Physiotherapy 93 (2007) 151–156

Review

Critical illness polyneuropathy and myopathy: a review of evidence and the implications for weaning from mechanical ventilation and rehabilitation Emily Ricks ∗ Physiotherapy Department, East Surrey Hospital, Canada Avenue, Redhill, Surrey RH1 5RH, UK

Abstract Critical illness polyneuropathy is the most commonly occurring neuromuscular dysfunction on the intensive care unit, and is often described in conjunction with critical illness myopathy. Both conditions are significant causes of weakness, increased length of stay, delayed weaning and prolonged rehabilitation. Sepsis, systemic inflammatory response syndrome and multi-organ dysfunction syndrome are the most reliable independent risk factors. The current evidence regarding critical illness polyneuropathy and critical illness myopathy is reviewed; in particular, the implications for weaning and rehabilitation. © 2006 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved. Keywords: Critical illness polyneuropathy; Critical illness myopathy; Weaning; Physiotherapy

Introduction It is widely recognised that patients admitted to the intensive care unit often develop subsequent difficulties with neuromuscular function [1,2]. These difficulties can manifest as delayed weaning due to respiratory muscle weakness, prolonged mechanical ventilation, and delayed progress with rehabilitation owing to limb weakness [3,4]. A longer period of dependency on support and rehabilitation services results in an increase in length of hospital stay, both of which have significant cost implications [2]. Although advancements in critical care have led to greater survival, they have also led to longer periods of support on the intensive care unit for those who are most seriously ill [5]. Consequently, the incidence (or detection) of acquired neuromuscular disorders has increased. Many authors agree that the most commonly occurring of these disorders is critical illness polyneuropathy [2,3,6–8]. Critical illness myopathy is often described as a common and significant cause of weakness on intensive care, either independently or co-existing with critical illness polyneuropathy. ∗

Tel.: +44 1737 231688; fax: +44 1737 231843. E-mail addresses: [email protected], [email protected].

This narrative review was undertaken using the OVID database, with search dates limited to 1995–2005. The search terms used were ‘critical illness polyneuropathy’, ‘critical illness myopathy’, ‘weaning’, ‘physiotherapy’ and ‘rehabilitation’.

Definitions Critical illness polyneuropathy and critical illness myopathy have been described separately and in combination. Bolton et al. [9] have defined critical illness polyneuropathy as ‘characterised by primary axonal degeneration of motor and sensory nerve fibres, accompanied by degeneration of skeletal muscles as a result of their denervation’. Some authors state that the distribution of critical illness polyneuropathy is predominantly to the motor nerves [6,10] and even more specifically in the terminal motor axons [11], but there is some disagreement [8,12]. Myopathy has been classified variably. Lacomis et al. [13] used the term critical illness myopathy to describe a group of myopathies, which commonly occur on the intensive care unit, including acute quadriplegic myopathy, thick filament myopathy and acute necrotising myopathy of intensive care. Latronico et al. [5] define critical illness myopathy

0031-9406/$ – see front matter © 2006 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.physio.2006.09.005

152

E. Ricks / Physiotherapy 93 (2007) 151–156

as ‘an acute primary myopathy causing muscle weakness and paralysis in critically ill patients’. In the latter, critical illness myopathy is the primary problem, rather than being secondary to muscle denervation. Many authors describe critical illness polyneuropathy and critical illness myopathy as co-existing, and the terms polyneuromyopathy [14] and critical illness polyneuromyopathy [1] have been used to acknowledge this. In the extreme, the most general term used is critical illness weakness [14], which describes the clinical observation.

Incidence The reported incidence of critical illness polyneuropathy or critical illness myopathy varies owing to patient selection, diagnostic criteria and the timing of examination. Studies using sepsis, systemic inflammatory response syndrome or multi-organ dysfunction syndrome as inclusion criteria show a higher percentage of patients developing critical illness polyneuropathy (50–80%) [5,6,15–17], but studies which exclude this selection bias report a lower incidence (1–58%) [3,18,19]. Critical illness myopathy has been reported at a lower incidence (0.09–7.0%) [5].

