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Primary Acute Neuromuscular Respiratory Failure
Primary Acute N e u ro m u s c u l a r R e s p i r a t o r y F a i l u re Sara Hocker,
MD
KEYWORDS Weakness Acute Neuromuscular respiratory failure Recognition Evaluation Management Guillain-Barre´ syndrome Myasthenic crisis KEY POINTS The diaphragm is the principal inspiratory muscle and normally carries two-thirds of the work of breathing. A paradoxic breathing pattern is a reliable marker of diaphragmatic failure. Concomitant disease of the airways, lungs, heart, or thoracic wall can precipitate ventilatory failure in patients with neuromuscular respiratory failure. The assessment of a patient with neuromuscular respiratory failure should include arterial blood gas analysis, chest radiograph, and bedside spirometry. Noninvasive ventilation can avert intubation and shorten the duration of hospitalization in patients with myasthenic crisis but should be initiated before the development of hypercapnia. Patients with Guillain-Barre´ syndrome who develop early signs of ventilatory insufficiency or have substantial bulbar weakness should be intubated early and mechanically ventilated.
INTRODUCTION
Patients with both defined and undiagnosed neuromuscular disorders are frequently admitted to hospital services and neurologists must be able to recognize and intervene appropriately when respiratory failure develops. Neurologists are also consulted to evaluate whether a neuromuscular disorder exists when there is difficulty liberating a patient from mechanical ventilation (invasive or noninvasive). Early recognition of acute neuromuscular respiratory failure (NRF) and determination of the cause is
Disclosure Statement: Dr S. Hocker has no relationship with a commercial company that has a direct financial interest in subject matter or materials discussed in article or with any company making a competing product. Department of Neurology, Division of Critical Care Neurology, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA E-mail address: [email protected] Neurol Clin 35 (2017) 707–721 http://dx.doi.org/10.1016/j.ncl.2017.06.007 0733-8619/17/ª 2017 Elsevier Inc. All rights reserved.
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imperative, as there are survival implications. When the cause of neuromuscular weakness and resultant NRF cannot be identified, the outcome is usually poor.1 This review focuses on the clinical recognition of primary NRF (eg, related to a neurologic disease), as well as its pathophysiology, diagnostic evaluation, and management. Secondary NRF resulting from systemic disease (eg, intensive care unit acquired weakness from multiorgan failure) is not covered here. RECOGNITION OF NEUROMUSCULAR RESPIRATORY FAILURE
NRF may rarely be the presenting feature of a neurologic disorder, but more often results from disease progression or exacerbation by a superimposed respiratory illness, to the point that compensatory mechanisms are overwhelmed. The clinical presentation of dyspnea and rapid shallow breathing may be readily apparent in acute neurologic disorders, such as the Guillain-Barre´ syndrome (GBS), whereas patients with subacute neurologic disease, such as amyotrophic lateral sclerosis (ALS), who have developed the weakness over time may appear deceptively comfortable despite ventilatory failure. The clinical signs of NRF are summarized in Box 1. Early in the development of NRF, the clinical signs are subtle. The patient may appear restless but otherwise relatively normal until questioning reveals that the patient pauses to take a breath in the middle of every sentence (so called staccato speech). Patients may describe a sensation of being unable to get a full breath. Close inspection may reveal sweat on the forehead or brow, rapid shallow breathing, and activation of the accessory muscles of respiration, signaling an increased work of breathing. Palpation of the accessory muscles will reveal contraction of the muscles before it is apparent by observation alone. Additional signs may include tachycardia, frequent coughing or throat clearing suggesting difficulty in handling oral and respiratory secretions, a weak cough, and abdominal paradox. The presence of a paradoxic breathing pattern is the most reliable sign of impending respiratory failure, as it reflects diaphragmatic failure2 and may be missed if the patient is not examined in the supine position. In patients with frank failure, nasal flaring and sternal retraction also may be seen and the patient will appear anxious and fatigued. ANATOMY AND PHYSIOLOGY OF NEUROMUSCULAR RESPIRATORY FAILURE
The clinical symptoms and signs of NRF result from failure of the breathing apparatus and therefore failure of ventilation. To review, the primary muscle of inspiration is the
Box 1 Clinical signs of neuromuscular respiratory failure Restlessness Diaphoresis Tachycardia Tachypnea Staccato speech Activation of accessory muscles during inspiration Weak cough Abdominal paradox
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diaphragm, responsible for more than two-thirds of the ventilatory effort. Innervated by the phrenic nerves, formed from nerve fibers arising from the C3 to C5 roots, the diaphragm is composed of both slow-twitch and fast-twitch muscle fibers and has a rich vascular supply making it resistant to fatigue. As the work of breathing increases, the additional load is absorbed by accessory inspiratory muscles, including the external intercostals, scalene, and sternocleidomastoid muscles. Normal function of the upper airway muscles is necessary to prevent pharyngeal collapse during inspiration and aspiration of saliva or gastric contents into the airway during swallowing. Normal expiration is facilitated by passive recoil of the thoracic cage. Activation of the internal intercostal and abdominal wall muscles is required for forceful expiration and coughing. When the diaphragm and intercostal muscles become sufficiently weak that they cannot lift the ribcage, accessory muscles attached to the ribcage are enlisted to move it and assist with ventilation. These compensatory mechanisms provide only partial compensation, resulting in microatelectasis at the lung bases. At this stage, the patient may be tachypneic and examination of the arterial blood gas (ABG) will show a respiratory alkalosis with normal or mildly reduced PO2. As the muscles fatigue, generalized hypoventilation develops. The patient compensates by increasing their respiratory rate further (rapid shallow breathing) and thus testing of the blood gas at this stage will reveal a normal PCO2. Further muscular fatigue leads eventually to hypercapnia and respiratory acidosis. Hypoventilation and incomplete lung expansion lead to further alveolar collapse (atelectasis), reduced air flow, and ultimately hypoxemia. Hypoxemia is therefore a late clinical finding in NRF. The system is designed such that there is sufficient reserve to accommodate substantial weakness, unilateral, or even bilateral phrenic nerve palsies without dyspnea at rest. Patients describe dyspnea when lying supine, bending forward, or with physical exertion, particularly in those with coexisting heart or lung disease or abdominal distension due to obesity, pregnancy, or cirrhosis. Ventilatory failure occurs when the strength of the diaphragm drops below 30% of normal.3 DIAGNOSTIC EVALUATION OF NEUROMUSCULAR RESPIRATORY FAILURE History
The evaluation of a patient with acute NRF begins with a focused, yet detailed, history and review of the medical records. In addition to asking open-ended questions about the patient’s symptomatology, the following questions are of particular importance: Have they had weakness in the past (limb weakness, diplopia, dysphagia, or changes in voice) and if so for how long? This may suggest the presence of a previously undiagnosed neurologic disorder. Does the patient already carry a diagnosis of a neuromuscular disorder? Several neurologic disorders are associated with respiratory failure as a result of disease progression or aspiration. Is there a preexisting medical disease that may provide a clue to the etiology of NRF? Malignancy may suggest infiltration of the nerves and nerve roots as can occur with lymphoma or metastatic carcinoma, or a paraneoplastic syndrome, such as Lambert-Eaton myasthenic syndrome, myasthenia gravis, or paraneoplastic motor neuronopathy. Previous bone marrow transplantation predisposes patients to autoimmune diseases like GBS and myasthenia gravis. The presence of monoclonal gammopathy may point toward chronic
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inflammatory demyelinating polyneuropathy (CIDP) or POEMS (polyneuropathy, organomegaly, endocrinopathy, M spike, skin changes) syndrome, both rarely associated with acute NRF.4,5 Infection with the human immunodeficiency virus is associated with GBS, CIDP, myopathy, myositis, and polyradiculopathy.6 Do they develop dyspnea when lying supine or bending forward? These features suggest diaphragmatic weakness, as vital capacity is greater when in the upright position.3 Do they sleep on a particular side? Patients with unilateral diaphragm weakness sleep better with the affected side positioned downward to facilitate full expansion of the normal lung.7 Do they become fatigued when combing their hair or climbing stairs? Are their symptoms (eg, fatigue, weakness, and diplopia) worse at the end of the day? An affirmative response to these questions suggests fatigability of the muscles and points toward a defect in neuromuscular transmission. Have they had a recent upper respiratory infection, gastrointestinal infection, or surgery? Each of these is a potential GBS trigger. Have they had recent abdominal pain, constipation, vomiting, or psychiatric symptoms? Gastrointestinal and psychiatric symptoms in the setting of muscle weakness suggests acute intermittent porphyria, which can result in NRF.8 Have they started any new medications? Although the evidence supporting an association is generally low, several medications have been implicated in the precipitation of a myasthenic crisis, specifically antibiotics, antiarrhythmics, neuromuscular junction blockers, immunosuppressants, antirheumatics, psychotropics, phenytoin, quinine, calcium channel blockers, b-blockers, magnesium, and iodinated contrast. Have they had neck or shoulder pain, neck injury, manipulation of the cervical spine, or chest or neck surgery? These factors may suggest phrenic nerve injury.
Physical Examination
Performance of a general physical examination and complete neurologic examination is equally important, with particular attention to the function of ventilatory and bulbar muscles,2 as significant involvement of the oropharyngeal muscles increases the risk of aspiration.9,10 Examination by a seasoned clinician can often confirm the presence of NRF before any ancillary testing, pinpoint the cause, and determine the appropriate patient disposition (eg, general care, progressive care unit, or intensive care unit). Table 1 provides an overview of important examination findings and their potential implications. Specific mention must be made of the examination of the respiratory muscles. Use of accessory muscles and paradoxic breathing are not always easily recognized by inspection alone. Palpation of the sternocleidomastoid muscles will reveal muscle contractions long before they are visually obvious. Paradoxic breathing is easily visualized by inspection in the supine position, but may not be recognized if the patient is in an upright position; this is important because the paradoxic breathing pattern is a late finding that indicates already severe diaphragmatic weakness and impending failure of ventilation. Laying one’s hands on the patient’s chest and abdomen simultaneously while he or she takes a deep breath will highlight the abnormal inward movement of the abdomen during inspiration.
