Clinical Neurology and Neurosurgery 108 (2006) 621627

Review

Neuromuscular disorders in critical illness

Lekha Pandit a, , Amit Agrawal b
a
b

Department of Neurology, KS Hedge Medical Academy, Deralakatte, Mangalore 575108, Karnataka, India
Department of Neurosurgery, KS Hedge Medical Academy, Deralakatte, Mangalore 575108, Karnataka, India
Received 13 January 2006; received in revised form 1 April 2006; accepted 3 April 2006

Abstract
Neuromuscular disorders in the background of critical illness are under diagnosed. Standardized screening for weakness in the intensive
care unit (ICU) setting is uncommon and persistent weakness as a sequel of critical illness is usually not recognized by physicians in the ICU
for whom survival from acute illness is the primary outcome. The spectrum of illness ranges from isolated nerve entrapment with focal pain or
weakness, to disuse muscle atrophy with mild weakness, and to severe myopathy or neuropathy with associated severe, prolonged weakness.
This update focuses on neuromuscular disorders occurring in the critical care set up associated with diffuse and severe weakness.
2006 Elsevier B.V. All rights reserved.
Keywords: Critical illness; Critical illness neuropathy; Critical illness myopathy; Persistant neuromuscular blockade

Contents
1.
2.

3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Critical illness polyneuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1. Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2. Aetiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.1. Systemic inflammatory response (SIRW) and multiorgan dysfunction (MOD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.2. Role of hyperglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.3. Role of drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.4. Nutrition and catabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3. Pathology and pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4. Clinical features of CIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5. Myopathy in critical illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6. Critical illness myopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.7. Thick-filament myopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.8. Acute necrotizing myopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.9. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prolonged neuromuscular blockade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2. Diagnosis of neuromuscular dysfunction in the critically ill . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3. Electrophysiology of neuromuscular dysfunction in critical illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.1. Critical illness neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.2. Critical illness myopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Corresponding author. Tel.: +91 824 2204471; fax: +91 824 22442075.
E-mail address: panditmng@sancharnet.in (L. Pandit).

0303-8467/$ see front matter 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.clineuro.2006.04.003

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3.4. Prolonged neuromuscular blockade. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.5. Differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6. Prevention and treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction

2.1. Incidence

Patients with weakness acquired in the intensive care unit

(ICU) are often sedated and mechanically ventilated, and
have unreliable sensory and motor examinations. Therefore,
diagnosis can be quite difficult. In addition, critical care
physicians are under pressure to move patients out of the
ICU shortly after the restoration of spontaneous ventilation.
These physicians rarely see the patient subsequently, either in
the hospital or as an outpatient. Therefore, long-term followup of these patients is unavailable to them. Recently, data
on long-term outcome of these survivors especially report
about their health-related quality of life and conditions that
impair that quality have become available [1,2]. These reports
indicate that there is high prevalence of persistent muscle
weakness and fatigue that cannot be explained by muscle
inactivity or weight loss resulting from prolonged illness.
Greater than 50% of patients mechanically ventilated for
more than 7 days will develop electro-physiologic abnormalities [3] with 2533% developing clinically overt weakness
[4,5].
Due to inconsistencies in reporting, methods of testing and
terminologies used, a clear classification of ICU-acquired
neuromuscular disorders is difficult. Many a time critical
illness polyneuropathy (CIPN) and critical illness myopathy (CIM) are frequently lumped together, in part because
it is difficult to discriminate between them on the basis of
electrodiagnostic testing and in part because they frequently
coexist. As a consequence there are several terminologies
used, such as ICU acquired paresis (ICUAP), critical illness neuromuscular abnormalities (CINMAs), critical illness
polyneuropathy (CIP or CIPN), critical illness polyneuropathy and myopathy (CIPNM), and acute quadriplegic myopathy (AQM). Nevertheless, publications have focused on a few
distinct types of generalized muscle weakness in the setting
of critical illness. These are critical illness polyneuropathy,
critical illness myopathy, acute quadriplegic myopathy, and
prolonged neuromuscular blockade (PNB).

