CE: Namrta; WCO 300512; Total nos of Pages: 7;

WCO 300512

REVIEW

CURRENT
OPINION Neuromuscular problems in the ICU
Maxwell S. Damian a and Ravi Srinivasan b

Purpose of review
Patients with acute life-threatening neuromuscular disease require close cooperation between neuromuscular
and intensive care specialists to achieve the best possible outcomes. The problems encountered by these
patients are different from those in traditional neuromuscular practice, and neurologists consulting in the
ICU need a specific skill set to provide useful guidance. However, outcomes can be very good if treatment
is instituted effectively. This review aims to provide an overview of the most important neuromuscular
conditions encountered in the ICU and enable a practical approach to patient management.
Recent findings
New research has provided improved knowledge of the impact of acute neuromuscular failure on the
mechanics of respiration, on the categories of neuromuscular disease in the ICU, and on the main factors
influencing outcomes. Pitfalls and risks in ICU treatment are better understood.
Summary
Evidence-based algorithms for monitoring and treatment have been developed. These advances enhance the
role of the neuromuscular specialist in acute care. The principles of best practice are discussed in this review.
Keywords
acute neuromuscular respiratory failure, Guillain–Barré syndrome, muscular dystrophy and hereditary
myopathy with early respiratory failure, myasthenic crisis, rhabdomyolysis and ICU-acquired weakness

INTRODUCTION in the Emergency Department or on the ward. A

Patients with neuromuscular problems in the ICU
fall into three broad categories:
(1) Patients with severe new onset acquired neuro-
muscular disease
(2) Patients who develop acute complications of
preexisting chronic neuromuscular disease and
(3) Patients whose neuromuscular problem arises in
the ICU
Neuromuscular disorders constitute only a small
proportion of admissions to the ICU, although there
is evidence that they may be increasing [1 ], and
&
neuromuscular specialists may struggle to provide
advice relevant to intensivists, who are seldom famil-
iar with neuromuscular conditions. Neuromuscular
problems are not uncommon in critically ill patients
admitted for medical conditions, but have only re-
cently become an area of scientific interest. This
review aims to provide an introduction to the specific
management of neuromuscular diseases in the ICU.
INITIAL CLINICAL ASSESSMENT IN
NEUROMUSCULAR EMERGENCIES
Neuromuscular intensive care begins with adequate
risk assessment of the acutely deteriorationg patient
neuromuscular emergency may require ICU admis-
sion for severe respiratory weakness and pulmonary
infection; bulbar weakness and aspiration; cardiomy-
opathy, or cardiac dysrhythmia due to conduction
defects; dysautonomia; or acute rhabdomyolysis and
renal failure. The initial approach needs to establish
whether it is of truly new onset, or whether there are
features suggesting chronic neuromuscular disease,
such as developmental problems, preexisting disabil-
ity, respiratory or cardiac problems or a family history
suggesting a neuromuscular disorder. In a previously
healthy patient, potentially toxic or neuromuscular
depressant medications need to be excluded. The
general assessment looks for contractures, cataracts,
or special constitutional features, as well as stigmata
of systemic diseases such as dermatomyositis,
a
Neurology and Neurointensive Care, Cambridge University Hospitals
and Ipswich Hospital, Cambridge and bNeurology and Intensive Care,
St.Georges Hospital, University of London, Blackshaw Road, London,
UK
Correspondence to Maxwell S. Damian, MD, PhD (Habil), FNCS, Neu-
rology and Neurointensive Care, Cambridge University Hospitals and
Ipswich Hospital, Hills Road, Cambridge CB2 0QQ, UK.
E-mail: msdd2@cam.ac.uk
Curr Opin Neurol 2017, 30:000–000
DOI:10.1097/WCO.0000000000000480

1350-7540 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. www.co-neurology.com

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512
Neuromuscular problems in the intensive care unit
KEY POINTS
 Neuromuscular intensive care begins with detailed
assessment and close monitoring of bulbar and
respiratory function in the acutely deteriorating patient.
 Outcomes in GBS in the ICU depend on recognising
risks and preventing complications in prolonged
treatment after immunomodulatory treatment.