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Table 1 Approach to the examination of patients with neuromuscular respiratory failure System
Examination Finding
Potential Implication
Vital signs
Dysautonomia Fever and hypotension
Polyradiculopathy or neuropathy Sepsis
Lung auscultation
Diminished breath sound at the bases, wheezing, crackles, rales
Early respiratory complications (eg, atelectasis or aspiration) Comorbid cardiopulmonary disease
Lymph nodes
Lymphadenopathy
Malignancy Systemic infection
Skin inspection/ palpation
Rash Palpable purpura Myalgia
Lyme disease Vasculitis Myopathy
Neurologic examination
Tachypnea, tachycardia, diaphoresis, restlessness Patient seated upright leaning forward, staccato speech, inability to count aloud to 20 in 1 breath, weakness of neck flexion, recruitment of accessory muscles, paradoxic breathing pattern Ophthalmoparesis, ptosis
Increased work of breathing
Preserved oculomotor function with severe extremity weakness
Oropharyngeal and laryngeal weakness (testing of cough, facial and masticatory muscle strength, swallowing) Sustained upgaze and repeat muscle group testing for fatigability Sensory level Ataxia Absence of reflexes Hyporeflexia
Hyperreflexia Proximal > distal limb weakness
Muscle atrophy, fasciculations
Reduced vital capacity Diaphragmatic weakness
GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission Spinal cord injury Motor neuron disease Myopathies ICU-acquired weakness (critical illness myoneuropathy) GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission Motor neuron disease Myasthenia gravis and other disorders causing impaired neuromuscular transmission Spinal cord pathology Miller-Fisher variant of GBS Some sensorimotor neuropathies GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission; myopathy Motor neuron disease Myasthenia gravis and other disorders causing impaired neuromuscular transmission; myopathy Motor neuron disease
Abbreviations: GBS, Guillain-Barre´ syndrome; ICU, intensive care unit.
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Ancillary Investigations
History and examination should be complemented with ancillary tests, including measurement of ABG, chest radiograph, bedside spirometry, and in many cases electrophysiologic studies and ultrasound evaluation of the diaphragm.9,11,12 Traditional bedside spirometry involves measurement of vital capacity, maximal inspiratory pressure (sometimes called negative inspiratory force), and maximal expiratory pressure by having the patient inhale or exhale through a mouthpiece connected to a small metal tube with fixed leak and pressure gauges. It recently has been demonstrated that in patients with significant facial weakness who are unable to seal their lips around the mouthpiece, use of facemask in place of the mouthpiece can provide accurate spirometry data. The accuracy and reproducibility of bedside spirometry results is highly dependent on patient effort and therefore also on coaching by the examiner. When performed well, however, they can provide support for the diagnosis of NRF and give useful information about the severity of respiratory muscle weakness, need for intubation, and even the likely duration of mechanical ventilation.13 Vital capacity is the volume of gas obtained from a slow complete forced expiration after maximal inspiration. Maximal inspiratory pressure is the volume of gas measured when the patient forcefully inspires against an occluded device after maximal expiration. Maximal expiratory pressure is the maximal pressure the patient can generate by forcefully expiring against an occluded airway after maximal inspiration. Comparing the vital capacity in the upright and supine positions can confirm the presence of diaphragmatic weakness, as clinically significant diaphragmatic weakness is unlikely when there is little or no reduction of the vital capacity in the supine position.14 Chest radiographs should be examined for consolidation or infiltrates suggestive of aspiration, basal atelectasis, or elevation of one or both hemidiaphragms. Chest radiography is reasonably sensitive for the detection of unilateral diaphragm paralysis (90%) but the specificity is low (44%).15 Elevation of both hemidiaphragms is not a reliable determiner of dysfunction, as it also may be seen in patients who are ventilator dependent, have poor inspiratory effort, or simply large abdominal girth limiting lung volumes. The primary role of ABG analysis is to help assess the stage of respiratory failure. Early in the course of NRF, the blood gas is normal. As the weakness progresses, microatelectasis develops in the lung bases and respiratory alkalosis develops while the PO2 remains normal or is only slightly reduced. As the muscles fatigue, generalized alveolar hypoventilation leads to tachypnea, which temporarily maintains the PCO2 in the normal range. Eventually hypercapnia develops and ABG analysis will be consistent with a respiratory acidosis. Patients who present with a chronic respiratory acidosis (low pH, high PCO2, and high HCO3) before initiation of mechanical ventilation are less likely to survive to hospital discharge and more likely to have severe disability if they survive, especially in those without a treatable diagnosis.13 Further supportive evidence for diaphragmatic dysfunction can be obtained through electrophysiological study of phrenic nerve conduction, diaphragm electromyogram (EMG), and bedside ultrasound.16–18 The accuracy and safety of diaphragm EMG and the sensitivity and specificity of phrenic nerve conduction studies can be enhanced with ultrasound.19–21 The utility of EMG and nerve conduction studies of the extremities is in the determination of the underlying cause of NRF. Table 2 details the characteristic EMG and nerve conduction velocity findings in different categories of neuromuscular disease.
Neuromuscular Respiratory Failure
Table 2 EMG characteristics in different categories of neuromuscular disease Disease Category
EMG-NCS Features
Motor neuronopathy
Reduced CMAP amplitudes Normal or mildly reduced motor CV Normal SNAPs Fibrillations, positive waves, and fasciculations in multiple myotomes Reduced recruitment, neurogenic MUs
Polyradiculopathy and neuropathy
Demyelinating: Significant slowing of CV Marked prolongation of distal latencies Conduction block, temporal dispersion SNAPs abnormal Fibrillations and positive waves if there is concomitant axonal loss Axonal: Reduced CMAP amplitudes Normal or mildly reduced motor CV SNAPs abnormal (except for AMAN) Fibrillations and positive waves in multiple myotomes Reduced recruitment, neurogenic MUs
Neuromuscular junction disorder
Postsynaptic: Normal baseline CMAP amplitude Normal SNAPs Decrement of CMAP amplitude with low-frequency (2–5 Hz) repetitive stimulation Needle EMG normal, or may show neurogenic or myopathic units Presynaptic: Low baseline CMAP amplitude Facilitation of CMAP amplitude after brief (ie, 10 s) exertion Facilitation of the CMAP amplitude with high-frequency (20–50 Hz) repetitive stimulation Decrement of the CMAP amplitude with low-frequency (2–5 Hz) repetitive stimulation
Myopathy
CMAP amplitude reduced or normal SNAPs normal Fibrillations and positive waves Myopathic (short duration polyphasic) units Early recruitment
Abbreviations: AMAN, acute motor axonal neuropathy; CMAP, compound muscle action potential; CV, conduction velocity; EMG, electromyography; MU, motor unit; NCS, nerve conduction study; SNAP, sensory nerve action potential. From Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin 2012;30(1):161–85. Reproduced exactly, as there have been no advancements in EMG/NCV.
CAUSES OF NEUROMUSCULAR RESPIRATORY FAILURE
The primary determining factor of prognosis in patients with primary NRF is the specific cause.1 Identification of the cause is thus a critical step, as it frequently dictates the management plan. Most patients with chronic neuromuscular conditions, such as muscular dystrophy, ALS, and myasthenia gravis are managed through specialized clinics that help guide the patient through all stages of the disease, including the progressive NRF that plagues progressive disorders like ALS. Those who choose to do so are set up with noninvasive ventilation (NIV) and suctioning equipment after undergoing sleep studies through outpatient mechanisms.
