Disclosures: Shawn J Bird, MD Nothing to disclose. Joshua M Levine, MD Nothing to disclose. Jeremy M Shefner, MD, PhD Grant/Research Support: Cytokinetics, Inc. [ALS]; Glaxo Smith Kline. Consultant/Advisory Board: Biogen Idec [ALS]; Cytokinetics, Inc. [ALS]; Kinemed [ALS]; Voyager Therapeutics [ALS]; ISIS Pharmaceuticals [SMA]. Ira N Targoff, MD Consultant/Advisory Boards: Oklahoma Medical Research Foundation Clinical Immunology Laboratory (myositis antibody testing). Polly E Parsons, MD Nothing to disclose. John F Dashe, MD, PhD Nothing to disclose. Geraldine Finlay, MD Nothing to disclose.
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DEFINITION — Myasthenic crisis is a life-threatening condition, which is defined as weakness from acquired myasthenia gravis that is severe enough to necessitate intubation or to delay extubation following surgery . The respiratory failure is due to weakness of respiratory muscles.
Severe bulbar (oropharyngeal) muscle weakness often accompanies the respiratory muscle weakness, or may be the predominant feature in some patients. When this results in upper airway obstruction or severe dysphagia with aspiration, intubation and mechanical ventilation are necessary.
This topic will review the evaluation and treatment of myasthenic crisis and rapidly worsening myasthenia gravis. Other aspects of myasthenia gravis are discussed separately. (See "Clinical manifestations of myasthenia gravis" and "Diagnosis of myasthenia gravis" and "Treatment of myasthenia gravis".)
EPIDEMIOLOGY — Although data are limited, the proportion of patients with myasthenia gravis who experience at least one myasthenic crisis may be as high as 10 to 20 percent , and the annual risk of myasthenic crisis among patients with myasthenia gravis is approximately 2 to 3 percent . In 13 to 20 percent of patients who present with myasthenic crisis, it is the first manifestation of myasthenia gravis [3-5]. Most myasthenic crises occur in the first few years after the diagnosis of myasthenia gravis, when the disease is often in its most active phase. (See "Clinical manifestations of myasthenia gravis", section on 'Clinical course'.)
The epidemiology of myasthenia gravis is reviewed in detail separately. (See "Clinical manifestations of myasthenia gravis", section on 'Epidemiology'.)
CLINICAL PRESENTATION — Patients who develop myasthenic crisis typically experience increasing generalized or bulbar weakness as a warning. Occasionally, a patient presents with respiratory insufficiency out of proportion to limb or bulbar weakness. In a report of 44 patients who developed 63 episodes of myasthenic crises, the crisis began with generalized weakness, bulbar symptoms, or weakness of respiratory muscles in 76, 19, and 5 percent, respectively .
One particular danger in myasthenic crisis is that the generalized weakness can mask the usual signs of respiratory distress, such as accessory muscle use. In addition, weak respiratory muscles may fatigue suddenly, producing precipitous respiratory collapse. On the other hand, some patients have weakness of the respiratory muscles that is out of proportion to the weakness in other skeletal muscles. In rare cases of myasthenic crisis, ventilatory failure is the only clinically overt manifestation [6,7].
Precipitants — Myasthenic crisis may be precipitated by a variety of factors, most often a concurrent infection . It can also follow a surgical intervention (eg, thymectomy), pregnancy, childbirth, or tapering of immunosuppressive medications. In addition, myasthenic crisis can occur spontaneously as part of the natural history of myasthenia gravis itself. A number of drugs can increase the weakness in myasthenia (table 1 and table 2) and should be considered as possible precipitants in this setting. This is of more concern with certain antibiotics (aminoglycosides, fluoroquinolones [eg, ciprofloxacin and levofloxacin], erythromycin, and azithromycin), cardiac drugs (beta-blockers, procainamide, and quinidine), and magnesium.
Cholinergic crisis — A potential major side effect of excessive anticholinesterase medication is weakness, which can be difficult to distinguish from worsening myasthenia gravis. This paradoxical weakening with anticholinesterase medications is called "cholinergic crisis." However, cholinergic crisis is rarely if ever seen with dose limitation of pyridostigmine to less than 120 mg every three hours. Cholinergic crisis is so rare that it should not be the presumed cause of increasing weakness unless the doses taken are known to significantly exceed this range. Otherwise, even in the presence of cholinergic side effects, it should be assumed that the patient's underlying myasthenia gravis is worsening and appropriate treatment should be initiated.
