Neuromuscular conditions

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Neuromuscular conditions
Table of Contents
 Preface
 Introduction
 Identifying and Assessing Weakness
 Determining the severity of weakness
 Characterising bulbar involvement
 Characterising respiratory muscle involvement
 Determining the cause of weakness
 Laboratory investigations
 General Issues In The Management of the Patient with Neuromuscular
Disease
 Predicting acute respiratory failure
 Airway protection and secretion management
 Ventilation and weaning
 Nutrition
 Thromboprophylaxis
 Sedation and mobilisation
 Selected Diseases Precipitating ICU Admission
 Guillain–Barré syndrome (GBS)
 Botulism
 Tetanus
 Myasthenia Gravis
 Motor neurone disease
 Myotonic dystrophy
 Rhabdomyolysis
 Drugs and toxins
 Neuromuscular Complications During and After Critical Illness
 Intensive Care Unit Acquired Weakness (ICU AW)
 Prolonged neuromuscular blockade
 Metabolic and electrolyte disorders
 Other Critical Care related complications
 Conclusion
 
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Preface?page_ref_id=1098
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Introduction?page_ref_id=1061
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Identifying+and+Assessing+Weakness?page_ref_id=1062
https://collaboration.esicm.org/Neuromuscular+conditions+-+Identifying+and+Assessing+Weakness%3A+Determining+the+severity+of+weakness?page_ref_id=1063
https://collaboration.esicm.org/Neuromuscular+conditions+-+Identifying+and+Assessing+Weakness%3A+Characterising+bulbar+involvement?page_ref_id=1064
https://collaboration.esicm.org/Neuromuscular+conditions+-+Identifying+and+Assessing+Weakness%3A+Characterising+respiratory+muscle+involvement?page_ref_id=1065
https://collaboration.esicm.org/Neuromuscular+conditions+-+Identifying+and+Assessing+Weakness%3A+Determining+the+cause+of+weakness?page_ref_id=1066
https://collaboration.esicm.org/Neuromuscular+conditions+-+Identifying+and+Assessing+Weakness%3A+Laboratory+investigations?page_ref_id=1067
https://collaboration.esicm.org/Neuromuscular+conditions%3A+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease?page_ref_id=1068
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Predicting+acute+respiratory+failure?page_ref_id=1069
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Airway+protection+and+secretion+management?page_ref_id=1070
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Ventilation+and+weaning?page_ref_id=1071
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Nutrition?page_ref_id=1072
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Thromboprophylaxis?page_ref_id=1073
https://collaboration.esicm.org/Neuromuscular+conditions+-+General+Issues+In+The+Management+of+the+Patient+with+Neuromuscular+Disease%3A+Sedation+and+mobilisation?page_ref_id=1074
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Selected+Diseases+Precipitating+ICU+Admission?page_ref_id=1075
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Guillain%E2%80%93Barr%C3%A9+syndrome+%28GBS%29?page_ref_id=1076
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Botulism?page_ref_id=1077
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Tetanus?page_ref_id=1078
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Myasthenia+Gravis?page_ref_id=1079
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Motor+neurone+disease?page_ref_id=1080
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Myotonic+dystrophy?page_ref_id=1081
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Rhabdomyolysis?page_ref_id=1082
https://collaboration.esicm.org/Neuromuscular+conditions+-+Selected+Diseases+Precipitating+ICU+Admission%3A+Drugs+and+toxins?page_ref_id=1083
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Neuromuscular+Complications+During+and+After+Critical+Illness?page_ref_id=1084
https://collaboration.esicm.org/Neuromuscular+conditions+%3A+Neuromuscular+Complications+During+and+After+Critical+Illness%3A+Intensive+Care+Unit+Acquired+Weakness+%28ICU+AW%29?page_ref_id=1085
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Neuromuscular+Complications+During+and+After+Critical+Illness%3A+Prolonged+neuromuscular+blockade?page_ref_id=1086
https://collaboration.esicm.org/Neuromuscular+conditions+-+Neuromuscular+Complications+During+and+After+Critical+Illness%3A+Metabolic+and+electrolyte+disorders?page_ref_id=1087
https://collaboration.esicm.org/Neuromuscular+conditions+-+Neuromuscular+Complications+During+and+After+Critical+Illness%3A+Other+Critical+Care+related+complications?page_ref_id=1088
https://collaboration.esicm.org/Neuromuscular+conditions%3A+Conclusion?page_ref_id=1089
Neuromuscular conditions
 
Current Status 2017
Awaiting major review 
This module is updated and maintained by the (NIC) section
Latest Update
Second Edition
Neuro-Intensive Care
Chair
Fabio Silvio Taccone MD, Assistant Professor, Department of Intensive Care,
Erasme Hospital, Professor of Emergency Medicine, the Université Libre de
Bruxelles (ULB), Brussels, Belgium
Deputy
Chiara Robba MD, PhD, Anaesthesia and Intensive Care, IRCCS for Oncology,
Genova, Italy
Section Editor
Valentina Della Torre MD, MSc, Department of Critical Care, Imperial College
NHS Foundation Trust, London, UK
ELearning Committee
Chair
Kobus Preller Dr., Consultant, John Farman ICU, Cambridge University Hospitals
NHS Foundation Trust, Cambridge, UK
Deputy
Mo Al-Haddad MD, Consultant in Anaesthesia and Critical Care, Queen Elizabeth
University Hospital; Honorary Clinical Associate Professor University of Glasgow,
Glasgow UK
Project Manager
Estelle Pasquier , European Society of Intensive Care Medicine
Second Edition 2017
Module Authors
Zudin Puthucheary PhD MRCP, Critical Care Consultant, Royal Brompton
Hospital
Hugh Montgomery , Dept of Cardiovascular Genetics and Cardiology Rayne
Institute London, United Kingdom
Nicola Latronico , Professor of Anesthesia and Critical Care Medicine, University
of Brescia, Italy; Department of Medical and Surgical Specialties, Radiological
Sciences and Public Health, University of Brescia; Clinical Director, Department of
Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital,
Brescia, Italy
Module Reviewers
Carol Hodgson MD, PhD FACP BAppSc(PT) Associate Professor and Deputy
Director, ANZIC-RC, Department of Epidemiology and Preventive Medicine,
School of Public Health and Preventive Medicine, Monash University; Heart
Foundation Fellow
Luuk Wieske MD, Academic Medical Center/University of Amsterdam,
Amsterdam, the Netherlands
Medical Editor
Mo Al-Haddad MD, Consultant in Anaesthesia and Critical Care, Queen Elizabeth
University Hospital; Honorary Clinical Associate Professor University of Glasgow,
Glasgow UK
Section Editor
Lara Prisco MD (IT), MSc (IT), Neurointensive Care Unit, John Radcliffe Hospital
and Nuffield Department of Clinical Neurosciences Oxford University Hospitals
NHS Foundation Trust and University of Oxford, Oxford, United Kingdom
CoBaTrICE Mapping
Cristina Santonocito MD, Dept. of Anesthesia and Intensive Care, IRCSS-
ISMETT-UPMC, Palermo, Italy
First Edition 2005
Module Authors
John Coakley , Dept of Intensive Care St. Bartholomew'sand Homerton
Hospitals London, United Kingdom
Lars Heslet , Intensive Care Unit Rigshospitalet University of Copenhagen
Copenhagen, Denmark
Module Reviewers
Nicola Latronico , Professor of Anesthesia and Critical Care Medicine, University
of Brescia, Italy; Department of Medical and Surgical Specialties, Radiological
Sciences and Public Health, University of Brescia; Clinical Director, Department of
Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital,
Brescia, Italy
Venkatesh Aiyagari , St. Louis, MO, USA
Medical Illustrator
Kathleen Brown , Triwords Limited, Tayport, UK
Update Info 
 
Learning Objectives
After studying this module on Neuromuscular conditions, you should be able to:
Identify causes of acute weakness.
Be familiar with the assessments and differential diagnosis in acute weakness.
Recognise the common acute and subacute causes of neuromuscular weakness
leading to ICU admission. Understand their prognosis and treatment.
Recognise the causes of acute weakness appearing after ICU admission.
Understand their prognosis and treatment.
 
eModule Information
COBATrICe competencies covered in this module:
Competencies
Manages the care of the critically ill patient with specific acute medical conditions
Recognises and manages the patient with neurological impairment
Recognises and manages the patient following intoxication with drugs or
environmental toxins
Faculty Disclosures: 
The authors of this module have not reported any disclosures.
Duration: 7 hours
Copyright©2017. European Society of Intensive Care Medicine. All rights reserved. 
ISBN 978-92-95051-61-4 - Legal deposit D/2005/10.772/8
https://collaboration.esicm.org/tracker24
1. Introduction
Weakness may precipitate Intensive Care Unit (ICU) admission and can result from
generalised disease states (such as malnutrition), the critical illness itself (such as
severe sepsis) or those specific states which primarily affect the neuromuscular
system e.g. myasthenia gravis, Guillain–Barré Syndrome (GBS). Weakness may result
from impacts on upper or lower motor neurones (in isolation or with involvement of
other peripheral or central nervous system elements), motor end plates
(neuromuscular transmission), or skeletal muscle itself. Whatever the cause, ICU
admission related to such conditions generally results from respiratory muscle
weakness and/or difficulty in swallowing, with or without consequent aspiration. Early
recognition and intervention is crucial: death can result from ventilatory failure and/or
aspiration pneumonia, and the autonomic instability which complicates some
conditions.
Weakness as a result of neuromuscular conditions can also complicate critical illness,
increasing the duration of mechanical ventilation and ICU and hospital stay, and
causing post-discharge morbidity and mortality.
You will find the following references helpful in understanding the broad range of
neuromuscular conditions encountered in the ICU.
In text References
(Latronico and Bolton. 2011; Howard, Tan and Z'Graggen. 2008; Stevens, Hart and
Herridge 2014) 
 