 Mortality in myasthenic crisis is higher than expected
and step-down care must be prepared to manage
setbacks.
 ICU-acquired weakness is newly recognised and
significantly influences ICU outcomes after sepsis and
critical illness.
vasculitis or sepsis. Clinical signs suggesting specific
neuromuscular disorders include typical patterns of
muscle weakness and atrophy in genetic myopathies,
or fatiguing in sustained innervation of limb and
ocular muscles for myasthenic syndromes. Areflexia,
dysautonomia and flaccid tone may suggest a neuro-
genic disorder such as Guillain–Barré syndrome
(GBS), whereas preserved reflexes are more likely in
acute myopathy.
The bedside assessment of respiratory and bul-
bar function takes in voice; counting in one breath;
ability to lie flat; strength of swallow, cough and
head flexion as well as use of auxiliary respiratory
muscles such as the sternomastoids, scalenes and
intercostals. Warning signs of impending respirato-
ry failure include increased work of breathing, nasal
flaring, mouth opening, anxiety and restlessness.
Respiratory monitoring should test not only forced
vital capacity (FVC), but also diaphragmatic func-
tion with measurement of inspiratory (PImax) and
expiratory (PEmax) mouth pressures, or sniff pres-
sure if there is facial weakness, as well as the ability
to clear airways through measurement of cough
&&
flow (Table 1) [2 ]. Critical values to consider intu-
bation according to the ‘20/30/40 rule’ are an FVC
less than 20 ml/kg body weight, maximum inspira-
tory pressure < 30 H2O and maximum expiratory
pressure < 40 cm H2O [3]. The criteria for ICU ad-
mission should be clear and objective and the deci-
sion should be a team approach that takes in the
patient’s background and specify when monitoring
in the high dependency unit, and when interven-
tions such as intubation, are appropriate (Fig. 1).
Emergency intubation of a patient in extremis, or in
a patient who has already developed significant
abnormalities of blood gases generally indicates
inadequate previous monitoring.
Severe new onset neuromuscular disease in the
ICU includes the following conditions:
2 www.co-neurology.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1. The main parameters used in bedside
neuromuscular respiratory monitoring – typical normal ranges
of pulmonary function tests, and critical values to consider
intubation and ventilatory support (the ‘20/30/40’ rule)
Parameter Normal value Critical value
Forced vital 40– ml/kg 15–20 ml/kg
capacity
Peak inspiratory Male: > 100 cm 30–40 cm H2O
pressure (PImax) H2O
Female: > -70 cm
H2O
Peak expiratory Male: >80 cm H2O 40 cm H2O
pressure (PEmax) Female: >80 cm H2O
Peak cough Male: > 330 l/min >160 l/min at
flow (PECF) Female: > 280 l/min mouth (or
>60 l/min at tube
for extubation)
(1) Guillain–Barré syndrome
(2) Other severe acute neuropathies and anterior
horn cell disease comprising the acute flaccid
paralysis syndrome with viral infections such as
West Nile Virus, enterovirus D68, enterovirus
71, varicella zoster and Zika
(3) Myasthenic crisis and other disorders of the
neuromuscular junction
(4) Acute myopathies
(5) New manifestations of unrecognised chronic
conditions
MANAGEMENT OF GBS IN THE ICU
Guillain–Barré syndrome is the best known neuro-
muscular entity in the ICU. The neurologist must
ensure competent early diagnosis, and be suspicious
of patients who do not present the typical symmet-
ric demyelinating neuropathy with elevated cere-
brospinal fluid protein and low cerebrospinal fluid
(CSF) cell count. Vasculitic neuropathy can be sus-
pected if there is evidence for a mononeuritis mul-
tiplex course, an acute disorder with systemic or skin
features or relevant serology. Paraneoplastic neuro-
pathy is often combined with encephalopathy,
axonal and demyelinating nerve conduction abnor-
malities and a poor responsive to treatment. Indi-
cators for acute porphyria can be abdominal pain,
asymmetry, a combination with acute psychosis or
excessive depression. Infectious neuropathies/neu-
ronopathies need to be excluded. Toxic neuropa-
thies may be caused by environmental agents such
as tick paralysis or by medications in severely ill
patients. Neoplastic infiltration or intravascular
lymphoma occasionally causes severe progressive
neuropathy. Intravenous immunoglobulins (IVIg)
and plasma exchanges (PLEX) are of comparable
Volume 30  Number 00  Month 2017
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512

Neuromuscular problems in the ICU Damian and Srinivasan

FIGURE 1. Criteria for admission of an acute neuromuscular patient to the ICU (Dr EFM Wijdicks, with permission).
