Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study.

OBJECTIVES: Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Multicenter ICU study. PATIENTS: Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION: Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS: In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Barriers and facilitators of thromboprophylaxis for medical-surgical intensive care unit patients: a multicenter survey.

BACKGROUND: The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU). METHODS: We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use. RESULTS: Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01). CONCLUSIONS: This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities.

Mild reactions to blood donation predict a decreased likelihood of donor return.

A growing body of evidence suggests that episodes of fainting can deter volunteer blood donors from returning to donate in the future. In contrast, relatively little is known about the effect of significantly more common mild reactions (e.g., faintness, dizziness, lightheadedness) on donor retention. In the present study, 1052 volunteer blood donors completed a standardized measure of subjective physiological reactions immediately after blood donation (Blood Donation Reactions Inventory), and individual scores were used to predict repeat donation behavior during a one-year follow-up. Results of a logistic regression analysis indicated that higher scores on the Blood Donation Reactions Inventory were associated with a significantly lower likelihood of repeat donation, and that novice donors who scored highest on the scale were less than half as likely to have returned to donate in the following year. These findings suggest that the Blood Donation Reactions Inventory is an effective method of assessing reactions that predict donor non-return, and therefore may be a useful addition to future studies aimed at enhancing donor satisfaction and retention.

Sweet taste and blood pressure-related analgesia.

To test the prediction that sweet taste modifies responses to cold induced pain, 72 young adults held sweet, bitter and water solutions in their mouths, in counterbalanced order, before and during a cold pain stimulus. To test whether or not blood pressure interacts with sweet taste analgesia, measurements of resting blood pressure were also obtained. A significant main effect of taste on pain tolerance was observed, as well as a significant interaction between resting mean arterial pressure (MAP) and taste on tolerance. Sweet taste was associated with a prolongation of tolerance compared to the bitter and water conditions. When participants were split along the median for MAP, sweet taste was associated with an 18.1% increase in pain tolerance compared with water for those with lower MAP. No significant impact of taste on pain sensitivity was observed among participants with higher MAP. Groupwise comparisons revealed a significant difference in pain tolerance between participants with higher and lower MAP in the water condition but not in the sweet condition, replicating previous findings of a reduced sensitivity to pain among those with higher blood pressure. The analgesic effects of sweet tasting solutions seen previously in human infants and children may also be present in adults. Individuals with higher blood pressure may not be as sensitive to the presumably opioid-mediated analgesic effects of sweet taste, perhaps due to opioid dysregulation.

Reducing reactions to blood donation with applied muscle tension: a randomized controlled trial.

BACKGROUND: Unpleasant blood donation-related symptoms may discourage otherwise healthy, altruistic individuals from becoming repeat donors. This study examined a behavioral technique called applied muscle tension (AMT) that might reduce reactions. STUDY DESIGN AND METHODS: A total of 605 donors at mobile clinics were assigned to either an AMT treatment condition, a no-treatment control condition, or a placebo control condition. AMT involves repeated tensing of major muscles and was taught using an instructional video. Participants in the placebo control group watched the same video but were told to practice the technique only from the time they got on the donation chair until insertion of the needle, without being told that reactions are unlikely during this period. RESULTS: There were no differences between men assigned to the three conditions. Women donors assigned to the AMT condition reported significantly fewer donation-related symptoms, required less chair reclining for reactions, and were more likely to produce a full unit of blood than women in both the no-treatment and placebo control conditions. Women in the AMT condition also said they would be more likely to recommend it to a friend who was going to give blood, but there were no significant effects of AMT on the rated probability of giving blood again or blood pressure change. CONCLUSIONS: Although it was not universally effective and the mechanisms of its effects are unclear, AMT is a simple behavioral technique that may be useful in reducing reactions to blood donation.