 References
Latronico N, Bolton CF., Critical illness polyneuropathy and myopathy: a
major cause of muscle weakness and paralysis., 2011, PMID:21939902
Howard RS, Tan SV, Z'Graggen WJ., Weakness on the intensive care unit.,
2008, PMID:18796583
Stevens RD, Hart N, Herridge MS, Textbook of Post-ICU Medicine: The
Legacy of Critical Care, 2014, ISBN:9780199653461
https://www.ncbi.nlm.nih.gov/pubmed/21939902
https://www.ncbi.nlm.nih.gov/pubmed/18796583
2. Identifying and Assessing Weakness
Where possible a detailed neuromuscular history should be taken and examination
performed,on ICU admission. This may identify the presence of existing disease
driving admission as well as helping determine its aetiology. If weakness is identified
only later ICU, it is essential to take a detailed history. In retrospect, were there any
signs or symptoms prior to ICU admission? What was the timecourse of their
progression?
This should focus on four elements:
1. Determining the severity of weakness
2. Characterising involvement of bulbar muscles (and thus risk of aspiration)
3. Characterising involvement of respiratory muscles
4. Determining the cause, such that appropriate treatment can be instigated.
 
2. 1. Determining the severity of weakness
Determining the presence of weakness- and its severity is evidently impossible in the
patient to whom neuromuscular blockers have been administered. It can also be
complicated where motor blocks from regional anaesthetic techniques is in play. It also
does generally require that the patient is sentient and able to follow commands. Even
then, some element of reduced attention, confusion or of demotivation may influence
assessment in patients with delirium. The presence of pain may also limit volitional
movement. Specific patterns of weakness should be sought (e.g. proximal myopathy,
nerve distribution, spinal cord level or cerebral hemispheric involvement). Gait should
be routinely assessed where practical and possible e.g. when considering patients for
ICU admission prior to high-risk surgery. Of note, weakness can change rapidly in
some conditions (see GBS, Task 3 ), and can also change with time of day or activity
(see, for example, myasthenia gravis, Task 3 ). Repeated examination, sometimes
with provocation testing, may thus be required.
 
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
https://collaboration.esicm.org/Neuromuscular%20conditions%20-%20Selected%20Diseases%20Precipitating%20ICU%20Admission:%20Guillain%E2%80%93Barr%C3%A9%20syndrome%20(GBS)?page_ref_id=1076
https://collaboration.esicm.org/Neuromuscular%20conditions%20-%20Selected%20Diseases%20Precipitating%20ICU%20Admission:%20Myasthenia%20Gravis?page_ref_id=1079
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.
 
2. 2. Characterising bulbar involvement
Is there a history of change in voice or phonation or articulation?
 Note
a hoarse voice may suggest recurrent laryngeal nerve involvement, or may
suggest chronic aspiration.
Is swallowing difficult? Does eating result in coughing? Ask about specific food types
and alterations in diet as a result (as semi-solids may be easier to swallow than thin
liquids). Is there nasal regurgitation or coughing/choking after swallowing? Ask about
features related to brainstem function/function of other cranial nerves, and perform
appropriate examination, seeking palatal deviation on swallowing or on phonation, and
tongue deviation on protrusion. Also seek evidence of tongue fasciculation (see motor
neurone disease, Task 3 ). Assess glottic closure by having the patient perform a
cough.
2. 3. Characterising respiratory muscle involvement
2. 3. 1. Clinical assessment
Respiratory muscle weakness may occur in the context of any generalized motor
neuropathy or myopathy, and is sometimes differentially affected. Impacts on
ventilatory function may also be much greater than those seen on distal movement (for
instance, where work of breathing is already high by virtue of lung or airway disease).
Where spinal cord compression is present, assessment of ventilatory muscle function
can also help identify the associated motor level. Thus, assessment of ventilatory
muscle function is important for diagnosis, prognosis andto guide clinical
management.
https://collaboration.esicm.org/Neuromuscular%20conditions%20-%20Selected%20Diseases%20Precipitating%20ICU%20Admission:%20Motor%20neurone%20disease?page_ref_id=1080
The respiratory muscles fall into three groups.
1. The diaphragm (supplied by C3,4,5 nerve roots) is active only in inspiration.
Normal inspiration causes flattening of the diaphragm, and the abdomen below
the ribs to bulge out. Failure for this to happen may suggest diaphragmatic
paresis. Further, indrawing of the upper abdomen during inspiration
(paradoxical movement) may also be observed in such circumstances.
2. The intercostal muscles (supplied by T1–12 nerve roots) are involved in
inspiration, and in forced or active expiration. On inspiration, ribs 1–6 move
anteriorly and ribs 7–10 laterally. The magnitude of this change should be
assessed. Cord compression may cause paralysis of these muscles below that
level, and the rib cage will move inwards paradoxically during rapid nasal
inspiration or ‘sharp sniffing’ (under the influence of the negative intrathoracic
pressure generated by the inspiration).
3. Accessory muscles of inspiration (such as sternocleidomastoids and latissimus
dorsi). Each component should be assessed, and appropriate causes of the
pattern of weakness identified.
Use of accessory muscles and the presence of nasal flaring may represent a high
work of breathing, or ‘air hunger’ where ventilation is inadequate through weakened
musculature. In the latter case, tidal volumes (Vt) may fall, and ventilatory rate (f) may
rise – causing their ratio (f/Vt, the ‘rapid shallow breathing index’ which is normally
<50/min/L) to increase. Ventilatory failure, by causing the partial pressure of carbon
dioxide in arterial blood (PaCO2) to rise, may lead to restlessness and subsequently to
a fall in conscious level.
 Note
In patients on ventilatory support, reducing the level of pressure support
(perhaps to zero) or a spontaneous breathing trial (SBT) for a diagnostic period
may help reveal patterns of weakness.
 Warning
Arterial blood gases are an extremely unreliable indicator of respiratory strength
or the need for mechanical ventilation in neuromuscular disorders. Patients with
rapid shallow breathing should be closely monitored even if blood gases are
normal.( module on Mechanical Ventilation .)
 
2. 3. 2. Additional tests
Information gained from clinical assessment is essential but can be further
substantiated through the use of spirometry.
https://collaboration.esicm.org/Mechanical%20ventilation:%20Weaning%20the%20patient%20from%20mechanical%20ventilation?page_ref_id=2570
More usefully, Forced Vital Capacity (FVC) assesses composite inspiratory and
expiratory force and lung volume and is easily performed at the bedside with minimal
training. FEV1 (the volume expired in 1 second of forced expiration) and peak
expiratory flow rate (PEFR) offer composite indices of expiratory muscle force and
airway resistance (note – they may be NORMAL in Guillain Barre Syndrome (GBS)). In
patients where disease progression may lead to respiratory failure, spirometry should
be performed at appropriate (and responsively changing) intervals. A fall in FVC when
assuming the supine position from the seated or standing one may suggest ventilatory
muscle weakness. However, few patients on ICU have such mobility, and testing in this
context is hard. Further, FVC may fall for many other reasons in these circumstances
(e.g. tense ascites) and, for these reasons, such testing is rarely clinically applicable
on ICU. An FVC of <1 L, or a decline of more than 50% from baseline and maximal
inspiratory force less negative than 20 cmH2O should lead to urgent consideration of
mechanical ventilatory support in cases of GBS.
Maximal negative inspiratory force (an index of inspiratory muscle function) and
maximal expiratory force (reflecting force of cough) can be measured by trained
specialists using an electronic strain gauge attached to a mouthpiece. Maximal
inspiratory force less negative than 20 cmH2O is predictive of a need for ventilatory
support.
See Vital Capacity in Respiratory assessment and monitoring module.
 Note
 
FVC is easy to perform at the bedside, but it is nonspecific diagnostically. Thus,
normal FVC excludes moderate to severe respiratory muscle weakness, but
reduced FVC can be due to respiratory muscle weakness, or pulmonary
disease, or both.
 Note
As an empirical means to estimate vital capacity at the bedside, the patient may
be asked to take a deep breath and then to count rapidly from 1 to 20. If unable
to reach ‘20’, vital capacity is likely to have fallen by some 15–18 mL/kg.
In text Reference
(Ropper. 1993) 
Assessment of arterial blood gases may also be of value. Note that oxygenation
(whether through monitoring of arterial oxygen saturation or of the partial pressure of
oxygen in arterial blood (PaO2)) is not an index of ventilation, and measurements may
only fall when PaCO2 is rising dangerously (in compliance with the alveolar gas
https://collaboration.esicm.org/Respiratory%20assessment%20and%20monitoring
equation). Otherwise, the presence of hypoxaemia points to other pathologies which
have resulted in ventilation/perfusion mismatch e.g. atelectasis, aspiration or
pulmonary embolus due to immobility.
The magnitude of hypercarbia reflects limitations in ventilation of functional alveoli
(reduced overall ventilation, or increased physiological deadspace, or both). The
resulting respiratory acidaemia may be metabolically compensated, if of sufficient
duration.

