsis and septic shock. Some authors actually consider ICU-AW an additional organ failure following severe sepsis and septic shock. The other four risk factors of ICU-AW involve muscle inactivity, disturbances in glucose metabolism resulting in hyperglycemia, administration of corticosteroids, and use of neuromuscular blocking agents (NMBAs) [Figure 2].
Figure 2:

Click here to view

Sepsis-induced muscle wasting and intensive care unit-acquired weakness

William Osler first commented on the 'rapid loss of flesh' that occurs with severe sepsis in 1892 [18]. Today, this phenomenon remains a frequent complication of critical illness - particularly sepsis - and is often referred to as ICU-AW. Sepsis-induced multiple organ failure has been identified as one of the primary risk factors for this major and frequent complication of critical illness [17]. Whereas ICU-AW is usually accompanied by muscle wasting, muscle wasting does not necessarily lead to neuromuscular dysfunction as overall muscle strength depends both on total muscle mass and force-generating capacity (force per cross-sectional area), which is affected in ICU-AW, but not necessarily in muscle wasting syndromes [19] [Figure 2].

It is unclear as to how systemic inflammatory response syndrome, sepsis, and multisystem organ dysfunction produce nerve and muscle injury; commonly invoked pathways include ischemia or injury by mediators of inflammation. De Letter et al. [20] have additionally showed evidence for low-level, local immune system activation with the release of both proinflammatory (interleukin-6 and tumor necrosis factor a) and anti-inflammatory cytokines in the muscle of patients with ICU-AW. Tissue injury may lead to the influx of inflammatory cells and the release of such cytokines. The expression of adhesion molecules on vascular endothelium suggests the possible contribution of increased vascular permeability.

Sepsis-associated muscle wasting

As mentioned above, muscle force capacity may remain stable in muscle wasting syndromes [19]. Muscle wasting can be triggered by conditions other than sepsis, including disuse, denervation, fasting, cancer, cardiac failure, and renal dysfunction. These conditions frequently coincide with sepsis as sepsis is often accompanied by prolonged bed rest/immobilization, application of sedatives, acute or chronic organ dysfunction, malignancy as an underlying disease, medication using glucocorticoids, and others.

An imbalance between muscle protein synthesis and muscle protein degradation causing net loss of muscle mass is considered to present the main mechanism of muscle atrophy in muscle wasting [19] [Figure 2].

Decreased muscle protein synthesis during sepsis

Animal models of sepsis clearly indicate that sepsis decreases protein synthesis in skeletal muscles [21] and preferentially inhibits myofibrillar and sarcoplasmatic protein synthesis within fast-twitch muscles [22].

One mechanism for decreased protein synthesis is impaired insulin/insulin-like growth factor 1 (IGF-1) signaling as decreased insulin sensitivity is a frequently observed complication of sepsis [23]. Further evidence for the contribution of impaired insulin signaling toward decreased protein synthesis comes from the observation that local IGF-1 application prevents sepsis-induced muscle atrophy [21], possibly by inhibition of sepsis-induced increases of muscle atrogin-1 and the proinflammatory cytokine interleukin-6 [24]. Nutritional aspects may contribute toward decreased muscle protein synthesis as well. Administration of the essential branched-chain amino acid leucine has been shown to increase protein synthesis in rat skeletal muscles during aging, exercise, or food deprivation [25]. However, under certain conditions, including sepsis, the muscle may be resistant to leucine-stimulated protein synthesis [21], although the exact mechanisms of sepsis-induced leucine resistance remain to be elucidated.

Increased muscle protein degradation during sepsis

Data from studies in animals and humans indicate an increase in sepsis-associated muscle protein degradation by several mechanisms, including the ubiquitin-proteasome system [26] and lysosomal systems [27]. Calcium-dependent nonlysosomal calpains and proapoptotic pathways (caspases) have also been associated with sepsis-induced muscle atrophy [28] as they are responsible for the cleavage of myofibrillar proteins preceding their proteasomal degradation [29]. Protein degradation by proteasomal and/or lysosomal systems may not be sepsis specific as various other conditions associated with muscle wasting share similar or identical pathways. During muscle wasting, defective insulin signaling may not only be involved in decreased muscle protein synthesis but also in increased muscle proteolysis [28].

Sepsis-induced myopathy

Three characteristics are commonly described in patients with CIM or CIMN [30]:

  1. Selective thick myosin filament loss.
  2. Predominant type II (fast-twitch) muscle fiber atrophy [Figure 3].
  3. Muscle membrane inexcitability.
Figure 3:

Click here to view

All three characteristics may result in different mechanisms leading to ICU-AW as loss of muscle mass (atrophy) correlates with decreased maximum force, thick filament loss represents an additional reduction of force-generating capacity by additional myofilament dysfunction, and nonexcitable muscle membrane may be considered as an incapability of the muscle to generate contraction-preceding action potentials. Less frequently described histological signs of CIM/CIMN include acute necrosis, regeneration as well as loss of myofibrillar ATPase staining [31], the latter affecting both type I and II muscle fibers.

Suggested subcellular abnormalities in sepsis-induced myopathy

A number of subcellular sites involved in excitation contraction coupling may be affected in sepsis-induced myopathy [19]. These include the sarcolemma, the sarcoplasmatic reticulum, the contractile apparatus, and the mitochondria. As described above, one of the key features of CIM/CIMN is that skeletal muscle becomes electrically inexcitable, which has led to the concept that CIM/CIMN could represent an acquired channelopathy involving dysregulation of sodium channels located at the sarcolemma. Altered calcium homeostasis has been observed in a number of studies on skeletal muscle during sepsis, with increases in calcium level in some subcellular compartments and decreases in others [19]. It is likely that free radical generation is involved in this mechanism as either a superoxide scavenger or an NO synthesis inhibitor significantly attenuated reduced endotoxin-induced force pCa relationships. Tumor necrosis factor α has been linked to decreases in titanic force generation because of changes in myofilament function as well [32]. A considerable amount of data indicate that sepsis also causes [19] decreased mitochondrial content and lower concentrations of energy-rich phosphates.


Bed rest and deep sedation have been found to potentiate ICU-AW [13]. However, repeated daily passive mobilization has prevented muscle atrophy on serial muscle biopsies in patients receiving mechanical ventilation and NMBAs [33]. Schweickert et al. [34] recently reported that patients receiving an ambitious protocol of early and determined mobilization were more frequently able to get out of bed, stand, and occasionally walk with assistance during mechanical ventilation, whereas standard regimens of physical therapy led to longer impairment in functional status and recovery time. Besides, early mobilization was associated with a shorter duration of delirium. In contrast, Eikermann et al. [35] showed that healthy patients undergoing limb immobilization did not show reductions in muscle force or fatigability. Seemingly, immobilization alone cannot create CIM.

Glycemic control

The link between elevated blood glucose levels and ICU-AW was established in a study [36] of critically ill patients with multisystem organ failure. More recently, a large randomized trial [37] of surgical patients undergoing tight glycemic control with insulin infusions versus conventional insulin therapy showed a 50% reduction in the evolution of CIP.


Many medications have been implicated as causes of weakness. Corticosteroids, the most widely studied [13], have a significant association with the development of ICU-AW. In animal models, administration of corticosteroids can produce selective muscle atrophy, particularly of fast-twitch fibers [38]. However, a thick filament myopathy identical to CIM can be best produced by combining denervation injury and corticosteroids [39]. Complete loss of muscle excitability was found, now ascribed to the inactivation of fast sodium channels [40]. This 'two-hit' hypothesis has been invoked to explain the profound forms of CIM described in patients with status asthmaticus. A recent prospective, randomized trial [41] of methylprednisolone for persistent ARDS showed no improvement in 60-day mortality despite evidence for early physiologic improvement of gas exchange and lung mechanics. The small numbers of patients with significant complications attributed to neuromyopathy were all in the methylprednisolone-treated arm. It is plausible that some benefits of corticosteroid treatment on lung function were offset by the adverse effects on strength.

