IMPACT OF MELATONIN ON SEDATIVE INFUSION REQUIREMENTS IN COVID-19-ASSOCIATED RESPIRATORY FAILURE

Sedative requirements on days following nightly melatonin administration ( I melatonin days i ) were compared to requirements on days following no nightly melatonin administration ( I non-melatonin days i ) using paired-sampled t- test. There was no difference in the dose of hydromorphone infusion (1.00 mg/hr vs 1.48 mg/hr;, p =0.31), average number of daily boluses (2.9 vs 2.2;p = 0.40), or average bolus doses (0.66 mg vs 0.69 mg;p=0.88) infused on melatonin vs non-melatonin days. B Conclusions: b Our data suggest that in mechanically ventilated COVID-19 patients, the administration of melatonin does not affect sedative infusion or bolus dosage requirements for commonly used ICU sedatives. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Declining Intensive Care Unit Mortality of COVID-19: A Multi-Center Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) mortality has waned significantly over time; however, factors contributing towards this reduction largely remain unidentified. The purpose of this study was to evaluate the trend in mortality at our large tertiary academic health system and factors contributing to this trend. METHODS: This is a retrospective cohort study of intensive care unit (ICU) patients diagnosed with COVID-19 between March and August 2020 admitted across 14 hospitals in the Philadelphia area. Collected data included demographics, comorbidities, admission risk of mortality score, laboratory values, medical interventions, survival outcomes, hospital and ICU length of stay (LOS) and discharge disposition. Chi-square (χ2) test, Fisher exact test, Cochran-Mantel-Haenszel method, multinomial logistic regression models, independent sample t-test, Mann-Whitney U test and one-way analysis of variance (ANOVA) were used. RESULTS: A total of 1,204 patients were included. Overall mortality was 39%. Mortality declined significantly from 46% in March to 14% in August 2020 (P < 0.05). The most common underlying comorbidities were hypertension (60.2%), diabetes mellitus (44.7%), dyslipidemia (31.6%) and congestive heart failure (14.7%). Hydroxychloroquine (HCQ) use was more commonly associated with the patients who died, while the use of remdesivir, tocilizumab, steroids and duration of these medications were not significantly different. Peak values of ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer levels were significantly higher in patients who died (P < 0.05). The mean hospital LOS was significantly longer in the patients who survived compared to the patients who died (18 vs. 12, P < 0.05). CONCLUSIONS: The mortality of patients admitted to our ICU system significantly decreased over time. Factors that may have contributed to this may be the result of a better understanding of COVID-19 pathophysiology and treatments. Further research is needed to elucidate the factors contributing to a reduction in the mortality rate for this patient population.

Tocilizumab in the Management of COVID-19: A Preliminary Report.

IMPORTANCE: Pneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness. OBJECTIVE: To evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab. DESIGN, SETTING, PARTICIPANTS: Retrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab. EXPOSURES: Confirmed COVID-19 pneumonia. MAIN OUTCOMES AND MEASURES: Outcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed. RESULTS: The average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p < 0.0001), progression to requiring mechanical ventilation (OR = 6.6, p < 0.0001), and increased length of stay (OR = 16.2, p < 0.0001). CONCLUSION AND RELEVANCE: Our retrospective analysis revealed an association between Tocilizumab administration and increased mortality, ICU admission, mechanical ventilation, and length of stay in subjects with COVID-19. Prospective trials are needed to evaluate the true effect of Tocilizumab in this condition.

The Use of High-Flow Nasal Oxygen in the ICU as a First-Line Therapy for Acute Hypoxemic Respiratory Failure Secondary to Coronavirus Disease 2019.

OBJECTIVES: Limited evidence is available regarding the role of high-flow nasal oxygen in the management of acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Our objective was to characterize outcomes associated with high-flow nasal oxygen use in critically ill adult patients with coronavirus disease 2019-associated acute hypoxemic respiratory failure. DESIGN: Observational cohort study between March 18, 2020, and June 3, 2020. SETTING: Nine ICUs at three university-affiliated hospitals in Philadelphia, PA. PATIENTS: Adult ICU patients with confirmed coronavirus disease 2019 infection admitted with acute hypoxemic respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 266 coronavirus disease 2019 ICU admissions during the study period, 124 (46.6%) received some form of noninvasive respiratory support. After exclusions, we analyzed 83 patients who were treated with high-flow nasal oxygen as a first-line therapy at or near the time of ICU admission. Patients were predominantly male (63.9%). The most common comorbidity was hypertension (60.2%). Progression to invasive mechanical ventilation was common, occurring in 58 patients (69.9%). Of these, 30 (51.7%) were intubated on the same day as ICU admission. As of June 30, 2020, hospital mortality rate was 32.9% and the median hospital length of stay was 15 days. Among survivors, the most frequent discharge disposition was home (51.0%). In comparing patients who received high-flow nasal oxygen alone (n = 54) with those who received high-flow nasal oxygen in conjunction with noninvasive positive-pressure ventilation via face mask (n = 29), there were no differences in the rates of endotracheal intubation or other clinical and utilization outcomes. CONCLUSIONS: We observed an overall high usage of high-flow nasal oxygen in our cohort of critically ill patients with acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Rates of endotracheal intubation and mortality in this cohort were on par with and certainly not higher than other published series. These findings should prompt further considerations regarding the use of high-flow nasal oxygen in the management algorithm for coronavirus disease 2019-associated acute hypoxemic respiratory failure.