Identifiers
Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)
Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equ...
Cites research funded by
8
NIHR (October 2023)
6
NIHR (September 2022)
1
Assistance Publique Hôpitaux de Paris
1
Northern Ireland Health and Social Care Research and Development Division
1
Fonds de Recherche du Québec - Santé
1
National Natural Science Foundation of China-Zhejiang Joint Fund for the Integration of Industrialization and Informatization
1
Young Scientists Fund
1
Sichuan Science and Technology Agency
2
National Natural Science Foundation of China
1
Ministry of Education - Singapore
1
National University of Singapore
1
Sichuan Science and Technology Program
1
McMaster University
1
Ministry of Health
1
Chinese University of Hong Kong
1
Chinese University of Hong Kong's
1
National Key R&D Program of China
4
Wellcome Trust
2
National Institute for Health Research (NIHR)
3
Medical Research Council
5
MRC
1
H2020_REST_ThirdPillar (Special project, May 2022)
1
H2020_REST (Special project, May 2022)
1
French Ministry of Health
1
Cancer Research UK
1
National Eye Institute
1
National Heart, Lung, and Blood Institute
6
NIH (Special project, May 2022)
1
Intramural NIH HHS
1
NCI NIH HHS
3
National Institute of Allergy and Infectious Diseases
1
HHS
1
World Health Organization
2
National Institute on Minority Health and Health Disparities
1
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
1
National Institute for Health Research
1
Zhejiang University
1
Bill and Melinda Gates Foundation
1
Ministry of Science and Technology of the People's Republic of China
2
Health Resources and Services Administration
1
Infectious Diseases Society of America
4
National Institutes of Health
2
U.S. Department of Health and Human Services
1
National Cancer Institute
1
Consejo Nacional de Ciencia y Tecnología
1
National Institutes of Allergy and Infectious Diseases
1
BBSRC (February 2022)
1
National Science and Technology Major Projects of Infectious Diseases
1
Research Grants Council, Hong Kong Special Administrative Region
1
the Theme-based Research Scheme
... and others
Citations
Cited by 42 other policy documents
(26 of them are from other policy sources)
Everything cited by this document (explore the cited scholarly articles) (explore the cited policy documents)
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Waleed Alhazzani et al. 2020
Guidelines in PubMed Central
and Critical Care medicine (DOI:10.1097/CCM.0000000000004363).
On
page 1
https://doi.org/10.1097/CCM.0000000000004363
On
page 1
New England Journal of Medicine (Massachusetts Medical Society)
Wei-jie Guan et al. 2020
Keywords: Coronavirus, COVID-19, SARS CoV-2, Clinical practice guidelines, Critical illness Introduction At the end of 2019, a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an acute respiratory illness epidemic in Wuhan, China [1].
On page 2
Moreover, the duration of asymptomatic shedding is not only variable but may also differ based on the anatomic level (upper versus lower) of the infection in the respiratory system [1, 34].
On page 8
In another Chinese study of 1099 patients with COVID-19 with similar severity of illness, only 12 (1.1%) developed shock [1].
On page 9
Wang et al. [43] 138 26 7 9 11 12 – Guan et al. [1] 1099 – – 1 5.1 2.3 1 Yang et al. [42] 52 100 23 35 55.8 42.3 62
On page 9
Recent reports from China showed that 4–13% of COVID-19 patients in these studies received non-invasive positive pressure ventilation (NIPPV), and that 2.3–12% required invasive mechanical ventilation (Table 3) [1, 12, 42, 43, 65].
On page 14
Risk factors for respiratory failure Risk factors associated with respiratory failure requiring mechanical ventilation are not clearly described in published reports, although from the limited available data, risk factors associated with a critical illness/ICU admission included older age (> 60 years), male gender, and the presence of underlying comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 42, 43].
On page 14
Rationale A recent study described the disease course of 1009 patients with COVID-19 in China and showed that 41% of all hospitalized patients and over 70% of those with severe disease required supplemental oxygen [1].