Although De Jonghe et al. [13] identified corticosteroid administration as the strongest predictor for ICU-AW, data from a recent meta-analysis do not indicate a clear relationship between systemic levels of corticosteroids and myotoxic effects in patients with sepsis [42]. Development of steroid-induced myopathy may be dependent on the steroid doses applied, which is in line with findings that do not indicate an association between low-dose hydrocortisone application and impaired muscle membrane excitability - one of the key features in ICU-AW patients with predominant myopathy [43]. Yet, as this observation has to be confirmed by other groups, strict indication is still warranted considering low-dose hydrocortisone administration.

The association of neuromuscular weakness with prolonged use of NMBAs has long been recognized and is the most prominent reason for a shift away from NMBA use in the critically ill [44]. There are well-described scenarios of ICU-AW with these agents. One scenario is that of prolonged neuromuscular blockade arising from a persistent drug effect, such as that occurring with agents (or their metabolites) that accumulate in the setting of renal and liver failure. The second scenario involves patients with severe acute asthma and ventilatory failure who undergo treatment with high-dose corticosteroids in combination with NMBAs. These patients may show severe and protracted myopathy [45]. As firm conclusions on the specific deleterious effects of NMBAs are precluded, cautious use is still warranted [17].

  Prevention/treatment Top

Data supporting specific approaches to prevent or treat ICU-AW are limited. It has been advocated that the clinician seek potentially reversible risk factors and adjust care accordingly [Figure 4] [46].
Figure 4:

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The best evidence for prevention comes from a secondary end point of a trial of strict glycemic control by intensive insulin therapy (maintenance of a blood glucose level from 80 to 110 mg/dl) in critically ill surgical patients [37]. This management seems appropriate, assuming a careful implementation with safeguards against potentially injurious hypoglycemia. However, it seems reasonable that protocol-based glycemic control targeting prevention of excessive blood glucose levels and variability help reduce the incidence of ICU-AW [18].

Given the evidence for reduced muscle atrophy with passive limb muscle stretching [33], strategies to mobilize patients, either with passive stretching or with active exercises with physical and occupational therapy, seem reasonable when approached in a safe, systematic manner. At the least, sedation protocols designed to minimize the use of sedatives and analgesics have been shown to decrease the duration of mechanical ventilation [47]. This strategy may help to promote earlier patient wakefulness, minimize sedative-induced immobility, and enable earlier recognition of weakness with earlier mobilization as tolerated.

It is possible that additional electrical muscle stimulation (EMS) assists in preventing ICU-AW as studies indicate that EMS partially prevents muscle atrophy and improves muscle membrane excitability in critically ill patients [48] and mitigates increased proteasome activation besides stimulating IGF in patients after major abdominal surgery [49]. EMS can be initiated immediately after ICU admission and could facilitate faster mobilization progression.

Medications that may increase the risk of weakness should be reviewed carefully. Corticosteroids should be used with caution, if at all, under circumstances in which benefit is obscure, such as late-phase ARDS [41]. Also, cautious use of NMBAs is still warranted [17].

It also seems prudent to maintain the internal milieu of the patient, with a focus on electrolyte disorders, including phosphate and magnesium depletion. Although not proven, adequate nutrition supplementation seems a necessity as the body will otherwise cannibalize muscle for sources of energy. Finally, standardized approaches to ventilator weaning, such as a respiratory therapist-driven protocol, must be used to minimize the duration of ventilator dependence [50].

  Acknowledgements Top

Conflicts of interest

None declared.

  References Top

1.Vincent J, Norrenberg M. Intensive care unit-acquired weakness: framing the topic. Crit Care Med 2009; 37:S296-S298.  Back to cited text no. 1
2. Herridge MS. Long-term outcomes after critical illness. Curr Opin Crit Care 2002; 8:331-336.  Back to cited text no. 2
3. De Jonghe B, Sharshar T, Hopkinson N, et al. Paresis following mechanical ventilation. Curr Opin Crit Care 2004; 10:47-52.  Back to cited text no. 3
4. Stevens RD, Marshall SA, Cornblath DR, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Crit Care Med 2009; 37:S299-S308.  Back to cited text no. 4
5. Latronico N, Rasulo FA. Presentation and management of ICU myopathy and neuropathy. Curr Opin Crit Care 2010; ■:■-■.  Back to cited text no. 5
6. Kleyweg RP, van der Meche FG, Meulstee J. Treatment of Guillain-Barré syndrome with high-dose g-globulin. Neurology 1988; 38:1639-1641.  Back to cited text no. 6
7. Kleyweg RP, van der Meche FG, Schmitz PI. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve 1991; 14:1103-1109.  Back to cited text no. 7
8. Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005; 32:140-163.  Back to cited text no. 8
9. Tennila A, Salmi T, Pettila V, et al. Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med 2000; 26:1360-1363.  Back to cited text no. 9
10.1Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000; 23:1785-1788.  Back to cited text no. 10
11.1Stibler H, Edstrom L, Ahlbeck K, et al. Electrophoretic determination of the myosin/actin ratio in the diagnosis of critical illness myopathy. Intensive Care Med 2003; 29:1515-1527.  Back to cited text no. 11
12.1Lefaucheur JP, Nordine T, Rodriguez P, et al. Origin of ICU acquired paresis determined by direct muscle stimulation. J Neurol Neurosurg Psychiatry 2006; 77:500-506.  Back to cited text no. 12
13.1De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002; 288:2859-2867.  Back to cited text no. 13
14.1Leijten FS, Harinck-de Weerd JE, Poortvliet DC, et al. The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation. JAMA 1995; 274:1221-1225.  Back to cited text no. 14
15.1Berek K, Margreiter J, Willeit J, et al. Polyneuropathies in critically ill patients: a prospective evaluation. Intensive Care Med 1996; 22:849-855.  Back to cited text no. 15
16.1De Jonghe B, Cook D, Sharshar T, et al. Acquired neuromuscular disorders in critically ill patients: a systematic review. Groupe de Reflexion et d′Etudesur les Neuromyopathies En Reanimation. Intensive Care Med 1998; 24:1242-1250.  Back to cited text no. 16
17.1DeJonghe B, Lacherade J, Sharshar T, Outin H. Intensive care unit-acquired weakness: risk factors and prevention. Crit Care Med 2009; 37:S309-S315.  Back to cited text no. 17
18.1Schefold JC, Bierbrauer J, Weber-Carstens S. Intensive care unit-acquired weakness (ICUAW) and muscle wasting in critically ill patients with severe sepsis and septic shock. J Cachexia Sarcopenia Muscle 2011; 2:147-157.  Back to cited text no. 18
19.1Callahan LA, Supinski GS. Sepsis-induced myopathy. Crit Care Med 2009; 37:S354-S367.  Back to cited text no. 19
20.2De Letter MA, van Doorn PA, Savelkoul HF, et al. Critical illness polyneuropathy and myopathy (CIPNM): evidence for local immune activation by cytokine-expression in the muscle tissue. J Neuroimmunol 2000; 106:206-213.  Back to cited text no. 20
21.2Lang CH, Frost RA, Vary TC. Regulation of muscle protein synthesis during sepsis and inflammation. Am J Physiol Endocrinol Metab 2007; 293:E453-E459.  Back to cited text no. 21
22.2Vary TC, Kimball SR. Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles. Am J Physiol 1992; 262:C1513-C1519.  Back to cited text no. 22
23.2Zauner A, Nimmerrichter P, Anderwald C, et al. Severity of insulin resistance in critically ill medical patients. Metabolism 2007; 56:1-5.  Back to cited text no. 23
24.2Frost RA, Nystrom GJ, Jefferson LS, Lang CH. Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle. Am J Physiol Endocrinol Metab 2007; 292:E501-E512.  Back to cited text no. 24
25.2Sugawara T, Ito Y, Nishizawa N, Nagasawa T. Supplementation with dietary leucine to a protein-deficient diet suppresses myofibrillar protein degradation in rats. J Nutr Sci Vitaminol 2007; 53:552-555.  Back to cited text no. 25
26.2Klaude M, Fredriksson K, Tjäder I, et al. Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis. Clin Sci 2007; 112:499-506.  Back to cited text no. 26