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Some, however, come to medical attention only when the respiratory muscles become involved, either because of a rapid progression of the disease, or previous misdiagnosis. In rare cases, respiratory failure may be the presenting clinical feature, prompting them to seek evaluation, and in some cases it is pneumonia or other concurrent cardiopulmonary illness that leads them to decompensate. Neurologists are typically called when the patient cannot be liberated from mechanical ventilation. Among 85 adults admitted with acute NRF to the intensive care unit over a 6-year period, the most frequent diagnoses were myasthenic crisis, GBS, myopathies, and ALS (27, 12, 12, and 12 patients, respectively). Remarkably, 55% of patients had no known neuromuscular diagnosis before admission, and 12% remained without a diagnosis on hospital discharge. Those without a neuromuscular diagnosis before admission were intubated longer, had longer intensive care unit stays and worse outcomes at discharge from the hospital, and 17% of these patients were ultimately diagnosed with ALS.1 Physicians should therefore consider ALS when asked to evaluate patients with unexplained acute respiratory failure of presumed neuromuscular cause. Box 2 summarizes the differential diagnosis of acute NRF. The remainder of this section reviews the management of acute NRF in the context of the 2 most common causes: GBS and myasthenic crisis. Acute Neuromuscular Respiratory Failure in Guillain-Barre´ Syndrome
GBS is an acute, self-limited, autoimmune-mediated, inflammatory polyradiculoneuropathy. GBS is an umbrella term for several well-characterized variants of the disorder. The most common form is primarily manifested by flaccid weakness with areflexia. Limb weakness, often with sensory and cranial nerve involvement, begins typically 1 to 2 weeks after an immune stimulus (eg, infection, vaccination, or surgery) and progresses to a nadir in 2 to 4 weeks.22 It is associated with dysautonomia, which can produce labile blood pressure, tachyarrhythmias, and severe bradyarrhythmias and conduction blocks. Disautonomia can worsen in response to physical stress (such as what occurs with acute NRF) or medications, such as betablockers.23 Respiratory failure from severe diaphragmatic and bulbar muscle weakness affects 20% to 30% of patients with GBS.24 Diaphragmatic failure can develop suddenly and force emergency intubation. This is made even more dangerous if the patient has dysautonomia. Predictors of the development of acute NRF in GBS include a short interval between the onset of symptoms and hospitalization, presence of bulbar or facial weakness, axonal involvement, or severe appendicular weakness as measured by the Erasmus GBS Respiratory Insufficiency Score.25 Respiratory muscle strength should be monitored frequently by physical examination (discussed previously) and serial bedside spirometry. A forced vital capacity of less than 20 mm Hg, maximal inspiratory pressure less than 30 cm H2O, maximal expiratory pressure less than 40 mm Hg, or a decrease in forced vital capacity of greater than 30% over 24 hours are reliable predictors of progression to respiratory failure and the need for invasive mechanical ventilation.26 Patients meeting any of these criteria should be promptly intubated before the development of frank ventilatory failure and hypercapnia. NIV is not a good option for patients with GBS (rationale discussed in the next section). Immune therapy with either plasma exchange or intravenous immunoglobulin (IVIG) is effective in speeding the rate of recovery and is most beneficial when started within 2 weeks of the onset of symptoms.24,27,28
Neuromuscular Respiratory Failure
Box 2 Differential diagnosis of acute neuromuscular respiratory failure Anterior Horn Cell Amyotrophic lateral sclerosis West Nile virus Poliomyelitis or post-polio syndrome Kennedy disease Tetanus Nerve Roots and Peripheral Nerves Congenital Charcot-Marie-Tooth Acquired Critical illness polyneuropathy Guillain-Barre´ syndrome Acute onset or exacerbation of chronic inflammatory demyelinating polyneuropathy Toxins (rarely result in respiratory failure) Vasculitis Paraneoplastic syndrome Porphyria Infiltrative disease (amyloid or lymphoma) Phrenic nerve injury Neuromuscular Junction Myasthenia gravis Lambert-Eaton myasthenic syndrome Neuromuscular blocking agents Toxins (organophosphate poisoning, tick paralysis, snake venom, botulism) Muscle Congenital Dystrophies (Duchenne, Becker, limb girdle) Myopathies (myofibrillary, mitochondrial, myotonia congenita) Acid maltase deficiency Acquired Critical illness myopathy Inflammatory myopathies (dermatomyositis, inclusion body) Metabolic myopathies (hyperthyroidism, hypophosphatemia, hyperkalemia, hypokalemia, and hypernatremia) Toxins (statins, colchicine, neuromuscular blocking agents, steroids) Rhabdomyolysis Adapted from Rabinstein AA. Acute neuromuscular respiratory failure. Continuum (Minneap Minn) 2015;21:1324–45; and Howard RS. Respiratory failure because of neuromuscular disease. Curr Opin Neurol 2016;29(5):592–601.
Acute Neuromuscular Respiratory Failure in Myasthenic Crisis
Myasthenia gravis is an autoimmune disorder resulting in impaired neuromuscular transmission variably characterized by fatigable weakness of the appendicular, bulbar, ocular, and respiratory muscles.29 Autoantibodies typically target either the postsynaptic nicotinic acetylcholine receptors in the muscle membrane.30 Myasthenia gravis also can be caused by antibodies against the muscle-specific tyrosine kinase,
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which result in more bulbar involvement and a higher predisposition to respiratory failure.31 Approximately one-fifth of patients will develop a myasthenic crisis over the course of their disease, defined by the development of respiratory failure and need for either invasive or noninvasive mechanical ventilation.32 A crisis may be triggered by infection, surgery, or medication changes (eg, initiation of a fluoroquinolone or aminoglycoside or change in the timing or dosage of the patient’s daily myasthenia gravis regimen). Patients often describe a preceding history of a weakening voice and worsening dysphagia, dysarthria, diplopia, or ptosis. Examination frequently shows ptosis, difficulty sustaining upgaze, bifacial weakness, weakness of jaw closure, hypophonia, weak cough, and fatigable extremity weakness (proximal > distal). Patients often describe an increase in oropharyngeal secretions most often due to the bulbar weakness and inability to effectively swallow them, but this must be distinguished from cholinergic excess due to additional pyridostigmine doses (either physician or patient directed) used to try to reduce the worsening symptoms. The value of bedside spirometry, although frequently used in this setting, is not well established largely due to the fluctuating and fatigable nature of the weakness. Treatment with either plasma exchange or IVIG speeds the rate of recovery,33,34 and a recent retrospective study showed that plasma exchange led to earlier extubation.35 Patients with myasthenic crisis must receive corticosteroids to be successfully liberated from mechanical ventilation (invasive or noninvasive). The optimal route and dose are not well established. Caution should be exercised when initiating highdose steroids in nonintubated patients, as between one-third and one-half of patients will develop clinically significant worsening of their weakness within days of starting this treatment.12 Early initiation of NIV with bilevel positive airway pressure (BiPAP) can prevent the need for endotracheal intubation in some patients (discussed in the next section).36,37 Patients should be intubated if they have severe hypercapnia, hypoxemia, lobar atelectasis, or copious secretions that require very frequent suctioning. Once intubated, most patients require between 8 and 14 days of mechanical ventilation. Few are successfully extubated within the first week, and some require tracheostomy and prolonged ventilatory support.32,37,38 The rate of extubation failure is 25%, which is high compared with that seen in general critical care and is more likely in patients with radiographically apparent atelectasis.37,39 Because ongoing weakness and a tendency to fatigue are common following extubation, it is good practice to extubate to BiPAP and continue NIV the first night to prevent ventilatory failure and alveolar collapse during rapid eye movement sleep when muscle tone is absent.40,41 NONINVASIVE VENTILATION, INVASIVE VENTILATION, AND TRACHEOSTOMY IN NEUROMUSCULAR RESPIRATORY FAILURE
Select patients presenting with acute NRF may benefit from NIV. NIV is safe in some situations but potentially dangerous in others, so an understanding of the nature of the underlying neuromuscular disorder; stage of respiratory failure; level of consciousness; volume of secretions; ability to expectorate; and presence of pulmonary edema, pneumonia, or significant atelectasis are all important in determining whether it is an appropriate intervention. NIV is well recognized as a life-prolonging tool in advanced stages of progressive neurologic disorders, such as ALS and muscular dystrophies, and in the case of ALS has been shown to improve the quality of life.42,43 Not infrequently, however, these patients and others with chronic neuromuscular disorders, such as myasthenia
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gravis, present to the emergency department in acute NRF when a concurrent disease precipitates a rapid decline. NIV combined with mobilization and careful pulmonary hygiene can avoid the need for intubation and tracheostomy in appropriately selected patients.44 NIV also can be used to support patients in the recovery phase of GBS, where progressive improvement in muscle strength is anticipated. NIV refers to either the mechanical delivery of continuous positive airway pressure (CPAP) or BiPAP.45,46 CPAP helps to overcome the resistance of the upper airways and keeps the alveoli open at end expiration, improving gas exchange, and therefore oxygenation. CPAP does not assist with ventilation and thus is not indicated for NRF where the primary problem is respiratory muscle fatigue and failure of ventilation. BiPAP provides both inspiratory and expiratory positive expiratory pressure, and the option of providing oxygen and a backup rate if required.47 Fitting the mask with sufficient comfort while minimizing air leaks is probably the most important and challenging step in initiating NIV.45 There are many options, including nasal, oronasal, and full face masks. Oronasal masks are preferred, as they avoid the claustrophobia of full face masks and are not limited by mouth breathing, common in neuromuscular disease, as are the nasal masks. Selection of the mask is ultimately determined by fit and patient comfort. A common misconception is that facial weakness is a contraindication to NIV, when, in fact, patients with facial and oropharyngeal weakness are often easier to ventilate, as they synchronize more readily with the mechanical delivery of air (they resist less, allowing for delivery of good tidal volumes). As discussed previously, NIV is particularly useful in patients with myasthenic crisis because of the nature of the disease itself. The muscle weakness in myasthenia gravis is fluctuating, worsens with exercise, and improves with rest. This, and because treatment can be expected to be effective over a period of days to weeks, explains why prompt support with NIV (rest) in this setting can reverse the worsening weakness and prevent the need for endotracheal intubation.36,37 BiPAP also has been shown to shorten the length of both intensive care unit and hospital stay in patients presenting with myasthenic crisis,37 primarily by reducing the frequency of pulmonary complications, such as atelectasis and pneumonia.11,37 Because pulmonary edema due to heart failure and chronic obstructive pulmonary disease are both conditions known to be successfully managed with NIV, it is also appropriate to consider NIV to treat neuromuscular disorders decompensated by these conditions.47 Box 3 lists indications for NIV in acute NRF. Unlike in myasthenic crisis, NIV is not a good option for acute NRF due to GBS for 2 reasons.48 First, the associated dysautonomia makes the prospect of emergency intubation even more dangerous, as it can lead to life-threatening dysrhythmias or severe blood pressure fluctuations.49 Second, patients with GBS who
Box 3 Indications for noninvasive ventilation in acute neuromuscular respiratory failure Myasthenic crisis Chronic neuromuscular disorders exacerbated by pulmonary edema or COPD exacerbation Progressive neuromuscular disorders (eg, ALS, muscular dystrophies) Resolving GBS, myasthenic crisis or inflammatory myopathy with persistent weakness after extubation Abbreviations: ALS, amyotrophic lateral sclerosis; COPD, chronic obstructive pulmonary disease; GBS, Guillain-Barre´ syndrome.
