3. Discussion of inhaled furosemide in COVID-19
Since the morbidity and mortality of COVID-19 infections arise in part
from the toxic overproduction of pro-inflammatory cytokines, the
application of anti-inflammatory agents is a mechanistically-sound
strategy for treatment development. Furosemide not only inhibits the
secretion of multiple cytokines implicated in COVID-19, it has also been
shown to provide relief of dyspnea via direct inhalation. Due to its
wide-spread use as diuretic, it is well-studied, commonly available
globally, and, since it is a small molecule, it can be produced and
stored at low cost. When given by inhalation, furosemide is simply
dissolved in normal saline solution; therefore, the distribution of
furosemide to COVID-19 patients in developed and developing countries
will be fast and facile.
However, the administration of furosemide to COVID-19-afflicted people
also has several potential drawbacks that need to be considered. First,
hypokalemia and electrolyte depletion have been found to be consequences
of SARS-CoV-2 induced pathology. Since one of furosemide’s main adverse
effects is hypokalemia (3.6%), this may lead to exacerbating potassium
depletion. On the other hand, hypokalemia is a side-effect of
systemically given furosemide. The diuretic effect is anticipated to be
very small or even absent upon nebulized inhaled administration.
Waskiw-Ford et al. (2018) have reported that diuresis does not
occur upon inhalation of furosemide except possibly at doses exceeding
100 mg. Nevertheless, patients should also be monitored closely for
enhanced production of urine which would accompany the risk of
hypokalemia. Another potential problem may arise from the procedure of
administering inhaled furosemide – will the resulting aerosols enhance
the spread of the SARS-CoV-2 virus to close bystanders. Whilst intubated
patients can be given furosemide with reduced risk to those nearby,
inhalation by nebulizer mask will cause aerosol development and may
thereby promote viral spread if done without physical distancing. This
risk, however, can easily be mitigated by appropriate personal
protecting equipment in nearby people or simply by having designated
inhalation sites that are physically separated from other individuals.
Furthermore, since cough is a primary mechanism of disease spread, and
since inhaled furosemide decreases coughing, once initiated, inhaled
furosemide may contribute to decreased disease spread.
Arguably, inhaled furosemide could be administered at any stage of the
COVID-19 disease presentation, from the early phases involving cough,
fever and shortness of breath, to the late stages requiring endotracheal
intubation. In the early stages, it is possible that furosemide might
prevent disease progression to pulmonary failure; in the late stages, it
is possible that furosemide might reduce the number of days of required
ventilator support.
Administering drugs to any severely ill individual person is not without
risk. The potential side-effects of furosemide, including hypokalemia
and dehydration, will be minimized by administration through inhalation;
nevertheless, these are-side effects that must be considered. In
addition, even though cytokine storms are known to play a major role in
severe viral pneumonias, the detailed mechanism of hypercytokinemia in
COVID-19 is not yet fully delineated.