Why are blood gases maintained in neuromuscular weakness until
respiratory arrest?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 As tidal volume decreases because of muscle weakness,
respiratory rate increases to maintain minute ventilation. Arterial blood
gases are maintained within the normal ranges, or arterial oxygenation
is slightly reduced because of impaired cough and microatelectasis.
Eventually the respiratory rate cannot be sustained, hypercapnia
develops and respiratory arrest supervenes.
The following reference addresses respiratory muscle testing in the non-intubated
patient in greater detail.
In text Reference
(Dancer and Thickett. 2012) 
Clinical examination of respiratory muscle function in the conscious intubated patient
should follow the pattern outlined above in the conscious patient. Whether conscious
or not, f/Vt ratio may be high in those with respiratory muscle weakness and has been
used to predict successful extubation (although poor sensitivity and specificity limit this
role). Diaphragm strength can be evaluated objectively using phrenic nerve stimulation
in conjunction with oesophageal manometry, although this is technically difficult,
expensive and only available in specialist centres.
Maximal Inspiratory Pressure (MIP), Maximal Expiratory Pressure (MEP) and Forced
Vital Capacity (FVC) can be measured in cooperative patients by disconnecting them
from the ventilator (some ventilators do not require disconnection), and performing a
manual occlusion in inspiration (MIP) or expiration (MEP). Again, these tests are
mainly used in clinical research rather than to guide management. Expiratory muscle
strength can be evaluated using cough peak flow in intubated patients – values of 35–
60 L/min being described as thresholds for successful extubation. These tests are
exclusively clinical and based on subjective evaluation, and their generalised
application and interpretation are therefore limited by the need for patient awareness
and co-operation.
In patients who develop muscle weakness on the ICU (Intensive Care Acquired
Weakness, ICU-AW), peripheral muscle weakness is paralleled by respiratory muscle
weakness. ICU-AW is diagnosed by the use of the Medical Research Council Sum
Score (MRC-SS, figure below). An arbitrary score of 48 is used as a diagnostic cut-off
for ICU-AW. The clinical utility of the MRC-SS is limited in the ICU – over 30–40% of
patients are unable to reliablyperform the required tests at awakening, and there are
concerns regarding inter-rater reliability. Handgrip strength has also been shown to be
useful in the diagnosis of ICU-AW, but similarly needs an awake, cooperative patient. 
 
Figure 1: Medical Research Council Sum Score as
described by Kleyweg et al in 1991.
Figure 1: Medical Research Council Sum Score as described by Kleyweg et al in 1991.
This has been adapted for use within the ICU, with an arbitrary cut‐off of 48 used to
define ICU‐AW
 Note
 
Use of the MRC requires an awake and fully cooperative patient. Patients with
sedation or delirium may not be assessable.
In text References
(Verceles et al. 2012; Patel et al. 2009; Smina et al. 2003; Polkey and Moxham. 2001;
Vitacca et al. 2006; De Jonghe et al. 2002; Hough, Lieu and Caldwell. 2011; Ali et al.
2008; Hermans et al. 2012) 
https://collaboration.esicm.org/dl808?display

What are the clinical signs indicating a bulbar involvement in
patients with muscle weakness?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 
Reduced cough strength, difficulty in swallowing, deviation of the tongue
on protrusion, or a change in the voice are common signs indicating
bulbar or cranial nerve involvement.

Why are signs of cranial nerve involvement important to detect in
patients with muscle weakness.
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 
Protective pharyngeal reflexes can be reduced in these patients, and
the risk of inhalation of gastric content or oral secretions is greatly
increased.

How can the respiratory muscle strength be assessed in
mechanically ventilated patients with suspected respiratory
muscle weakness?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 
Inspiratory and expiratory muscle strength can be assessed by
measuring the Maximal Inspiratory Pressure (MIP), the Maximal
Expiratory Pressure (MEP) and Forced Vital Capacity (FVC). MIP and
MIP can be measured during a forced expiration and a forced
inspiration respectively, against a manual occlusion of the respiratory
circuit. Forced Vital Capacity (FVC) can be easily measured at the
bedside using a spirometer.
 
 References
Ropper AH. , Critical care of Guillain-Barré syndrome. In: Neurological and
neurosurgical intensive care., 1993, ISBN: 0781731968
Dancer R, Thickett D. , Pulmonary function tests. , 2012,
http://www.medicinejournal.co.uk/article/S1357-3039(12)00010-2/fulltext
Verceles AC, Diaz-Abad M, Geiger-Brown J, Scharf SM., Testing the
prognostic value of the rapid shallow breathing index in predicting
successful weaning in patients requiring prolonged mechanical ventilation.,
2012, PMID:22770598
Patel KN, Ganatra KD, Bates JH, Young MP., Variation in the rapid shallow
breathing index associated with common measurement techniques and
conditions., 2009, PMID:19863829
Smina M, Salam A, Khamiees M, Gada P, Amoateng-Adjepong Y, Manthous
CA., Cough peak flows and extubation outcomes., 2003, PMID:12853532
Polkey MI, Moxham J., Clinical aspects of respiratory muscle dysfunction in
the critically ill., 2001, PMID:11243977
Vitacca M, Paneroni M, Bianchi L, Clini E, Vianello A, Ceriana P, Barbano L,
Balbi B, Nava S., Maximal inspiratory and expiratory pressure measurement
in tracheotomised patients., 2006, PMID:16452590
De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand Zaleski I,
Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphaël JC, Outin H,
Bastuji-Garin S, Groupe de Réflexion et d Etude des Neuromyopathies en
Réanimation., Paresis acquired in the intensive care unit a prospective
multicenter study., 2002, PMID:12472328
Hough CL, Lieu BK, Caldwell ES., Manual muscle strength testing of
critically ill patients: feasibility and interobserver agreement., 2011,
PMID:21276225
Ali NA, O Brien JM Jr, Hoffmann SP, Phillips G, Garland A, Finley JC,
Almoosa K, Hejal R, Wolf KM, Lemeshow S, Connors AF Jr, Marsh CB,
Midwest Critical Care Consortium., Acquired weakness, handgrip strength,
and mortality in critically ill patients., 2008, PMID:18511703
Hermans G, Clerckx B, Vanhullebusch T, Segers J, Vanpee G, Robbeets C,
Casaer MP, Wouters P, Gosselink R, Van Den Berghe G., Interobserver
agreement of Medical Research Council sum-score and handgrip strength
http://www.medicinejournal.co.uk/article/S1357-3039(12)00010-2/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/22770598
https://www.ncbi.nlm.nih.gov/pubmed/19863829
https://www.ncbi.nlm.nih.gov/pubmed/12853532
https://www.ncbi.nlm.nih.gov/pubmed/11243977
https://www.ncbi.nlm.nih.gov/pubmed/16452590
https://www.ncbi.nlm.nih.gov/pubmed/12472328
https://www.ncbi.nlm.nih.gov/pubmed/21276225
https://www.ncbi.nlm.nih.gov/pubmed/18511703
https://www.ncbi.nlm.nih.gov/pubmed/22190301
in the intensive care unit., 2012, PMID:22190301
2. 4. Determining the cause of weakness
2. 4. 1. Clinical assessment
History and clinical examination should help localise the pathogenic origin of
weakness to upper and lower motor neurones, neuromuscular junctions or to skeletal
muscle itself (see below). Signs will vary depending on the anatomical localisation of
the lesion, and whether it is acute or chronic. 
For example, flaccid symmetric limb paralysis with exaggerated deep tendon reflexes,
Babinski sign, urinary urgency, retention or incontinence, and a sensory level indicates
an acute spinal cord lesion with complete transverse myelopathy. Hyperreflexia and
the Babinski sign may be absent and hypotension can be a prominent feature in the
spinal shock syndrome. Brain lesions with damage to the upper motor neurons (i.e. a
lesion above the anterior horn cell of the spinal cord or motor nuclei of the cranial
nerves ) usually present with increased muscle tone, hyperreflexia and Babinski sign,
but may acutely present with areflexia and immediate muscle flaccidity. A clinical
examination that reveals symmetrical signs with mixed motor and sensory deficits
usually indicates a peripheral nerve origin.
Standard textbooks of clinical examination and clinical signs may be used to refresh
knowledge of neurological examination and lesion localisation but Table 1 summarises
the process of lesion localisation (upper motor, lower motor, neuromuscular junction or
muscle lesion) on the basis of the clinical signs.
Table 1: Classical localising signs in neuromuscular disease
Site
Upper Motor
Neuron
Lower
Motor
Neuron
Neuromuscular
Junction
Muscle
Focal
signs
Present
Absent
(usually)
Absent Absent
Tone Increased Decreased Decreased Normal
Reflexes
Increased(*)
(±clonus)
Absent or
reduced
Normal(**) Normal
Sensation May be altered
May be
altered
Unaltered Unaltered
Muscle
Late wasting: 
Arms:
Extensor>Flexor Early
ti
Late wasting
Varied
(proximal
pattern is
https://www.ncbi.nlm.nih.gov/pubmed/22190301
https://en.wikipedia.org/wiki/Anterior_grey_column
https://en.wikipedia.org/wiki/Cranial_nerve_nucleus
https://en.wikipedia.org/wiki/Cranial_nerves
(*)In the acute stage, deep tendon reflexes can be absent. 
(**)Deep tendon reflexes are absent if neuromuscular transmission is abolished, as
with use of neuromuscular blocking agents.
 Think
Remember that the appearance of focal neurological deficits (i.e. monoparesis,
hemiparesis) should always suggest a central nervous system pathology, such
as ischaemic or haemorrhagic stroke.
 Think
Remember that intact sensation suggests an alteration of the neuromuscular
transmission, as in myasthenia gravis, or a myopathic process.
 Note
Upper motor neuron lesions cause limb muscle weakness, not respiratory
muscle weakness.
2. 5. Laboratory investigations
Most neuromuscular conditions are not associated with pathognomic abnormalities on
routine analysis of blood samples. Serum myoglobin and creatine kinase (CK) activity
are elevated in rhabdomyolysis and many myopathies. Gross elevation suggests
widespread destruction of muscle (as in rhabdomyolysis, polymyositis, and some of
the muscular dystrophies). Elevated erythrocyte sedimentation rate (ESR) or C-
reactive protein suggests an inflammatory process, althoughsepsis would need to be
excluded. Urine dipstick may be positive for blood if myoglobin is present (they cross-
react) as a result of rhabdomyolysis, although this is not a sensitive test (up to 50%
can be negative in myoglobinuria). Specific antibody tests may assist (e.g. anti-
acetylcholine receptor antibodies or anti-MUSK in myasthenia gravis; anti-synthetase
in polymyositis; anti-Ro, anti-La, anti-Sm, or anti-ribonucleoprotein antibodies in mixed
connective tissue disease; in autoimmune encephalitis, a variety of auto-antibodies
have been identified).
In text Reference
mass Legs:
Flexor>Extensor
wasting
g p
the most
common)
Others
Babinski and
Hoffman signs
Fasciculation
Fatigability may be
present
Muscle
pain
(Graus et al. 2016) 
2. 5. 1. Radiological investigations
Techniques such as computed tomography (CT) or magnetic resonance imaging (MRI)
may help localise and define the causes of upper and lower motor neurone lesions –
for instance cord compression, transverse myelitis, extradural abscess, and
demyelination. Specific angiography might be urgently required to exclude vascular
causes. Rapid diagnoses (or exclusion) of these processes should be mandatory in
the acute setting.
2. 5. 2. Cerebrospinal fluid analysis
With raised intracranial pressure appropriately excluded, analysis of cerebrospinal fluid
can prove helpful. In Guillan Barré Syndrome, raised protein content (0.5–2.0 g/L) with
no increase in cells characteristically present in over 90% of patients two weeks post-
onset, but needs to be differentiated from other causes of high CSF protein (such as
tuberculosis, neurosarcoidosis and malignancy). A white cell count of >5 cells/mm3
also may suggest an infective cause (tuberculosis, polio, encephalitis, extradural
abscess or transverse myelitis), or a haematological malignancy.
2. 5. 3. Skeletal muscle biopsy
If acute inflammatory myositis, a treatable disease, is suspected, the muscle biopsy
may be helpful in determining diagnosis. In patients developing critical illness
myopathy, the biopsy may distinguish between thick-filament myopathy (i.e. a
myopathy where only the myosin filaments are lost) and muscle fibre necrosis which
carries a worse prognosis. Muscle biopsy may also be indicated when concerns exist
of a rare underlying myopathy (leading to weakness, and thus ventilator dependence).
In such cases, biopsy site may be guided by prior magnetic resonance imaging (for
instance, in suspected cases of dermatomyositis or polymyositis).

