The Management of Chronic Hypoventilation: Pharmacologic Management
Progestational agents cause hyperventilation during pregnancy and stimulate ventilatory drive in normal nonpregnant subjects. They may occasionally ameliorate hypercarbia in patients with central hypoventilation and the obesity hypoventilation syndrome and a therapeutic trial may be worthwhile in otherwise stable patients. At doses of medroxyprogesterone up to 50 mg orally three times daily, adverse side effects are minimal, but they include acne, ageusia, and sexual dysfunction. Unfortunately, results with progestational agents in the therapy of uncomplicated obstructive sleep apnea have been disappointing.
Almitrine bismesylate, a peripheral chemoreceptor agonist, improves oxygenation in patients with COPD during both sleep and wakefulness. This effect, however, appears to be more a result of improved V/Q relationships rather than direct respiratory stimulation and the role of almitrine in the treatment of chronic hypoventilation remains questionable.
Tricyclic antidepressants have been used in the therapy of sleep apnea syndrome, although they are not central respiratory stimulants per se. They appear to act by either suppressing the rapid eye movement stage of sleep during which apneic episodes are most likely to occur or by increasing upper airway muscle tone. They are effective in only a minority of patients with sleep apnea and probably do not act to reverse hypoventilation.
In addition to its many other actions, aminophylline is a central respiratory stimulant. When given intravenously to COPD patients with chronic C02 retention, aminophylline reduces hypercarbia in the short term. However, long-term studies on effects of aminophylline in patients with COPD and chronic hypercarbia have not consistently shown reversal of chronic hypoventilation. The authors’ experience with aminophylline in patients with chronic hypercarbia due to neuromuscular disease is equally disappointing (Hill NS, unpublished observations).
Doxapram hydrochloride has been shown to acutely stimulate ventilation both in normal subjects and in patients with exacerbations of COPD. Unfortunately, it has many adverse side effects, including muscle spasms, agitation, and seizures, is available only in the intravenous form, and is not recommended for more than two hours of use with each administration. Thus, it has virtually no role in the management of chronic hypoventilation.