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Tuesday, July 13, 2021

AHEAD OF PRINT: Nebulized Furosemide Makes All the Difference for Patients with Dyspnea at the End of Life

Nebulized Furosemide Makes All the Difference
for Patients with Dyspnea at the End of Life

BY RICHARD PESCATORE, DO

Certain clinical experiences you just remember, moments in medical time that stick with you through years of encounters that sometimes become rote or at least stray from the remarkable. Often, these stand out to me as foundational experiences, instances that go on to define a lifetime of medical practice. These moments too often happen in the throes of resuscitation, as we learn of heroic interventions and cutting-edge advances to prolong life. I can remember a lesson learned, however, from a different kind of end-of-life encounter.

My patient was an older man, sent by his facility yet again to the emergency department. I found him awake and mostly alert, surrounded by tearful family. He was in dire straits: His body had been wracked by a long course of treatment for pancreatic cancer, and his critical state was readily apparent. He was dying, but in a way that is rare in the ED—everyone was ready for it. All the documents were signed, all the proper measures were in place, and it was apparent to everyone that he would die in the emergency department that night.

I was a trainee, familiar enough with palliative measures from tours in the ICU and the occasional morphine drip ordered in the ED. I ordered a familiar refrain of analgesics, anxiolytics, and anticholinergics, all designed to help alleviate pain and discomfort at the end of life. My attending, though, added an additional palliative element, one I have since incorporated into my palliative armamentarium: nebulized furosemide.

Dyspnea and air hunger in chronic terminal disease and at the end of life are common and distressing symptoms, often addressed with opioids or benzodiazepines. There remains a need for increased and targeted interventions for the palliation of dyspnea. Nebulized opioids have previously been examined (Am J Health Syst Pharm. 2017;74[14]:1053), but limited evidence suggests that nebulized furosemide may be a simple and effective treatment for managing dyspnea.

No Great Explanation
One report found that nebulized furosemide blocked chloride channels at several cellular sites in the airway, including mast cells, epithelial cells, and nerves. Another manuscript reported that furosemide inhalation prevented bronchoconstriction in patients with asthma by inhibiting chloride secretion. (J Pain Symptom Manage. 2003;26[4]:962; https://bit.ly/3q7Wsh3.)
Ultimately, however, there is no great explanation for the mechanistic effect, though various theories ranging from anticholinergic effects to activation of pulmonary stretch receptors have been proposed. Nonetheless, the common loop diuretic nebulized furosemide has been tested as a treatment for dyspnea, and is attractive from physiological and management perspectives.

The potential to achieve adjunctive benefits to management with bronchodilator therapy in asthma or chronic obstructive pulmonary disease and in malignancy is an attractive option. The capacity to administer the drug noninvasively with a low adverse effect profile in ambulatory care and home-based settings is also favorable. (J Pain Symptom Manage. 2008;36[4]:424; https://bit.ly/3wsNlK5.)

Two studies have examined the efficacy of nebulized furosemide for alleviating dyspnea in end-stage cancer patients, and a small number of limited investigations have found relief of dyspnea for four hours within 20-30 minutes of administering 20 mg of nebulized furosemide. This reduced the respiratory rate and accessory muscle use in patients refractory to opioid treatment. (Rambam Maimonides Med J. 2019;10[1]:e0006; https://bit.ly/2RWgnme.) Generally, however, the literature is limited to small case series and pilot trials.

Alleviating Dyspnea
Interestingly, nebulized furosemide has been investigated with some success in a host of breathless complaints, ranging from asthma and COPD—where one meta-analysis found a statistically significant improvement in airflow obstruction with no evident adverse events when inhaled furosemide was used as an adjunctive treatment for acute asthma exacerbation (Crit Care. 2014;18[6]:621; https://bit.ly/3pVPpHT)—to pulmonary edema, with one adventurous randomized controlled trial recently suggesting that inhaled furosemide might have a role to play in patients with congestive heart failure. (I doubt it.) (Health Sci Rep. 2021;4[1]: e235; https://bit.ly/3pUaJ0B.)

Confirmatory data are likely years away, if ever. But bedside moments are often the site of clinical innovation. We discussed the risks and benefits of nebulized furosemide with the patient and his family, and after consent, administered 20 mg of furosemide in 0.9% saline by nebulizer, with significant relief in the patient, family, and physicians. The patient experienced significant improvement in his air hunger and discomfort in a short time. Then, over the next hour or so, he slowly slipped toward the next great adventure.

Since that learning moment, I have incorporated nebulized furosemide into my palliative regimen for patients at the end of life in the emergency department. Most patients do well with standard interventions (and swift consultation of palliative care specialists, if available), and limited literature and reasonable clinical experience support consideration of nebulized furosemide for the palliative alleviation of dyspnea in patients with chronic terminal illness and those at the end of life.

Dr. Pescatore is the chief physician for the Delaware Division of Public Health and an emergency physician at Einstein Healthcare Network in Philadelphia. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine: http://bit.ly/EMNLive. Follow him on Twitter @Rick_Pescatore, and read his past columns at http://bit.ly/EMN-Pescatore.