Pathophysiology Critical illness polyneuropathy and critical illness myopathy may have a very similar clinical presentation. The most commonly described symptoms are severe, general weakness [20], failure to wean from mechanical ventilation and, specifically in the presence of critical illness polyneuropathy, sensory defects [21,22]. In the longer term, prolonged rehabilitation is a reported feature [16]. The precise mechanism of nerve and muscle injury is not known [3]. Critical illness polyneuropathy is caused by axonal degeneration of both the motor and sensory nerve fibres, predominantly to the peripheral nerves [11] with sparing of the cranial nerves and autonomic functions [8]. The myelin sheath remains intact and there are no inflammatory changes on biopsy [23]. It has been proposed that the peripheral nerves are adversely affected by a change in their microcirculation as a result of sepsis [24]. Critical illness myopathy can be identified histologically. Muscle fibre atrophy, without muscle necrosis or inflammatory changes, can be seen to affect predominantly type II muscle fibres. The number of muscle units remains normal, but the myopathic injury results in reduced muscle action potentials [25]. The spectrum of acquired neuromuscular disorders on the intensive care unit is significant. With such similar clinical features, critical illness polyneuropathy and critical illness myopathy may be misdiagnosed, or may co-exist to include either condition predominantly [1,15]. It is these patients that would most suit a description of critical illness polyneu-

romyopathy, but it is also vital to exclude other causes of weakness on intensive care, such as muscle wasting due to catabolism.

Risk factors The causes of critical illness polyneuropathy and critical illness myopathy have not yet been established. Sepsis and systemic inflammatory response syndrome are associated with a disturbance of microcirculation throughout the body, including the peripheral nervous system, leading to axonal damage. The release of inflammatory mediators during sepsis/systemic inflammatory response syndrome may increase the permeability of the capillaries, allowing the passage of toxic substances (e.g. neuromuscular-blocking agents, corticosteroids, certain antibiotics), which may have a detrimental effect on the nerves [6,15]. In a prospective study of 98 patients on mechanical ventilation, it was found that systemic inflammatory response syndrome was a significant, independent risk factor for the development of critical illness polyneuromyopathy [3], and other studies support this hypothesis [1,10,26]. Multi-organ dysfunction syndrome (occasionally referred to as multi-organ failure), is also a significant risk factor for the development of critical illness polyneuropathy and critical illness myopathy [16–18,23]. Multi-organ dysfunction syndrome has been defined as the presence of two or more organ dysfunctions [15]. It is acknowledged that the mechanism by which multi-organ dysfunction syndrome leads to critical illness polyneuropathy and critical illness myopathy remains unknown [3,11]. de Letter et al. [21] chose to use the Acute Physiology and Chronic Health Evaluation III (APACHE III) score to reflect the extent of multiple organ dysfunction in the critically ill patient rather than a direct diagnosis of multi-organ dysfunction syndrome. Their results showed that a high APACHE III score is also an independent risk factor for critical illness polyneuromyopathy. The use of neuromuscular-blocking agents such as vecuronium has been associated with critical illness polyneuropathy and critical illness myopathy [7,10,11]. Prospective studies [16,21] have found to the contrary. The administration of neuromuscular-blocking agents often coincides with the development of critical illness polyneuropathy or critical illness myopathy, but is not an independent risk factor. It may be more likely that this association reflects the greater use of neuromuscular-blocking agents with the most severely ill patients. Aminoglycosides have been cited as a risk factor [1,15], but have not been shown to be an independent risk factor [16,21]. However, it is hypothesised that they may adversely affect axons in the hyperpermeable state associated with sepsis [6]. Other factors are often identified as risk factors for critical illness polyneuropathy and critical illness myopathy. How-

E. Ricks / Physiotherapy 93 (2007) 151–156

153

ever, as with length of intensive care stay, many of these are associated with severely unwell patients who are more likely to have sepsis, systemic inflammatory response syndrome or multi-organ dysfunction syndrome, for example, corticosteroids, neurological failure [15], malnutrition, prolonged mechanical ventilation [3], overfeeding [2] and vasopressor support [10]. The evidence suggests that sepsis, systemic inflammatory response syndrome and multi-organ dysfunction syndrome are the most reliable independent risk factors for the development of critical illness polyneuropathy and critical illness myopathy.

The results of diagnostic tests will be mixed if critical illness polyneuropathy and critical illness myopathy co-exist. Authors debate the value of electrophysiological studies in the management and outcome of critical illness polyneuropathy and critical illness myopathy [5,16]. Electrophysiological signs of critical illness polyneuropathy/critical illness myopathy may not necessarily correlate with clinical signs, which may result in a diagnosis of critical illness polyneuropathy or critical illness myopathy in a patient with little or no demonstrable weakness. Diagnosis will allow a more accurate prognosis for survivors, but may add little to the management of the patients.

Diagnosis

Medical management, prognosis and outcome

Critical illness polyneuropathy and critical illness myopathy have been diagnosed on clinical features, but there are other tests which can establish a more definite diagnosis and differentiate critical illness polyneuropathy and critical illness myopathy from other causes of weakness on the intensive care unit. Electrophysiological studies provide useful information about the nature and extent of nerve injury. As critical illness polyneuropathy is an axonal neuropathy, the reduction in the number of nerve fibres causes a reduced nerve action potential [5]. The myelin sheath is preserved, therefore, the conduction velocity is not reduced [10]. This differentiates critical illness polyneuropathy from, for example, Guillain–Barr´e syndrome, in which demyelination results in reduced conduction velocity, but nerve action potentials remain normal [27]. Electromyography can indicate neuromuscular dysfunction through abnormal spontaneous activity [6,11]. Unfortunately, differentiation between myopathy and neuropathy requires some amount of voluntary effort from the patient [25], which is often not possible with critically ill patients receiving sedation or those with impaired neurological status. Magnetic stimulation has been discussed as a method of examining neuromuscular function that can be carried out on uncooperative patients, particularly in relation to the diaphragm [5,10]. Nerve biopsy is not a recommended diagnostic tool due to the nerve damage which results. In the presence of critical illness polyneuropathy, reported abnormalities include primary axonal degeneration (greater distally) and an intact myelin sheath. The results of nerve biopsy are not always consistent with electrophysiological studies [10]. Muscle biopsy is less damaging than nerve biopsy. Type II fibre atrophy may be observed if innervation loss is the primary problem (critical illness polyneuropathy). When diagnosing weakness in the intensive care unit, it is essential to consider other potential causes, including those which are present before intensive care admission [6]. Weakness acquired on intensive care may be due to muscle atrophy or the administration of neuromuscular-blocking agents.

Treatment of the underlying cause of critical illness polyneuropathy and critical illness myopathy is said to be the most effective management [1,3,8,10,15,18,21]. Several authors have associated the severity of critical illness polyneuropathy with prognosis, but no scale of severity for critical illness polyneuropathy is described. Mild to moderate critical illness polyneuropathy may resolve completely within weeks, while patients with severe critical illness polyneuropathy may take months to recover, possibly not fully, facing a greater length of intensive care and hospital stay, and even a higher mortality [1,3,6]. However, GarnachoMontero et al. [15] found no evidence that critical illness polyneuropathy causes increased mortality, suggesting that the greater severity of illness which precipitates critical illness polyneuropathy is the cause of the increased mortality. Investigators suggest that 50% of patients with critical illness polyneuropathy make a complete recovery [10,12], but it is noted that chronic weakness may still be apparent up to 5 years after discharge from the intensive care unit [3]. The recognition and diagnosis of critical illness polyneuropathy and critical illness myopathy is a prognostic indicator for critically ill patients [11]. Exclusion of other neuromuscular dysfunctions can allow more focused counselling for the patient and their family, and allows the health care team to predict with greater accuracy what level of care a patient may need and for how long [6]. Both qualitative and quantitative measures have been used to describe the outcome of patients with critical illness polyneuropathy, while the outcome for critical illness myopathy specifically is seldom reported [7,22]. Fletcher et al. [7] used various quantitative outcome measures in a study of patients with long-term intensive care unit stays, including clinical examination, a disability index and electrophysiological studies. Zifko [22] used a qualitative quality-of-life tool with patients diagnosed with critical illness polyneuropathy. However, the tool used was one specifically designed for use with stroke patients. A generalised quality-of-life tool may yield more meaningful results in the absence of one designed for critical illness polyneuropathy or critical illness myopathy.