DIAGNOSIS — In patients with a known diagnosis of myasthenia gravis, myasthenic crisis is defined by increasing respiratory muscle and/or bulbar muscle weakness from the disorder that is severe enough to necessitate intubation or, in some cases, to delay extubation following surgery.
In a minority of cases, myasthenic crisis is the first manifestation of myasthenia gravis and the cause of neuromuscular respiratory failure may be unknown at presentation. In such instances, the diagnosis of myasthenia gravis should be confirmed, if possible, with immunologic or electrophysiologic testing (table 3). (See "Diagnosis of myasthenia gravis".)
Other than myasthenia gravis, the most common causes of acute neuromuscular respiratory failure are Guillain-Barré syndrome and amyotrophic lateral sclerosis [8,9]. (See "Clinical features and diagnosis of Guillain-Barré syndrome in adults" and "Epidemiology, clinical features, and diagnosis of Guillain-Barré syndrome in children" and "Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease".)
Less common causes of acute neuromuscular respiratory failure include chronic inflammatory demyelinating polyneuropathy, severe rhabdomyolysis, and various types of myopathy. A cause will be undetermined in 5 to 10 percent of patients without known neuromuscular disease at admission [8,9]. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation" and "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis" and "Clinical manifestations and diagnosis of rhabdomyolysis".)
EVALUATION AND MANAGEMENT — There are a number of general concepts common to the treatment of patients with myasthenic crisis or severe exacerbations of myasthenia gravis (table 4) [1,10-12]. These include the following:
●Admit to intensive care unit
●Frequently monitor respiratory muscle strength (see 'Assessment of respiratory function' below)
●Electively intubate if clinical evaluation or tests of respiratory muscle strength suggest impending respiratory failure; temporarily stop anticholinesterase medications for intubated patients (see 'Elective intubation' below)
●Begin rapid therapy with plasma exchange or intravenous immune globulin (IVIG) (see 'Rapid therapies' below)
●Begin immunomodulating therapy with high-dose glucocorticoids; consider azathioprine, mycophenolate mofetil, or cyclosporine if glucocorticoids are contraindicated or previously ineffective (see 'Immunomodulating therapy' below)
●Initiate weaning from mechanical ventilation when respiratory muscle strength is improving, but only after starting treatment with plasma exchange or IVIG (see 'Weaning from ventilatory support' below)
Intercurrent infections are often a contributing factor and should be sought out and treated aggressively, as should any factors or drugs (table 1 and table 2) that may have precipitated or exacerbated the patient's weakness. (See 'Precipitants' above.)
Assessment of respiratory function — Patients with severe or rapidly increasing generalized weakness secondary to an exacerbation of myasthenia gravis should be admitted to an intensive care unit. This is particularly important for the frequent monitoring that is required to detect those at risk for respiratory failure who potentially require ventilatory support.
Clinical — Symptoms and signs that should alert the clinician to respiratory failure include:
●Dyspnea (also reported by patients as "suffocation" or "drowning") that occurs or worsens when the patient lies supine. This symptom is thought to be due to the increased dependence on gravity for diaphragmatic function during a myasthenic crisis.
●Severe dysphagia with weak cough and difficulty clearing secretions.
●Signs of respiratory muscle weakness, such as hypophonia, pausing during speech to take a breath, poor respiratory effort, increased respiratory rate with shallow breaths, use of accessory muscles of respiration, and paradoxical abdominal breathing. However, these signs of respiratory distress may become less apparent as muscle weakness progresses, misleading the clinician into believing that the patient is comfortable and does not need intubation. Therefore, it is critically important to assess measures of respiratory muscle function as discussed below.
●Low baseline vital capacity (VC) that is <30 mL/kg of ideal body weight, even if the patient is breathing without distress.
Measures of respiratory muscle function — When increasing muscle weakness becomes apparent, tests of respiratory muscle strength may help to identify impending respiratory failure and allow elective rather than emergent intubation. The VC and the maximal inspiratory pressure (MIP) are the main respiratory parameters that are used to monitor respiratory muscle strength. They are particularly useful as objective indicators of the inability to breathe in patients who are without obvious respiratory distress [10,12-14]. The maximal expiratory pressure (MEP) is a more useful tool for assessing expiratory muscle strength, which is important for cough and secretion clearance.