PF: Pulmonary function tests; 20/30/40: the 20/30/40 rule, see text. Note: Guillain–Barré is the most common condition for
which these criteria are used; however, they can be applied to neuromuscular conditions in general, with the two caveats that
in Myasthenia Gravis the possibility of rapid fluctuation must be considered in monitoring frequency; and that in chronic
disorders such as muscular dystrophies, the baseline status may be significantly reduced with altered baseline values for PF but
also less reserve for deterioration. Reproduced with permission from [2 ]. &&

benefit and risk. IVIg is more readily available, but
significantly more expensive in most countries; it
may be more effective in particular immunological
subtypes (IgG vs. GM1, GM1b or GalNac-GD1a).
Repeat treatment may be considered if patients fail
to improve. Kuitwaard et al. [4] have provided ob-
servational data suggesting patients whose IgG fails
to rise after the initial course of IVIg might benefit
from repeat treatment.
Some 30% of patients develop respiratory failure
and need intubation [3]. Inadequate protection of
airways through bulbar weakness, or a cough that is
too weak to clear airways in borderline respiratory
failure may also constitute a need for intubation.
Noninvasive ventilation (NIV) as a temporizing
measure for patients with GBS is unhelpful and
possibly unsafe, and 78% of GBS patients who are
intubated need ventilation for more than 3 weeks
[5]. Prediction of extubation success is difficult, and
half of the attempted extubations fail [6]. A weak
cough, measured by the peak expiratory cough flow
(PECF) may indicate a risk of delayed failure of
extubation through inadequate clearing of excre-
tions, when less than 160 l/min (or 60 l/min at the
endotracheal tube) at extubation [7]. With further
research, novel weaning parameters such as neutral-
ly adjusted ventilatory assist (NAVA) [8] may help
find the right time for extubation.
Autonomic dysfunction occurs in 60% of the
patients, and includes orthostatic hypotension, dia-
betes insipidus, sensitivity to drugs and ileus. Car-
diac dysrythmia is the most feared autonomic
feature, and it is uncertain to predict when a com-
mon dysrhymia such as moderate tachycardia and
absence of heart rate variability will develop into a
life-threatening complication such as the brady/
tachycardia syndrome or asystole. Life-threatening
autonomic symptoms occur in approximately 20%
of the patients. No single autonomic test will accu-
rately predict severe risk. Vagal spells with bronchor-
rhea, bradycardia and hypotension may be triggered
by invasive procedures and cholinergic drugs. Syn-
drome of inadequate antidiuretic hormone (SIADH)
secretion may cause hyponatremia. Hypertension
and persistent tachycardia affect over 50% of venti-
lated GBS patients [9]. The posterior reversible en-
cephalopathy syndrome (PRES) may occur as a
central autonomic disturbance in GBS, affecting
mainly women who are over 55 years of age [10].
Takotsubo cardiomyopathy in GBS may be related to
autonomic dysfunction [11].
After 6 months, 75% of patients ventilated in
the ICU are able to walk again, but 40% of the
patients retain residual neurological deficits. Ulti-
mately, inability to wean off the ventilator is ex-
tremely rare. Mortality is the highest in patients who

1350-7540 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. www.co-neurology.com 3

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512
Neuromuscular problems in the intensive care unit
are elderly, have pulmonary disease, autonomic
involvement, bulbar dysfunction or rapid progres-
sion (Hughes score 3 on admission). Twenty percent
of GBS patients requiring ventilation die [12], com-
pared with an overall mortality of 5–10%. Cardiac
arrhythmia accounts for 20–30% of deaths and may
occur unpredictably during both demyelinating or
remyelinating phases, sometimes triggered by med-
ications. Pulmonary infections and sepsis are the
leading causes of death and urinary tract infections
add up to a further risk. Two-thirds of the deaths
occur after ICU discharge, so there is still a risk of
&
death during recovery [1 ], and the quality of step-
down care is crucial.
