DYSPNEA AND MECHANICAL VENTILATION: APPLYING PHYSIOLOGY TO GUIDE THERAPY.

While advances in our understanding of mechanical ventilation have improved mortality from acute respiratory distress syndrome, recent studies indicate a rising incidence of post-ventilation mental health sequelae, including post-traumatic stress disorder (PTSD). Concurrent research on the physiology of dyspnea provides insights about the role of multiple sources of sensory information underlying respiratory discomfort along with the contribution of efferent-afferent dissociation to dyspnea, and the subsequent relationship of dyspnea to a range of affective responses, including fear and anxiety. An understanding of the mechanisms of dyspnea may provide holistic approaches to managing acute respiratory failure that can achieve the best physical and emotional outcomes for patients requiring mechanical ventilation.

Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

Aerosol furosemide for dyspnea: High-dose controlled delivery does not improve effectiveness.

Published studies have shown great variability in response when aerosolized furosemide has been tested as a palliative treatment for dyspnea. We hypothesized that a higher furosemide dose with controlled aerosol administration would produce consistent dyspnea relief. We optimized deposition by controlling inspiratory flow (300-500mL/s) and tidal volume (15% predicted vital capacity) while delivering 3.4µm aerosol from either saline or 80mg of furosemide. We induced dyspnea in healthy subjects by varying inspired PCO2 while restricting minute ventilation. Subjects rated "Breathing Discomfort" on a Visual Analog Scale (BDVAS, 100% Full Scale≡intolerable). At the PETCO2 producing 60% BDVAS pre-treatment, furosemide produced a clinically meaningful reduction of BDVAS (i.e., >20% FS) in 5/11 subjects; saline reduced dyspnea in 3/11 subjects; neither treatment worsened dyspnea in any subject. Furosemide and saline treatment effects were not statistically different. There were no significant adverse events. Higher furosemide dose and controlled delivery did not improve consistency of treatment effect compared with prior studies.

Redesigning the MCAT exam: balancing multiple perspectives.

The authors of this commentary discuss the recently completed review of the current Medical College Admission Test (MCAT), which has been used since 1991, and describe the blueprint for the new test that will be introduced in 2015. The design of the MCAT exam reflects changes in medical education, medical science, health care delivery, and the needs of the populations served by graduates of U.S. and Canadian medical schools. The authors describe how balancing the ambitious goals for the new exam and the varying priorities of the testing program's many stakeholders made blueprint design complex. They discuss the tensions and trade-offs that characterized the design process as well as the deliberations and data that shaped the blueprint.The blueprint for the MCAT exam balances the assessment of a broad range of competencies in the natural, social, and behavioral sciences and critical analysis and reasoning skills that are essential to entering students' success in medical school. The exam will include four sections: Biological and Biochemical Foundations of Living Systems; Chemical and Physical Foundations of Biological Systems; Psychological, Social, and Biological Foundations of Behavior; and Critical Analysis and Reasoning Skills.The authors also offer recommendations for admission committees, advising them to review applicants' test scores, course work, and other academic, personal, and experiential credentials as part of a holistic admission process and in relation to their institutions' educational, scientific, clinical, and service-oriented goals.