The VC and MIP are the most useful measures of respiratory muscle involvement in myasthenic crisis:
●The VC reflects the mechanical function of both inspiratory and expiratory muscle strength. It can be performed easily at the bedside. The patient is instructed to take a deep breath in and then to exhale maximally into a spirometer (usually a slow vital capacity maneuver). Some experts recommend assessing both supine and sitting VC, as diaphragmatic weakness is more apparent on the supine measurement. However, the predicted values of VC are based upon measurements in the sitting position. (See "Overview of pulmonary function testing in adults", section on 'Spirometry'.)
●The MIP (also known as negative inspiratory force [NIF]) provides information on inspiratory muscle strength. The patient is instructed to maximally inhale against a closed valve (usually starting from resting tidal volume) and the force/pressure that is generated at the mouth is recorded. Inspiration is a negatively generating force and thus values are recorded as negative numbers; a MIP below one-third of normal (eg, 0 to -30 cmH2O) predicts severe respiratory muscle weakness and probable hypercarbic respiratory failure while a MIP of -60 cmH2O is usually associated with a weak cough only. (See "Tests of respiratory muscle strength".)
The VC and MIP should always be interpreted in the context of the clinical symptoms and signs of respiratory failure. Neither measurement has been shown to be superior, so the two measures are usually analyzed in combination. Both parameters should be measured frequently, as often as every two hours in some cases, but typically every four hours. In most cases, the absolute values are less important than the trend in numbers over time. However, caveats exist. As examples, patients with myasthenia gravis may precipitously fatigue with the rapid development of respiratory failure before a downward trend in VC is noted. In contrast, some patients with facial weakness caused by myasthenia gravis who cannot make a good seal with the mask have a falsely low VC. Values that may prompt elective intubation (table 4) are discussed in the section below. (See 'Elective intubation' below.)
Oxygenation should be monitored continuously, although abnormalities of arterial blood gases (eg, hypoxemia and hypercarbia) are insensitive measures of respiratory muscle weakness because they often develop only after the onset of life-threatening respiratory failure [10,12-14]. However, the development of progressive hypercarbic respiratory acidosis despite therapy may provide supportive evidence that prompts early rather than late intubation.
Elective intubation — We and others prefer that endotracheal intubation be performed as an elective procedure rather than as an emergent response to precipitous respiratory collapse [10,13,14]. This is usually achieved with close monitoring of the patient's respiratory muscle strength using clinical and objective parameters of the VC and MIP. (See 'Assessment of respiratory function' above.)
Elective intubation should be considered if serial measurements demonstrate one or both of the following:
●VC falls below 15 to 20 mL/kg
●MIP is less negative than -25 to -30 cmH20 (ie, between 0 and -30 cmH20)
Additional indications for mechanical ventilation include clinical signs of respiratory distress, progressive hypercapnic respiratory acidosis despite therapy, and inadequate secretion clearance (eg, recurrent episodes of acute hypoxemia due to mucus plugging).
In most cases, ventilatory assistance should consist of endotracheal intubation with positive pressure mechanical ventilation. Invasive mechanical ventilation has the advantage of adequate secretion clearance and full support for those suspected to have prolonged courses of crisis. The optimal mode of mechanical ventilation is unknown. In general, we use assist control modes of volume controlled ventilation and low levels of positive end-expiratory pressure (PEEP) with subsequent adjustments to achieve adequate gas exchange. It is important to avoid overventilation, which may impair respiratory drive especially when attempting to wean from ventilatory support. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation" and "Overview of mechanical ventilation" and "Respiratory muscle weakness due to neuromuscular disease: Management".)
For intubation, succinylcholine is safe in myasthenia gravis but increased doses are needed. The techniques and medications for rapid sequence intubation in adults are discussed separately. (See "Rapid sequence intubation in adults" and "Neuromuscular blocking agents (NMBA) for rapid sequence intubation in adults", section on 'NMBAs for myasthenia gravis'.)
Noninvasive positive pressure ventilation (NPPV) may be used on a case-by case basis in those expected to resolve quickly who have adequate cough and can tolerate the mask. We prefer to avoid the prolonged use of NPPV (eg, days) and suggest that failure to respond to NPPV early in the course of its application is another indication for invasive mechanical ventilation. Limited retrospective evidence supports this approach in patients with myasthenic crisis [2,15,16]. However, NPPV is frequently ineffective or can cause complications in those with severe bulbar dysfunction, upper airway obstruction, retention of respiratory secretions, or inadequate cough, and in patients who are unable to achieve a satisfactory interface or are poorly cooperation. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Noninvasive positive pressure ventilation'.)