MYASTHENIA GRAVIS IN THE ICU
Myasthenic crisis is the predominant cause for ICU
admission in myasthenia gravis with severe weakness
and respiratory failure either overtaking incremental
treatment during the early course, or triggered by
infection, general illness or medication errors. Pupil-
lary dilatation, sweating and tachycardia are in con-
trast to cholinergic crisis induced by excessive
cholinesterase inhibitor treatment, where weakness
is accompanied by cholinergic symptoms such as
bradycardia, dry skin, bronchial secretions, abdomi-
nal pain, twitching, cramping and miosis. Patients in
crisis who are unresponsive to cholinesterase inhib-
itors may develop a combination of both.
The best management of myasthenic crisis is
preventive, by recognising incipient myasthenic
crisis early through regularly testing fatigability,
respiratory function, cough and swallowing. Inten-
sivists should appreciate that myasthenia has a more
erratic course than GBS. Priority is given to securing
airways, and the patient should be intubated if in
doubt. Apart from treating infection and rehydra-
tion, medications that impair neuromuscular trans-
mission should be avoided, such as betablockers
given for tachycardia. Pyridostigmine can be discon-
tinued initially during ventilation, and reintroduced
gradually for weaning. If the patient is on parenteral
medication, one must observe intravenous dose
requirements with intravenous pyridostigmine ca.
30 , and intravenous neostigmine ca. 60 more
effective than the oral dose of pyridostigmine. In a
ventilated patient it is feasible to start steroids in high
doses such as 21 g i.v. then 100 mg oral. Many
workers feel that plasma exchanges have a more rapid
effect than IVIg, although the evidence is limited.
Intensive respiratory therapy and initial non-
invasive bilevel positive air pressure (BiPAP) may
reduce ventilator days. Tracheostomy should be
deferred, as a rapid recovery is possible. However,
there is a relatively high risk of reintubation as
standard predictors of extubation success are
4 www.co-neurology.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
unreliable [13]. Extubation success is particularly
hard to predict in myasthenia gravis, where fatigu-
ability can develop rapidly in a patient who hours
before seemed to fulfil all criteria for success. Cau-
tious postextubation monitoring is crucial to avoid
false estimation of wardability’.
Death from myasthenic crisis is below 5% in
most recent literature. However, these data from
selected centres may not reflect real life. Mortality
in UK ICUs was found to be 8.7% overall, and acute
hospital mortality after an ICU stay from myasthen-
&
ic crisis reaches 22% [1 ]. Causes of mortality are due
to belated admission to the ICU and suggesting
ward-based monitoring is sometimes inadequate.
In other cases, patients may be inappropriately
transferred from ITU to the general ward, and recur-
rent crises may be refused re-admission. It is impor-
tant to recognise that extubation failure is by no
means predictive of outcome and ‘futility’ can never
be an argument to deny reintubation.
Perioperative management must be well
planned. Patients should be stabilized as well as
possible prior to surgery, for which preoperative IVIg
or PLEX are useful. The patient’s specialist clinic
should provide a preoperative neurological status.
Customary medications should be taken with as
little interruption as possible, by giving pyridostig-
mine via nasogastric tube or intravenously (see dose
conversion above). Prednisolone should remain un-
changed, but for a major surgery hydrocortisone can
be given as perioperative stress cover, for example,
50 mg hydrocortisone at induction, and postopera-
tively 25 mg three times daily. Sugammadex can
reverse vecuronium-induced neuromuscular block-
ade. Postoperative FVCs should be monitored once
in 8 h, or more often if clinically indicated, and any
weakness or reduced mobility needs to be docu-
mented and prompt formal assessment should be
made, best using quantified myasthenia scores.
Anti-muscle-specific kinase (MuSK) antibody-
positive myasthenia gravis may present with a
bulbar onset and a rapidly progressive course with
respiratory crises. The response to pyridostigmine is
often unsatisfactory, and early PLEX and escalation of
immunosuppressive treatment are advised, for in-
stance to second line steroid sparing agents such as
Rituximab. The recently described LRP4 antibody is
also said to be associated with a more severe course.
