What is the effect of high altitude on treatment-emergent central sleep apnea (CSA)?

Effect of High Altitude on Treatment-Emergent Central Sleep Apnea

High altitude significantly exacerbates treatment-emergent central sleep apnea (CSA) due to hypobaric hypoxia, which triggers physiological adaptations that can worsen breathing disturbances during sleep and increase the risk of cardiac decompensation in susceptible individuals. 1, 2

Pathophysiological Mechanisms

High altitude exposure causes several physiological changes that impact central sleep apnea:

• Hypobaric hypoxia: Decreased barometric pressure reduces partial pressure of oxygen in inspired air 1
• Respiratory adaptations: Rapid increases in respiratory rate and tidal volume leading to respiratory alkalosis 1
• Hypoxic pulmonary vasoconstriction: Leads to pulmonary hypertension, a trigger for high altitude pulmonary edema 1
• Sympathetic activation: Increases heart rate and stroke volume to compensate for lower arterial oxygen content 1
• Periodic breathing: Universal at altitudes above 2,500m, increasing in severity with ascent 2, 3

Impact on Treatment-Emergent CSA

Treatment-emergent CSA (previously called complex sleep apnea) occurs in approximately 1% of patients initiating CPAP therapy for obstructive sleep apnea 1. At high altitude:

• CSA severity increases with ascent, with universal occurrence above 5,000m 2
• Periodic breathing persists for more than a month at 5,000m despite acclimatization 2
• The interaction between hypocapnia and NREM sleep stages 1-2, combined with increased loop gain, exacerbates CSA 2

Management Recommendations

For patients with treatment-emergent CSA traveling to high altitude:

1. Continue positive airway pressure therapy:

   • CPAP alone is recommended for treatment-emergent CSA (conditional recommendation, low certainty) 4
   • Consider auto-adjusting CPAP which can adapt to changing pressure requirements at altitude 5

2. Add acetazolamide:

   • Recommended dosage: 125-250mg twice daily 5, 6
   • Benefits include:
     • Reduces central apneas emerging at altitude 7, 4, 2
     • Improves oxygenation 6
     • Prevents excessive blood pressure elevation 6
     • Stimulates ventilation 6

3. Consider supplemental oxygen:

   • Particularly beneficial for patients with comorbid cardiopulmonary disease 7
   • Recommended for CSA due to high altitude (conditional recommendation, very low certainty) 4

4. Consider adaptive servo ventilation (ASV):

   • Suggested over no ASV for treatment-emergent CSA (conditional recommendation, low certainty) 4
   • Caution: Prior to initiating ASV in patients with heart failure with reduced ejection fraction, shared decision-making is essential 4

Special Considerations for Heart Failure Patients

Patients with heart failure require additional precautions:

• Travel to intermediate altitude (~2,000m) is generally safe only for patients with good exercise tolerance at sea level 1
• Medications for heart failure may interfere with altitude adaptation:
  • ACE inhibitors and ARBs reduce renal erythropoietin production, limiting compensatory rise in hematocrit 1
  • Non-selective beta-blockers (e.g., carvedilol) reduce peak exercise ventilation and VO2 more than selective beta-blockers (e.g., nebivolol) 1
• Diuretic therapy should be carefully adjusted based on signs of dehydration or fluid gain 1

Altitude Recommendations Based on Cardiac Status

• NYHA class I-II: Travel to high altitude advisable if patient is stable 1
• NYHA class III: Travel advisable if stable; consider supplemental oxygen during air travel 1
• NYHA class IV: Travel not advisable; if unavoidable, supplemental oxygen and medical assistance required 1

Conclusion

Treatment-emergent CSA is significantly affected by high altitude exposure through multiple physiological mechanisms. Management should focus on continuing PAP therapy with the addition of acetazolamide and possibly supplemental oxygen. Careful consideration of underlying cardiac conditions is essential when planning travel to high altitude locations.