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.