154

E. Ricks / Physiotherapy 93 (2007) 151–156

Implications for weaning Failure to wean is often one of the initial clinical signs of critical illness polyneuropathy and critical illness myopathy. Reintubation and failure to wean are both associated with increased intensive care morbidity and mortality [28,29]. It is first necessary to exclude other causes of delayed wean, such as a previous history of chronic obstructive pulmonary disease, smoking, cardiac dysfunction and a very high or low body mass index [30]. Polkey and Moxham [4] suggest that respiratory muscle strength measurements be taken in all ventilator-dependent patients who do not present a respiratory or cardiac reason for ventilation. Electrophysiological studies are suggested if respiratory muscle weakness is discovered. It is worth noting, however, that diaphragmatic denervation has been detected on electrophysiological studies in only half of those patients found to have critical illness polyneuropathy [31], suggesting that this is not a valid test for critical illness polyneuropathy. There are very few specific references to the effect of critical illness myopathy (or the more generic critical illness polyneuromyopathy) on weaning. Critical illness myopathy affects mainly type II (fast twitch) muscle fibres. The diaphragm and intercostal muscles are composed of approximately 40% type II muscle fibres [32]. The effect of critical illness myopathy may be a reduced ability to alter breathing patterns to accommodate periods of high demand. Weaning, itself, is a demanding process of reconditioning, which critical illness myopathy could hinder.

Implications for physiotherapy and rehabilitation Optimal treatment for critical illness polyneuropathy and critical illness myopathy is widely agreed to be maximal supportive therapy for the underlying cause. Several authors recommend a rehabilitation programme or intensive physiotherapy as a vital part of a patient’s recovery [1,7,10,33–35], but there is little definitive evidence that rehabilitation improves outcome. In part, this is due to the lack of research undertaken into the long-term functional outcomes for patients with critical illness polyneuropathy and critical illness myopathy. However, carrying out prospective randomised controlled trials would require a control group to be denied rehabilitation. The implication of critical illness polyneuromyopathy on rehabilitation is described by Watson et al. [20]. They studied the rehabilitation outcome and length of stay of a brain-injured patient with a diagnosis of critical illness polyneuromyopathy. The diagnosis allowed the rehabilitation team to enrol the patient into an appropriate in-patient programme as soon as possible and to anticipate a ‘prolonged but favourable’ recovery. Functional outcome improved markedly following rehabilitation, but as anticipated, length of rehabilitation stay increased from 21 days, in a comparable non-critical illness polyneuromyopathy group, to 36 days.

The financial burden for service providers is much greater during the in-patient period, but may be off-set by the saving in social support services if an optimal functional outcome is achieved. There is little literature addressing the cost benefit of intensive in-patient rehabilitation programmes for patients with critical illness polyneuromyopathy. Prolonged recovery demands focused practice by critical care physiotherapists [12]. Short- and long-term goals need to be reviewed regularly with the patient, their family and the multidisciplinary team. In the early stages, physiotherapy goals may include respiratory muscle training to aid weaning from mechanical ventilation and maintenance post intensive care discharge to reduce readmission to the intensive care unit due to respiratory failure. Strength, endurance and balance programmes can be used throughout the rehabilitation process, progressing to application of these abilities and skills to complex, unfamiliar situations, the patients’ hobbies and favourite activities. This would enable a patient to reintegrate into their community with greater ease, confidence and safety. Critical illness polyneuromyopathy-specific physiotherapy regimens are not described in the literature, but Griffiths and Jones [2] refer to an intensive care rehabilitation manual containing a graded exercise programme for the general intensive care population. Zanotti et al. [36] suggest that the use of electrical stimulation in conjunction with active limb movements can be applied in the intensive care environment to promote muscle strength and functional recovery. This study involved application of this technique to ventilated patients with chronic obstructive pulmonary disease. The results of application of electrical stimulation to patients with critical illness polyneuropathy or critical illness myopathy is not addressed, therefore, further investigation may be needed to ascertain if efficacy of the technique is affected. The amount of therapy time required would likely increase, and the boundaries between the in-patient and community settings may be challenged, but with greater continuity for the patient and their family. Physiotherapy involvement in multidisciplinary intensive care follow-up clinics may allow early identification of ongoing problems and timely referral and intervention. Available outcome measures would reflect this high level of therapy input in different ways. Cost and length of stay may increase, but functional and quality of life outcomes may improve. Structured, intensive rehabilitation programmes may provide an opportunity for patients to re-establish a normal sleep pattern, and may contribute to reduction of psychological problems associated with prolonged intensive care stay, such as anxiety and depression [2]. The most significant implication for physiotherapy with critical illness polyneuromyopathy may be the associated increase in length of rehabilitation stay [12], rather than a specific clinical complexity challenge. There remains much that can be done to optimise physiotherapy and rehabilitation services to this group of patients.

