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Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.
Am J Respir Crit Care Med. 2018 03 15; 197(6):757-767.AJ

Abstract

RATIONALE

Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation.

OBJECTIVES

To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS.

METHODS

ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders.

MEASUREMENTS AND MAIN RESULTS

Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005).

CONCLUSIONS

Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

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Authors+Show Affiliations

Arabi YM
1 College of Medicine. 2 Intensive Care Department and.
Mandourah Y
3 Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Al-Hameed F
4 Department of Intensive Care, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
Sindi AA
5 Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Almekhlafi GA
3 Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Hussein MA
6 Department of Biostatistics and Bioinformatics, and.
Jose J
6 Department of Biostatistics and Bioinformatics, and.
Pinto R
7 Sunnybrook Hospital, University of Toronto, Toronto, Ontario, Canada.
Al-Omari A
8 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. 9 Department of Intensive Care, Dr. Sulaiman Al-Habib Group Hospitals, Riyadh, Saudi Arabia.
Kharaba A
10 Department of Critical Care, King Fahad Hospital, Al-Madinah Al-Monawarah, Saudi Arabia. 11 Department of Critical Care, Ohoud Hospital, Al-Madinah Al-Monawarah, Saudi Arabia.
Almotairi A
12 Department of Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.
Al Khatib K
13 Intensive Care Department, Al-Noor Specialist Hospital, Makkah, Saudi Arabia.
Alraddadi B
8 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. 14 Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
Shalhoub S
15 Division of Infectious Diseases, Department of Medicine, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
Abdulmomen A
16 Department of Critical Care Medicine, King Saud University, Riyadh, Saudi Arabia.
Qushmaq I
14 Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
Mady A
17 Department of Anesthesiology and Intensive Care, Tanta University Hospitals, Tanta, Egypt. 18 Intensive Care Department, King Saud Medical City, Riyadh, Saudi Arabia.
Solaiman O
19 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Al-Aithan AM
20 Intensive Care Department, King Abdulaziz Hospital, Al Ahsa, Saudi Arabia.
Al-Raddadi R
21 Department of Research, Ministry of Health, Jeddah, Saudi Arabia.
Ragab A
22 Intensive Care Department, King Fahd Hospital, Jeddah, Saudi Arabia.
Balkhy HH
1 College of Medicine. 23 Department of Infection Prevention and Control, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia.
Al Harthy A
17 Department of Anesthesiology and Intensive Care, Tanta University Hospitals, Tanta, Egypt.
Deeb AM
24 Research Office, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Al Mutairi H
24 Research Office, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Al-Dawood A
1 College of Medicine. 2 Intensive Care Department and.
Merson L
25 International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University, Oxford, United Kingdom.
Hayden FG
25 International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University, Oxford, United Kingdom. 26 Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.
Fowler RA
27 Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; and. 28 Department of Critical Care Medicine and. 29 Department of Medicine, Sunnybrook Hospital, Toronto, Ontario, Canada.
Saudi Critical Care Trial Group
No affiliation info available

MeSH

Adrenal Cortex HormonesCohort StudiesCoronavirus InfectionsCritical CareCritical IllnessFemaleHumansMaleMiddle AgedRetrospective StudiesSaudi ArabiaTreatment Outcome

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

29161116

Clinical Trial Links

Glucocorticoid Therapy for COVID-19 Critically Ill Patients With Severe Acute Respiratory Failure
Cyclosporine A Plus Low-steroid Treatment in COVID-19 Pneumonia

Citation

Arabi, Yaseen M., et al. "Corticosteroid Therapy for Critically Ill Patients With Middle East Respiratory Syndrome." American Journal of Respiratory and Critical Care Medicine, vol. 197, no. 6, 2018, pp. 757-767.
Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767.
Arabi, Y. M., Mandourah, Y., Al-Hameed, F., Sindi, A. A., Almekhlafi, G. A., Hussein, M. A., Jose, J., Pinto, R., Al-Omari, A., Kharaba, A., Almotairi, A., Al Khatib, K., Alraddadi, B., Shalhoub, S., Abdulmomen, A., Qushmaq, I., Mady, A., Solaiman, O., Al-Aithan, A. M., ... Fowler, R. A. (2018). Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. American Journal of Respiratory and Critical Care Medicine, 197(6), 757-767. https://doi.org/10.1164/rccm.201706-1172OC
Arabi YM, et al. Corticosteroid Therapy for Critically Ill Patients With Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018 03 15;197(6):757-767. PubMed PMID: 29161116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. AU - Arabi,Yaseen M, AU - Mandourah,Yasser, AU - Al-Hameed,Fahad, AU - Sindi,Anees A, AU - Almekhlafi,Ghaleb A, AU - Hussein,Mohamed A, AU - Jose,Jesna, AU - Pinto,Ruxandra, AU - Al-Omari,Awad, AU - Kharaba,Ayman, AU - Almotairi,Abdullah, AU - Al Khatib,Kasim, AU - Alraddadi,Basem, AU - Shalhoub,Sarah, AU - Abdulmomen,Ahmed, AU - Qushmaq,Ismael, AU - Mady,Ahmed, AU - Solaiman,Othman, AU - Al-Aithan,Abdulsalam M, AU - Al-Raddadi,Rajaa, AU - Ragab,Ahmed, AU - Balkhy,Hanan H, AU - Al Harthy,Abdulrahman, AU - Deeb,Ahmad M, AU - Al Mutairi,Hanan, AU - Al-Dawood,Abdulaziz, AU - Merson,Laura, AU - Hayden,Frederick G, AU - Fowler,Robert A, AU - ,, PY - 2017/11/22/pubmed PY - 2019/8/23/medline PY - 2017/11/22/entrez KW - Saudi Arabia KW - coronavirus KW - corticosteroid KW - pneumonia KW - respiratory distress syndrome SP - 757 EP - 767 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 197 IS - 6 N2 - RATIONALE: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation. OBJECTIVES: To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. METHODS: ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS: Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005). CONCLUSIONS: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/29161116/full_citation L2 - https://www.atsjournals.org/doi/10.1164/rccm.201706-1172OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -