Letter to the Editor: "Use of inhaled epoprostenol with high flow nasal oxygen in non-intubated patients with severe COVID-19".

PURPOSE: Acute lung injury associated with COVID-19 contributes significantly to its morbidity and mortality. Though invasive mechanical ventilation is sometimes necessary, the use of high flow nasal oxygen may avoid the need for mechanical ventilation in some patients. For patients approaching the limits of high flow nasal oxygen support, addition of inhaled pulmonary vasodilators is becoming more common but little is known about its effects. This is the first descriptive study of a cohort of patients receiving inhaled epoprostenol with high flow nasal oxygen for COVID-19. MATERIALS AND METHODS: We collected clinical data from the first fifty patients to receive inhaled epoprostenol while on high flow nasal oxygen at our institution. We compared the characteristics of patients who did and did not respond to epoprostenol addition. RESULTS: The 18 patients that did not stabilize or improve following initiation of inhaled epoprostenol had similar rates of invasive mechanical ventilation as those who improved or stabilized (50% vs 56%). Rates of mortality were not significantly different between the two groups (17% and 31%). CONCLUSIONS: In patients with COVID-19 induced hypoxemic respiratory failure, the use of inhaled epoprostenol with high flow nasal oxygen is feasible, but physiologic signs of response were not related to clinical outcomes.

Development and Implementation of a Multicomponent Protocol to Promote Sleep and Reduce Delirium in a Medical Intensive Care Unit.

BACKGROUND: Evidence suggests that poor sleep increases risk of delirium. Because delirium is associated with poor outcomes, institutions have developed protocols to improve sleep in critically ill patients. OBJECTIVE: To assess the impact of implementing a multicomponent sleep protocol. METHODS: In this prospective, preimplementation and postimplementation evaluation, adult patients admitted to the medical intensive care unit (ICU) over 42 days were included. Outcomes evaluated included median delirium-free days, median Richards-Campbell Sleep Questionnaire (RCSQ) score, median optimal sleep nights, duration of mechanical ventilation (MV), ICU and hospital length of stay (LOS), and in-hospital mortality. RESULTS: The preimplementation group included 78 patients and postimplementation group, 84 patients. There was no difference in median delirium-free days (1 day [interquartile range, IQR, = 0-2.5] vs 1 day [IQR = 0-2]; P = 0.48), median RCSQ score (59.4 [IQR = 43.2-71.6] vs 61.2 [IQR = 49.9-75.5]; P = 0.20), median optimal sleep nights (1 night [IQR = 0-2] vs 1 night [IQR = 0-2]; P = 0.95), and in-hospital mortality (16.7% vs 17.9%, P = 1.00). Duration of MV (8 days [IQR = 4-10] vs 4 days [IQR = 2-7]; P = 0.03) and hospital LOS (13 days [IQR = 7-22.3] vs 8 days [IQR = 6-17]; P = 0.05) were shorter in the postimplementation group, but both were similar between groups after adjusting for age and severity of illness. CONCLUSIONS AND RELEVANCE: This report demonstrates that implementation of a multicomponent sleep protocol in everyday ICU care is feasible, but limitations exist when evaluating impact on measurable outcomes. Additional evaluations are needed to identify the most meaningful interventions and best practices for quantifying impact on patient outcomes.

Energy Expenditure in Critically Ill Adult Patients With Acute Brain Injury: Indirect Calorimetry vs. Predictive Equations.

Introduction: Predictive equations (PE) are used in lieu of indirect calorimetry (IC) due to cost and limited resources; however, these equations may not be as accurate as IC in estimating resting energy expenditure (REE) in critically ill patients, putting them at risk of malnutrition. The purpose of this study is to compare predicted and measured energy expenditure (MEE) in critically ill adults with acute brain injury. Materials and Methods: This was a retrospective review of adult patients admitted to the Neurosciences ICU with acute brain injury between May 1st, 2014 and April 1st, 2016 who had IC performed. The Harris Benedict (HBE), Penn State University, and Mifflin St Jeor (MSJ) PE were used in comparison to IC results. Subgroup analyses stratified patients based on BMI and type of acute brain injury. Results: One hundred and forty-four patients met inclusion criteria. Comparing predicted and MEE found no significant difference (p = 0.1). High degrees of interpatient variability were discovered, with standard deviations ranging from 17 to 29% of each PE. Pearson's correlations indicated weak associations when HBE, Penn State, and MSJ were individually compared to MEE (r = 0.372, 0.409, and 0.372, respectively). A significant difference was found between predicted and MEE in patients with a BMI < 30 kg/m2 (p < 0.01) and in those with aneurysmal subarachnoid hemorrhage (p < 0.01). Discussion: Due to interpatient variability that exists among REE of critically ill patients with acute brain injury, IC should be used when feasible.

Effects of herbal supplements on the bioactivation of chemotherapeutic agents.

OBJECTIVES: The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan. METHODS: Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements. KEY FINDINGS: The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway. CONCLUSIONS: Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial.