PCO2 Threshold for NIV in Myasthenia Gravis
In myasthenia gravis, NIV should be initiated at ANY elevation of PCO2 above normal in an acutely unwell patient—do not wait for acidosis or a specific PCO2 threshold to develop. 1
Critical Distinction: MG is NOT Like COPD
The approach to hypercapnia in neuromuscular disease (including MG) fundamentally differs from COPD management:
In COPD: The degree of acidosis matters more than absolute PCO2, with specific thresholds (PCO2 ≥6.5 kPa/49 mmHg with pH <7.35) guiding NIV initiation 2
In Myasthenia Gravis: ANY elevation of PCO2 may herald an impending crisis because patients have minimal respiratory reserve 1
The BTS/ICS guidelines explicitly state: "In contrast to AECOPD, where the degree of acidosis is more important than the degree of hypercapnia, any elevation of pCO2 in NMD/CWD may herald an impending crisis" 1
When to Start NIV in MG: The Algorithm
Initiate NIV if ANY of the following are present:
1. Any hypercapnia in an acutely unwell/breathless patient 1
- Do not wait for respiratory acidosis to develop
- Minor infections (even coryza) can trigger progressive hypercapnia over 24-72 hours
2. Known vital capacity <1 L with respiratory rate >20, even if normocapnic 1
- These patients are at imminent risk despite normal PCO2
3. PCO2 >45 mmHg (6.0 kPa) with any respiratory symptoms 1, 3
- Research data shows PCO2 >45 mmHg predicts BiPAP failure and need for intubation 3
- The American College of Chest Physicians uses PCO2 >45 mmHg as a threshold for NMD 1
Evidence-Based PCO2 Thresholds from Research
The strongest research evidence comes from a 2008 Mayo Clinic study examining 60 episodes of myasthenic crisis 3:
- PCO2 >45 mmHg at BiPAP initiation was the only predictor of NIV failure (P=0.04) 3
- When BiPAP was started before hypercapnia developed, intubation was avoided in 58% of cases 3
- Mean BiPAP duration when successful was only 4.3 days 3
- Early BiPAP treatment significantly reduced ventilation duration (P<0.007) 3
A 2009 study confirmed that serum bicarbonate <30 mmol/L (indicating less metabolic compensation) predicted NIV success, while higher bicarbonate suggested chronic compensation and higher failure risk 4
Critical Pitfalls to Avoid
Don't Wait for Acidosis
- Tolerance of hypercapnia varies considerably in MG—some patients are excessively sleepy with minimal PCO2 elevation, others remain alert despite severe hypercapnia 1
- Waiting for pH <7.35 (as in COPD protocols) risks missing the narrow window for successful NIV 1
Don't Apply COPD Thresholds
- The widely-cited PCO2 ≥6.5 kPa (49 mmHg) threshold is specifically for COPD, not neuromuscular disease 2
- Using COPD criteria in MG delays intervention and increases intubation risk 1
Assess Bulbar Function
- Bulbar dysfunction renders NIV more difficult and requires higher EPAP to overcome upper airway obstruction 1
- Bulbar weakness increases aspiration risk and may necessitate earlier intubation 5
Ventilator Settings for MG
Start with low pressure support (unlike COPD):
- Initial IPAP 8-12 cm H2O pressure difference 1
- Set inspiratory/expiratory time ratio at 1:1 initially 1
- Consider pressure-controlled ventilation (PCV) as triggering is commonly inadequate in neuromuscular disease 1
Monitoring for NIV Failure
Consider intubation if:
- PCO2 continues rising despite NIV 3
- pH deteriorates on NIV 1
- Patient develops severe respiratory distress 1
- Maximal expiratory pressure (MEP) <40 cm H2O predicts extubation failure 4
- Poor cough strength leads to sputum retention (most common cause of extubation failure in MG) 4
The key principle: In MG, early NIV at the first sign of hypercapnia prevents prolonged intubation, reduces pulmonary complications, and shortens ICU stay 3. The specific PCO2 number matters less than recognizing any elevation as a warning sign requiring immediate intervention.