The actual incidence of CIP that has been reported has

varied depending on the criteria used for detection. A 5-year
retrospective evaluation of 497 critically ill patients revealed
no identifiable case of severe prolonged generalized weakness [7]. Subsequently, the same research group completed a
2-year prospective study and diagnosed six patients with CIP.
Based on clinical evaluation alone, an incidence of 2536%
has been shown in prospective studies [4,5]. When neurophysiologic testing was done, it revealed that neuropathy and
or myopathy is present in 5257% of patients in the ICU
for 7 days or more [3,8] and in 68100% of patients with
sepsis or systemic inflammatory response syndrome (SIRS)
[9,10].

2. Critical illness polyneuropathy

The first comprehensive report on CIP was published
in 1984. Bolton et al. [6] reported five patients who were
critically ill and had difficulty in weaning from mechanical
ventilation. These patients had sensory motor neuropathy
and electrophysiological studies revealed primary axonal
neuropathy.

2.2. Aetiology
2.2.1. Systemic inammatory response (SIRW) and
multiorgan dysfunction (MOD)
It is now recognized that CIP and CIM occur in the
background of respiratory insufficiency in patients with systemic inflammatory response syndrome and multiple organ
dysfunction. Both retrospective and prospective studies have
shown a significant association [5,9,11,12]. Presumably
the same basic mechanisms that lead to multiple organ
dysfunction, such as inflammation, apoptosis, thrombosis,
and oxidant injury have caused peripheral neuromuscular
dysfunction. In sepsis the mechanism is probably a complex disturbance of the systemic microcirculation, in which
peripheral nerves suffer impaired perfusion, leading to severe
energy deficits and a predominantly distal axonal degeneration [13]. The increased permeability of the blood nerve
barrier to circulating toxins could directly damage the axons
[14].
2.2.2. Role of hyperglycemia
Hyperglycemia has been associated with an increased risk
of CIPNM in multiple studies [5,8,14]. When tight glycemic
control was achieved with intensive insulin therapy, the rate
of CIPNM defined by neurophysiologic testing was reduced
from 51.9% among control subjects to 28.7% among insulin
treated patients [8].
The link between hyperglycemia and CIPNM may be
related to the toxic effects of hyperglycemia that may be countered by the neuroprotective and anti-inflammatory effects of
insulin [15,16].

L. Pandit, A. Agrawal / Clinical Neurology and Neurosurgery 108 (2006) 621627

2.2.3. Role of drugs

Though experimental evidence suggest the possibility of
neuromuscular dysfunction especially myopathy with steroid
and neuromuscular blocking agents, in actual practice there
are conflicting reports. A few observational studies support
the role of these agents [5,17]. One of the first cases of
weakness after ICU admission was reported in a patient
who had received both neuromuscular blocking agents and
corticosteroid therapy for acute asthma [18], and the danger of this combination has been subsequently confirmed
in larger studies [19,20]. Though some earlier studies have
exonerated antibiotics and particularly aminoglycosides as
causative factors [14], they have been considered by others
as additional risk factors [3]. Catecholamines/vasopressors
[8,21] and renal replacement therapy are additional risk factors identified. Since these potential risk factors were present
in the background of sepsis and critical illness, it is not clear
whether there is a direct causal relationship.
2.2.4. Nutrition and catabolism
Abnormal serum lipid profiles are observed in critically ill
patients [22,23]. Recent evidence points to alteration in organ
function (including nerve function) consequent to abnormal serum lipid profiles. Skeletal muscle catabolism may
also contribute to critical illness myopathy [24]. Critically
ill patients exhibit hypermetabolism [25] with reduced rates
of tissue protein synthesis despite nutritional support [26].
Severe malnourishment has been shown in other situations
to cause respiratory muscle weakness [27]. Electrolyte disturbance is also recognized to impair tension generation in
skeletal muscle [28]. Therefore, the contribution of these factors cannot be ruled out.
Other disease-specific factors shown to be associated with
CIPNM in multiple studies include severity of illness [3,4]
and duration of ICU stay [5,14,22]. Patient-specific factors
may also increase the risk of CIPNM, including female sex
[5] and increased age [3].