E. Ricks / Physiotherapy 93 (2007) 151–156

Discussion and recommendations Critical illness polyneuropathy and critical illness myopathy are significant causes of weakness on the intensive care unit, leading to increased length of stay, delayed weaning and prolonged rehabilitation. Timely and intensive rehabilitation programmes, although initially costly, may reduce rehabilitation length of stay and lead to greater functional gains. A formal multidisciplinary follow-up at intervals over 1 or 2 years, with ongoing exercise prescription, may be appropriate, using clinical, functional and quality of life outcome measures. The amount of therapy time required would increase, and the boundaries between the in-patient and community setting may be challenged, but with greater continuity for the patient and their family. Physiotherapy involvement in multidisciplinary intensive care follow-up clinics may allow early identification of ongoing problems and timely referral and intervention. Long-term prospective studies are needed to determine best practice, and the effect of an intensive rehabilitation programme on weaning, physical and psychological outcome, length of rehabilitation and length of intensive care/hospital stay and the cost implication. The management aim must be to optimise the care available to and provided for critical illness polyneuromyopathy patients in the short- and long-term. Key aspects central to this are: • Increasing awareness of critical illness polyneuropathy and critical illness myopathy amongst health care professionals on intensive care units. • Promoting diagnosis, both clinical and neurophysiological. • Educating patients and their families/carers about outcome and prognosis. • Streamlining rehabilitation to provide a highly effective, financially viable service.

Acknowledgements This literature review was undertaken as part of the Postgraduate Certificate in Advanced Cardiorespiratory Physiotherapy at University College London (2004/2005). The author would like to thank Dr. Jennifer Pryor for her encouragement and suggestions in the preparation of this review. Conflict of interest: None.

References [1] Deem S, Lee CM, Curtis JR. Acquired neuromuscular disorders in the intensive care unit. Am J Respir Crit Care Med 2003;167(7):735–9. [2] Griffiths RD, Jones C. Intensive care aftercare. 1st ed. Oxford: Butterworth–Heinemann; 2002. [3] Keaveney AM. Critical illness polyneuropathy on adults after cardiac surgery: a case study. Am J Crit Care 2004;13(5):421–4.

