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Online Letters to the Editor

Declines in Mortality Over Time for Critically Ill Adults With Coronavirus Disease 2019

Auld, Sara C. MD, MSc; Caridi-Scheible, Mark MD; Robichaux, Chad MPH; Coopersmith, Craig M. MD; Murphy, David J. MD, PhD; The Emory COVID-19 Quality and Clinical Research Collaborative

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doi: 10.1097/CCM.0000000000004687
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To the Editor:

We are writing with an update on mortality over time for our recent report (1) published in Critical Care Medicine. In our initial report of patients admitted from March 6, 2020, to April 17, 2020, hospital mortality was 30.9% (67/217) and mortality among those receiving mechanical ventilation was 35.7% (59/165).

ICU ADMISSIONS AND MORTALITY

Since our earlier report, ICU admission numbers initially declined—from 143 patients in March and 155 in April to 67 in May and 86 in June—before increasing to 212 admissions in July (Fig. 1 and Table 1). This second wave of admissions in July did require the expansion of ICU capacity in order to accommodate critically ill patients with and without coronavirus disease 2019 (COVID-19). Nonetheless, and despite similar comorbidities and severity of illness throughout this time period (as measured by the Elixhauser comorbidity index, initial Sequential Organ Failure Assessment score, and Pao2/Fio2 ratio), hospital mortality declined from a peak of 34.3% in March, to 28.4% in April, 17.9% in May, 22.1% in June, and 26.9% in July. Of note, there are 15 patients (7.1%) who remain in the ICU at the time of this letter (September 4, 2020).

TABLE 1. - Characteristics and Clinical Outcomes for Patients Admitted to a Coronavirus Disease ICU From March 2020 to July 2020
Characteristics March April May June July
No. of ICU admits 143 155 67 86 212
Age 65 (56–73) 65 (54–76) 61 (52–71) 62 (49–73) 62 (49–73)
Body mass index 31 (27–36) 30 (25–37) 30 (25–37) 29 (25–36) 31 (27–38)
Black, n (%) 103 (72.0) 104 (67.1) 37 (55.2) 86 (61.6) 147 (69.3)
Elixhauser comorbidity index 7 (5–9) 8 (6–10) 7 (5–9) 7 (5–9) 6 (4–8)
Initial Sequential Organ Failure Assessment score 6 (5–7) 7 (5–9) 6 (5–8) 7 (4–11) 7 (4–11)
Mechanical ventilation 116 (81.1) 100 (64.5) 30 (44.8) 50 (58.1) 107 (50.5)
 Initial Pao 2/Fio 2 ratio for patients  receiving mechanical ventilation 164 (118–220) 167 (125–251) 145 (116–182) 152 (104–240) 132 (85–202)
 Initial SOFA score for patients  receiving mechanical ventilation 7 (6–7) 8 (6–10) 11 (9–12) 11 (8–12) 11 (8–14)
Ventilation days 8 (4–13) 11 (5–19) 15 (6–23) 9 (4–17) 13 (8–25)a
Ventilation deaths, n (%) 45 (38.8) 34 (34.0) 10 (33.3) 16 (32.0) 25 (40.0)a
Hospital length of stay 14 (9–23) 14 (9–24) 13 (6–23) 13 (7–21) 13 (8–19)a
Hospital deaths, n (%) 49 (34.3) 44 (28.4) 12 (17.9) 19 (22.1) 30 (26.8)a
Values are median (interquartile range) unless otherwise noted.

Figure 1.
Figure 1.:
ICU admission numbers, changes in medical management, and patient outcomes over time for patients admitted to the ICU with coronavirus disease 2019 (COVID-19) from March 2020 to July 2020. ACTT = Adaptive COVID-19 Treatment Trial, RECOVERY = Randomized Evaluation of COVID-19 Therapy.

MECHANICAL VENTILATION

The proportion of patients receiving mechanical ventilation also declined, from a peak of 81.1% in March, to 64.5% in April, 44.8% in May, 58.1% in June, and 50.5% in July. However, ventilator mortality, which initially declined from 38.3% in March to 32.0% in June, increased to 43.0% in July. Of note, our institution did not support the use of heated high-flow oxygen until March 25, which likely contributed to higher intubation rates in March.