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out accompanying findings on nerve and muscle biopsy [30].

These observations suggest that functional changes precede
structural alterations in CIP.
2.4. Clinical features of CIN
Patients are very often identified by their inability to wean
from the ventilator. Patients with prolonged mechanical
ventilation (4180 days) may demonstrate decreased spontaneous limb movement and flaccid passive movement that
progresses from moderate to severe symmetrical paresis.
Patients are commonly men over 50 years of age admitted
to an ICU for various causes, who develop respiratory
failure and SIRS and remain in the ICU for more than 5
days. Primary conditions on admission to the ICU include
infection, trauma, surgery, and burns. Weakness affects legs
more often than arms [6,31]. In addition, muscle wasting,
reduced or absent deep-tendon reflexes, and slight sensory
disturbances are present in patients with CIP The pattern of
involvement is usually distal more than proximal. Rarely,
involvement of proximal (including facial and paraspinal)
muscles is striking. Tendon reflexes may be preserved
especially in patients with concomitant central nervous
system [32]. Since there is considerable overlap with CIP,
CIM may not have any additional differentiating clinical
features.
2.5. Myopathy in critical illness
Prospective studies that include muscle biopsy confirm
that myopathy is common among ICU patients, demonstrating an incidence from 48 to 96% [10]. Three subtypes of
critical illness myopathy have been described that are often
grouped together as acute quadriplegic myopathy, critical
illness myopathy, thick-filament myopathy, and necrotizing
myopathy [33]. These can be differentiated based on clinical
features and muscle biopsy.

2.3. Pathology and pathophysiology

2.6. Critical illness myopathy
Pathological findings in CIP include mildly reduced
myelin-fiber density with sporadic axonal degeneration to
marked fiber loss with abundant degenerative changes without any evidence of primary demyelinization or inflammatory
infiltrates. Distal nerve segments were affected most severely.
Changes in the microcirculation of the peripheral nerve have
been suggested to play a role in the pathogenesis of the nerve
lesion.
Immunohistochemical studies have shown enhanced
expression of E-selectin in endothelium of epineurial and
endoneurial vessels, suggesting endothelial cell activation,
possibly due to sepsis, in critically ill patients with neuromuscular disorders [29]. These findings confirm that axonal
degeneration is the major pathological feature of CIP. In some
critically ill patients, abnormalities in electrophysiological
evaluation of nerve and muscle have been demonstrated with-

CIM is characterized by a diffuse non-necrotizing myopathy accompanied by fiber atrophy, fatty degeneration of
muscle fibers, and fibrosis [30,34]. This type of myopathy has
been classically described with corticosteroid or neuromuscular blocker use, but is now also known to occur with sepsis
and multiorgan failure. Clinically, patients with CIM may
demonstrate weakness, failure to wean, or paresis. Creatine
phosphokinase (CPK) levels are relatively normal. It is difficult to differentiate CIM from CIN clinically and may occur
together in the same patient. Muscle biopsy offers a definitive
diagnosis. Such an invasive procedure may be justified since
it could provide useful prognostic information. The prognosis
of CIM has not been well studied, but it appears that younger
patients with status asthmaticus fare better than other
patients.