155

[4] Polkey MI, Moxham J. Clinical aspects of respiratory muscle dysfunction in the critically ill. Chest 2001;119(3):926–39. [5] Latronico N, Peli E, Botteri M. Critical illness myopathy and neuropathy. Curr Opin Crit Care 2005;11:126–32. [6] Bolton CF. Critical illness polyneuropathy. A useful concept. Muscle Nerve 1999;22:419–22. [7] Fletcher SN, Kennedy DD, Ghosh IR, Misra VD, Kiff K, Coakley JH, et al. Persistent neuromuscular and neurophysiologic abnormalities in long term survivors of prolonged critical illness. Crit Care Med 2003;31(4):1012–6. [8] Sanap MN, Worthley LIG. Neurologic complications of critical illness. Part II: polyneuropathies and myopathies. Crit Care Resusc 2002;4:133–40. [9] Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. J Neurol Neurosurg Psych 1984;47:1223–31. [10] Van Mook W, Huliseiv´e-Evers R. Critical illness polyneuropathy. Curr Opin Crit Care 2002;8:302–10. [11] Kennedy DD, Coakley J, Griffiths RD. Neuromuscular problems and physical weakness. In: Griffiths RD, Jones C, editors. Intensive care aftercare. 1st ed. Oxford: Butterworth–Heinemann; 2002. p. 7–18. [12] Van der Schaaf M, Beelen A, de Groot IJ. Critical illness polyneuropathy: a summary of the literature in rehabilitation outcome. Disabil Rehabil 2000;22:808–10. [13] Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000;23:1785–8. [14] Breuer AC. Critical illness polyneuropathy. An outdated concept. Muscle Nerve 1999;22:422–4. [15] Fletcher SN, Kennedy DD, Ghosh IR, Misra VD, Kiff K, Coakley JH, et al. Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med 2001;27:1288–96. [16] Tennila A, Salmi T, Pettila V, Roine RO, Varpula T, Takkunen O. Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med 2000;26:1360–3. [17] Tepper M, Rakic S, Haas JA. Incidence and onset of critical illness polyneuropathy in patients with septic shock. Neth J Med 2000;56:211–4. [18] Polkey MI, Lyall RA, Moxham J, Leigh PN. Respiratory aspects of neurological disease. J Neurol Neurosurg Psychiatry 1999;66: 5–15. [19] Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359–67. [20] Watson E, Morioka S, Wells J, McElligott J. The influence of critical illness polyneuropathy and myopathy on rehabilitation outcome and length of stay of the brain injured patient: a case report. Am J Phys Med Rehabil 2005;84(3):204–5. [21] de Letter MA, Schmitz PI, Visser LH, Verheul FA, Schellens RL, Op de Coul DA, et al. Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 2001;29: 2281–6. [22] Zifko UA. Long term outcome of critical illness polyneuropathy. Muscle Nerve 2000;52(Suppl 9):49–52. [23] Carillo ER, Alem´an ACE, S´anchez MVL. Polineuroptia del enfermo grave (polyneuropathy of critical illness). Rev Asoc Mex Med Crit Ter Int 1998;12(2):65–70. [24] Hund E. Critical illness polyneuropathy. Curr Opin Neurol 2001;14: 649–53. [25] Trojaborg W, Kaufmann P, Gooch CL. Motor unit estimate number in the anterior tibial muscle: normative data versus findings in critically ill patients in intensive care units. J Clin Neuromusc Dis 2002;3(4):139–42. [26] Bolton CF. Critical illness polyneuropathy and myopathy. Crit Care Med 2001;29(12):2388–90. [27] de Letter MA, van Doorn PA, Savelkoul HFJ. Critical illness polyneuropathy and myopathy (CIPNM): evidence for local immune

156

[28] [29] [30]

[31]

E. Ricks / Physiotherapy 93 (2007) 151–156 activation by cytokine-expression in the muscle tissue. Neuroimmunology 2000;106:206–13. Frutos-Vivar F, Esteban A. Critical illness polyneuropathy: a new (or old?) reason for weaning failure. Crit Care Med 2005;33(2):452–3. Epstein SK, Vuong V. Lack of influence of gender on outcomes of mechanically ventilated medical ICU patients. Chest 1999;25:1302–6. Garnacho-Montero J, Amaya-Villar R, Garcia-Garmendia JL, Madrazo-Osuna J, Oritz-Leyba C. Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med 2005;33(2):349–54. Sander HW, Saadeh PB, Chandswang N. Diaphragmatic denervation in intensive care unit patients. Electromyogr Clin Neurophysiol 1999;39:3–5.

[32] Koulouris NG, Dimitroulis I. Structure and function of the respiratory muscles. Pneumonologia 2001;14(2):91–108. [33] Behbehani 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;115:1627–31. [34] Jones C, McDermott K. Rehabilitation after critical illness. Brit J Intensive Care 2004:123–8. [35] Kennedy DD, Fletcher N, Hinds C. Neuromuscular dysfunction in critical illness; what are we dealing with? Curr Opin Anaesthesiol 2000;13:93–8. [36] Zanotti E, Felicetti G, Maini M, Fracchia C. Peripheral muscle strength training in bed-bound patients with COPD receiving mechanical ventilation: effect of electrical stimulation. Chest 2003;124:292–6.