Does the differentiation of inflammatory from non-inflammatory
muscle damage influence therapy?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Inflammatory myopathies include various forms such as
polymyositis, dermatomyositis, inclusion body myositis, and immune-
mediated necrotising myopathy. Steroids may be used if there is
evidence of muscle inflammation, sometimes with dramatic effect.
In text Reference
(Oddis 2016) 
2. 5. 4. Sleep studies
While hypercarbia may be a sign of respiratory muscle weakness, so too may it be a
sign of reduced respiratory drive or of an increase in physiological deadspace. Sleep
studies can be useful in differentiating these, and in the specific diagnosis of sleep-
related disorders. The apnoea-hypopnoea index (AHI) is a measure of the total
number of episodes per hour of sleep in which breathing ceases or is partially
obstructed. Each episode must last >10 seconds, and must be associated with arterial
deoygenation. Nocturnal hypercapnia can be the first presentation of type II respiratory
failure in Chronic Obstructive Pulmonary Disease. Finally the presence of nocturnal
hypoventilation in chronic neuromuscular diseases is a marker of disease progression,
and the need for both domiciliary non-invasive ventilation and for multidisciplinary
discussions regarding future intubation and ventilation. The presence of a severe
sleep disorder should prompt right heart investigations, as cor pulmonale requires
specific management in critically ill patients.
 Note
 
Apnoea-hypopnoea index (AHI) values are typically categorised as mild (5–
15/hr); moderate (15–30/hr) and severe (>30/h). A severe AHI (or >20% sleep
time spent with SaO2 <90%) indicates a high risk of a ‘difficult airway’ and of
post- operative respiratory failure.
 
2. 5. 5. Neurophysiological studies
 
2. 5. 5. 1. Nerve conduction studies
These can measure nerve conduction velocity and nerve action potential amplitude.
Sensory nerves are evaluated by stimulating them while recording the transmitted
action potential. Motor nerves are evaluated by stimulating them while recording the
compound muscle action potential from the innervated muscle. Slowed nerve
conduction occurs when nerves are demyelinated, the most common cause in the ICU
patients being the acute inflammatory demyelinating subtype of GBS.
2. 5. 5. 2. Compound muscle action potential (CMAP)
Reduction in amplitude suggests an axonal motor neuropathy. If associated with an
increase in duration, it suggests a myopathy.
2. 5. 5. 3. Sensory nerve action potentials (SNAP)
Reduction suggests an axonal sensory neuropathy.
2. 5. 5. 4. Repetitive stimulation
A 10% decrement suggests neuromuscular failure due to persistence of
neuromuscular blocking agents (NMBAs) or myasthenia gravis. It may also be used to
monitor the response to edrephonium in myasthenia gravis.
2. 5. 5. 5. Electromyography (EMG)
EMG is the electrophysiological examination of muscle. At rest (no patient
collaboration required), EMG abnormal muscle electrical activity such as fibrillation
potentials or positive sharp waves may suggest muscle denervation or acute myopathy
(the normal response after needle insertion into the muscle is electrical silence). With
minimal voluntary muscle contraction (patient’s collaboration required), EMG may
show low amplitude, short-duration, polyphasic motor unit potentials indicating
myopathy, or large amplitude, long-duration, polyphasic motor unit potentials indicating
neuropathy. With maximal voluntary contraction, EMG may show single oscillations or
transitional pattern indicating neuropathy, or normal interference pattern. Therefore,
EMG can differentiate myopathy from neuropathy if the patient is able to collaborate
with testing.
2. 5. 5. 6. Single-fibre electromyography (SFEMG)
When a motor axon is depolarised, the action potentials travel distally and excite the
muscle fibres at more or less the same time. SFEMG is a selective EMG recording
technique that allows the measurement of the variability in the arrival time of action
potentials belonging to the same motor unit to the micro-recording electrode.
Increased variability (jitter) reflects defective neuromuscular transmission, and is most
valuable in the patient with suspected myasthenia gravis (see Task 3 ).
2. 5. 5. 7. Direct muscle stimulation (DMS)
In DMS, both the stimulating and the recording electrodes are placed in the muscle
distal to the end-plate zone. A patient with neuropathy will have a reduced or absent
action potential when using conventional stimulation (i.e. through the motor nerve), but
normal action potential when using DMS; in case of myopathy, the action potential will
be reduced or absent after both conventional stimulation and DMS.
Nerve conduction studies and electromyography can be useful in patients who do not
respond to initial treatment, or in whom prognosis is uncertain – see Critical Illness
Polyneuropathy (CIP) and Critical Illness Myopathy (CIM) and the Patient Challenges.
Neurophysiological testing is also essential for the diagnosis of peripheral nerve injury
– both foot drop and entrapment syndromes are common and, untreated, lead to
functional disability. Further it can be used to distinguish other less common causes of
weakness (detailed below) that are unmasked by critical illness (e.g. motor neurone
disease).
https://collaboration.esicm.org/Neuromuscular%20conditions%20-%20Selected%20Diseases%20Precipitating%20ICU%20Admission:%20Myasthenia%20Gravis?page_ref_id=1079#DiagnosisTherefore, nerve conduction studies should be carried out when clinically indicated:
On clinical diagnosis of a peripheral nerve lesion
When weakness occurs acutely, and the diagnosis is unclear (or for confirmation
of diagnosis)
To investigate weakness noted late in the course of disease if clinically not in
keeping with ICU-AW
If ICU-AW does not improve despite rehabilitation.
In text References
(Latronico and Bolton. 2011) 
 How is the ICU-acquired weakness assessed in the ICU?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 The Medical Research Council (MRC) Sum Score is commonly
used to evaluate muscle strength clinically. An MRC sum score of less
than 48/60 identifies patients with significant muscle weakness.