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L. Pandit, A. Agrawal / Clinical Neurology and Neurosurgery 108 (2006) 621627

2.7. Thick-lament myopathy

Selective loss of myosin filaments is the predominant finding in thick-filament myopathy. Large proportions of patients
have received corticosteroids and/or neuromuscular blocking agents in the setting of prolonged disuse, such as status asthmaticus or organ transplantation [35]. Progression
to myonecrosis may occur, raising the question of whether
thick-filament myopathy is an early stage of acute necrotizing
myopathy.
2.8. Acute necrotizing myopathy
Acute necrotizing myopathy of critical illness is characterized by prominent myonecrosis, with vacuolization and
phagocytosis of muscle fibers. Attention was first drawn to
this condition when initial reports appeared about the development of acute myopathy during the treatment of severe
asthma [36]. Though these reports focused on the role of corticosteroids in the causation of muscle weakness, in the 1990s
it became clear that the use of prolonged neuromuscular
blocking drugs (NMBD) was also associated with the development of acute necrotizing myopathy [19,37]. Although,
the type and dose of corticosteroid do not appear to be risk
factors for the development of myopathy, increasing duration of neuromuscular blockade does appear to be a risk
factor. In one series, Helliwell et al. [11] described necrotizing myopathy in 15 out of 31 critically ill patients. The
presence of necrosis was significantly related to the total number of organ failures. Unlike CIM, the majority of patients
developed elevated CPKs and rarely may progress to rhabdomyolysis [38].
2.9. Pathophysiology
The pathophysiology of CIM is complex, involving
metabolic, inflammatory, and bioenergetic alterations. Protein catabolism, an increase in urinary nitrogen loss, and
muscle wasting are observed in critical illness myopathy.
Muscle biopsies in critically ill patients demonstrate low
glutamine levels, low protein/DNA levels, and high concentrations of extracellular water. The increased flux of glutamine in muscle in these patients is thought to be insufficient
to meet the bodys requirement for glutamine, and thus in
critical illness this amino acid may be classified as conditionally essential [39]. Electrodiagnostic studies reveal
findings of a myopathic process, often with evidence of muscle membrane inexcitability. Based on animal model studies
the loss of muscle membrane excitability may be related
to inactivation of sodium channels at the resting potential
[40]. In critical illness myopathy, there is also upregulation of proteolytic pathways, involving calpain and ubiquitin, in conjunction with increased apoptosis [41]. Brealy
et al. [42] have shown an association between mitochondrial dysfunction and severity and outcome of septic shock.
In septic patients, they found an association between nitric

oxide overproduction, antioxidant depletion, mitochondrial

dysfunction, and decreased ATP concentrations that relate to
organ failure and eventual outcome. The damage or inhibition of complex I of the respiratory chain may be thus, an
important cause of muscle ATP depletion and bioenergetic
failure.
The exact role of steroids and NMBD agents in the causation of myopathy in critical illness is not clearly understood.
The NMBD agents possibly cause pharmacological denervation, which in turn facilitates the toxic effects of other
agents such as corticosteroids or inflammatory mediators.
In addition, the functional denervation resulting from nerve
injury in CIPNM may provide a link between CIPNM and
CIM. In animal studies, denervation results in proliferation
of steroid receptors on muscle membrane and subsequent
steroid administration results in muscle thick filament loss
and loss of membrane excitability [43], providing some support to the potentiating role of NMBDs or acquired polyneuropathy in the development of CIM.

3. Prolonged neuromuscular blockade

3.1. Etiology
Neuromuscular blocking drugs are sometimes administered to critically ill patients in conjunction with sedation in
an effort to facilitate mechanical ventilation, reduce oxygen
consumption, and control intracranial pressure. Most of the
NMBDs rely to various degrees on a combination of hepatic
metabolism and renal elimination for termination of effect.
Thus, large doses of NMBDs in the setting of renal failure
can result in prolonged neuromuscular blockade after only
a few hours of administration. The metabolites of pancuronium and vecuronium in the liver have 5060% of the potency
of the parent compounds and are renally cleared [44]. As a
result, renal failure is an important determinant of prolonged
neuromuscular blockade sometimes lasting days and even
weeks after discontinuation of drug administration [45,46].
Additional risk factors for prolonged neuromuscular blockade include hypermagnesemia, metabolic acidosis, and the
concomitant use of various antibiotics, including aminoglycosides and clindamycin. None of these factors, however, is
likely to be as important as renal failure.
3.2. Diagnosis of neuromuscular dysfunction in the
critically ill
A heightened awareness among critical care physicians is
important for early evaluation of patients with suspected neuromuscular dysfunction in the critical care setting. Diagnostic
testing including nerve conduction studies and electromyographic studies should be considered in every patient with
failure to wean from ventilator and in those who have evidence of weakness during or after recovery from critical
illness.

