Elsevier

The Lancet Neurology

Volume 10, Issue 10, October 2011, Pages 931-941
The Lancet Neurology

Review
Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis

https://doi.org/10.1016/S1474-4422(11)70178-8Get rights and content

Summary

Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of critical illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are critically ill and cause chronic disability in survivors of critical illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of critical illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

Introduction

In the early 1980s, when first described, critical illness polyneuropathy (CIP) seemed to be a very rare complication of sepsis and multiorgan failure.1 However, the past 25 years of research have shown that CIP affects between a third and half of the most severely critically ill patients, and is the most frequent acute polyneuropathy in intensive care units (ICU). CIP presents with limb and respiratory muscle weakness and is strongly associated with failed weaning of patients from the ventilator; despite improvement, patients have varying degrees of disability after discharge from the acute care hospital. The muscles can be primarily involved without the nerves necessarily being affected.2 Early names for this primary myopathy were acute quadriplegic myopathy, critical care myopathy, acute necrotising myopathy of intensive care, thick filament myopathy, critical illness myopathy, acute corticosteroid myopathy, acute hydrocortisone myopathy, acute myopathy in severe asthma, and acute corticosteroid and pancuronium associated myopathy. Critical illness myopathy (CIM) is now deemed to be the appropriate term.3, 4, 5

Increasingly, survivors of critical illness are being recognised as a population with profound residual disability.6 Many survivors of critical illness complain of weakness for months to years after discharge from hospital7 and have persistent exercise limitations.8, 9, 10 Although the cause might be multifactorial,5 CIP and CIM have a major role and clinical neurologists should be familiar with the diagnosis of these disorders.

Diagnosis of CIP and CIM is difficult in the ICU, because either the pre-existing disorder or complications arising during the ICU stay can cause muscle weakness. Moreover, the patient's condition might preclude careful clinical examination, and the attention of the physician when the patient is first admitted to intensive care will be directed towards survival, thus delaying diagnosis of CIP and CIM. Electrophysiological investigations of peripheral nerves and muscles can help to achieve diagnosis of CIP and CIM at an early stage and to define prognosis, but they are time consuming and need skilled personnel. Therefore, a guided approach to diagnosis is valuable. Management of CIP and CIM rests on supportive treatment, treatment of ongoing sepsis and multiorgan failure, and control of hyperglycaemia. Recent evidence suggests that early rehabilitation can be safely and effectively implemented in the ICU to maintain patients' physical function, provided that patients are given little or no sedation.

In this Review, we describe the incidence, major risk factors, and the clinical, electrophysiological, and histological features of CIP and CIM. We present a diagnostic flowchart for an ordered approach to clinical and electrophysiological testing. We also discuss the major advances in early rehabilitation and protocols of little or no sedation in the ICU, which effectively improve the functional independence of patients.

Section snippets

Clinical features

CIP is a distal axonal sensory-motor polyneuropathy affecting limb and respiratory muscles (panel 1).12 Facial muscles are usually not affected. Limb involvement is symmetrical; it is most prominent in the lower extremities and can be severe. When less severe, muscle weakness is usually more pronounced distally than proximally.

CIP is often preceded by septic encephalopathy.13 In this disorder, the level of consciousness deteriorates. Because encephalopathy is not usually structural,14 recovery

Clinical features

CIM is a primary myopathy that is not secondary to muscle denervation, with distinctive electrophysiological and morphological findings (panel 2, figure 2).3, 4 The clinical features are often much the same as for CIP, with difficulty in weaning from the ventilator, flaccid limbs, and possible reduction in deep tendon reflexes but, if testable, normal sensation.

