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Chronic respiratory failure
  1. G P Bootsma,
  2. Y Heijdra,
  3. M Wagenaar
  1. P O Box 9101, Nijmegen 6500 HB, The Netherlands; g.bootsma{at}long.umcn.nl

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The recent case report by Smyth and Riley1 describes an extremely uncommon chronic respiratory failure due to hypoventilation secondary to brainstem stroke, and documents a new treatment option with medroxyprogesterone acetate.

We recently saw two patients also with central hypoventilation resulting in chronic type II respiratory failure and treated both with, among other things, medroxyprogesterone acetate (30 mg twice daily) with good results. The first patient, a 69 year old man with a medical history of glomus caroticum resection due to malignancy with postoperative radiotherapy in 1979, presented to our outpatient clinic with polyglobulia. Arterial blood gas analysis revealed marked hypoxaemia (Pao2 4.8 kPa) and hypercapnia (Paco2 6.9 kPa). An intensive search for the cause showed no abnormalities; his lung function indicated only marginal chronic obstructive pulmonary disease (FEV1/VC 68%) but his hypoxic ventilatory response was markedly decreased and his hypercapnic ventilatory response was absent. The patient was treated with acetazolamide, theophylline, and medroxyprogesterone acetate and his blood gas tensions improved within days to normal values (Pao2 10.3 kPa, Paco2 5.1 kPa).

The second patient, a 38 year old woman, was known from birth to have a hypothalamic pituitary gland deficiency with (stable) adipositas (quetelet index 53). She had complained of dizziness, general malaise, and dyspnoea on several occasions before being sent to our department. Arterial blood gas analysis revealed hypoxaemia and marked hypercapnia (Pao2 8.0 kPa, Paco2 7.2 kPa). She probably suffers from Pickwick syndrome and formal polysomnographic measurements will be performed shortly, but she also has a complete absence of hypoxic and hypercapnic ventilatory responses. Again, treatment with theophylline, acetazolamide, and medroxyprogesterone acetate normalised her arterial blood gas tensions within days. Furthermore, she now follows an intense weight reduction programme and has lost more than 10 kg in weeks.

Acetazolamide has been shown to augment both the hypoxic and hypercapnic ventilatory response and to decrease Paco2 levels significantly in patients with chronic obstructive pulmonary disease (COPD).2,3 The mechanism of the effect is possibly due to a direct effect on the peripheral chemoreceptors (carotid bodies) as well as to an effect on cerebral blood flow regulation.2,4

It has been shown that medroxyprosterone acetate also acts on the peripheral chemoreceptors (directly) as well as on the central chemoreceptors (indirectly) and progesterone receptors in the hypothalamus in cats.5 This was also found in hypercapnic COPD patients, indicating that medroxyprogesterone acetate acts centrally on the respiratory centres.3 This supports the use of medroxyprogesterone acetate in central hypoventilation. Furthermore, the combined treatment of acetazolamide and medroxyprogesterone acetate increases ventilation and improves arterial blood gas values—that is, it decreases Paco2 to normocapnic values and increases Pao2 to almost normoxic values in hypercapnic and hypoxic patients with COPD.3

In conclusion, we agree with Smyth and Riley that medroxyprogesterone acetate can be used in patients with central hypoventilation disorders.

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