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3.3. Electrophysiology of neuromuscular dysfunction in

critical illness
3.3.1. Critical illness neuropathy
The most commonly reported abnormality is an axonal
neuropathy [47,48]. Neurography shows reduced amplitude
of compound muscle and sensory action potentials with normal or slightly delayed nerve conduction velocities. Approximately 23 weeks after the start of the process, fibrillation
potentials and positive sharp waves may be observed during
electromyographic examination. However, this denervation
activity may also occur in myopathic processes and cannot be
used to distinguish between axonal neuropathy and myopathy
[49].
3.3.2. Critical illness myopathy
Most, but not all investigators consider CIM to be less
common than axonal neuropathy, although, because of the
similarity of their electrophysiologic features, separating the
two entities can be difficult. Normal compound motor action
potential (CMAP), normal F wave latency and normal repetitive stimulation response is seen [50]. Muscle is seldom
excitable by direct stimulation [40]. Direct muscle stimulation has therefore an important diagnostic role. Denervation
activity (positive sharp waves and fibrillation potentials) can
also be found when there is concomitant neuropathy present.
Lefaucheur et al. [51] have developed a useful algorithm
to differentiate CIP from CIM electrophysiologically incorporating some of the criteria established earlier by Rich et
al. [52]. Latency and amplitude of direct muscle stimulation (DMS-amp) and motor nerve stimulation (MNS-amp)
were measured along with sensory nerve action potentials
(SNAP). Criteria for myopathic process were reduced DMSamp, increased MNS/DMS-amp-ratio (>0.5) or prolonged
DMS-lat. The specific criterion for motor neuropathy was
a reduced MNS/DMS-amp-ratio (<0.5). Normal SNAP-amp
at the lower limbs eliminated polyneuropathy.
3.4. Prolonged neuromuscular blockade
Peripheral nerve stimulation has an important role in
monitoring the effect of NMBD. Peripheral nerve stimulation with measurement of the response to four equal pulses
over 2 s (train of four, or TOF) is the gold standard for
monitoring neuromuscular blockade in the operating room.

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The diagnosis of prolonged neuromuscular blockade is made

by documentation of lack of or attenuated response to TOF
stimulation.
3.5. Differential diagnosis
A variety of pre-existing conditions can worsen during
critical illness causing failure to wean of ventilator (Table 1).
Conditions mimicking neuromuscular dysfunction associated with critical illness may also be acquired in the ICU
set up. These include Guillain-Barre syndrome, drug- and
metabolism-induced neuropathies, myasthenia gravis and
myopathy associated with electrolyte disturbances, and uremia and diabetes.
Guillain-Barre syndrome is usually characterized by symmetric weakness of extremities accompanied by distal paresthesia with sensory loss and generalized areflexia. Cerebrospinal fluid examination shows significant elevation of
protein with normal cellularity from the second week of illness. Electrophysiology will show evidence of conduction
block or slowing of conductions in both motor and sensory
nerves.
Myasthenia gravis is usually characterized by extraocular
cranial nerve paresis with sparing of pupillary reaction, tendency for muscle fatigue with exercise and preserved deep
tendon reflexes. Repetitive nerve stimulation at 35 Hz frequency demonstrates a reduction in compound motor action
potential which is reversible with infusion of acetylcholine
esterase inhibitors [50].
3.6. Prevention and treatment
Efforts to prevent and aggressively treat sepsis will likely
reduce the incidence of CIPNM. If duration of intensive care
is associated with CIPNM, measures that reduce ICU length
of stay may also decrease CIPNM. Beyond these measures at
this point in time, no treatments for established CIPNM have
been proven to be effective.
The risk of acute myopathy in association with corticosteroid and NMBD administration appears to increase after
2448 h of therapy [19]. The use of these agents should
be limited to as short a time course as possible. Estimation of serum creatine phosphokinase will identify those
at risk of rhabdomyolysis. Treatments for critical illness
myopathies range from primary prevention, i.e., avoiding