The pattern of distribution of muscle weakness is typical in
patients with ICU- acquired weakness. Can you describe the main
features and their implication for the differential diagnosis?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 “Weakness is diffuse (involving both proximal and distal muscles),
symmetric and flaccid. It affects the limbs and the diaphragm with
relative sparing of the cranial nerves so that facial grimace is usually
preserved. If muscle weakness is limited to a single limb, other causes
should be sought e.g. entrapment neuropathy.
In text References
(Stevens et al. 2009; Sharshar et al. 2014) 
Challenge
Consider discussing with the Critical Care senior staff the routine implementation of
limb and respiratory muscle strength evaluation in patients with suspected
neuromuscular disorders. If agreed, contact your hospital’s neurophysiology
department and discuss the possibilities of undertaking such studies in the ICU
starting with a representative critically ill patient.
Anecdote
A 47-year-old man with a history of diabetes was noted to have altered ambulation
with a steppage gate pattern during rehabilitation after a three-week ICU stay for
community-acquired pneumonia and acute respiratory failure. Physical examination
showed severe muscle wasting, and ankle dorsiflexion weakness at the left leg. Nerve
conduction study eventually diagnosed a left peroneal nerve palsy. Mechanisms of
nerve injury in the ICU can be multifactorial (e.g. fractures, plasters, surgery,
immobilisation, poor pressure area care to name a few) and can remain undetermined.
Since peroneal nerve injuries usually occur at the region of the fibular head, rapid
muscle wasting resulting in loss of the fat pad over the fibular head may predispose to
pressure related nerve injury. Compression of the nerve against a bed railing may
cause nerve injury, and is easily avoided with careful attention to the patient’s
positioning in the bed.
 References
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I,
Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R,
Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl
M, Rosenfeld MR, Rostásy K, Saiz A, , A clinical approach to diagnosis of
autoimmune encephalitis., 2016, PMID:26906964
Oddis CV, Update on the pharmacological treatment of adult myositis.,
2016, PMID:27098592
Latronico N, Bolton CF., Critical illness polyneuropathy and myopathy: a
major cause of muscle weakness and paralysis., 2011, PMID:21939902
Stevens RD, Marshall SA, Cornblath DR, Hoke A, Needham DM, de
Jonghe B, Ali NA, Sharshar T., A framework for diagnosing and classifying
intensive care unit-acquired weakness., 2009, PMID:20046114
Sharshar T, Citerio G, Andrews PJ, Chieregato A, Latronico N, Menon DK,
Puybasset L, Sandroni C, Stevens RD., Neurological examination of
critically ill patients: a pragmatic approach. Report of an ESICM expert
panel., 2014, PMID:24522878
https://www.ncbi.nlm.nih.gov/pubmed/26906964
https://www.ncbi.nlm.nih.gov/pubmed/27098592
https://www.ncbi.nlm.nih.gov/pubmed/21939902
https://www.ncbi.nlm.nih.gov/pubmed/20046114
https://www.ncbi.nlm.nih.gov/pubmed/24522878
3. General Issues In The Management of the Patient with
Neuromuscular Disease
The evidence base underpinning the general ICU management of neuromuscular
disease (NM) is limited.
3. 1. Predicting acute respiratory failure
The majority of the data regarding prediction of acute respiratory failure in
neuromuscular disease relate to GBS patients, amongst whom hourly measurements
of respiratory function should be performed by competent staff. The presence of facial
weakness may make it impossible to perform measurement of FVC, and is a strong
predictor of the need for future intubation. The following parameters have been
demonstrated to predict imminent respiratory failure in GBS, and mandate transfer to
the ICU for consideration of elective intubation. Such values might pragmatically be
applied to other neuromuscular conditions, albeit without a strong evidence base to
support this:
FVC of <20 mL/kg or a rapid decline
Maximum Inspiratory Pressure <30 cmH2O
Maximum Expiratory pressure <40 cmH2O
Clinical features can also highlight those at risk of respiratory failure in GBS:
 
Time of onset to admission less than seven days
Presence of bulbar dysfunction
Low Medical Research Council (MRC) score at admission
Inability to cough
Inability to stand
Inability to lift the elbows
Inability to lift the head.
In patients with GBS, the Erasmus GBS Respiratory Insufficiency Score (EGRIS) may
help to predict the risk of developing respiratory failure requiring intubation with good
discriminative ability as follows: 1) low risk: 4% (95% CI 1–6%) with EGRIS of 0-2,
intermediate risk: 24% (95% CI 19–30%) with (EGRIS 3-4), and high risk: 65%; 95%
CI, 54–76% with EGRIS 5-7.
Table 2: Erasmus GBS Respiratory Insufficiency Score (EGRIS)
Measure Categories Score
Days between onset of
weakness and admission
>7
4-7
<4
0
1
2
Facial/bulbar weakness
at admission
Absence
Presence
0
1
MRC Sum Score
60-51
50-41
40-31
30-21
≤20
0
1
2
3
4
EGRIS = 0-7 
EGRIS = Erasmus GBS Respiratory Insufficiency Score. 
MRC = Medical Research Council.
 Think
 
Proper diagnosis requires accurate consideration of the patient’s clinical history,
as the same pattern of neurophysiological abnormalities (of peripheral nerves
and muscles) may characterise different diseases.
In text References
(Lawn et al. 2001; Sharshar et al. 2003; Durand et al. 2006; Winer 2008; Walgaard et
al. 2010)
 
 References
Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF.,
Anticipating mechanical ventilation in Guillain-Barré syndrome., 2001,
PMID:11405803
Sharshar T, Chevret S, Bourdain F, Raphaël JC, French Cooperative Group
on Plasma Exchange in Guillain-Barré Syndrome., Early predictors of
mechanical ventilation in Guillain-Barré syndrome., 2003, PMID:12545029
https://www.ncbi.nlm.nih.gov/pubmed/11405803
https://www.ncbi.nlm.nih.gov/pubmed/12545029
Durand MC, Porcher R, Orlikowski D, Aboab J, Devaux C, Clair B, Annane
D, Gaillard JL, Lofaso F, Raphael JC, Sharshar T., Clinical and
electrophysiological predictors of respiratory failure in Guillain-Barré
syndrome: a prospective study., 2006, PMID:17110282
Winer JB, Guillain-Barré syndrome., 2008, PMID:18640954
Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen
MJ, van Doorn PA, Steyerberg EW, Jacobs BC., Prediction of respiratory
insufficiency in Guillain-Barré syndrome., 2010, PMID:20517939
3. 2. Airway protection and secretion management
The indications for intubation are worsening spirometry, rising PaCO2, inability to
manage secretions and the risk of aspiration (worsening swallow or speech). Particular
attention is paid to bronchopulmonary toilet, as secretions may be increased (e.g. by
anticholinesterase treatment in myasthenia gravis) or difficult to clear due to ineffective
cough, causing pneumonia or atelectasis. In intubated patients, subglottic secretion
drainage may be of use, as this has been shown to decrease the incidence of
ventilator-acquired pneumonia in a general ICU population.

Why are oral hygiene and bronchopulmonary toilet important in
patients with NM disease?
COMPLETETASK THEN CLICK TO REVEAL THE ANSWER
 Secretions may accumulate in the oral cavity because some drugs
used in the treatment of the NM disease have anticholinesterase
effects, and patients may be unable to swallow their secretions. As
infections of the lower respiratory tract are preceded by colonisation or
infection of the upper airway, the risk of micro- or macro-aspiration of
infected secretions from the upper airway is increased in these patients.
Moreover, the epiglottis can be partially or completely incompetent in
protecting the airway, further favouring the inhalation of secretions and
pneumonia.
 Think
https://www.ncbi.nlm.nih.gov/pubmed/17110282
https://www.ncbi.nlm.nih.gov/pubmed/18640954
https://www.ncbi.nlm.nih.gov/pubmed/20517939
Oral care is an essential element of the nursing care in the ICU and an
important strategy to reduce the risk of nosocomial pneumonia.
In text References
(Lacherade et al. 2010; Nguyen et al. 2006) 
 References
Lacherade JC, De Jonghe B, Guezennec P, Debbat K, Hayon J, Monsel A,
Fangio P, Appere de Vecchi C, Ramaut C, Outin H, Bastuji-Garin S.,
Intermittent subglottic secretion drainage and ventilator-associated
pneumonia: a multicenter trial., 2010, PMID:20522796
Nguyen TN, Badjatia N, Malhotra A, Gibbons FK, Qureshi MM, Greenberg
SA., Factors predicting extubation success in patients with Guillain-Barré
syndrome., 2006, PMID:17290095
3. 3. Ventilation and weaning
Respiratory weakness generally results in reduced tidal volumes and an increase in
respiratory rate (see f/Vt, above). Higher inspiratory flow rates and levels of pressure
support may be needed in spontaneous modes of ventilation to prevent air hunger,
and ventilator trigger sensitivity may need to be increased (as patient-generated
inspiratory pressures or flows may be inadequate to trigger the ventilator). Neurally
Adjusted Ventilator Assist (NAVA) may offer advantages in this situation, given that
triggering is not based on flow or pressure, but on diaphragm electrical activity.
Weaning can only occur in the context of improving neuromuscular function. In a
series of 44 patients with GBS, the best predictor of successful weaning was an
increase of 4 mL/kg in vital capacity from pre-intubation values. In most NM diseases,
active pulmonary pathology (infection, atelectasis) or autonomic instability greatly
increases the risk of extubation failure.