On page 14
The diagnostic difficulty is reflected in high rates of intravenous antibiotics administered in Wuhan: 53% with non-severe disease and > 90% of patients admitted to hospital or the ICU [1, 42, 43].
On page 23
Data on the prevalence of bacterial superinfection in patients with COVID-19 are limited, as in larger case studies clinicians were often too overwhelmed to systematically obtain high-quality samples [1].
On page 23
In the largest report from China, the median temperature across 1099 patients was 38.3 °C (IQR 37.8–38.9) [1].
On page 23
1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for C (2020) Clinical characteristics of Coronavirus Disease 2019 in China. N Engl J Med. https://doi.org/10.1056/NEJMoa2002032
On
page 27
Intensive Care Medicine (Springer Science and Business Media LLC)
Waleed Alhazzani et al. 2018
Management of conflict of interests All panel members completed a conflict of interests (COI) form prior to joining the guideline panel [3, 4].
On page 2
3. Alhazzani W, Lewis K, Jaeschke R, Rochwerg B, Moller MH, Evans L, Wilson KC, Patel S, Coopersmith CM, Cecconi M, Guyatt G, Akl EA (2018) Conflicts of interest disclosure forms and management in critical care clinical practice guidelines. Intensive Care Med 44:1691–1698
On
page 27
Intensive Care Medicine (Springer Science and Business Media LLC)
Per Olav Vandvik et al. 2018
Management of conflict of interests All panel members completed a conflict of interests (COI) form prior to joining the guideline panel [3, 4].
On page 2
4. Vandvik PO, Alhazzani W, Moller MH (2018) Understanding conflicts of interest. Intensive Care Med 44:1738–1740
On
page 27
Journal of Clinical Epidemiology (Elsevier BV)
Gordon H. Guyatt et al. 2011
Grading of Recommendations Assessment, Development and Evaluation
To facilitate rapid development of recommendations, we did not perform a novel systematic prioritization of outcomes, but used the outcome prioritization informed by the ongoing SSC guideline 2020 work and expert input [5].
On page 2
5. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, Alderson P, Glasziou P, Falck-Ytter Y, Schunemann HJ (2011) GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 64:395–400
On
page 27
PLoS ONE (Public Library of Science (PLoS))
Elie A. Akl et al. 2013
We obtained intention-to-treat data whenever available; otherwise we used complete case data, i.e. ignoring missing data [6].
On page 3
6. Akl EA, Johnston BC, Alonso-Coello P, Neumann I, Ebrahim S, Briel M, Cook DJ, Guyatt GH (2013) Addressing dichotomous data for participants excluded from trial analysis: a guide for systematic reviewers. PLoS ONE 8:e57132
On
page 27
BMJ (BMJ)
Gordon H Guyatt et al. 2008
Guidelines in PubMed Central
Quality of evidence We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence [7], i.e. our confidence in the estimate of the effect to support a recommendation [8].
On page 3
7. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Schunemann P, Schunemann HJ, Group GW (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926
On
page 27
Journal of Clinical Epidemiology (Elsevier BV)
Howard Balshem et al. 2011
Grading of Recommendations Assessment, Development and Evaluation
Quality of evidence We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence [7], i.e. our confidence in the estimate of the effect to support a recommendation [8].
On page 3
8. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, Vist GE, Falck-Ytter Y, Meerpohl J, Norris S, Guyatt GH (2011) GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 64:401–406
On
page 27
Journal of Clinical Epidemiology (Elsevier BV)
Jeff Andrews et al. 2013
Grading of Recommendations Assessment, Development and Evaluation
9. Andrews J, Guyatt G, Oxman AD, Alderson P, Dahm P, Falck-Ytter Y, Nasser M, Meerpohl J, Post PN, Kunz R, Brozek J, Vist G, Rind D, Akl EA, Schunemann HJ (2013) GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 66:719–725
On
page 27
Journal of Clinical Epidemiology (Elsevier BV)
Holger J. Schünemann et al. 2017
Grading of Recommendations Assessment, Development and Evaluation
Recommendation formulation We used the principles outlined in the evidence to decision framework (EtD) to formulate recommendations, but because of the tight timelines we did not complete the online EtD tables [11].