27.2Voisin L, Breuillé D, Combaret L, et al. Muscle wasting in a rat model of long-lasting sepsis results from the activation of lysosomal, Ca 2+ -activated, and ubiquitin-proteasome proteolytic pathways. J Clin Invest 1996; 97:1610-1617.  Back to cited text no. 27
28.2Zhao J, Brault JJ, Schild A, et al. FoxO 3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 2007; 6:472-483.  Back to cited text no. 28
29.2Du J, Wang X, Miereles C, et al. Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 2004; 113:115-123.  Back to cited text no. 29
30.3Larsson L, Li X, Edström L, et al. Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels. Crit Care Med 2000; 28:34-45.  Back to cited text no. 30
31.3Showalter CJ, Engel AG. Acute quadriplegic myopathy: analysis of myosin isoforms and evidence for calpain-mediated proteolysis. Muscle Nerve 1997; 20:316-322.  Back to cited text no. 31
32.3Hardin BJ, Campbell KS, Smith JD, et al. TNF-alpha acts via TNFR1 and muscle-derived oxidants to depress myofibrillar force in murine skeletal muscle. J Appl Physiol 2008; 104:694-699.  Back to cited text no. 32
33.3Griffiths RD, Palmer TE, Helliwell T, et al. Effect of passive stretching on the wasting of muscle in the critically ill. Nutrition 1995; 11:428-432.  Back to cited text no. 33
34.3Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373:1874-1882.  Back to cited text no. 34
35.3Eikermann M, Koch G, Gerwig M, et al. Muscle force and fatigue in patients with sepsis and multiorgan failure. Intensive Care Med 2006; 32:251-259.  Back to cited text no. 35
36.3Witt NJ, Zochodne DW, Bolton CF, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 1991; 99:176-184.  Back to cited text no. 36
37.3Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345:1359-1367.  Back to cited text no. 37
38.3Kelly FJ, McGrath JA, Goldspink DF, et al. A morphological/biochemical study on the actions of corticosteroids on rat skeletal muscle. Muscle Nerve 1986; 9:1-10.  Back to cited text no. 38
39.3Rouleau G, Karpati G, Carpenter S, et al. Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers. Muscle Nerve 1987; 10:428-438.  Back to cited text no. 39
40.4Rich MM, Pinter MJ. Crucial role of sodium channel fast inactivation in muscle fibre inexcitability in a rat model of critical illness myopathy. J Physiol 2003; 547:555-566.  Back to cited text no. 40
41.4Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671-1684.  Back to cited text no. 41
42.4Stevens RD, Dowdy DW, Michaels RK, et al. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med 2007; 33:1876-1891.  Back to cited text no. 42
43.4Weber-Carstens S, Deja M, Koch S, et al. Risk factors in critical illness myopathy (CIM) during the early course of critical illness: a prospective observational study. Crit Care 2010; 14:R119.  Back to cited text no. 43
44.4Garnacho-Montero J, Madrazo-Osuna J, Garcia-Garmendia JL, et al. Critical illness polyneuropathy: risk factors and clinical consequences: a cohort study in septic patients. Intensive Care Med 2001; 27:1288-1296.  Back to cited text no. 44
45.4Behbehani NA, Al-Mane F, D′Yachkova Y, et al. Myopathy following mechanical ventilation for acute severe asthma: the role of muscle relaxants and corticosteroids. Chest 1999; 115:1627-1631.  Back to cited text no. 45
46.4Schweickert WD, Hall J. ICU-acquired weakness. Chest 2007; 131:1541-1549.  Back to cited text no. 46
47.4Kress JP, Pohlman AS, O′Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471-1477.  Back to cited text no. 47
48.4Gerovasili V, Stefanidis K, Vitzilaios K, et al. Electrical muscle stimulation preserves the muscle mass of critically ill patients: a randomized study. Crit Care 2009; 13:R161.  Back to cited text no. 48
49.4Strasser EM, Stättner S, Karner J, et al. Neuromuscular electrical stimulation reduces skeletal muscle protein degradation and stimulates insulin-like growth factors in an age- and current-dependent manner: a randomized, controlled clinical trial in major abdominal surgical patients. Ann Surg 2009; 249:738-743.  Back to cited text no. 49
50.5Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335:1864-1869.  Back to cited text no. 50


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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