Antistriational antibodies, which include anti-Titin,
anti-Ryanodine receptor and anti-Kv1.4 antibodies,
are associated with thymoma, and should prompt a
tumour search if found in a patient where rescue
treatments provide only short respite. Anti-Kv1.4
has been associated with myocarditis [14]
Inherited defects of the neuromuscular junction
cause congenital myasthenic syndromes. Some are
Volume 30  Number 00  Month 2017
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512
associated with episodic respiratory arrest and re-
quire home apnoea monitors; however, respiratory
arrest becomes less frequent in adolescence and
disappears before adulthood, so they rarely require
ICU admission in adult life. Anticholinesterases
help in some cases; alternative drugs include 3,4-
diaminopyridine, salbutamol, ephedrine and selec-
tive serotonin reuptake inhibitors.
NEW ONSET MYOPATHIES IN THE ICU
Acute inflammatory myopathy may require ICU
admission. Myositis-associated antibodies can help
differentiate clinic-serological spectra rather than
the older definitions as polymyositis or dermatomy-
ositis [15]. In the authors’ experience, inflammatory
myopathies in the dermatomyositis spectrum, often
associated with malignancy, and in the necrotizing
spectrum with anti-signal recognition particle (SRP)
and anti-HMG CoA reductase (HMGCR) antibodies
are most often seen in the ICU.
Acute necrotizing myopathy (NAM) associated
with the anti-SRP antibody may present as a rapidly
progressive proximal myopathy. Most cases will
need a second line immunosuppressant such as
rituximab or tacrolimus in addition to steroid treat-
&
ment [16 ,17]; on the other hand, the risk of an
underlying neoplasm is lower than in NAM related
to the anti-HMGCR antibody or seronegative NAM
[18]. In both the conditions, it is important to
request for a thorough histological assessment of
the muscle biopsy as well as antibody studies,
because not only the immune-mediated nature of
the condition may not be apparent in routine histo-
logical stains but also not to delay effective immune
treatment. The ICU team must be reassured that
there is a high chance of good recovery, even with
severe prolonged weakness. Early physiotherapy
and suitable splinting in the ICU are important to
avoid disabling contractures.
Rhabdomyolysis is loosely defined through very
high creatine kinase (CK) potentially causing renal
failure. It can be due to muscle ischemia, toxicity
such as pravastatin combined with warfarin, myop-
athy with anti-MAS or anti-SRP antibodies or para-
neoplastic myopathy. Some cases may also be due to
unrecognised genetic disease such as McArdle dis-
ease or other glycogen storage diseases, carnitine
palmitoyltransferase (CPT2) deficiency, defects of
oxidative phosphorylation and beta-oxidation, pe-
riodic paralyses or muscle hyperactivity syndromes
such as malignant hyperthermia or the malignant
&
neuroleptic syndrome [19 ]. The prime ICU concern
is to avoid renal failure by adequate hydration, treat
with renal replacement if necessary, and remove any
causes of toxicity.
1350-7540 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Neuromuscular problems in the ICU Damian and Srinivasan
PRE-EXISTING NEUROMUSCULAR
DISEASE PRESENTING ACUTELY TO THE
ICU
Respiratory failure may be the presenting feature of
otherwise mild disease, for instance in the ‘Heredi-
tary myopathy with early respiratory failure’
(HMERF) variant of Titinopathy [20], or glycogen
storage disorders, particularly GSD 2 (acid maltase
deficiency– Pompe disease) and GSD3 (Debrancher
deficiency). Other hereditary myopathies occasion-
ally presenting with respiratory failure as their
initial manifestation include mitochondrial myo-
pathy, myofibrillar myopathies (desminopathy,
aB-crystallin, myotilinopathy) [21], limb-girdle
muscular dystrophies (calpainopathy-LGMD 2A,
FKRP-LGMD2I), oculopharyngodistal muscular dys-
trophy with cardiomyopathy, distal myopathy with
early respiratory failure, and variants of congenital
myopathies (nemaline rod, centronuclear and cap
myopathies).