Meticulous attention to pulmonary toilet is required for patients with myasthenic crisis because of an ineffective cough mechanism. In a retrospective study, "aggressive" respiratory treatment that consisted of the use of suction, intermittent positive-pressure breathing or bronchodilator treatments, sighs, and chest physiotherapy, appeared to decrease the risk of prolonged respiratory complications compared with historical controls . This observation needs to be validated in a prospective study.
After intubation, cholinesterase inhibitor therapy used for myasthenia gravis (eg, pyridostigmine) is usually withdrawn temporarily to avoid the excess secretions that may complicate pulmonary management. These agents can be reintroduced after successful extubation and once dysphagia has largely resolved.
Rapid therapies — The main therapies for myasthenic crisis are plasma exchange and IVIG. These start to work within several days, but the benefits last only a few weeks (table 5). Therefore, initiation of high-dose glucocorticoids is also necessary for most patients. (See 'Immunomodulating therapy' below.)
Plasma exchange — Plasma exchange (plasmapheresis) directly removes acetylcholine receptor antibodies from the circulation, and its clinical efficacy roughly correlates with the reduction in antibody levels. The supportive evidence is discussed separately. (See "Treatment of myasthenia gravis", section on 'Plasmapheresis'.)
Plasma exchange is an established treatment for seriously ill patients in the midst of myasthenic crisis [18-20], although it has never been studied in a randomized, controlled trial for this indication. The beneficial clinical effect usually lasts only three to four weeks. In addition, the acetylcholine receptor antibody levels rebound within weeks if concurrent immunotherapy (eg, glucocorticoids) is not used.
A typical course of treatment consists of five exchanges (3 to 5 L of plasma each) over 7 to 14 days. Although performed daily in some circumstances, exchanges done every other day are probably more effective in reducing the antibody levels due to the time it takes for the extravascular immunoglobulin to regain equilibrium after each exchange. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)
Intravenous immune globulin — IVIG is used in the same setting as plasma exchange to quickly reverse an exacerbation of myasthenia. IVIG is the pooled immunoglobulins from thousands of donors and acts in myasthenia via uncertain mechanisms. (See "Overview of intravenous immune globulin (IVIG) therapy", section on 'Mechanisms of action'.)
The total dose of IVIG is 2 g/kg, usually over two to five days (eg, 400 mg/kg per day over five days). However, there are only limited data directly comparing different IVIG doses for the treatment of myasthenia gravis exacerbations or crisis. One clinical trial, involving 173 patients with acute exacerbation of myasthenia gravis, found no significant difference in the primary outcome measure (the myasthenic muscular score) after IVIG 2 g/kg (given as 1 g/kg on two consecutive days) compared with IVIG 1 g/kg (given as 1 g/kg on day one and placebo on day two) . The investigators concluded that IVIG 1 g/kg administered in a single dose may be the optimal IVIG dose, given the high cost of IVIG infusions.
Spreading the IVIG dose over more days may be preferable in those who have renal disease or heart failure and in older adults.
Like plasma exchange, IVIG has never been compared directly against placebo in a randomized, controlled trial for treatment of myasthenic crisis. Data supporting the use of IVIG in patients with myasthenia gravis outside of the setting of myasthenic crisis are discussed separately. (See "Treatment of myasthenia gravis", section on 'Intravenous immune globulin'.)
Choosing rapid therapy — There are limited data comparing the two rapid therapies for treatment of myasthenic crisis, and the available evidence has not shown a significant advantage for either.
●The Myasthenia Gravis Clinical Study Group trial randomly assigned 87 patients with severe clinical exacerbation of myasthenia gravis to treatment with IVIG or plasma exchange . About 50 percent of the patients reached the target 20 point improvement on the myasthenia muscle score by day 9 in the plasma exchange group and day 12 in the IVIG group. However, there were no functional or strength differences in the two treatment groups at day 15, and the rate of adverse events was lower in the IVIG group.
●Similarly, a systematic review comparing trials of plasma exchange versus IVIG found no convincing difference in the beneficial effects of these therapies for treating exacerbation or worsening of myasthenia gravis .
●A retrospective series of 54 patients in myasthenic crisis found plasma exchange to be superior to IVIG . The study reported a more prominent clinical improvement (scored by a uniform scheme) one week after initiation of treatment with plasma exchange than with IVIG, even though patients in the plasma exchange group had only received three or four treatments, while the IVIG group had completed the five treatments.