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develop respiratory muscle involvement are likely to continue to decline and to have prolonged nadir and recovery phases with no immediate option to reverse the process. Thus, temporizing with NIV will not be effective. Patients with GBS should therefore be electively intubated when they have (1) severe or rapidly progressive weakness, (2) marked bulbar weakness, or (3) early signs of impaired ventilation. Other contraindications to NIV include a reduced level of consciousness, such that patients could not communicate distress or protect their airway, and extremely agitated patients who may require sedation to facilitate treatment and ensure safety. This level of agitation must be distinguished from the restlessness seen in patients with acute NRF that results from air hunger, which will improve when their work of breathing and air hunger are reduced by NIV. Clinical situations in which a patient may present with both a reduced level of consciousness and NRF include trauma and West Nile encephalomyelitis, and these patients should be electively intubated for airway protection.50 Patients with upper cervical spinal cord injury are anticipated to have long-term NRF and should thus be intubated and, once stabilized, undergo tracheostomy. Intubation is also necessary in patients who are systemically unstable, such as those in septic shock. Dysphagia and pooling of oral and respiratory secretions do not represent an absolute contraindication to a trial of treatment but should be carefully monitored, and in many cases patients will suction themselves and require assistance only with taking the BiPAP off and on. NIV is effective only when initiated before the development of frank hypercapnia and severe respiratory or mixed acidosis, where it has been shown that the chances of BiPAP failure are unacceptably high.36,37 Indications for endotracheal intubation are listed in Box 4. The use of succinylcholine for induction is contraindicated in all neuromuscular disorders because of the risk of severe hyperkalemia.51–54 In those patients who are intubated for NRF, tracheostomy should be pursued as soon as it is clear that a prolonged period of mechanical ventilation will be required. Tracheostomy facilitates suctioning, improves patient comfort, allows for the eventual possibility of oral intake and speech, and aids in weaning from mechanical ventilation by reduction of dead space.
Box 4 Indications for intubation Current or anticipated sedation Reduced level of consciousness Excessive secretions Increasing oxygen requirements Failure to improve with bilevel positive airway pressure trial Significant atelectasis or consolidation on chest radiograph Hypercapnia with respiratory acidosis Hemodynamic instability Active coronary ischemia Rapid progression of weakness Guillain-Barre´ syndrome Acute spinal cord injury
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REFERENCES
1. Cabrera Serrano M, Rabinstein AA. Causes and outcomes of acute neuromuscular respiratory failure. Arch Neurol 2010;67:1089–94. 2. Rabinstein AA, Wijdicks EF. Warning signs of imminent respiratory failure in neurological patients. Semin Neurol 2003;23:97–104. 3. McCool FD, Tzelepis GE. Dysfunction of the diaphragm. N Engl J Med 2012;366: 932–42. SA, Peltier AC, Iacob T, et al. Chronic inflammatory demyelinating poly4. Zivkovic neuropathy and ventilatory failure: report of seven new cases and review of the literature. Acta Neurol Scand 2011;124(1):59–63. 5. Wu SG, Kuo PH, Yang PC. Successful weaning after plasma exchange for polyneuropathy related to POEMS syndrome. J Clin Apher 2009;24(4):170–2. 6. Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin 2012;30(1):161–85. 7. Baltzan MA, Scott AS, Wolkove N. Unilateral hemidiaphragm weakness is associated with positional hypoxemia in REM sleep. J Clin Sleep Med 2012;8:51–8. 8. Mehta M, Rath GP, Padhy UP, et al. Intensive care management of patients with acute intermittent porphyria: clinical report of four cases and review of literature. Indian J Crit Care Med 2010;14(2):88–91. 9. Hutchinson D, Whyte K. Neuromuscular disease and respiratory failure. Pract Neurol 2008;8:229–37. 10. Flower O, Bowles C, Wijdicks E, et al. Emergency neurological life support: acute nontraumatic weakness. Neurocrit Care 2012;17(Suppl 1):S79–95. 11. Rabinstein AA. Update on respiratory management of critically ill neurologic patients. Curr Neurol Neurosci Rep 2005;5:476–82. 12. Rabinstein AA. Acute neuromuscular respiratory failure. Continuum (Minneap Minn) 2015;21:1324–45. 13. Cabrera Serrano M, Rabinstein AA. Usefulness of pulmonary function tests and blood gases in acute neuromuscular respiratory failure. Eur J Neurol 2012; 19(3):452–6. 14. Mier-Jedrzejowicz A, Brophy C, Moxham J, et al. Assessment of diaphragm weakness. Am Rev Respir Dis 1988;137:877–83. 15. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Respir Med 2005;99:39–44. 16. Amirjani N, Hudson AL, Butler JE, et al. An algorithm for the safety of costal diaphragm electromyography derived from ultrasound. Muscle Nerve 2012;46: 856–60. 17. Bellani G, Mauri T, Coppadoro A, et al. Estimation of patient’s inspiratory effort from the electrical activity of the diaphragm. Crit Care Med 2013;41:1483–91. 18. Jenkins JA, Sakamuri S, Katz JS, et al. Phrenic nerve conduction studies as a biomarker of respiratory insufficiency in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2016;17:213–20. 19. Johnson NE, Utz M, Patrick E, et al. Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies. Muscle Nerve 2014;49:669–75. 20. Boon AJ, Sekiguchi H, Harper CJ, et al. Sensitivity and specificity of diagnostic ultrasound in the diagnosis of phrenic neuropathy. Neurology 2014;83:1264–70. 21. Boon AJ, O’Gorman C. Ultrasound in the assessment of respiration. J Clin Neurophysiol 2016;33:112–9.
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22. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barre´ syndrome. Lancet 2016; 388(10045):717–27. 23. Zochodne DW. Autonomic involvement in Guillain–Barre syndrome: a review. Muscle Nerve 1994;17:1145–55. 24. Fokke C, van den Berg B, Drenthen J, et al. Diagnosis of Guillain-Barre´ syndrome and validation of Brighton criteria. Brain 2014;137(Pt 1):33–43. 25. Walgaard C, Lingsma HF, Ruts L, et al. Prediction of respiratory insufficiency in Guillain-Barre´ syndrome. Ann Neurol 2010;67(6):781–7. 26. Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical ventilation in Guillain–Barre syndrome. Arch Neurol 2001;58:893–8. 27. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for GuillainBarre´ syndrome. Cochrane Database Syst Rev 2014;(9):CD002063. 28. Raphae¨l JC, Chevret S, Hughes RA, et al. Plasma exchange for Guillain-Barre´ syndrome. Cochrane Database Syst Rev 2002;(2):CD001798. 29. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015;14:1023–36. 30. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 2009;8:475–90. 31. Deymeer F, Gungor-Tuncer O, Yilmaz V, et al. Clinical comparison of anti-MuSKvs anti-AChR- positive and seronegative myasthenia gravis. Neurology 2007;68: 609–11. 32. Thomas CE, Mayer SA, Gungor Y, et al. Myasthenic crisis: clinical features, mortality, complications, and risk factors for prolonged intubation. Neurology 1997; 48(5):1253–60. 33. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev 2012;(12):CD002277. 34. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database Syst Rev 2002;(4):CD002275. 35. Liu Z, Yao S, Zhou Q, et al. Predictors of extubation outcomes following myasthenic crisis. J Int Med Res 2016;44(6):1524–33. 36. Rabinstein A, Wijdicks EF. BiPAP in acute respiratory failure due to myasthenic crisis may prevent intubation. Neurology 2002;59:1647–9. 37. Seneviratne J, Mandrekar J, Wijdicks EF, et al. Noninvasive ventilation in myasthenic crisis. Arch Neurol 2008;65:54–8. 38. Kalita J, Kohat AK, Misra UK. Predictors of outcome of myasthenic crisis. Neurol Sci 2014;35(7):1109–14. 39. Rabinstein AA, Mueller-Kronast N. Risk of extubation failure in patients with myasthenic crisis. Neurocrit Care 2005;3:213–5. 40. Irfan M, Selim B, Rabinstein AA, et al. Neuromuscular disorders and sleep in critically ill patients. Crit Care Clin 2015;31:533–50. 41. Rabinstein AA. Noninvasive ventilation for neuromuscular respiratory failure: when to use and when to avoid. Curr Opin Crit Care 2016;22(2):94–9. 42. Radunovic A, Annane D, Rafiq MK, et al. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2013;(3):CD004427. 43. Villanova M, Brancalion B, Mehta AD. Duchenne muscular dystrophy: life prolongation by noninvasive ventilatory support. Am J Phys Med Rehabil 2014;93: 595–9. 44. Bach JR, Goncalves MR, Hamdani I, et al. Extubation of patients with neuromuscular weakness: a new management paradigm. Chest 2010;137:1033–9.
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45. Gregoretti C, Pisani L, Cortegiani A, et al. Noninvasive ventilation in critically ill patients. Crit Care Clin 2015;31:435–57. 46. Hill NS, Brennan J, Garpestad E, et al. Noninvasive ventilation in acute respiratory failure. Crit Care Med 2007;35:2402–7. 47. Nava S, Hill N. Noninvasive ventilation in acute respiratory failure. Lancet 2009; 374:250–9. 48. Wijdicks EF, Roy TK. BiPAP in early Guillain-Barre´ syndrome may fail. Can J Neurol Sci 2006;33(1):105–6. 49. Henderson RD, Lawn ND, Fletcher DD, et al. The morbidity of Guillain–Barre syndrome admitted to the intensive care unit. Neurology 2003;60:17–21. 50. Wang H, Siddharthan V, Kesler KK, et al. Fatal neurological respiratory insufficiency is common among viral encephalitides. J Infect Dis 2013;208:573–83. 51. Racca F, Mongini T, Wolfler A, et al. Recommendations for anesthesia and perioperative management of patients with neuromuscular disorders. Minerva Anestesiol 2013;79(4):419–33. 52. Wijdicks EFM. The practice of emergency and critical care neurology. 2nd edition. New York: Oxford University Press; 2016. 53. Wijdicks EFM. Handling difficult situations. New York: Oxford University Press; 2014. 54. Rabinstein AA. Practical management of Guillain-Barre´ syndrome and myasthenic crisis. In: Manno EM, editor. Emergency management in neurocritical care. Oxford (United Kingdom): Wiley-Blackwell; 2012. p. 141–51.
