THE CASE: In a fictitious urban hospital a 28-year-old female, no pmhx, recently dx with “asthma”, presents with exertional shortness of breath for three months and an accompanying 40lb weight loss. Review of systems is negative for anxiety, wheezing, cough, chest pain, fevers, chills, night sweats, PE risk factors, recent travel, or HIV risk factors.
In the emergency department the patient was found to have hypercapnia and generalized weakness. The patient was admitted to the hospital for evaluation of hypoventilation.
THE COURSE: While in the hospital, the patient had respiratory arrest, likely secondary to oxygen induced hypercapnia (huh? to be reviewed….at the end). The patient was intubated, diagnosed with a neuromuscular disease. She had positive anti-ACHase antibodies and anti-voltage gated calcium channel antibodies. The final diagnoses were Myasthenia Gravis and Lambert Eaton.
MYASTENIA GRAVIS (MG):While uncommon (incidence 10-20 per million), MG carries a significant morbidity. It has a bimodal age of onset during early life (20-30) and again later in life (60-80). It is caused by antibodies to the nicotinic acetylcholinesterase receptors on the neuromuscular endplate. The antibodies occupy the receptors. When acetylcholine is released at the neuromuscular junction, it cannot bind to the receptor (occupied with autoantibodies). Subsequently there is no muscle contraction. Clinically the patient has weakness- fatigable weakness. The most common presentation is with diplopia due to bulbar weakness of the ocular muscles. However, the concern is for respiratory muscle weakness ultimately causing hypoventilation and type 2 respiratory failure. 30% of people diagnosed with MG have a concomitant thymoma, thought to be generating the auto-antibodies.
TREATMENT FOR MYASTHENIA GRAVIS: There is no consensus on treatment strategy, but here are some options:
Thymectomy
Plasmapheresis
IVIG
Corticosteroids
Acetylcholinesterase inhibitors are used for long-term treatment but have little role in the acute phase.
EMERGENCY DEPARTMENT EVALUATION: When a patient is found to have hypercapnia in the ED, it is essential to understand the cause. The differential diagnosis of hypercapnia in the ED includes primary respiratory problems (COPD, severe asthma), neurologic disorders (Guillian-Barre, ALS, MG), and central causes for hypoventilation (OHS, others). Bedside PFTs in the ED are performed to evaluate for impending respiratory failure. Negative Inspiratory Force (NIF) and FVC are the best tests (also performed bedside) to determine the likelihood of respiratory failure. NIF value higher than -25cmH₂O is suggestive of impending respiratory failure. These patients require ICU level of care. Said differently, if you cannot generate a force of -25cmH₂O or more (normal is -80cmH2O) on forced inhalation, it is highly predictive of the need for prolonged mechanical ventilation (Serrano and Rabinstein in the European Journal of Neurology, referenced below).
HOW DO YOU KNOW IF YOUR PATIENT IS HYPERCAPNEIC?
Does venous blood gas correlate well to arterial values? In a meta-analysis by Bloom et al, 12 articles were reviewed showing the correlation between venous and arterial blood samples. The pooled data showed that there was correlation within 4.41mmHg for PCO₂, with a 95% confidence interval of 2.55-6.27mmHg. The data was presented for all the values of co-oximetry. Ultimately, there is best correlation when the VBG/ABG are within normal limits. When the VBG value for CO₂/O₂/pH are outside normal limits, then ABG should be performed to obtain accurate values.
WHAT ABOUT HYPERCAPNEIC RESPIRATORY FAILURE DUE TO CARBON DIOXIDE RETENTION?
Our whole lives we have been taught not to “over-do it” with oxygen for COPD patients. The old dogma was that COPD patients have a hypoxic drive set for the partial pressure of oxygen, and when too much oxygen is delivered they stop breathing. This is not the case.
Hypercapnia can be induced in patients with elevated alveolar CO₂ pressure when delivered a high fraction of inspired oxygen. Simply, you can induce hypercapnia by giving too much oxygen. The lungs have a physiologic means of maintaining our arterial oxygen levels at the level of the capillary-alveolar interface. When the tension of oxygen in alveoli is decreased, local mediators are released causing capillary vasoconstriction, preventing a shunt and ventilation/perfusion (V/Q) mismatch. This physiologic mechanism is called hypoxic pulmonary vasoconstriction. If you deliver at high FiO₂ to an area with poor ventilation (hypoventilation syndrome, MG, COPD), the hypoxic pulmonary vasoconstriction mechanism is inhibited. As a result, there are areas of lung that have are poorly ventilated but are well perfused. This increases V/Q mismatch. This essentially causes increased dead-space and increased V/Q mismatch, causing oxygen induced hypercapnia. So while our instincts tell us to hammer the hypoxic patient with high-flow oxygen, physiology tells us to titrate to 88-92% in patients who have chronic ventilation abnormalities.
HYPEROXIA IN GENERAL: Don’t do it. Administering high concentrations of oxygen is associated with worse outcomes. While HYPoxia kills, HYPERoxia has deleterious effects. In several studies including a review article (Gordo-Vidal et al. 2010) high PO₂ administered in the first 24 hours of mechanical ventilation is associated with increased rates of acute lung injury as well as higher mortality. Rincon et. al in 2014 found that PaO₂ over 300mmHg was associated with higher mortality in patients with acute stroke. Bottom line: maintain physiologic PaO₂ levels in general. More is NOT better.
TAKE HOME POINTS:
- Myasthenia gravis is an autoimmune disease affecting post synaptic receptors at the NMJ.
- MG is treated with immune suppression and acetylcholinesterase inhibitors.
- Suspect neuromuscular disease in patients with SOB and generalized weakness.
- Call respiratory for a bedside NIF. Should be more negative than -25cmH₂O.
- If NIF is less negative than -25cmH₂O, the patient requires ICU care for impending respiratory failure (type II).
- Do not hammer hypoxic patients with high concentration O₂ if they have impaired ventilation.
- VBG and ABG correlate fine- within the normal ranges. If they don’t correlate, do ABG.
- Hyperoxia in general is dangerous. Less is more. Physiologic PaO₂ is best. High PaO₂ delivery is associated with higher mortality.
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Diaz-Manera J, Martinez-Hernandez E, Querol L, et al. Long-lasting treatment effect of rituximab in MuSK myasthenia [published online ahead of print January 4, 2012]. Neurology 2012; 78:189–193. doi:10.1212/WNL.0b013e3182407982
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Trikha I, Singh S, Goyal V, Shukla G, Bhasin R, Behari M. Comparative efficacy of low dose, daily versus alternate day plasma exchange in severe myasthenia gravis: a randomised trial [published online ahead of print August 11, 2007]. J Neurol 2007; 254:989–995. doi:10.1007/s00415-006-0235-7
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Goldenberg WD, Sinert RH. Emergent Management of Myasthenia Gravis. Medscape Reference. Updated November 05, 2014.
Abdo and Heunks. Oxygen Induced Hypercapnia in COPD: myhs and facts. Critical Care 2012, 16:323.
Burakgazi AZ, Höke A. Respiratory muscle weakness in peripheral neuropathies. Peripher Nerv Syst. 2010 Dec;15(4):307-13.
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