Table 1
Differential diagnosis of neuromuscular disorders in the intensive care unit
Disease location

Pre-existing disease

Acquired disease

AHC/nerve

Motor neurone disease, poliomyeltis, Guillain-Barre syndrome, chronic

inflammatory demyelinating polyneuropathy drug induced/toxic neuropathy,
metabolic neuropathy-diabetus, uremia, hypothyroid, vasculitis, porphyria
Myasthenia gravis, Eaton-Lamberts syndrome, drug induced, e.g.
aminoglycosides and anti-arrhythmic drugs, Botulism, Tick paralysis
Congenital myopathy/dystrophy, polymyositis, hypothyroid myopathy,
metabolic hypokalemia, hypomagnesemia

Critical illness neuropathy Guillain-Barre syndrome

Neuromuscular
Muscle

Persistent neuromuscular blockade aminoglycosides,

anti-arrhythmic drugs
Critical illness myopathy, steroid myopathy,
metabolic

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myopathy-induced drugs, to novel nutritional therapies, such

as glutamine and glutathione supplementation. One should
be particularly vigilant for the development of myopathies
in critically ill alcoholic patients, who may have a chronic
alcoholic myopathy at baseline. In the past decade, advances
have been made in characterizing and identifying patients
with myopathies due to critical illness. Additional studies,
however, must be performed in order to develop appropriate
therapies for this potentially devastating disorder.
Deep sedation may be a safer alternative to the use of
NMBD, in the ICU set up [4,5]. Prolonged neuromuscular
blockade is best avoided by limiting the dose and duration
of NMBD administration, particularly in high-risk settings,
such as renal or hepatic failure, and by frequently monitoring
the drug effect. Frequent scheduled drug holidays with
clear evidence of recovery from neuromuscular blockade
(patient movement) may be the best insurance against
prolonged neuromuscular blockade in the ICU, and will also
guarantee that the paralyzed patient is adequately sedated.
Treatment of persistent neuromuscular blockade consists
primarily of waiting for clearance of NMBD. Pharmacologic
reversal of neuromuscular blockade with a cholinesterase
inhibitor may also be useful in establishing a diagnosis
but recovery will likely be incomplete or short-lived in
the presence of high concentrations of NMBDs or their
metabolites.

3.7. Conclusion
Neuromuscular weakness that is acquired as a result of
critical illness and/or therapy is more common than recognized and may result in substantial excess morbidity, mortality, and costs. All ICU patients should be clinically screened
for weakness to help plan treatment, avoid potential toxin
re-exposure, and identify patients for rehabilitative treatments. Although sepsis, multi-organ failure and steroids are
often cited as risk factors, uncertainty remains due to the
poor methodological quality of studies, or because of inferences that are exclusively based on animal studies. New
simplified diagnostic techniques and machines for electrophysiological investigations of peripheral nerves and muscles
in the intensive care unit patient would also be welcome.
Electrophysiology-based algorithms may be useful in differentiating CIM from CIN. Recently, a report of electrophoretic
determination of the myosin/actin ratio, being a reliable test
in the diagnosis of critical illness myopathy, is a step in the
right direction [53]. Future studies should also better define
the population at risk of developing neuromuscular dysfunction in a critical care set up.

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