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KEYWORDS Weakness Acute Neuromuscular respiratory failure Recognition Evaluation Management Guillain-Barre´ syndrome Myasthenic crisis KEY POINTS The diaphragm is the principal inspiratory muscle and normally carries two-thirds of the work of breathing. A paradoxic breathing pattern is a reliable marker of diaphragmatic failure. Concomitant disease of the airways, lungs, heart, or thoracic wall can precipitate ventilatory failure in patients with neuromuscular respiratory failure. The assessment of a patient with neuromuscular respiratory failure should include arterial blood gas analysis, chest radiograph, and bedside spirometry. Noninvasive ventilation can avert intubation and shorten the duration of hospitalization in patients with myasthenic crisis but should be initiated before the development of hypercapnia. Patients with Guillain-Barre´ syndrome who develop early signs of ventilatory insufficiency or have substantial bulbar weakness should be intubated early and mechanically ventilated.
INTRODUCTION
Patients with both defined and undiagnosed neuromuscular disorders are frequently admitted to hospital services and neurologists must be able to recognize and intervene appropriately when respiratory failure develops. Neurologists are also consulted to evaluate whether a neuromuscular disorder exists when there is difficulty liberating a patient from mechanical ventilation (invasive or noninvasive). Early recognition of acute neuromuscular respiratory failure (NRF) and determination of the cause is
Disclosure Statement: Dr S. Hocker has no relationship with a commercial company that has a direct financial interest in subject matter or materials discussed in article or with any company making a competing product. Department of Neurology, Division of Critical Care Neurology, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA E-mail address: [email protected] Neurol Clin 35 (2017) 707–721 http://dx.doi.org/10.1016/j.ncl.2017.06.007 0733-8619/17/ª 2017 Elsevier Inc. All rights reserved.
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imperative, as there are survival implications. When the cause of neuromuscular weakness and resultant NRF cannot be identified, the outcome is usually poor.1 This review focuses on the clinical recognition of primary NRF (eg, related to a neurologic disease), as well as its pathophysiology, diagnostic evaluation, and management. Secondary NRF resulting from systemic disease (eg, intensive care unit acquired weakness from multiorgan failure) is not covered here. RECOGNITION OF NEUROMUSCULAR RESPIRATORY FAILURE
NRF may rarely be the presenting feature of a neurologic disorder, but more often results from disease progression or exacerbation by a superimposed respiratory illness, to the point that compensatory mechanisms are overwhelmed. The clinical presentation of dyspnea and rapid shallow breathing may be readily apparent in acute neurologic disorders, such as the Guillain-Barre´ syndrome (GBS), whereas patients with subacute neurologic disease, such as amyotrophic lateral sclerosis (ALS), who have developed the weakness over time may appear deceptively comfortable despite ventilatory failure. The clinical signs of NRF are summarized in Box 1. Early in the development of NRF, the clinical signs are subtle. The patient may appear restless but otherwise relatively normal until questioning reveals that the patient pauses to take a breath in the middle of every sentence (so called staccato speech). Patients may describe a sensation of being unable to get a full breath. Close inspection may reveal sweat on the forehead or brow, rapid shallow breathing, and activation of the accessory muscles of respiration, signaling an increased work of breathing. Palpation of the accessory muscles will reveal contraction of the muscles before it is apparent by observation alone. Additional signs may include tachycardia, frequent coughing or throat clearing suggesting difficulty in handling oral and respiratory secretions, a weak cough, and abdominal paradox. The presence of a paradoxic breathing pattern is the most reliable sign of impending respiratory failure, as it reflects diaphragmatic failure2 and may be missed if the patient is not examined in the supine position. In patients with frank failure, nasal flaring and sternal retraction also may be seen and the patient will appear anxious and fatigued. ANATOMY AND PHYSIOLOGY OF NEUROMUSCULAR RESPIRATORY FAILURE
The clinical symptoms and signs of NRF result from failure of the breathing apparatus and therefore failure of ventilation. To review, the primary muscle of inspiration is the
Box 1 Clinical signs of neuromuscular respiratory failure Restlessness Diaphoresis Tachycardia Tachypnea Staccato speech Activation of accessory muscles during inspiration Weak cough Abdominal paradox
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diaphragm, responsible for more than two-thirds of the ventilatory effort. Innervated by the phrenic nerves, formed from nerve fibers arising from the C3 to C5 roots, the diaphragm is composed of both slow-twitch and fast-twitch muscle fibers and has a rich vascular supply making it resistant to fatigue. As the work of breathing increases, the additional load is absorbed by accessory inspiratory muscles, including the external intercostals, scalene, and sternocleidomastoid muscles. Normal function of the upper airway muscles is necessary to prevent pharyngeal collapse during inspiration and aspiration of saliva or gastric contents into the airway during swallowing. Normal expiration is facilitated by passive recoil of the thoracic cage. Activation of the internal intercostal and abdominal wall muscles is required for forceful expiration and coughing. When the diaphragm and intercostal muscles become sufficiently weak that they cannot lift the ribcage, accessory muscles attached to the ribcage are enlisted to move it and assist with ventilation. These compensatory mechanisms provide only partial compensation, resulting in microatelectasis at the lung bases. At this stage, the patient may be tachypneic and examination of the arterial blood gas (ABG) will show a respiratory alkalosis with normal or mildly reduced PO2. As the muscles fatigue, generalized hypoventilation develops. The patient compensates by increasing their respiratory rate further (rapid shallow breathing) and thus testing of the blood gas at this stage will reveal a normal PCO2. Further muscular fatigue leads eventually to hypercapnia and respiratory acidosis. Hypoventilation and incomplete lung expansion lead to further alveolar collapse (atelectasis), reduced air flow, and ultimately hypoxemia. Hypoxemia is therefore a late clinical finding in NRF. The system is designed such that there is sufficient reserve to accommodate substantial weakness, unilateral, or even bilateral phrenic nerve palsies without dyspnea at rest. Patients describe dyspnea when lying supine, bending forward, or with physical exertion, particularly in those with coexisting heart or lung disease or abdominal distension due to obesity, pregnancy, or cirrhosis. Ventilatory failure occurs when the strength of the diaphragm drops below 30% of normal.3 DIAGNOSTIC EVALUATION OF NEUROMUSCULAR RESPIRATORY FAILURE History
The evaluation of a patient with acute NRF begins with a focused, yet detailed, history and review of the medical records. In addition to asking open-ended questions about the patient’s symptomatology, the following questions are of particular importance: Have they had weakness in the past (limb weakness, diplopia, dysphagia, or changes in voice) and if so for how long? This may suggest the presence of a previously undiagnosed neurologic disorder. Does the patient already carry a diagnosis of a neuromuscular disorder? Several neurologic disorders are associated with respiratory failure as a result of disease progression or aspiration. Is there a preexisting medical disease that may provide a clue to the etiology of NRF? Malignancy may suggest infiltration of the nerves and nerve roots as can occur with lymphoma or metastatic carcinoma, or a paraneoplastic syndrome, such as Lambert-Eaton myasthenic syndrome, myasthenia gravis, or paraneoplastic motor neuronopathy. Previous bone marrow transplantation predisposes patients to autoimmune diseases like GBS and myasthenia gravis. The presence of monoclonal gammopathy may point toward chronic
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inflammatory demyelinating polyneuropathy (CIDP) or POEMS (polyneuropathy, organomegaly, endocrinopathy, M spike, skin changes) syndrome, both rarely associated with acute NRF.4,5 Infection with the human immunodeficiency virus is associated with GBS, CIDP, myopathy, myositis, and polyradiculopathy.6 Do they develop dyspnea when lying supine or bending forward? These features suggest diaphragmatic weakness, as vital capacity is greater when in the upright position.3 Do they sleep on a particular side? Patients with unilateral diaphragm weakness sleep better with the affected side positioned downward to facilitate full expansion of the normal lung.7 Do they become fatigued when combing their hair or climbing stairs? Are their symptoms (eg, fatigue, weakness, and diplopia) worse at the end of the day? An affirmative response to these questions suggests fatigability of the muscles and points toward a defect in neuromuscular transmission. Have they had a recent upper respiratory infection, gastrointestinal infection, or surgery? Each of these is a potential GBS trigger. Have they had recent abdominal pain, constipation, vomiting, or psychiatric symptoms? Gastrointestinal and psychiatric symptoms in the setting of muscle weakness suggests acute intermittent porphyria, which can result in NRF.8 Have they started any new medications? Although the evidence supporting an association is generally low, several medications have been implicated in the precipitation of a myasthenic crisis, specifically antibiotics, antiarrhythmics, neuromuscular junction blockers, immunosuppressants, antirheumatics, psychotropics, phenytoin, quinine, calcium channel blockers, b-blockers, magnesium, and iodinated contrast. Have they had neck or shoulder pain, neck injury, manipulation of the cervical spine, or chest or neck surgery? These factors may suggest phrenic nerve injury.
Physical Examination
Performance of a general physical examination and complete neurologic examination is equally important, with particular attention to the function of ventilatory and bulbar muscles,2 as significant involvement of the oropharyngeal muscles increases the risk of aspiration.9,10 Examination by a seasoned clinician can often confirm the presence of NRF before any ancillary testing, pinpoint the cause, and determine the appropriate patient disposition (eg, general care, progressive care unit, or intensive care unit). Table 1 provides an overview of important examination findings and their potential implications. Specific mention must be made of the examination of the respiratory muscles. Use of accessory muscles and paradoxic breathing are not always easily recognized by inspection alone. Palpation of the sternocleidomastoid muscles will reveal muscle contractions long before they are visually obvious. Paradoxic breathing is easily visualized by inspection in the supine position, but may not be recognized if the patient is in an upright position; this is important because the paradoxic breathing pattern is a late finding that indicates already severe diaphragmatic weakness and impending failure of ventilation. Laying one’s hands on the patient’s chest and abdomen simultaneously while he or she takes a deep breath will highlight the abnormal inward movement of the abdomen during inspiration.