MEDICAL MANAGEMENT

Our ICU care and treatments also changed over time. In early April, our institution introduced a COVID-specific anticoagulation strategy with an intermediate level of prophylaxis for a d-dimer greater than or equal to 3,000 ng/mL. While analyses on the impact of this strategy are underway, published reports suggest a survival benefit with anticoagulation in COVID-19 (2,3). Our institution was also a study site for Adaptive COVID-19 Treatment Trial (ACTT)-1 and ACTT-2. From March 11 to April 19, 96 patients enrolled in ACTT-1 and, from May 8 to June 30, 77 patients enrolled in ACTT-2. Although ACTT-1 did not show a benefit for remdesivir in patients requiring high-flow oxygen or mechanical ventilation (4), ACTT-2 results are pending and it is possible that the combination of remdesivir and baricitinib (which approximately half of patients would have received) could have contributed to the improved mortality in May and June. Likewise, after the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial data were made available in mid-June (5), 45 of 86 (52%) and 177 of 212 (83%) patients received dexamethasone in June and July, respectively, of whom 31 (68.9%) and 127 (72%) survived.

We are gratified to report these improvements in mortality over time, which echo the findings of a recent meta-analysis and published data from the United Kingdom (6,7). These declines in ICU mortality and in the number of patients receiving mechanical ventilation over time likely reflect improvements in our provision of critical care based on both our greater experience with this novel pathogen and a broader evidence base of treatments supported by randomized clinical trials. While a smaller proportion of patients were intubated in July, the higher ventilator mortality for that month may indicate a greater severity of illness, which is supported by the lower Pao2/Fio2 ratio and higher SOFA scores, among patients who did require mechanical ventilation. However, the rapidly changing landscape of COVID-19, both in terms of local case numbers and the evidence base for clinical care, underscores the importance of continuing to assess outcomes so that we can better understand how best to care for our patients.

ACKNOWLEDGEMENTS

Emory COVID-19 Quality and Clinical Research Collaborative members (in alphabetical order) are: Max W. Adelman, Scott Arno, Sara C. Auld, Theresa Barnes, William Bender, James M. Blum, Gaurav Budhrani, Stephanie Busby, Laurence Busse, Mark Caridi-Scheible, David Carpenter, Nikulkumar Chaudhari, Craig M. Coopersmith, Lisa Daniels, Johnathan A. Edwards, Jane Fazio, Babar Fiza, Eliana Gonzalez, Dale Gordon, Ria Gripaldo, Charles Grodzin, Robert Groff, Alfonso C. Hernandez-Romieu, Max Hockstein, Dan Hunt, Craig S. Jabaley, Jesse T. Jacob, Colleen Kraft, Greg S. Martin, Samer Melham, Nirja Mehta, Chelsea Modlin, David J. Murphy, Jung Park, Deepa Patel, Cindy Powell, Amit Prabhaker, Jeeyon Rim, Ramzy Rimawi, Chad Robichaux, Nicholas Scanlon, Milad Sharifpour, Bashar Staitieh, Michael Sterling, Jonathan Suarez, Colin Swenson, Nancy Thakkar, Alexander Truong, Hima Veeramachaneni, Alvaro Velasquez, Aimee Vester, Michael Waldmann, Max Weinmann, Thanushi Wynn, and Joel Zivot.

Sara C. Auld, MD, MSc, Emory Critical Care Center, Atlanta, GA, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, and Department of Epidemiology, Emory University, Atlanta, GA; Mark Caridi-Scheible, MD, Emory Critical Care Center, Department of Anesthesiology, Emory University, Atlanta, GA; Chad Robichaux, MPH, Department of Biomedical Informatics, Emory University, Atlanta, GA, and Georgia Clinical and Translational Science Alliance (CTSA), Atlanta, GA; Craig M. Coopersmith, MD, Emory Critical Care Center, Department of Surgery, Emory University, Atlanta, GA; David J. Murphy, MD, PhD, Emory Critical Care Center, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Office of Quality and Risk, Emory Healthcare, Atlanta, GA; The Emory COVID-19 Quality and Clinical Research Collaborative

REFERENCES

1. Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019. Crit Care Med. 2020;48:e799–e804
2. Paranjpe I, Fuster V, Lala A, et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol. 2020;76:122–124.
3. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18:1094–1099.
4. Beigel JH, Tomashek KM, Dodd LE, et al.; ACTT-1 Study Group Members: Remdesivir for the treatment of Covid-19 - preliminary report. N Engl J Med. 2020;383:993–994.
5. The RECOVERY Collaborative Group: Dexamethasone in hospitalized patients with Covid-19 - Preliminary report. N Engl J Med. 2020 Jul 17. [online ahead of print].
6. Armstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID-19: A systematic review and meta-analysis of observational studies. Anaesthesia. 2020;75:1340–1349.
7. Intensive Care National Audit and Research Centre: ICNARC Report on COVID-19 in Critical Care. 2020. Available at: https://www.icnarc.org/About/Latest-News/2020/04/04/Report-On-2249-Patients-Critically-Ill-With-Covid-19. Accessed July 27, 2020.
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