Given that ventilator-associated pneumonia (VAP) and atelectasis
are frequent complications in patients with NM disease in the ICU,
explain how the chest X-ray may be useful in patient management?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
https://www.ncbi.nlm.nih.gov/pubmed/20522796
https://www.ncbi.nlm.nih.gov/pubmed/17290095
 VAP can be suspected if new infiltrates appear on chest X-ray.
Lobar atelectasis can also be diagnosed with chest X-ray showing
increased opacification of the airless lobe, displacement of hilar, cardiac
and mediastinal structures toward the side of collapse and elevation of
the ipsilateral hemidiaphragm.
See the ESICM modules on Mechanical ventilation and Lung imaging .
 
3. 4. Nutrition
Both the nutritional needs and the mode of delivery need to be assessed. Inadequate
nutrition may have led to weakness (e.g. via skeletal muscle wasting, or vitamin D
deficiency). Neuromuscular disease may also impair swallowing or gastrointestinal
motility (e.g. autonomic dysfunction secondary to Guillain–Barré syndrome, tetanus).
In the context of pharyngeal dysfunction, oral intake may have to be avoided. If
gastroparesis is present, jejeunostomy and jejunal feeding is recommended in order to
avoid as far as possible the use of parenteral feeding. On extubation, poor cough and
reduced pharyngeal strength can place patients at risk of aspiration, and this needs to
be proactively assessed.
 Note
The insertion of feeding tubes that terminate beyond the pylorus, in the first or
second part of the duodenum, may overcome the problem of altered gastric
motility, and may reduce the risk of pulmonary aspiration in patients with severe
gastroesophageal reflux and oesophagitis.
See the ESICM modules on Mechanical ventilation and Nutrition .
Challenge
You might like to talk to your hospital’s gastroenterologists to define the best nutritional
approach to patients with difficulty in gastric feeding delivery.
https://collaboration.esicm.org/Mechanical%20ventilation
https://collaboration.esicm.org/Lung%20imaging%20in%20ARDS
https://collaboration.esicm.org/Mechanical%20ventilation
https://collaboration.esicm.org/Nutrition
3. 5. Thromboprophylaxis
All patients who suffer from neuromuscular diseases are at greater risk of deep vein
thrombosis compared to many other critically ill patients, despite thromboprophylaxis.
Some clinicians advocate full anticoagulation, although there is little evidence for this
and the opportunity for harm is present. Low molecular weight subcutaneous heparin
should be used and mechanical prophylaxis may be additionally considered.
 Note
NM diseases may cause prolonged immobility, increasing the risk of deep
venous thrombosis. Thromboprophylaxis is indicated in such cases.
 Warning
 
Low molecular weight heparin, fondaparinux, or other antithrombotic agents
which are primarily cleared by the kidneys should be used with caution in
patients with acute kidney failure. A decrease in the usual dose of the drug or
use of an alternative form of thromboprophylaxis may be required.
3. 6. Sedation and mobilisation
Mobilisation may be complicated by postural hypotension as a result of autonomic
dysfunction, and therefore early mobilisation may not be practical. The importance of
postural alterations in ventilation/perfusion matching is increased, and care should be
taken to ensure the optimum amount of time is spent sitting up or out of bed. In
critically ill patients, protocols to achieve light sedation can minimise the total dose of
sedatives and analgesics, thus reducing rates of delirium and post-traumatic stress
disorder (see also the ESICM module on Sedation and Analgesia). In these patients,
who are committed to a significant period of ventilation, the additional benefit of regular
physiotherapy requires consideration. Passive movement maintains muscle
architecture (but not muscle bulk), and helps prevent contractures. Foot drop is
common and is treated with specific splints.

While debate exists as to its timing, mobilisation (at least after the
most severe component of the critical illness) can be of value in
speeding the patient’s functional recovery but postural changes
may cause hypotension. How can you manage this problem?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Postural manœuvres can be impractical in patients with severe
autonomic dysfunction and are better delayed until the patient’s medical
and neurological condition stabilises.
In text References
(Schweickert et al. 2009; Schaller et al. 2016) 
Challenge
Discuss with the ICU physiotherapist the best strategy to maintain a physical activity in
patients with autonomic dysfunction.
Challenge
Discuss with the nursing staff how to implement a nurse-directed protocol targeting
light sedation.
Anecdote
A 43-year-old previously healthy man was diagnosed with GBS characterised by a
progressive ascending paralysis requiring mechanical ventilation. He was fully awake
and oriented in time and place, and tolerated well the oral tracheal tube with no need
for sedation. On day three, he became confused and agitated. Blood chemistry
showed rapid progressive reduction of serum sodium from 139 mmol/L to 112 mmol/L.
The electrolyte profile was consistent with Syndrome of Inappropriate Anti-Diuretic
Hormone, with a low serum sodium and osmolality, and increased urine sodium
concentration and osmolality with normovolaemia. Fluid restriction and hypertonic
saline administration corrected the electrolyte abnormality, and the patient regained
normal mental status. Hyponatraemia may cause brain oedema, and should be
actively soughtin GBS. Rapid correction is only safe when the fall in serum sodium
has been rapid. If prolonged, rapid increases can lead to central pontine myelinolysis.
See the ESICM module on Electrolytes and Homeostasis (hypo and hypernatraemia)
 .
https://collaboration.esicm.org/Electrolytes%20and%20Homeostasis
 
 References
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook
CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A,
Barr R, McCallister KE, Hall JB, Kress JP., Early physical and occupational
therapy in mechanically ventilated, critically ill patients: a randomised
controlled trial., 2009, PMID:19446324
Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis I,
Heim M, Houle T, Kurth T, Latronico N, Lee J, Meyer MJ, Peponis T, Talmor
D, Velmahos GC, Waak K, Walz JM, Zafonte R, Eikermann M, International
Early SOMS-guided Mobilization Resea, Early, goal-directed mobilisation in
the surgical intensive care unit: a randomised controlled trial., 2016,
PMID:27707496
https://www.ncbi.nlm.nih.gov/pubmed/19446324
https://www.ncbi.nlm.nih.gov/pubmed/27707496
4. Selected Diseases Precipitating ICU Admission
 
4. 1. Guillain–Barré syndrome (GBS)
GBS is an acute autoimmune demyelinating motor polyneuropathy often preceded by
an infection (often a flu-like episode or campylobacter jejuni infection with
gastroenteritis). It is characterised by an ascending symmetrical limb weakness (often
beginning in the legs), accompanied by absent tendon reflexes, paraesthesia,
numbness and sometimes pain. In one third of patients, symptoms involve the four
limbs simultaneously, and in 12% progression can be from the upper to the lower
limbs. Facial muscles are frequently involved, an important differential criterion from
critical illness polyneuropathy (see Task 4). Very occasionally, autonomic dysfunction
(detailed below) is the presenting complaint.
The most common variant form is acute inflammatory demyelinating
polyradiculoneuropathy (AIDP), but others include the axonal variants (acute motor
axonal neuropathy, AMAN; acute motor and sensory axonal neuropathy, AMSAN) and
Miller Fisher’s syndrome (MFS). MFS classically presents with ophthalmoplegia,
areflexia and ataxia, and 25% also develop limb muscle weakness. GBS usually
progresses over several weeks, and by four weeks, the majority of patients will have
their severest manifestations
4. 1. 1. Diagnosis
Diagnosis of GBS comes from the clinical features (which are important in
distinguishing variants) and from cerebrospinal fluid (CSF) examination and
neurophysiological studies. The latter are necessary as the differential diagnoses are
extensive, and include lesions affecting the cerebellum,
compressive/infective/inflammatory myelopathies, toxic neuropathies, and metabolic
myopathies.
CSF protein content is typically elevated with a normal white cell count, although
protein concentration can also be normal in the first week. At lumbar puncture,
bacterial and viral meningitis should be excluded. The presence of >5 white cells/mm3
CSF, a sensory level or persistent asymmetrical weakness calls the diagnosis of GBS
into doubt (see Task 1, cerebrospinal fluid analysis). Neurophysiological investigations
are of primary importance not only to achieve a proper diagnosis (i.e. axonal
neuropathy versus demyelination) but in gauging response to treatment (using serial
measurements) and in prognostication, but in the early stages of disease they can be
normal.

Given that CSF protein concentration in patients is often normal in
the first week of GBS, what is the value of lumbar puncture in
diagnosing GBS?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 GBS is diagnosed clinically. The CSF protein is increased in more
than 90% of the patients at the end of the second week. Therefore, the
lumbar puncture is not indicated in the initial diagnostic workup unless
other diagnoses must be excluded.

Are neurophysiological studies of the peripheral nerves useful in
patients with suspected GBS?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Repeated neurophysiological studies are extremely important in
differentiating the various sub-types of the syndrome (i.e. demyelinating
versus axonal), and in gaining prognostic information.
4. 1. 2. Pathology
GBS is an autoimmune, acute peripheral neuropathy which is often preceded by an
infection, whose signs (fever) have subsided (to a symptom-free interval) by the time
the neurological signs and symptoms start – often described as a 3-phase evolution of
disease.

Can you provide a mechanistically plausible explanation for this 3-
phase pattern?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Infection sets the scene for an aberrant autoimmune response to
develop. The symptom-free interval is thought to serve for the
autoimmune response to mount (autoantibodies against various
gangliosides, activation of T cells, complement and macrophages).
Finally, the activated macrophages invade the Schwann cell, the myelin
sheath or the nodes of Ranvier, causing nerve damage.
4. 1. 3. Specific treatment
These are plasma exchange and intravenous immunoglobulin. While plasma
exchange improves muscle strength and decreases ventilator dependency, it requires
specialist staff. On the other hand, the administration of intravenous immunoglobulin is
as effective. Plasma exchange may be superior to intravenous immunoglobulin in
patients with acute respiratory failure requiring mechanical ventilation. Glucocorticoids
are ineffective in the treatment of GBS.

Is a timely diagnosis of GBS important to its optimum
management?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Yes. GBS is amenable to specific treatments, which should be
started at an early stage to achieve maximum benefit.
In text References
(Raphaël et al. 2012; Hughes, Swan and van Doorn. 2012; Cao-Lormeau et al. 2016) 
 
4. 1. 4. Controlling autonomic instability
There is often a sinus tachycardia, and blood pressure may fluctuate spontaneously,
with postural hypotension a particularly prominent feature. Dramatic autonomic
features may be precipitated by tracheal suction: sinus bradycardia, and even
asystole, may occur (and a need for temporary cardiac pacing has been described).
Drugs with an effect on autonomic nerve function (such as cisapride and
metoclopramide) should be used with caution in GBS.
 Warning
Cardiovascular complications of GBS may be life-threatening.
4. 1. 5. Pain control
There may be exquisite muscle tenderness, particularly as the patient is recovering.
This can be very distressing for the patient and staff, particularly because it is difficult
to treat. Gabapentin and Carbamazepine have been used in both the acute and long-
term settings. Morphine is effective in the short term but is practically difficult to use
well in the context of autonomic instability.
4. 1. 6. Prognosis
Approximately 20-30% of patients with GBS require mechanical ventilation. Up to 5%
die (from infection, haemodynamic instability or thromboembolic complications), but
85% recover to near–normality. Most patients reach maximal weakness at 2 weeks
although progression for up to 4 weeks is possible.
In text References
(Willison, Jacobs and van Doorn. 2016) 
 
 References
Raphaël JC, Chevret S, Hughes RA, Annane D., Plasma exchange for
Guillain-Barré syndrome., 2012, PMID:22786475
Hughes RA, Swan AV, van Doorn PA., Intravenous immunoglobulin for
Guillain-Barré syndrome., 2012, PMID:22786476
Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J,
Dub T, Baudouin L, Teissier A, Larre P, Vial AL, Decam C, Choumet V,
Halstead SK, Willison HJ, Musset L, Manuguerra JC, Despres P, Fournier
E, Mallet HP, Musso D, Fontanet A, Neil J, Ghaw, Guillain-Barré Syndrome
outbreak associated with Zika virus infection in French Polynesia: a case-
control study., 2016, PMID:26948433
Willison HJ, Jacobs BC, van Doorn PA., Guillain-Barré syndrome., 2016,
PMID:26948435
https://www.ncbi.nlm.nih.gov/pubmed/22786475
https://www.ncbi.nlm.nih.gov/pubmed/22786476https://www.ncbi.nlm.nih.gov/pubmed/26948433
https://www.ncbi.nlm.nih.gov/pubmed/26948435
4. 2. Botulism
Clostridium botulinum is found in soil, and may contaminate food – the result of
careless processing or preserving. It may also be introduced as a result of soil or
bone-meal contamination of drugs such as heroin (usually introduced when drugs are
‘cut’ with other substances) injected subcutaneously or intramuscularly (‘skin-popping’
and ‘muscle-popping’).
4. 2. 1. Pathology
The organism produces neurotoxins, types A, B, E, and (rarely) F which interfere with
the production or release of ACh and cause neuromuscular blockade and flaccid
paralysis in humans. The rapidity of onset and the severity of paralysis depend on the
amount of toxin absorbed into the circulation. Symptoms appear six hours to eight
days after ingestion of food- source toxin, or four to 18 days after wound contamination
(due to the time taken for local toxin synthesis). Wound and food botulism are similar
clinically in all other respects except for the lack of gastrointestinal symptoms in wound
botulism. Inhalational botulism has been described in laboratory workers or after
deliberate dissemination of botulinum.
4. 2. 2. Diagnosis
Further to the history, the four cardinal clinical features are:
Symmetrical descending neurological manifestations
Intact mental processes
Lack of sensory impairment, although vision may be affected due to extra-ocular
muscle involvement
Absence of fever (unless secondary complications are concurrent).
Microbiological diagnoses via serum and wound toxin assays are not always reliable,
despite their in vitro sensitivity.
4. 2. 3. Specific therapies
Patients with suspected botulism should be admitted immediately to the ICU. Patients
receiving specific anti-toxin early have shorter ventilator times and hospital stays.
Wound debridement is mandatory to remove toxin and spores. The clinical course is
shortened by early treatment.
In text References
(Latronico and Fagoni 2016; Brett, Hallas and Mpamugo. 2004; Galldiks et al. 2007;
Arnon et al. 2001; Sobel. 2009) 
 
 References
Latronico N, Fagoni N, Neuromuscular disorders & ICU acquired
neuromuscular weakness. , 2016, ISBN:9780198739555
Brett MM, Hallas G, Mpamugo O., Wound botulism in the UK and Ireland.,
2004, PMID:15150338
Galldiks N, Nolden-Hoverath S, Kosinski CM, Stegelmeyer U, Schmidt S,
Dohmen C, Kuhn J, Gerbershagen K, Bewermeyer H, Walger P, Biniek R,
Neveling M, Jacobs AH, Haupt WF., Rapid geographical clustering of
wound botulism in Germany after subcutaneous and intramuscular injection
of heroin., 2007, PMID:17356188
Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher
MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT,
O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K, Working
Group on Civilian Biodefense., Botulinum toxin as a biological weapon:
medical and public health management., 2001, PMID:11209178
Sobel J., Diagnosis and treatment of botulism: a century later, clinical
suspicion remains the cornerstone., 2009, PMID:19435432
4. 3. Tetanus
Tetanus is caused by Clostridium tetani, the spores of which are present in soil. In the
United Kingdom, 15–20 cases of tetanus are reported per year. Mortality in the
developed world is less often secondary to acute respiratory failure than to sepsis or
autonomic instability (and thus cardiac death).
4. 3. 1. Pathological features
Once the organism enters tissue (usually via wounds), it releases tetanospasmin, a
neurotoxin affecting inhibitory synaptic vesicle release. The time from inoculation with
C. tetani to the first symptom can be as short as 24 hours or as long as many months,
reflecting the distance the toxin must travel within the nervous system, and may be
related to the quantity of toxin released. The period of onset is the time between the
first symptom and the start of spasms. These periods are important prognostically, the
shorter the incubation period or period of onset the more severe the disease.
4. 3. 2. Clinical manifestations
https://www.ncbi.nlm.nih.gov/pubmed/15150338
https://www.ncbi.nlm.nih.gov/pubmed/17356188
https://www.ncbi.nlm.nih.gov/pubmed/11209178
https://www.ncbi.nlm.nih.gov/pubmed/19435432
The diagnosis of tetanus is made on clinical suspicion. The precise manifestation of
tetanus is dependent on the parts of the nervous system to which the toxin is
transported. Localised (including pure cephalic, from head and ear injuries) and
generalised (from spinal cord involvement) are thus described. Localised tetany of the
vocal cords has been reported, leading to life-threatening laryngospasm. Generalised
tetanus usually presents initially with jaw and neck signs, before spasms and rigidity
begin to spread, to affect all muscle groups. Opisthotonus – severe hyperextension
and spasticity, causing the head, neck and back to form an arch or ‘bridging’ posture –
is a classical manifestation of tetanus. This can be induced by minor stimuli, is
extremely painful and can lead to laryngeal obstruction causing asphyxia.