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Table 1 Approach to the examination of patients with neuromuscular respiratory failure System
Examination Finding
Potential Implication
Vital signs
Dysautonomia Fever and hypotension
Polyradiculopathy or neuropathy Sepsis
Lung auscultation
Diminished breath sound at the bases, wheezing, crackles, rales
Early respiratory complications (eg, atelectasis or aspiration) Comorbid cardiopulmonary disease
Lymph nodes
Lymphadenopathy
Malignancy Systemic infection
Skin inspection/ palpation
Rash Palpable purpura Myalgia
Lyme disease Vasculitis Myopathy
Neurologic examination
Tachypnea, tachycardia, diaphoresis, restlessness Patient seated upright leaning forward, staccato speech, inability to count aloud to 20 in 1 breath, weakness of neck flexion, recruitment of accessory muscles, paradoxic breathing pattern Ophthalmoparesis, ptosis
Increased work of breathing
Preserved oculomotor function with severe extremity weakness
Oropharyngeal and laryngeal weakness (testing of cough, facial and masticatory muscle strength, swallowing) Sustained upgaze and repeat muscle group testing for fatigability Sensory level Ataxia Absence of reflexes Hyporeflexia
Hyperreflexia Proximal > distal limb weakness
Muscle atrophy, fasciculations
Reduced vital capacity Diaphragmatic weakness
GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission Spinal cord injury Motor neuron disease Myopathies ICU-acquired weakness (critical illness myoneuropathy) GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission Motor neuron disease Myasthenia gravis and other disorders causing impaired neuromuscular transmission Spinal cord pathology Miller-Fisher variant of GBS Some sensorimotor neuropathies GBS and its variants Myasthenia gravis and other disorders causing impaired neuromuscular transmission; myopathy Motor neuron disease Myasthenia gravis and other disorders causing impaired neuromuscular transmission; myopathy Motor neuron disease
Abbreviations: GBS, Guillain-Barre´ syndrome; ICU, intensive care unit.
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Ancillary Investigations
History and examination should be complemented with ancillary tests, including measurement of ABG, chest radiograph, bedside spirometry, and in many cases electrophysiologic studies and ultrasound evaluation of the diaphragm.9,11,12 Traditional bedside spirometry involves measurement of vital capacity, maximal inspiratory pressure (sometimes called negative inspiratory force), and maximal expiratory pressure by having the patient inhale or exhale through a mouthpiece connected to a small metal tube with fixed leak and pressure gauges. It recently has been demonstrated that in patients with significant facial weakness who are unable to seal their lips around the mouthpiece, use of facemask in place of the mouthpiece can provide accurate spirometry data. The accuracy and reproducibility of bedside spirometry results is highly dependent on patient effort and therefore also on coaching by the examiner. When performed well, however, they can provide support for the diagnosis of NRF and give useful information about the severity of respiratory muscle weakness, need for intubation, and even the likely duration of mechanical ventilation.13 Vital capacity is the volume of gas obtained from a slow complete forced expiration after maximal inspiration. Maximal inspiratory pressure is the volume of gas measured when the patient forcefully inspires against an occluded device after maximal expiration. Maximal expiratory pressure is the maximal pressure the patient can generate by forcefully expiring against an occluded airway after maximal inspiration. Comparing the vital capacity in the upright and supine positions can confirm the presence of diaphragmatic weakness, as clinically significant diaphragmatic weakness is unlikely when there is little or no reduction of the vital capacity in the supine position.14 Chest radiographs should be examined for consolidation or infiltrates suggestive of aspiration, basal atelectasis, or elevation of one or both hemidiaphragms. Chest radiography is reasonably sensitive for the detection of unilateral diaphragm paralysis (90%) but the specificity is low (44%).15 Elevation of both hemidiaphragms is not a reliable determiner of dysfunction, as it also may be seen in patients who are ventilator dependent, have poor inspiratory effort, or simply large abdominal girth limiting lung volumes. The primary role of ABG analysis is to help assess the stage of respiratory failure. Early in the course of NRF, the blood gas is normal. As the weakness progresses, microatelectasis develops in the lung bases and respiratory alkalosis develops while the PO2 remains normal or is only slightly reduced. As the muscles fatigue, generalized alveolar hypoventilation leads to tachypnea, which temporarily maintains the PCO2 in the normal range. Eventually hypercapnia develops and ABG analysis will be consistent with a respiratory acidosis. Patients who present with a chronic respiratory acidosis (low pH, high PCO2, and high HCO3) before initiation of mechanical ventilation are less likely to survive to hospital discharge and more likely to have severe disability if they survive, especially in those without a treatable diagnosis.13 Further supportive evidence for diaphragmatic dysfunction can be obtained through electrophysiological study of phrenic nerve conduction, diaphragm electromyogram (EMG), and bedside ultrasound.16–18 The accuracy and safety of diaphragm EMG and the sensitivity and specificity of phrenic nerve conduction studies can be enhanced with ultrasound.19–21 The utility of EMG and nerve conduction studies of the extremities is in the determination of the underlying cause of NRF. Table 2 details the characteristic EMG and nerve conduction velocity findings in different categories of neuromuscular disease.
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Table 2 EMG characteristics in different categories of neuromuscular disease Disease Category
EMG-NCS Features
Motor neuronopathy
Reduced CMAP amplitudes Normal or mildly reduced motor CV Normal SNAPs Fibrillations, positive waves, and fasciculations in multiple myotomes Reduced recruitment, neurogenic MUs
Polyradiculopathy and neuropathy
Demyelinating: Significant slowing of CV Marked prolongation of distal latencies Conduction block, temporal dispersion SNAPs abnormal Fibrillations and positive waves if there is concomitant axonal loss Axonal: Reduced CMAP amplitudes Normal or mildly reduced motor CV SNAPs abnormal (except for AMAN) Fibrillations and positive waves in multiple myotomes Reduced recruitment, neurogenic MUs
Neuromuscular junction disorder
Postsynaptic: Normal baseline CMAP amplitude Normal SNAPs Decrement of CMAP amplitude with low-frequency (2–5 Hz) repetitive stimulation Needle EMG normal, or may show neurogenic or myopathic units Presynaptic: Low baseline CMAP amplitude Facilitation of CMAP amplitude after brief (ie, 10 s) exertion Facilitation of the CMAP amplitude with high-frequency (20–50 Hz) repetitive stimulation Decrement of the CMAP amplitude with low-frequency (2–5 Hz) repetitive stimulation
Myopathy
CMAP amplitude reduced or normal SNAPs normal Fibrillations and positive waves Myopathic (short duration polyphasic) units Early recruitment
Abbreviations: AMAN, acute motor axonal neuropathy; CMAP, compound muscle action potential; CV, conduction velocity; EMG, electromyography; MU, motor unit; NCS, nerve conduction study; SNAP, sensory nerve action potential. From Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin 2012;30(1):161–85. Reproduced exactly, as there have been no advancements in EMG/NCV.
CAUSES OF NEUROMUSCULAR RESPIRATORY FAILURE
The primary determining factor of prognosis in patients with primary NRF is the specific cause.1 Identification of the cause is thus a critical step, as it frequently dictates the management plan. Most patients with chronic neuromuscular conditions, such as muscular dystrophy, ALS, and myasthenia gravis are managed through specialized clinics that help guide the patient through all stages of the disease, including the progressive NRF that plagues progressive disorders like ALS. Those who choose to do so are set up with noninvasive ventilation (NIV) and suctioning equipment after undergoing sleep studies through outpatient mechanisms.
