Wilcock, A., Walton, A., Manderson, C., Feathers, L., El Khoury, B., Lewis, M., . . . Tattersfield, A. (2008). Randomised, placebo controlled trial of nebulised furosemide for breathlessness in patients with cancer. Thorax, 63(10), 872-875.

The objective of the study is to assess the benefit of nebulized furosemide on breathlessness and respiratory function in patients with cancer.

Patients were assigned to receive 40 mg nebulized furosemide, nebulized 0.9% saline, and no treatment on three consecutive days in random order. Subjects were familiarized with the equipment and surrounding on day one of study and underwent assessments before and after administration of the assigned treatment. Spirometry was administered before and after nebulizer treatments. Following 10 minutes of rest, subjects underwent a reading test and arm exercise test and then rated their sensation of breathlessness intensity on a Borg scale. On nontreatment days, patients also underwent spirometry before and after the arm exercise test. Patients finally were asked if they had perceived benefits from the nebulized saline or furosemide treatments and whether they noted a difference between the two.

• The study reported on a sample of 15 patients.
• The mean age was 66 years.
• Of the sample, eight were females and seven were males.
• Patients had primary non-small cell lung (7), secondary lung cancer (breast) (2), pancreatic cancer (1), thymus cancer (1), uterine cancer (1), unknown (1), or mesothelioma (2).
• Participants experienced increased breathlessness on low levels of exertion or at rest, as patients with chronic obstructive pulmonary disease were accepted in the study if they had stable disease and breathlessness was cancer-related.
• Patients were excluded if breathlessness could be relieved by drainage of a pleural effusion or blood transfusion.

The study was conducted on a single-site, inpatient palliative care unit in England.

Patients were undergoing end-of-life and palliative care.

• Dyspnea Exertion Scale (range 0–5)
• Spirometric values [to compare forced expiratory volume (FEV1) and forced vital capacity (FVC) before and after intervention]
• Number Reading Scale (to measure breathlessness at rest)
• Arm exercise test (to measure breathlessness on minimal physical exertion)
• Borg Scale

All 13 patients who completed the arm exercise test experienced increased breathlessness, but no significant difference between exercise duration and Borg score at maximum equivalent workload between the furosemide, saline, and no treatment group were observed. Average score at maximum equivalent workload indicated no significant difference among the three treatments. Six of 15 patients perceived improved ventilation following nebulized treatment, with 3 preferring saline, 1 preferring furosemide, and 2 finding either treatment equally beneficial.

Results do not support benefit of nebulized furosemide in patients with cancer-related breathlessness.

• The study had a small sample size of less than 30.
• No standard or constant minimally effective dose or volume nebulized furosemide and saline treatment were established in the study that could have served as a basis for comparing dosing adequacy.
• Baseline performance scores were not established at the beginning of the study to determine activity level and ability to perform ADLs.
• Data are relevant/significant to individuals with primary or secondary lung cancer or mesothelioma and otherwise not truly representative/generalizable to other symptomatic groups (because breathlessness and treatment response in the study group may be related to or dependent on underlying cancer pathology).
• Patients could not have been blinded to nontreatment days.
• Although the authors state that treatments were prepared by a pharmacist, they appear to have been delivered by someone else, so no treatment days also could not have been blinded from investigators.

Results do not support the use of nebulized furosemide in the management of dyspnea.