Tetanus can be life-threatening even if localised. Can you explain
why?
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Cephalic tetanus is a rare form of local tetanus that follows head
or facial trauma, or ear infection. The incubation period is a few days,
laryngospam is a feared complication explaining high mortality.
4. 3. 2. 1. Autonomic instability
The leading cause of death in developed world from tetanus is autonomic instability,
which manifests as labile periods of tachycardia and hypertension followed by
hypotension and bradycardias, leading to cardiac arrest. Non-cardiac manifestations
are common, and include ileus, diarrhoea, salivation and increased bronchial
secretions and pyrexia.
4. 3. 3. Specific therapies
Three goals exist: control of toxin, treating spasms and haemodynamic instability.
There is a lack of evidence-based literature, and the majority of treatments are based
on case reports.
4. 3. 3. 1. Toxin control
Clostridium tetani is an anaerobic organism and exposure of the wound +/-
debridement will minimise the anaerobic environment. Metronidazole is the antibiotic
of choice. Intravenous immunoglobulin given as a single dose of 500 IU is of use in
treating systemic toxin, and may reduce complications and length of ventilation. The
benefit of higher doses or of intrathecal therapy has not been demonstrated.
Unfortunately, this does not treat toxin already present within neuronal tissue.
Supportive care is needed until recovery, which may take up to 4–6 weeks
4. 3. 3. 2. Management of muscle spasm
General anaesthetics (including volatile agents) relieve the muscle spasm by
increasing activity of inhibitory postsynaptic receptors. Baclofen has been reported to
be of use, but when used intrathecally carries a risk of respiratory failure. Maintaining
serum magnesium concentrations at 2–4 mmol/L reduces muscle spasm and
cardiovascular instability. While the response to depolarising and non-depolarising
agents is no different from normal patients, case reports exist of hyperkalaemic cardiac
arrest following succinylcholine use in established tetanus. Deep sedation with
benzodiazepines and occasional neuromuscular blockade is often needed, which may
also address issues with haemodynamic instability. Intrathecal Baclofen is currently an
experimental alternative.. Case series exist of ketamine and dantrolene use, but with
little evidence base.

Explain why magnesium administration may reduce the
requirement for other drugs to control muscle spasms and
cardiovascular instability in tetanus.
COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER
 Magnesium is a cofactor in vital enzymatic reactions, including
glycolysis, the Krebs cycle and the respiratory chain, which represent
the core of energy metabolism. It also antagonises calcium through
calcium channel blocking properties at the level of smooth and skeletal
muscle, and conduction system. As such, magnesium inducesmuscle
relaxation, which may control spasms, and cardiovascular effects such
as vasodilatation, and reduction of heart rate (not in healthy people),
and of systemic catecholamine release, which may improve the effects
of autonomic dysfunction.
 
4. 3. 3. 3. Managing haemodynamic instability
Unfortunately ‘autonomic storms’ occur without precipitants. Both norepinephrine and
epinephrine can be released (the latter to levels associated with
phaeochromocytoma), as can acetylcholine, with para-sympathetic effects. Alterations
in systemic vascular resistance cause fluctuating systemic blood pressure. Case
reports exist of successful use of epidural and spinal bupivicane to control refractory
autonomic storms, but with vasopressor support.
Similarly, successful treatments of resistant haemodynamic instability using continuous
atropine infusions have been described.
 Note
 
A single gram of toxin, evenly dispersed and inhaled, has the potential to kill
more than 1 million people. In current times, this should perhaps not be
considered an unlikely but perhaps a possible situation.
In text References
(Trujillo et al. 1987; Kabura et al. 2006; Gibson et al. 2009; Taylor. 2006; Thwaites et
al. 2006; Dolar 1992) 
 References
Trujillo MH, Castillo A, España J, Manzo A, Zerpa R., Impact of intensive
care management on the prognosis of tetanus. Analysis of 641 cases.,
1987, PMID:3595250
Kabura L, Ilibagiza D, Menten J, Van den Ende J., Intrathecal vs.
intramuscular administration of human antitetanus immunoglobulin or
equine tetanus antitoxin in the treatment of tetanus: a meta-analysis., 2006,
PMID:16827708
Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J., Tetanus in
developing countries: a case series and review., 2009, PMID:19296192
Taylor AM. , Tetanus. , 2006,
http://ceaccp.oxfordjournals.org/content/6/3/101.full
Thwaites CL, Yen LM, Loan HT, Thuy TT, Thwaites GE, Stepniewska K,
Soni N, White NJ, Farrar JJ., Magnesium sulphate for treatment of severe
tetanus: a randomised controlled trial., 2006, PMID:17055945
Dolar D, The use of continuous atropine infusion in the management of
severe tetanus., 1992, PMID:1578043
4. 4. Myasthenia Gravis
https://www.ncbi.nlm.nih.gov/pubmed/3595250
https://www.ncbi.nlm.nih.gov/pubmed/16827708
https://www.ncbi.nlm.nih.gov/pubmed/19296192
http://ceaccp.oxfordjournals.org/content/6/3/101.full
https://www.ncbi.nlm.nih.gov/pubmed/17055945
https://www.ncbi.nlm.nih.gov/pubmed/1578043
Myasthenia gravis (MG) is an autoimmune disease, most commonly caused by
pathogenic antibodies directed at the acetylcholine receptor (ACh R), and (sometimes)
muscle specific tyrosine kinase receptors. In about 10% to 15% of MG patients no
muscle antibodies are detected after standard testing with commercially available kits
(seronegative MG subgroup). Modification of the synaptic cleft is postulated to damage
the postsynaptic neuromuscular membrane. Receptor blockade and destruction result,
reducing the number of receptors available for ACh to bind to and increasing the
threshold for a muscle action potential.
Muscle weakness and fatigability result. Ocular symptoms are near-universal, often
appear early and can indeed be the sole feature. Limb weakness is common, and is
worse after exertion. Bulbar involvement may lead to difficulty in speaking and
swallowing. Weakness of laryngeal muscles is associated with a hoarse, breathy
voice. Incomplete glottic closure during swallowing may lead to aspiration. Respiratory
fatigue leads to dyspnoea and ultimately ventilatory failure. Treatment is with tailored
doses of anticholinesterase drugs. In the United States, while rare (annual incidence
0.01/1000 persons/year), it carries a mortality of 2.2% (and 4.7% in myasthenic crises
– see below).
 Warning
 
Anticholinesterases may increase respiratory secretions in intubated patients
and delay weaning.
 Warning
Caution must be exercised in the use of competitive NMBAs in patients with
myasthenia gravis – their duration of action may be greatly prolonged. Short-
acting non-depolarising agents are preferred.
In text References 
(Meriggioli and Sanders. 2009; Alshekhlee et al. 2009; Gilhus. 2016) 
4. 4. 1. Common presentations
Patients with Myasthenia often present in respiratory failure after surgery. This may be
due to cessation of anticholinergics or directly as a result of thymectomy (see below).
Other presentations include myasthenic crises, with a rapid deterioration in muscle
strength. Respiratory failure may also occur in previously-undiagnosed patients, and in
those receiving inadequate doses of anticholinesterase medications.
Patients may present in respiratory failure requiring mechanical ventilation. It is
important to underline that – contrary to GBS, where a steady decrease of ventilatory
capacity is generally observed, thereby rendering ventilatory tests such as FVC
reliable in predicting the need for ventilatory support – the reduction in ventilatory
performance can be sudden in MG. Therefore, ventilatory tests such as the FVC are
not reliable in predicting the need for ventilatory support in patients with MG.
Other than after surgery, infection, trauma or the post-partum state may cause an
acute deterioration/myasthenic crisis and precipitate ICU admission.
Several drugs commonly used in the ICU may also aggravate the muscle weakness or,
rarely, unmask a previously-undiagnosed myasthenia gravis. These include non-
depolarising NMBA, antibiotics (aminoglycosides, polymixin B, clindamycin), drugs
with neuromuscular blocking-like action (lidocaine, procainamide, quinidine,
phenytoin), calcium channel blockers, magnesium, beta blockers (especially
propranolol), diuretics (via loss of electrolytes) and quinolones.
Overtreatment with anticholinesterases can lead to cholinergic crises. Weakness and
ventilatory failure occur, with increased salivation, abdominal colic, diarrhoea, sweating
and small pupils.
4. 4. 2. Immediate measures
As in most acute medical situations, the patients’ diagnostic and treatment needs
evolve concurrently.
Priorities in the myasthenic patient with respiratory failure are:
• Rapid assessment of the need for respiratory support 
• Increase in anticholinesterase drugs 
• Corticosteroid introduction/increase (which may or may not aid acute recovery, but
will aid longer term muscle strength) 
• Plasma exchange or intravenous immunoglobulin in cases which do not respond to
anticholinesterases and corticosteroids.
If the weakness and ventilatory failure is due to overtreatment with
anticholinesterases, the treatment is to withdraw drug therapy for at least 24 hours,
maintain monitoring and supportive measures, and to reintroduce drugs at a lower
dose.
If NMBA agents are suspected as the cause of weakness and ventilatory failure –
particularly in the postoperative phase – sugammadex, particularly in the case of
rocuronium use (or less specifically when other steroid NMBAs have been used), may
be used to reverse NMBA effect.
In text References 
(Hilton-Jones 2007) 
4. 4. 2. 1. Specific ventilation issues
A single study has attempted to use non-invasive ventilation to prevent intubation.
Weaning should begin only once plasmapheresis or intravenous immunoglobulin has
been given, and the patient shows signs of improvements in vital capacity/ negative
inspiratory force generation. Extubation failure is common (44%), the best predictor of
which is the presence of atelectasis. The mean ventilation time in a recent series of
ventilated patients was two weeks.
In text References 
(Seneviratne et al. 2008; Seneviratne et al. 2008) 
4. 4. 3. Diagnosis
Diagnosis of MG is confirmed by the presence of acetylcholine receptor antibodies,
which are specific for this disease, although not found in all cases. Anti-striated muscle
antibody is also positive in some patients, particularly those with a thymoma, but is not
specific.
Challenge
This should only be performed in patients with obvious ocular signs – a positive test is
subjectively determined