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Some, however, come to medical attention only when the respiratory muscles become involved, either because of a rapid progression of the disease, or previous misdiagnosis. In rare cases, respiratory failure may be the presenting clinical feature, prompting them to seek evaluation, and in some cases it is pneumonia or other concurrent cardiopulmonary illness that leads them to decompensate. Neurologists are typically called when the patient cannot be liberated from mechanical ventilation. Among 85 adults admitted with acute NRF to the intensive care unit over a 6-year period, the most frequent diagnoses were myasthenic crisis, GBS, myopathies, and ALS (27, 12, 12, and 12 patients, respectively). Remarkably, 55% of patients had no known neuromuscular diagnosis before admission, and 12% remained without a diagnosis on hospital discharge. Those without a neuromuscular diagnosis before admission were intubated longer, had longer intensive care unit stays and worse outcomes at discharge from the hospital, and 17% of these patients were ultimately diagnosed with ALS.1 Physicians should therefore consider ALS when asked to evaluate patients with unexplained acute respiratory failure of presumed neuromuscular cause. Box 2 summarizes the differential diagnosis of acute NRF. The remainder of this section reviews the management of acute NRF in the context of the 2 most common causes: GBS and myasthenic crisis. Acute Neuromuscular Respiratory Failure in Guillain-Barre´ Syndrome
GBS is an acute, self-limited, autoimmune-mediated, inflammatory polyradiculoneuropathy. GBS is an umbrella term for several well-characterized variants of the disorder. The most common form is primarily manifested by flaccid weakness with areflexia. Limb weakness, often with sensory and cranial nerve involvement, begins typically 1 to 2 weeks after an immune stimulus (eg, infection, vaccination, or surgery) and progresses to a nadir in 2 to 4 weeks.22 It is associated with dysautonomia, which can produce labile blood pressure, tachyarrhythmias, and severe bradyarrhythmias and conduction blocks. Disautonomia can worsen in response to physical stress (such as what occurs with acute NRF) or medications, such as betablockers.23 Respiratory failure from severe diaphragmatic and bulbar muscle weakness affects 20% to 30% of patients with GBS.24 Diaphragmatic failure can develop suddenly and force emergency intubation. This is made even more dangerous if the patient has dysautonomia. Predictors of the development of acute NRF in GBS include a short interval between the onset of symptoms and hospitalization, presence of bulbar or facial weakness, axonal involvement, or severe appendicular weakness as measured by the Erasmus GBS Respiratory Insufficiency Score.25 Respiratory muscle strength should be monitored frequently by physical examination (discussed previously) and serial bedside spirometry. A forced vital capacity of less than 20 mm Hg, maximal inspiratory pressure less than 30 cm H2O, maximal expiratory pressure less than 40 mm Hg, or a decrease in forced vital capacity of greater than 30% over 24 hours are reliable predictors of progression to respiratory failure and the need for invasive mechanical ventilation.26 Patients meeting any of these criteria should be promptly intubated before the development of frank ventilatory failure and hypercapnia. NIV is not a good option for patients with GBS (rationale discussed in the next section). Immune therapy with either plasma exchange or intravenous immunoglobulin (IVIG) is effective in speeding the rate of recovery and is most beneficial when started within 2 weeks of the onset of symptoms.24,27,28
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Box 2 Differential diagnosis of acute neuromuscular respiratory failure Anterior Horn Cell Amyotrophic lateral sclerosis West Nile virus Poliomyelitis or post-polio syndrome Kennedy disease Tetanus Nerve Roots and Peripheral Nerves Congenital Charcot-Marie-Tooth Acquired Critical illness polyneuropathy Guillain-Barre´ syndrome Acute onset or exacerbation of chronic inflammatory demyelinating polyneuropathy Toxins (rarely result in respiratory failure) Vasculitis Paraneoplastic syndrome Porphyria Infiltrative disease (amyloid or lymphoma) Phrenic nerve injury Neuromuscular Junction Myasthenia gravis Lambert-Eaton myasthenic syndrome Neuromuscular blocking agents Toxins (organophosphate poisoning, tick paralysis, snake venom, botulism) Muscle Congenital Dystrophies (Duchenne, Becker, limb girdle) Myopathies (myofibrillary, mitochondrial, myotonia congenita) Acid maltase deficiency Acquired Critical illness myopathy Inflammatory myopathies (dermatomyositis, inclusion body) Metabolic myopathies (hyperthyroidism, hypophosphatemia, hyperkalemia, hypokalemia, and hypernatremia) Toxins (statins, colchicine, neuromuscular blocking agents, steroids) Rhabdomyolysis Adapted from Rabinstein AA. Acute neuromuscular respiratory failure. Continuum (Minneap Minn) 2015;21:1324–45; and Howard RS. Respiratory failure because of neuromuscular disease. Curr Opin Neurol 2016;29(5):592–601.
Acute Neuromuscular Respiratory Failure in Myasthenic Crisis
Myasthenia gravis is an autoimmune disorder resulting in impaired neuromuscular transmission variably characterized by fatigable weakness of the appendicular, bulbar, ocular, and respiratory muscles.29 Autoantibodies typically target either the postsynaptic nicotinic acetylcholine receptors in the muscle membrane.30 Myasthenia gravis also can be caused by antibodies against the muscle-specific tyrosine kinase,
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which result in more bulbar involvement and a higher predisposition to respiratory failure.31 Approximately one-fifth of patients will develop a myasthenic crisis over the course of their disease, defined by the development of respiratory failure and need for either invasive or noninvasive mechanical ventilation.32 A crisis may be triggered by infection, surgery, or medication changes (eg, initiation of a fluoroquinolone or aminoglycoside or change in the timing or dosage of the patient’s daily myasthenia gravis regimen). Patients often describe a preceding history of a weakening voice and worsening dysphagia, dysarthria, diplopia, or ptosis. Examination frequently shows ptosis, difficulty sustaining upgaze, bifacial weakness, weakness of jaw closure, hypophonia, weak cough, and fatigable extremity weakness (proximal > distal). Patients often describe an increase in oropharyngeal secretions most often due to the bulbar weakness and inability to effectively swallow them, but this must be distinguished from cholinergic excess due to additional pyridostigmine doses (either physician or patient directed) used to try to reduce the worsening symptoms. The value of bedside spirometry, although frequently used in this setting, is not well established largely due to the fluctuating and fatigable nature of the weakness. Treatment with either plasma exchange or IVIG speeds the rate of recovery,33,34 and a recent retrospective study showed that plasma exchange led to earlier extubation.35 Patients with myasthenic crisis must receive corticosteroids to be successfully liberated from mechanical ventilation (invasive or noninvasive). The optimal route and dose are not well established. Caution should be exercised when initiating highdose steroids in nonintubated patients, as between one-third and one-half of patients will develop clinically significant worsening of their weakness within days of starting this treatment.12 Early initiation of NIV with bilevel positive airway pressure (BiPAP) can prevent the need for endotracheal intubation in some patients (discussed in the next section).36,37 Patients should be intubated if they have severe hypercapnia, hypoxemia, lobar atelectasis, or copious secretions that require very frequent suctioning. Once intubated, most patients require between 8 and 14 days of mechanical ventilation. Few are successfully extubated within the first week, and some require tracheostomy and prolonged ventilatory support.32,37,38 The rate of extubation failure is 25%, which is high compared with that seen in general critical care and is more likely in patients with radiographically apparent atelectasis.37,39 Because ongoing weakness and a tendency to fatigue are common following extubation, it is good practice to extubate to BiPAP and continue NIV the first night to prevent ventilatory failure and alveolar collapse during rapid eye movement sleep when muscle tone is absent.40,41 NONINVASIVE VENTILATION, INVASIVE VENTILATION, AND TRACHEOSTOMY IN NEUROMUSCULAR RESPIRATORY FAILURE
Select patients presenting with acute NRF may benefit from NIV. NIV is safe in some situations but potentially dangerous in others, so an understanding of the nature of the underlying neuromuscular disorder; stage of respiratory failure; level of consciousness; volume of secretions; ability to expectorate; and presence of pulmonary edema, pneumonia, or significant atelectasis are all important in determining whether it is an appropriate intervention. NIV is well recognized as a life-prolonging tool in advanced stages of progressive neurologic disorders, such as ALS and muscular dystrophies, and in the case of ALS has been shown to improve the quality of life.42,43 Not infrequently, however, these patients and others with chronic neuromuscular disorders, such as myasthenia
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gravis, present to the emergency department in acute NRF when a concurrent disease precipitates a rapid decline. NIV combined with mobilization and careful pulmonary hygiene can avoid the need for intubation and tracheostomy in appropriately selected patients.44 NIV also can be used to support patients in the recovery phase of GBS, where progressive improvement in muscle strength is anticipated. NIV refers to either the mechanical delivery of continuous positive airway pressure (CPAP) or BiPAP.45,46 CPAP helps to overcome the resistance of the upper airways and keeps the alveoli open at end expiration, improving gas exchange, and therefore oxygenation. CPAP does not assist with ventilation and thus is not indicated for NRF where the primary problem is respiratory muscle fatigue and failure of ventilation. BiPAP provides both inspiratory and expiratory positive expiratory pressure, and the option of providing oxygen and a backup rate if required.47 Fitting the mask with sufficient comfort while minimizing air leaks is probably the most important and challenging step in initiating NIV.45 There are many options, including nasal, oronasal, and full face masks. Oronasal masks are preferred, as they avoid the claustrophobia of full face masks and are not limited by mouth breathing, common in neuromuscular disease, as are the nasal masks. Selection of the mask is ultimately determined by fit and patient comfort. A common misconception is that facial weakness is a contraindication to NIV, when, in fact, patients with facial and oropharyngeal weakness are often easier to ventilate, as they synchronize more readily with the mechanical delivery of air (they resist less, allowing for delivery of good tidal volumes). As discussed previously, NIV is particularly useful in patients with myasthenic crisis because of the nature of the disease itself. The muscle weakness in myasthenia gravis is fluctuating, worsens with exercise, and improves with rest. This, and because treatment can be expected to be effective over a period of days to weeks, explains why prompt support with NIV (rest) in this setting can reverse the worsening weakness and prevent the need for endotracheal intubation.36,37 BiPAP also has been shown to shorten the length of both intensive care unit and hospital stay in patients presenting with myasthenic crisis,37 primarily by reducing the frequency of pulmonary complications, such as atelectasis and pneumonia.11,37 Because pulmonary edema due to heart failure and chronic obstructive pulmonary disease are both conditions known to be successfully managed with NIV, it is also appropriate to consider NIV to treat neuromuscular disorders decompensated by these conditions.47 Box 3 lists indications for NIV in acute NRF. Unlike in myasthenic crisis, NIV is not a good option for acute NRF due to GBS for 2 reasons.48 First, the associated dysautonomia makes the prospect of emergency intubation even more dangerous, as it can lead to life-threatening dysrhythmias or severe blood pressure fluctuations.49 Second, patients with GBS who
Box 3 Indications for noninvasive ventilation in acute neuromuscular respiratory failure Myasthenic crisis Chronic neuromuscular disorders exacerbated by pulmonary edema or COPD exacerbation Progressive neuromuscular disorders (eg, ALS, muscular dystrophies) Resolving GBS, myasthenic crisis or inflammatory myopathy with persistent weakness after extubation Abbreviations: ALS, amyotrophic lateral sclerosis; COPD, chronic obstructive pulmonary disease; GBS, Guillain-Barre´ syndrome.
