The successful treatment of hypercapnic respiratory failure with oral modafinil

Abstract

Hypercapnic respiratory failure is common in advanced chronic obstructive pulmonary disease and is usually treated by nasal ventilation. Not all patients requiring such ventilation can tolerate it, with anxiety and phobia influencing their reaction, along with treatment failure. We report the case histories of six patients with hypercapnic respiratory failure who were at risk of death due to refusal of nasal ventilation or its failure despite ongoing treatment. We report their improvement with oral modafinil 200 mg tablets used as a respiratory stimulant, which led to discharge, improved arterial blood gases, and offset further admissions with hypercapnic respiratory failure. This drug is licensed for narcolepsy and is said to stimulate the respiratory system via the central nervous system. Its use in respiratory failure is an unlicensed indication, and there are no case reports or studies of such use in the literature. Its respiratory stimulant effects appear better than those with protriptyline, which was a drug previously used until its production was discontinued. Our findings suggest that a study of modafinil in hypercapnic respiratory failure would be warranted, especially for patients with treatment failure or intolerance to nasal ventilation. This may offer a way of shortening hospital stay, improving outcome and quality of life, and reducing death and readmissions.

Modafinil: a novel alternative to non-invasive ventilation in hypercapnic respiratory failure?

“…Parnell et al used modafinil, out of label, in a very small heterogeneous group of hypercapnic respiratory failure patients unwilling to carry out NIV, with good results (benefic effects in blood gases, exacerbation admissions, with no adverse effects). 3 …”

Disharmony between wake- and respiration-promoting activities: effects of modafinil on ventilatory control in rodents

“…Firstly, one time application of modafinil may not be sufficient for the evaluation of a change in ventilatory control as judged from a report of gradual alleviation of respiratory failure in COPD patients during chronic daily dosing of modafinil [9]. Secondly, the present study was conducted in healthy animals.…”

“…It was thus a reasonable assumption that modafinil would enhance ventilation and its responses. The assumption was strengthened by a recent report demonstrating that modafinil, given orally on a daily basis, alleviated hypercapnic respiratory failure in COPD patients (i.e., improving oxygenation, and lowering the arterial carbon dioxide level) without adverse effects [9]. This off-label use of modafinil opens a new door to regulate hypercapnic respiratory failure in noncompliance patients with non-invasive ventilation [10].…”