On page 3
11. Schunemann HJ, Wiercioch W, Brozek J, Etxeandia-Ikobaltzeta I, Mustafa RA, Manja V, Brignardello-Petersen R, Neumann I, Falavigna M, Alhazzani W, Santesso N, Zhang Y, Meerpohl JJ, Morgan RL, Rochwerg B, Darzi A, Rojas MX, Carrasco-Labra A, Adi Y, AlRayees Z, Riva J, Bollig C, Moore A, Yepes-Nunez JJ, Cuello C, Waziry R, Akl EA (2017) GRADE evidence to decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT. J Clin Epidemiol 81:101–110
On
page 27
JAMA (American Medical Association (AMA))
Zunyou Wu et al. 2020
The report describes that 14.8% (247 of 1668) of infected healthcare workers had severe or critical illness, and that 5 died [12].
On page 4
In a recent report summarizing the epidemiological characteristics of 44,415 Chinese patients with COVID-19, 2087 (5%) were diagnosed as critical cases, defined as severe hypoxemia and/or the presence of other organ failure, including shock [12].
On page 9
Ventilatory support The prevalence of hypoxic respiratory failure in patients with COVID-19 is 19% [12].
On page 14
Recent reports from China showed that 4–13% of COVID-19 patients in these studies received non-invasive positive pressure ventilation (NIPPV), and that 2.3–12% required invasive mechanical ventilation (Table 3) [1, 12, 42, 43, 65].
On page 14
Although the true incidence of hypoxic respiratory failure in patients with COVID-19 is not clear, it appears that about 14% will develop severe disease requiring oxygen therapy, and 5% will require ICU admission and mechanical ventilation [12].
On page 14
Risk factors for respiratory failure Risk factors associated with respiratory failure requiring mechanical ventilation are not clearly described in published reports, although from the limited available data, risk factors associated with a critical illness/ICU admission included older age (> 60 years), male gender, and the presence of underlying comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 42, 43].
On page 14
The presence of pre-existing comorbid conditions such as cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancer were associated with higher risk of death [12].
On page 14
12. Wu Z, McGoogan JM (2020) Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in china: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. https://doi.org/10.1001/jama.2020.2648
On
page 27
PLoS Pathogens (Public Library of Science (PLoS))
Donald K. Milton et al. 2013
Surgical masks (also known as medical masks) are designed to block large particles, droplets and sprays, but are less effective in blocking small particle aerosols (< 5 μm) [14].
On page 4
14. Milton DK, Fabian MP, Cowling BJ, Grantham ML, McDevitt JJ (2013) Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks. PLoS Pathog 9:e1003205
On
page 27
Emerging Infectious Diseases (Centers for Disease Control and Prevention (CDC))
Shiing-Jer Twu et al. 2003
Negative pressure rooms have proven to be an effective measure that helped to avoid cross-contamination during the SARS epidemic [15].
On page 7
15. Twu SJ, Chen TJ, Chen CJ, Olsen SJ, Lee LT, Fisk T, Hsu KH, Chang SC, Chen KT, Chiang IH, Wu YC, Wu JS, Dowell SF (2003) Control measures for severe acute respiratory syndrome (SARS) in Taiwan. Emerg Infect Dis 9:718–720
On
page 27
World Health Organization
org/10.1056/nejmoa2001282 195. World Health Organization (2020) Informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection.
On page 33
Accordingly, for aerosolgenerating procedures, the WHO guidance on COVID- 19 recommends the use of negative pressure rooms with a minimum of 12 air changes per hour or at least 160 L/ second/patient in facilities with natural ventilation [16].
On page 7
16. World Health Organization, Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. 2020, March 14. https://www.who.int/docs/default-source/coronaviruse/ clinical-management-of-novel-cov.pdf?sfvrsn=bc7da517_10&downl oad=true
On
page 27
The Lancet (Elsevier BV)
Luca Cabrini et al. 2020
Non-invasive ventilation is also at high risk of aerosolization, and strategies have been described to contain the risk [17] of virus spread, also according to a previous report on SARS infection [18].