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develop respiratory muscle involvement are likely to continue to decline and to have prolonged nadir and recovery phases with no immediate option to reverse the process. Thus, temporizing with NIV will not be effective. Patients with GBS should therefore be electively intubated when they have (1) severe or rapidly progressive weakness, (2) marked bulbar weakness, or (3) early signs of impaired ventilation. Other contraindications to NIV include a reduced level of consciousness, such that patients could not communicate distress or protect their airway, and extremely agitated patients who may require sedation to facilitate treatment and ensure safety. This level of agitation must be distinguished from the restlessness seen in patients with acute NRF that results from air hunger, which will improve when their work of breathing and air hunger are reduced by NIV. Clinical situations in which a patient may present with both a reduced level of consciousness and NRF include trauma and West Nile encephalomyelitis, and these patients should be electively intubated for airway protection.50 Patients with upper cervical spinal cord injury are anticipated to have long-term NRF and should thus be intubated and, once stabilized, undergo tracheostomy. Intubation is also necessary in patients who are systemically unstable, such as those in septic shock. Dysphagia and pooling of oral and respiratory secretions do not represent an absolute contraindication to a trial of treatment but should be carefully monitored, and in many cases patients will suction themselves and require assistance only with taking the BiPAP off and on. NIV is effective only when initiated before the development of frank hypercapnia and severe respiratory or mixed acidosis, where it has been shown that the chances of BiPAP failure are unacceptably high.36,37 Indications for endotracheal intubation are listed in Box 4. The use of succinylcholine for induction is contraindicated in all neuromuscular disorders because of the risk of severe hyperkalemia.51–54 In those patients who are intubated for NRF, tracheostomy should be pursued as soon as it is clear that a prolonged period of mechanical ventilation will be required. Tracheostomy facilitates suctioning, improves patient comfort, allows for the eventual possibility of oral intake and speech, and aids in weaning from mechanical ventilation by reduction of dead space.
Box 4 Indications for intubation Current or anticipated sedation Reduced level of consciousness Excessive secretions Increasing oxygen requirements Failure to improve with bilevel positive airway pressure trial Significant atelectasis or consolidation on chest radiograph Hypercapnia with respiratory acidosis Hemodynamic instability Active coronary ischemia Rapid progression of weakness Guillain-Barre´ syndrome Acute spinal cord injury
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REFERENCES
1. Cabrera Serrano M, Rabinstein AA. Causes and outcomes of acute neuromuscular respiratory failure. Arch Neurol 2010;67:1089–94. 2. Rabinstein AA, Wijdicks EF. Warning signs of imminent respiratory failure in neurological patients. Semin Neurol 2003;23:97–104. 3. McCool FD, Tzelepis GE. Dysfunction of the diaphragm. N Engl J Med 2012;366: 932–42. SA, Peltier AC, Iacob T, et al. Chronic inflammatory demyelinating poly4. Zivkovic neuropathy and ventilatory failure: report of seven new cases and review of the literature. Acta Neurol Scand 2011;124(1):59–63. 5. Wu SG, Kuo PH, Yang PC. Successful weaning after plasma exchange for polyneuropathy related to POEMS syndrome. J Clin Apher 2009;24(4):170–2. 6. Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin 2012;30(1):161–85. 7. Baltzan MA, Scott AS, Wolkove N. Unilateral hemidiaphragm weakness is associated with positional hypoxemia in REM sleep. J Clin Sleep Med 2012;8:51–8. 8. Mehta M, Rath GP, Padhy UP, et al. Intensive care management of patients with acute intermittent porphyria: clinical report of four cases and review of literature. Indian J Crit Care Med 2010;14(2):88–91. 9. Hutchinson D, Whyte K. Neuromuscular disease and respiratory failure. Pract Neurol 2008;8:229–37. 10. Flower O, Bowles C, Wijdicks E, et al. Emergency neurological life support: acute nontraumatic weakness. Neurocrit Care 2012;17(Suppl 1):S79–95. 11. Rabinstein AA. Update on respiratory management of critically ill neurologic patients. Curr Neurol Neurosci Rep 2005;5:476–82. 12. Rabinstein AA. Acute neuromuscular respiratory failure. Continuum (Minneap Minn) 2015;21:1324–45. 13. Cabrera Serrano M, Rabinstein AA. Usefulness of pulmonary function tests and blood gases in acute neuromuscular respiratory failure. Eur J Neurol 2012; 19(3):452–6. 14. Mier-Jedrzejowicz A, Brophy C, Moxham J, et al. Assessment of diaphragm weakness. Am Rev Respir Dis 1988;137:877–83. 15. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Respir Med 2005;99:39–44. 16. Amirjani N, Hudson AL, Butler JE, et al. An algorithm for the safety of costal diaphragm electromyography derived from ultrasound. Muscle Nerve 2012;46: 856–60. 17. Bellani G, Mauri T, Coppadoro A, et al. Estimation of patient’s inspiratory effort from the electrical activity of the diaphragm. Crit Care Med 2013;41:1483–91. 18. Jenkins JA, Sakamuri S, Katz JS, et al. Phrenic nerve conduction studies as a biomarker of respiratory insufficiency in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2016;17:213–20. 19. Johnson NE, Utz M, Patrick E, et al. Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies. Muscle Nerve 2014;49:669–75. 20. Boon AJ, Sekiguchi H, Harper CJ, et al. Sensitivity and specificity of diagnostic ultrasound in the diagnosis of phrenic neuropathy. Neurology 2014;83:1264–70. 21. Boon AJ, O’Gorman C. Ultrasound in the assessment of respiration. J Clin Neurophysiol 2016;33:112–9.
719
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Hocker
22. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barre´ syndrome. Lancet 2016; 388(10045):717–27. 23. Zochodne DW. Autonomic involvement in Guillain–Barre syndrome: a review. Muscle Nerve 1994;17:1145–55. 24. Fokke C, van den Berg B, Drenthen J, et al. Diagnosis of Guillain-Barre´ syndrome and validation of Brighton criteria. Brain 2014;137(Pt 1):33–43. 25. Walgaard C, Lingsma HF, Ruts L, et al. Prediction of respiratory insufficiency in Guillain-Barre´ syndrome. Ann Neurol 2010;67(6):781–7. 26. Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical ventilation in Guillain–Barre syndrome. Arch Neurol 2001;58:893–8. 27. Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for GuillainBarre´ syndrome. Cochrane Database Syst Rev 2014;(9):CD002063. 28. Raphae¨l JC, Chevret S, Hughes RA, et al. Plasma exchange for Guillain-Barre´ syndrome. Cochrane Database Syst Rev 2002;(2):CD001798. 29. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015;14:1023–36. 30. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 2009;8:475–90. 31. Deymeer F, Gungor-Tuncer O, Yilmaz V, et al. Clinical comparison of anti-MuSKvs anti-AChR- positive and seronegative myasthenia gravis. Neurology 2007;68: 609–11. 32. Thomas CE, Mayer SA, Gungor Y, et al. Myasthenic crisis: clinical features, mortality, complications, and risk factors for prolonged intubation. Neurology 1997; 48(5):1253–60. 33. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev 2012;(12):CD002277. 34. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database Syst Rev 2002;(4):CD002275. 35. Liu Z, Yao S, Zhou Q, et al. Predictors of extubation outcomes following myasthenic crisis. J Int Med Res 2016;44(6):1524–33. 36. Rabinstein A, Wijdicks EF. BiPAP in acute respiratory failure due to myasthenic crisis may prevent intubation. Neurology 2002;59:1647–9. 37. Seneviratne J, Mandrekar J, Wijdicks EF, et al. Noninvasive ventilation in myasthenic crisis. Arch Neurol 2008;65:54–8. 38. Kalita J, Kohat AK, Misra UK. Predictors of outcome of myasthenic crisis. Neurol Sci 2014;35(7):1109–14. 39. Rabinstein AA, Mueller-Kronast N. Risk of extubation failure in patients with myasthenic crisis. Neurocrit Care 2005;3:213–5. 40. Irfan M, Selim B, Rabinstein AA, et al. Neuromuscular disorders and sleep in critically ill patients. Crit Care Clin 2015;31:533–50. 41. Rabinstein AA. Noninvasive ventilation for neuromuscular respiratory failure: when to use and when to avoid. Curr Opin Crit Care 2016;22(2):94–9. 42. Radunovic A, Annane D, Rafiq MK, et al. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2013;(3):CD004427. 43. Villanova M, Brancalion B, Mehta AD. Duchenne muscular dystrophy: life prolongation by noninvasive ventilatory support. Am J Phys Med Rehabil 2014;93: 595–9. 44. Bach JR, Goncalves MR, Hamdani I, et al. Extubation of patients with neuromuscular weakness: a new management paradigm. Chest 2010;137:1033–9.
Neuromuscular Respiratory Failure
45. Gregoretti C, Pisani L, Cortegiani A, et al. Noninvasive ventilation in critically ill patients. Crit Care Clin 2015;31:435–57. 46. Hill NS, Brennan J, Garpestad E, et al. Noninvasive ventilation in acute respiratory failure. Crit Care Med 2007;35:2402–7. 47. Nava S, Hill N. Noninvasive ventilation in acute respiratory failure. Lancet 2009; 374:250–9. 48. Wijdicks EF, Roy TK. BiPAP in early Guillain-Barre´ syndrome may fail. Can J Neurol Sci 2006;33(1):105–6. 49. Henderson RD, Lawn ND, Fletcher DD, et al. The morbidity of Guillain–Barre syndrome admitted to the intensive care unit. Neurology 2003;60:17–21. 50. Wang H, Siddharthan V, Kesler KK, et al. Fatal neurological respiratory insufficiency is common among viral encephalitides. J Infect Dis 2013;208:573–83. 51. Racca F, Mongini T, Wolfler A, et al. Recommendations for anesthesia and perioperative management of patients with neuromuscular disorders. Minerva Anestesiol 2013;79(4):419–33. 52. Wijdicks EFM. The practice of emergency and critical care neurology. 2nd edition. New York: Oxford University Press; 2016. 53. Wijdicks EFM. Handling difficult situations. New York: Oxford University Press; 2014. 54. Rabinstein AA. Practical management of Guillain-Barre´ syndrome and myasthenic crisis. In: Manno EM, editor. Emergency management in neurocritical care. Oxford (United Kingdom): Wiley-Blackwell; 2012. p. 141–51.
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