●An observational report identified 1606 patients admitted for the treatment of myasthenia gravis from an administrative database . Among the 698 patients with myasthenic crisis, those treated with plasma exchange (n = 529) had significantly higher mortality and complication rates than those treated with IVIG (n = 169). However, the strength of this finding is limited by the observational nature of this study, which does not exclude possible selection bias (eg, sicker patients were more likely to be treated with plasma exchange). Among the whole group of myasthenics, the adjusted mortality and complication rates were not significantly different between the two treatment groups.
Although the trials do not show a clear difference between IVIG and plasma exchange in the treatment of myasthenia exacerbations or crisis, there is suggestive evidence and personal clinical experience that plasma exchange works more quickly than IVIG in seriously ill patients with myasthenia gravis. Most neuromuscular experts still prefer plasma exchange as a first-line therapy for myasthenic crisis, in part because the onset of action appears to be more rapid [11,24,25]. However, others prefer IVIG because it is easier to administer and has a lower incidence of serious side effects, but similar efficacy, compared with plasma exchange [26,27].
Immunomodulating therapy — Glucocorticoids are started at high dose (eg, prednisone 60 to 80 mg daily) for most patients with myasthenic crisis in order to provide a longer period of benefit beyond the few weeks of benefit provided by the more rapid but short-lived therapies (plasma exchange and IVIG). The onset of benefit with glucocorticoids for myasthenia gravis generally begins within two to three weeks and peaks after a mean of 5.5 months. (See "Chronic immunomodulating therapies for myasthenia gravis", section on 'Glucocorticoids'.)
The initiation of high-dose glucocorticoids is associated with a transient worsening of weakness and myasthenic symptoms that is serious in up to 50 percent, and additionally with respiratory failure requiring mechanical ventilation in up to 10 percent. The transient worsening usually occurs 5 to 10 days after the initiation of glucocorticoids and lasts about 5 or 6 days. However, concern regarding initial worsening of myasthenia gravis with high-dose glucocorticoids is ameliorated when the patient is receiving concurrent treatment with plasma exchange or IVIG. The quick onset of action of these rapid therapies helps to prevent the transient worsening that would otherwise occur due to the glucocorticoids. (See "Chronic immunomodulating therapies for myasthenia gravis", section on 'Glucocorticoids'.)
Other immunomodulating treatments for myasthenia gravis, such as azathioprine, mycophenolate mofetil, and cyclosporine, can be considered if glucocorticoids are contraindicated or if an inadequate therapeutic response has been observed with glucocorticoids. However, these agents have a delayed onset of action compared with glucocorticoids (table 6). They are discussed in detail separately. (See "Chronic immunomodulating therapies for myasthenia gravis".)
Weaning from ventilatory support — The decision to initiate weaning from mechanical ventilation should be individualized for each patient. The principles of weaning in patients with a myasthenic crisis should be the same as for the general population. However, particular attention should be paid to measuring indices of respiratory muscle strength and secretion clearance.
There is no agreed-upon best approach to weaning in this population. However, similar to the general population, the performance of daily spontaneous breathing trials (SBTs) is our preferred method of weaning. A SBT refers to a patient spontaneously breathing through the endotracheal tube (ETT) for a set period of time (usually 30 minutes to two hours) either with or without a small amount of ventilator support. (See "Methods of weaning from mechanical ventilation", section on 'Choosing a weaning method'.)
Generally, for patients with a myasthenic crisis, SBTs should only begin after the patient has started treatment with plasma exchange or IVIG and the patient shows evidence of improving respiratory muscle strength, ie, with a VC >15 to 20 mL/kg and a MIP more negative than -25 to -30 cmH2O (eg, -30 to -60 cmH2O). When a patient successfully passes a SBT and no contraindication to extubation is present (eg, patient has adequate cough and excessive secretions requiring frequent suctioning are absent), the ETT is typically removed; if a patient fails or a contraindication is present then the patient cannot be liberated from mechanical ventilation. (See "Methods of weaning from mechanical ventilation".)
All patients should be closely monitored following extubation for early failure using VC and MIP measurements to detect those who may need reintubation. In many patients, early aggressive management with oxygenation and airway clearance can prevent reintubation. The value of noninvasive positive pressure ventilation is this setting is unknown. (See "Extubation management".)
