Primary Alveolar Hypoventilation Syndrome (Ondine’s Curse)

Epidemiology

  • Rare disorder
  • Predisposing factors:
    • Sex: M>F
    • Peak age: aged 20-50 (but can occur at any age)
    • Familial cases: have been reported
  • Definition: idiopathic hypoventilation in the absence of any neuromuscular disease or mechanical ventilatory defect

Physiology

  • Central hypoventilation due to abnormal chemoreceptor function, some lesion of medullary reticular formation, or abnormal carotid body chemoreceptor function
  • Resultant central hypoventilation leads to hypoxia/ acidosis (with resultant pulmonary vasoconstriction)
  • Nocturnal hypoventilation: disorder is often worse during sleep due to greater physiologic reliance on metabolic control during sleep
  • Ventilatory response to hypoxemia/ hypercapnia: decreased (supplemental oxygen may increase or decrease ventilation)

Diagnosis

  • ABG: hypoxemia (usually normal A-a gradient, occasion-ally elevated due to V/Q mismatch or microatelectasis)/ hypercapnia (pCO2 may be normal during wakefulness in some cases/ elevated serum bicarb may be only clue to disorder)
    • Patients can voluntarily decrease pCO2 on demand
  • PFT’s
    • FEV1: normal
    • VC: normal
    • TLC: normal
    • MVV: normal
    • MIP/MEP: normal
  • Exercise test: increase in pCO2 and decrease in pO2
  • CBC: polycythemia
  • EMG/NCV: normal

Clinical

(asymptomatic or insidious onset)

  • Dyspnea: uncommon
  • Fatigue/ lethargy
  • Disturbed sleep
  • Excessive daytime somnolence
  • Morning headache
  • Severe respiratory depression after sedation/anesthesia
  • Cyanosis
  • Prolonged breathold (without dyspnea)
  • Sleep-disordered breathing (usually CSA-CSR)
  • Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension)
  • Acute/Chronic Hypoventilation (see Acute Hypoventilation and Chronic Hypoventilation)

Treatment

  • Avoid respiratory depressants
  • Progesterone (40 mg/day): useful over long-term in patients with obesity-hypoventilation/hypercapnic COPD
    • Benefit is predicted by ability to decrease pCO2 by hyperventilation
  • Acetazolamide (Diamox): for patients with primary metabolic alkalosis with CO2 retention, but not pure respiratory acidosis
  • Nocturnal oxygen: exacerbates nocturnal hypercapnia in most cases
  • Phrenic nerve pacing: test phrenic nerve for viability (using diaphragmatic electrodes)
  • Implant cervical or thoracic (preferred, better pacing) electrodes
    • Begin pacing gradually and assess function (rib cage moves paradoxically inward during paced breaths) with fluoro/ PFT’s: best to pace for 6-12 hours each side alternating
    • Complications: nerve damage/ infection/ upper airway occlusion (due to negative pressures/solved by trach or pacing from SCM EMG)
  • Mechanical ventilation (Rocking bed, positive pressure, etc.): usually required/nocturnal use alleviates daytime symptoms
    • Negative pressure may predispose upper airway collapse during sleep

References

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