Cardiac failure and arrhythmia may be the
presenting symptom of otherwise minimal muscle
disease. Particularly young patients with oligosymp-
tomatic myotonic dystrophy may present with
cardiac arrest in the context of physical exertion
[22]. Genetic classification is important, in order to
decide on appropriate cardiac treatment, for in-
stance, patients with Lamin A/C mutations require
implanted cardioverter/defibrillators [23]. A larger
number of genetic myopathies feature cardiomyop-
athy in the later course: dystrophinopathies, and
some limb-girdle muscular dystrophies (particularly
LGMD1A (myotilinopathy), LGMD 1B (laminop-
athy), LGMD 1E (desminopathy), 2C-F (sarcoglyca-
nopathies), LGMD2I, Fukuyama congenital
muscular dystrophy, Barth myopathy (taffazin),
Danon disease (lamp-2), and various myofibrillar
myopathies. Advanced inflammatory myopathies
can be associated with severe cardiomyopathy, ei-
ther as a consequence of interstitial lung disease and
pulmonary hypertension, or through inflammation
of the heart muscle directly.
CRITICAL CARE IN SEVERE CHRONIC
NEUROMUSCULAR DISEASE
Coordinated multidisciplinary care and timely
interventions have vastly improved the quality of
life in patients with severe muscular dystrophy,
doubling life expectancy for patients with
Duchenne muscular dystrophy (DMD) [24]. The
age margin for patients with DMD to benefit from
critical care treatment is much wider today. Timely
discussion of issues such as ventilation and trache-
otomy allows the patients an informed decision
on their preferences. Many features that influence
www.co-neurology.com 5
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512
Neuromuscular problems in the intensive care unit
recovery after ICU treatment are determined by the
quality of care, for instance through cardiac moni-
toring and providing patients with percutaneous
gastrostomy or cough-assist devices in timely fash-
ion [25]. Long-term home ventilation has made
weaning from the ventilator a less central concern
before starting ICU treatment. Anaesthetic compli-
cations in patients with DMD include intraoperative
heart failure, inhaled anaesthetic-related rhabdo-
myolysis and a malignant hyperthermia-like syn-
drome, succinylcholine-induced rhabdomyolysis
and hyperkalemia [26], but complex surgical proce-
dures such as scoliosis correction are now better
tolerated through improved understanding of risks.
Patients with cardiomyopathy as part of a chronic
muscle disease can benefit from transplantation:
patients with Becker muscular dystrophy constitute
approximately one half of the muscular dystrophy
patients who undergo cardiac transplantation, and
providing transplantation is not deferred until late
complications reduce the chances of success, they
have outcomes comparable to controls without
muscle disease [27].
NEUROMUSCULAR DISEASE ARISING IN
THE ICU
Some patients in the ICU without preexisting neu-
romuscular disease fail to wean from mechanical
ventilation appropriately and are found to be awake,
but with flaccid paralysis. After exclusion of acute
cerebral and spinal disorders, the patient must be
investigated for toxic effects through drugs used on
the ICU (amiodarone; metronidazole, voriconazole
and other causes of neuropathy; propofol or hydro-
chloroquine causing myopathy); other cases can
follow immunological derangements through
Graft-versus-Host disease or drugs such as immune
&
checkpoint inhibitors [28 ]. Excluding these,
patients with symmetric weakness, often sparing
facial muscles most often have a combination of
critical illness polyneuropathy (CIP) and critical
illness myopathy (CIM) often termed as ‘ICU-ac-
quired weakness (ICU-AW)’. About one third of
patients who are ventilated for over 7 days, and
two thirds or more of those with sepsis and multiple
organ failure have a neuromuscular disturbance;
this often shows both neurogenic and myopathic
features in electromyography [29]. Muscle biopsies
show three overlapping myopathic subtypes: acute
myosin-loss myopathy; acute necrotizing myopathy
and diffuse Type 2 fibre atrophy [30]. Acute myosin-
loss myopathy is most frequently described in
patients receiving steroids and neuromuscular
blocking agents, but inflammatory processes, abnor-
mal protein metabolism in sepsis and abnormal
6 www.co-neurology.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
insulin metabolism have all been implicated as well
[31–33]. There is no known specific treatment, and
in current clinical practice, muscle biopsy is rarely
required, as long as a careful history and examina-
tion excludes evidence of neuromuscular weakness
developing before the ICU stay and antibody tests
can exclude anti-SRP or anti-HMGCR mediated
NAM. Approximately one half of patients with
ICU-AW recover fully, but half of the rest may retain
a long-term disability. The combination of myopa-
thy with significant neuropathy significantly wor-
sens prognosis [30]. Coordinated research efforts
have been initiated to provide better understanding
&
of mechanisms of ICU-AW and its prevention [34 ].
CONCLUSION
Neuromuscular specialists can provide important
guidance to intensivists for the growing number
of patients with neuromuscular disease seen in
the ICU, both through optimizing pre-ICU care,
and through guiding diagnostic procedures, moni-
toring, and outcomes in the ICU and after step
down. Understanding the priorities for ICU man-
agement and the specific risks and complications
encountered in the ICU is crucial for
patients’ benefit.
Acknowledgements
The authors would like to thank Dr EFM Wijdicks for
support and advice in the practice of Neurotintensive
Care and in the preparation of this manuscript.
Financial support and sponsorship
The authors would further like to acknowledge support by
the Departments of Neurology, Cambridge University
Hospitals and Ipswich Hospital; the Division of Anaes-
thesia, University of Cambridge, and the Neurosciences
Intensive Care Unit, St. Georges Hospital, University of
London.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Damian MS, Ben-Shlomo Y, Howard R, et al. The effect of secular trends and
& specialist neurocritical care on mortality for patients with intracerebral hae-
morrhage, myasthenia gravis and Guillain-Barré syndrome admitted to critical
care: an analysis of the Intensive Care National Audit & Research Centre
(ICNARC) national United Kingdom database. Intensive Care Med 2013;
39:1405–1412.
The largest survey of outcomes and mortality in neurological conditions comparing
outcomes in specialist vs. general ICU management in real life.
Volume 30  Number 00  Month 2017
CE: Namrta; WCO 300512; Total nos of Pages: 7;
WCO 300512
2. Wijdicks EFM. The neurology of acutely failing respiratory mechanics. Ann
&& Neurol 2017; 81:489–498.
An outstanding review of respiratory physiology, monitoring, and management in
neurological disorders
3. Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical
ventilation in Guillain-Barré syndrome. Arch Neurol 2001; 58:893–
898.
4. Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokinetics of intravenous
immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol 2009;
66:597–603.
5. Lawn ND, Wijdicks EF. Tracheostomy in Guillain-Barré syndrome. Muscle
Nerve 1999; 22:1058–1062.
6. Nguyen TN, Badjatia N, Malhotra A, et al. Factors predicting extubation
success in patients with Guillain-Barré syndrome. Neurocrit Care 2006;
5:230–234.
7. Winck JC, LeBlanc C, Soto JL, Plano F. The value of cough peak flow
measurements in the assessment of extubation or decannulation readiness.
Rev Port Pneumol 2015; 21:94–98.
8. Dugernier J, Bialais E, Reychler G, et al. Neurally adjusted ventilatory assist
during weaning from respiratory support in a case of Guillain-Barré syndrome.
Respir Care 2015; 60:e68–e72.
9. Pfeiffer G, Schiller B, Kruse J, Netzer J. Indicators of dysautonomia in severe
Guillain-Barré syndrome. J Neurol 1999; 246:1015–1022.
10. Rigamonti A, Basso F, Scaccabarozzi C, Lauria G. Posterior reversible
encephalopathy syndrome as the initial manifestation of Guillain-Barré syn-
drome: case report and review of the literature. J Peripher Nerv Syst 2012;
17:356–360.
11. Martins RP, Barbarot N, Coquerel N, et al. Takotsubo cardiomyopathy
associated with Guillain-Barré syndrome: a differential diagnosis from dys-
autonomia not to be missed. J Neurol Sci 2010; 291:100–102.
12. Fletcher DD, Lawn ND, Wolter TD, Wijdicks EF. Long-term outcome in
patients with Guillain-Barré syndrome requiring mechanical ventilation.
Neurology 2000; 54:2311–2315.
13. Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Predictors
of extubation failure in myasthenic crisis. Arch Neurol 2008; 65:929–
933.
14. Suzuki S, Utsugisawa K, Nagane Y, Suzuki N. Three types of striational
antibodies in myasthenia gravis. Autoimmune Dis 2011; 2011:7.
15. Tansley SL, McHugh NJ. Myositis specific and associated autoantibodies in
the diagnosis and management of juvenile and adult idiopathic inflammatory
myopathies. Curr Rheumatol Rep 2014; 16:464.
16. Allenbach Y, Benveniste O. Acquired necrotizing myopathies. Curr Opin
& Neurol 2013; 26:554–560.
An authoritative review on this group of severe myopathies
17. Watanabe Y, Uruha A, Suzuki S, et al. Clinical features and prognosis in anti-
SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry
2016; 87:1038–1044.
1350-7540 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Neuromuscular problems in the ICU Damian and Srinivasan
18. Allenbach Y, Keraen J, Bouvier AM, et al. High risk of cancer in autoimmune
necrotizing myopathies: usefulness of myositis specific antibody. Brain 2016;
139:2131–2135.
19. Scalco RS, Gardiner AR, Pitceathly RD, et al. Rhabdomyolysis: a genetic
& perspective. Orphanet J Rare Dis 2015; 10:51.
A comprehensive review of the genetic conditions requiring consideration in the
diagnosis of recurrent rhabdomyolysis
20. Pfeffer G, Elliott HR, Griffin H, et al. Titin mutation segregates with hereditary
myopathy with early respiratory failure. Brain 2012; 135:1695–1713.
21. Foroud T, Pankratz N, Batchman AP, et al. A mutation in myotilin causes
spheroid body myopathy. Neurology 2005; 65:1936–1940.
22. Bassez G, Lazarus A, Desguerre I, et al. Severe cardiac arrhythmias in young
patients with myotonic dystrophy type 1. Neurology 2004; 63:1939–1941.
23. Finsterer J, Stöllberger C, Maeztu C. Sudden cardiac death in neuromuscular
disorders. Int J Cardiol 2016; 203:508–515.
24. Bushby K, Finkel R, Birnkrant DJ, et al., DMD Care Considerations Working
Group. Diagnosis and management of Duchenne muscular dystrophy, part 2:
implementation of multidisciplinary care. Lancet Neurol 2010; 9:177–189.
25. Hill NS. Neuromuscular disease in respiratory and critical care medicine.
Respir Care 2006; 51:1065–1071.
26. Gurnaney H, Brown A, Litman RS. Malignant hyperthermia and muscular
dystrophies. Anesth Analg 2009; 109:1043–1048.
27. Wu RS, Gupta S, Brown RN, et al. Clinical outcomes after cardiac trans-
plantation in muscular dystrophy patients. J Heart Lung Transplant 2010;
29:432–438.
28. Hottinger AF. Neurologic complications of immune checkpoint inhibitors. Curr
& Opin Neurol 2016; 29:806–812.
An important review of a novel emerging class of neurimmunological disease
29. Fernández-Lorente J, Esteban A, Salinero E, et al. Critical illness myopathy.
Neurophysiological and muscular biopsy assessment in 33 patients. Rev
Neurol 2010; 50:718–726.
30. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired
weakness. Crit Care 2015; 19:274.
31. van Hees HW, Schellekens WJ, Linkels M, et al. Plasma from septic shock
patients induces loss of muscle protein. Crit Care 2011; 15:R233.
32. Hermans G, Wilmer A, Meersseman W, et al. Impact of intensive insulin
therapy on neuromuscular complications and ventilator dependency in the
medical intensive care unit. Am J Resp Crit Care Med 2007; 175:480–489.
33. Witteveen E, Wieske L, van der Poll T, et al., Molecular Diagnosis and Risk
Stratification of Sepsis (MARS) Consortium. Increased early systemic inflam-
mation in ICU-acquired weakness; a prospective observational cohort study.
Crit Care Med 2017; 45:972–979.
34. Latronico N, Herridge M, Hopkins RO, et al. The ICM research agenda on
& intensive care unit-acquired weakness. Int Care Med 2017; 1–12. doi:
10.1007/s00134-017-4757-5.
An important review of the current status of understanding ICU acquired weakness
and related research priorities.
www.co-neurology.com 7