Electrophysiological and histological features

Major features are abnormal reduction in the amplitude of CMAPs and an increase in their duration, normal SNAPs, reduced muscle

Combined CIP and CIM

Combined CIP and CIM, which is usually mild but occasionally severe, could be the most common manifestation of neuromuscular weakness in the ICU.2, 23, 24, 29 In mild forms, electrophysiologically, CMAPs can be reduced, with possibly only borderline abnormalities in the duration of the CMAP and in recording of SNAPs. Needle electromyography studies of muscle might show only a few fibrillation potentials30 and positive sharp waves, and normal or mildly myopathic motor unit potentials. Muscle

Effect on outcome

CIP and CIM can cause prolonged severe disability after critical illness. There is substantial evidence that CIP and CIM cause limb and diaphragm weakness that persist for months or years after resolution of critical illness.8, 31, 32, 33, 34 As a result, nearly a third of patients with CIP, CIM, or both do not recover independent walking or spontaneous ventilation.35 Muscle weakness is only one of several contributors to disability after critical illness, but it is by no means the least

Incidence and risk factors

Exact incidence of CIP and CIM is unknown because of wide variation in the patient population, risk factors, and the diagnostic criteria used, and in the timing of assessment.37 In patients with mechanical ventilation of 4–7 days' duration18, 38 or with increased risk of developing multiorgan failure, the incidence was 25–33% on clinical assessment16, 18, 38 and 30–58% with electrophysiological assessment.8, 39, 40 Incidence was 34–60% in patients with acute respiratory distress syndrome,41, 42

Pathophysiological mechanisms

One unexplained aspect of electrophysiological changes of peripheral nerves and muscles during critical illness is their rapid onset within hours of normal action potential generation39 and their reversibility.55 Onset of clinical signs can also be rapid and reversible.56 The histological appearance of failing nerves and muscles can be normal or provide evidence of minimal muscle necrosis.2, 28 These findings suggest that the defect is mainly functional,2 as it is for other failing organs.57

Diagnosis

ICU staff will have difficulty in weaning some patients who are critically ill from mechanical ventilation (panel 1 and panel 2), which cannot be explained by increased respiratory or cardiac load, metabolic disturbances, nutritional disorders, profound anaemia, or delirium.79 When sedation is withdrawn in patients with CIP or CIM, staff might note that limbs have become weak and flaccid. In patients who are comatose, a painful stimulus will induce facial grimacing, but little limb movement.

Differential diagnosis

CIP and CIM are complications arising after the onset of critical illness, usually after admission to the ICU. Several disease processes involving the brain, spinal cord, peripheral nerves, neuromuscular transmission, or muscles can cause muscle weakness or paralysis in a patient who is critically ill.80 Ionic abnormalities such as hypokalaemia and hypophosphataemia can cause acute myopathic processes; hypermagnesaemia can impair neuromuscular transmission. Sepsis by itself does not cause a

Diagnostic algorithm

Alert, collaborative patients with muscle weakness arising as a complication of critical illness should be assessed clinically with the MRC scale (figure 3). In non-collaborative patients, diagnosis is usually deferred. To decide, clinicians should assess whether diagnosis will affect management or provide useful prognostic information. For example, in comatose patients with primary neurological diseases, such as head trauma or subarachnoid haemorrhage, who develop severe muscle weakness or

Management

No specific treatment—including nutritional, antioxidant, hormonal therapy, and immunoglobulins—has been shown to reduce the incidence and severity of CIP and CIM.52 Intensive insulin therapy to maintain normal blood glucose concentrations (4·4 to 6·1 mmol/L) reduces the incidence of electrophysiologically diagnosed CIP and the need for lengthy mechanical ventilation in both surgical and medical patients in the ICU.45, 46 However, the optimum blood glucose target is undetermined,92 because

Conclusions and future directions

CIP and CIM alone or in combination are common complications causing weakness of respiratory and limb muscles in patients who are critically ill. Substantial progress has been made in understanding their pathophysiology. Diagnosis can be achieved at an early stage, prompting control of hyperglycaemia and rehabilitation. Specific diagnosis based on electrophysiological and muscle biopsy investigations can help to establish the prognosis of chronic disability in survivors of critical illness.

Search strategy and selection criteria

References for this Review were identified through searches of PubMed from 1982 to July 2011 with the terms: “critical illness myopathy” OR “critical illness polyneuropathy” OR “critical illness polyneuromyopathy” OR (“neuromuscular diseases” [MeSH Terms] AND “intensive care unit”). We supplemented the search with a continuous review of publications in intensive care, neurological, and general medical journals about critical illness myopathy and neuropathy.

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