Regardless of the approach used, weaning should proceed in a manner that prevents respiratory muscle fatigue and allows for adequate rest between weaning trials. In one series of patients with myasthenic crisis, both extubation failure (44 percent) and reintubation (26 percent) were not uncommon . Lower VC at the time of extubation, atelectasis, and need for bilevel positive airway pressure (BPAP) ventilation after extubation predicted the need for reintubation.
Some patients may require a tracheostomy for prolonged weaning. The indications for tracheostomy and management of patients requiring prolonged mechanical ventilation are discussed separately. (See "Overview of tracheostomy" and "Management and prognosis of patients requiring prolonged mechanical ventilation".)
Complications — The most common complications associated with myasthenic crisis are various causes of fever and infection, including pneumonia, bronchitis, urinary tract infection, colitis caused by Clostridium difficile, bacteremia, and sepsis [2,29]. Patients with myasthenic crisis are at increased risk for vascular complications including deep vein thrombosis, heart failure, acute myocardial infarction, cardiac arrhythmias, and cardiac arrest . There are also several case reports of stress-induced cardiomyopathy (Takotsubo cardiomyopathy) associated with myasthenic crisis .
PROGNOSIS — With advances in therapy and intensive care management, the prognosis in myasthenic crisis dramatically improved from a mortality rate of approximately 75 percent in the 1950s and 1960s to a rate of approximately 5 percent by the 1990s [10,23,31]. However, myasthenic crisis is still associated with substantial morbidity. As an example, a 1997 review found that patients with myasthenic crisis required mechanical ventilation for a mean duration of two weeks, similar to the duration of mechanical ventilation reported in a prior review of myasthenic crisis at the same institution in the 1960s .
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient information: Myasthenia gravis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Myasthenic crisis is a life-threatening condition characterized by neuromuscular respiratory failure. Myasthenic crisis may be precipitated by a variety of factors including infection, surgery, or tapering of immunosuppression. Often, the crisis occurs as a spontaneous event. A number of medications can increase the weakness in myasthenia (table 1 and table 2) and should also be considered as possible precipitants. (See 'Precipitants' above.)
●In a minority of cases, myasthenic crisis is the first manifestation of myasthenia gravis and the cause of neuromuscular respiratory failure may be unknown at presentation. (See 'Diagnosis' above.)
●Patients with moderate to severe exacerbations of myasthenia who are deteriorating should be admitted to an intensive care setting so they can be closely monitored (table 4). Vital capacity (VC) and/or maximal inspiratory pressure (MIP) should be measured frequently, as often as every two hours in some cases. (See 'Evaluation and management' above.)
●Consider elective intubation based upon overall clinical status, particularly when the VC falls below 15 to 20 mL/kg body weight, the MIP is less negative than -30 cmH2O, or when clinical signs of respiratory distress are present. (See 'Elective intubation' above.)
●For patients with myasthenic crisis who are intubated, we suggest withdrawal of anticholinesterase medications used for myasthenia gravis (eg, pyridostigmine) in order to reduce airway secretions (Grade 2C). These medications can be restarted at a low dose after the patient has shown a response to plasma exchange or intravenous immune globulin (IVIG). (See 'Elective intubation' above.)
●We recommend rapid therapy with plasma exchange or IVIG to treat patients with rapidly worsening myasthenia gravis or myasthenic crisis (Grade 1B) (table 5). We suggest the use of plasma exchange over IVIG for most patients with severe myasthenia gravis or myasthenic crisis because it has a slightly more rapid onset of action (Grade 2C). (See 'Rapid therapies' above.)
●We recommend concurrent initiation of chronic immunomodulating therapy with rapid therapy (Grade 1B), anticipating that the chronic immunotherapy will provide benefit for myasthenia gravis after the transient benefit of the rapid therapy has dissipated (table 6). The choice of specific agent (ie, prednisone, azathioprine, mycophenolate mofetil, or cyclosporine) depends on many factors. This issue is discussed separately. (See "Chronic immunomodulating therapies for myasthenia gravis".)
●Weaning from mechanical ventilation with spontaneous breathing trials should be considered after the patient has started treatment with plasma exchange or IVIG and shows evidence of improving respiratory muscle strength (ie, VC >15 to 20 mL/kg and MIP more negative than -25 to -30 cmH2O), has an adequate cough, and has manageable respiratory secretions. (See 'Weaning from ventilatory support' above.)
●Myasthenic crisis is associated with substantial morbidity, including prolonged mechanical ventilation, and a mortality rate of approximately 5 percent. (See 'Prognosis' above.)
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