On page 7
17. Cabrini L, Landoni G, Zangrillo A (2020) Minimise nosocomial spread of 2019-nCoV when treating acute respiratory failure. Lancet 395:685
On
page 27
Building Simulation (Springer Science and Business Media LLC)
Hua Qian et al. 2010
HEPA filters have been demonstrated to reduce virus transmission in simulated settings [19].
On page 7
19. Qian H, Li Y, Sun H, Nielsen PV, Huang X, Zheng X (2010) Particle removal efficiency of the portable HEPA air cleaner in a simulated hospital ward. Build Simul 3:215–224
On
page 27
Canadian Medical Association Journal (Joule Inc.)
Jeffrey D. Smith et al. 2016
20. Smith JD, MacDougall CC, Johnstone J, Copes RA, Schwartz B, Garber GE (2016) Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis. CMAJ 188:567–574
On
page 27
JAMA (American Medical Association (AMA))
Lewis J. Radonovich et al. 2019
We updated the most recent systematic review and meta-analysis of RCTs [20], and identified one new RCT [21].
On page 7
Overall, 4 RCTs (5549 individuals) randomized healthcare workers to N95 respirators or medical masks [21–25].
On page 7
21. Radonovich LJ Jr, Simberkoff MS, Bessesen MT, Brown AC, Cummings DAT, Gaydos CA, Los JG, Krosche AE, Gibert CL, Gorse GJ, Nyquist AC, Reich NG, Rodriguez-Barradas MC, Price CS, Perl TM, Pi R (2019) N95 respirators vs medical masks for preventing influenza among health care personnel: a randomized clinical trial. JAMA 322:824–833
On
page 27
JAMA (American Medical Association (AMA))
Mark Loeb et al. 2009
Overall, 4 RCTs (5549 individuals) randomized healthcare workers to N95 respirators or medical masks [21–25].
On page 7
On testing for seasonal coronavirus (OC43, HKU1, 229E, NL63) by means of PCR in this non-cluster RCT, 4.3% (9/212) of nurses in the medical mask group had RT-PCR confirmed coronavirus infection as compared with 5.7% (12/210) in the N95 respirator group [22].
On page 8
22. Loeb M, Dafoe N, Mahony J, John M, Sarabia A, Glavin V, Webby R, Smieja M, Earn DJ, Chong S, Webb A, Walter SD (2009) Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA 302:1865–1871
On
page 27
Influenza and Other Respiratory Viruses (Wiley)
Chandini Raina MacIntyre et al. 2011
Overall, 4 RCTs (5549 individuals) randomized healthcare workers to N95 respirators or medical masks [21–25].
On page 7
23. MacIntyre CR, Wang Q, Cauchemez S, Seale H, Dwyer DE, Yang P, Shi W, Gao Z, Pang X, Zhang Y, Wang X, Duan W, Rahman B, Ferguson N (2011) A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influenza Other Respir Viruses 5:170–179
On
page 27
Preventive Medicine (Elsevier BV)
C. Raina MacIntyre et al. 2014
Overall, 4 RCTs (5549 individuals) randomized healthcare workers to N95 respirators or medical masks [21–25].
On page 7
24. MacIntyre CR, Wang Q, Rahman B, Seale H, Ridda I, Gao Z, Yang P, Shi W, Pang X, Zhang Y, Moa A, Dwyer DE (2014) Efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers. Prev Med 62:1–7
On
page 27
A Randomized Clinical Trial of Three Options for N95 Respirators and Medical Masks in Health Workers
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
C. Raina MacIntyre et al. 2013
Overall, 4 RCTs (5549 individuals) randomized healthcare workers to N95 respirators or medical masks [21–25].
On page 7
25. MacIntyre CR, Wang Q, Seale H, Yang P, Shi W, Gao Z, Rahman B, Zhang Y, Wang X, Newall AT, Heywood A, Dwyer DE (2013) A randomized clinical trial of three options for N95 respirators and medical masks in health workers. Am J Respir Crit Care Med 187:960–966
On
page 27
Journal of Evidence-Based Medicine (Wiley)
Youlin Long et al. 2020
26. Long Y, Hu T, Liu L, Chen R, Guo Q, Yang L, Cheng Y, Huang J, Du L (2020) Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. https://doi. org/10.1111/jebm.12381
On
page 27
Annals of Internal Medicine (American College of Physicians)
Ashleigh R. Tuite et al. 2020
Specifically, an early estimate of the reproductive number (R 0 ) of SARS-CoV-2, the average number of people an infected person subsequently infects as a function of biological properties of the pathogen in combination with social and environmental factors, is 2.3 [27].
On page 8
27. Tuite AR, Fisman DN (2020) Reporting, epidemic growth, and reproduction numbers for the 2019 novel coronavirus (2019-nCoV) epidemic. Ann Intern Med. https://doi.org/10.7326/M20-0358
On
page 27
PLoS ONE (Public Library of Science (PLoS))
Khai Tran et al. 2012
While SARS-CoV-2 appears to be predominantly spread by large respiratory droplets, intubation is likely a small particle (less than 5 μm) aerosol-generating procedure, which increases the risk of transmission to healthcare workers [29].
On page 8
In addition, in SARS, there are reports of increased transmission of disease to healthcare workers, especially nurses, during endotracheal intubation (OR 6.6, 95% Cl 2.3–18.9) [29, 75, 76].
On page 15
In addition, NIPPV is an aerosol-generating procedure that can increase the risk of transmission of disease to healthcare workers [29].
On page 16
29. Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J (2012) Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS ONE 7:e35797
On
page 28
British Journal of Anaesthesia (Elsevier BV)
S.R. Lewis et al. 2017
30. Lewis SR, Butler AR, Parker J, Cook TM, Schofield-Robinson OJ, Smith AF (2017) Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation: a Cochrane systematic review. Br J Anaesth 119:369–383
On
page 28
Journal of Perioperative Practice (SAGE Publications)
Terrie-Marie Russell et al. 2018
In patients with difficult airways, the first-attempt success rate may be improved with video-laryngoscopy [32].
On page 8
32. Russell TM, Hormis A, Rotherham NHSFT (2018) Should the Glidescope video laryngoscope be used first line for all oral intubations or only in those with a difficult airway? A review of current literature. J Perioper Pract 28:322–333
On
page 28
Centers for Disease Control and Prevention (CDC)
Real-time polymerase chain reaction (RT-PCR) is the gold standard for similar viral infections, including SARS [33].
On page 8
33. Center of Disease Control, Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19). 2020, February 14. https:// www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-speci mens.html
On
page 28
Journal of Clinical Medicine (MDPI AG)
Natalie M. Linton et al. 2020
34. Linton NM, Kobayashi T, Yang Y, Hayashi K, Akhmetzhanov AR, Jung SM, Yuan B, Kinoshita R, Nishiura H (2020) Incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: a statistical analysis of publicly available case data. J Clin Med. https://doi.org/10.3390/jcm9020538
On
page 28
Eurosurveillance (European Centre for Disease Control and Prevention (ECDC))
Victor M Corman et al. 2020
The procedures involved in laboratory RT-PCR testing for SARS-CoV-2 using a number of assays currently in use are well described [35].
On page 9
35. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DKW, Bleicker T, Brunink S, Schneider J, Schmidt ML, Mulders D, Haagmans BL, van der Veer B, van den Brink S, Wijsman L, Goderski G, Romette JL, Ellis J, Zambon M, Peiris M, Goossens H, Reusken C, Koopmans MPG, Drosten C (2020) Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. https://doi.org/10.2807/1560-7917. ES.2020.25.3.2000045
On
page 28
Clinical Chemistry (Oxford University Press (OUP))
Daniel K W Chu et al. 2020
Despite the generally high sensitivity and specificity of RT-PCR-based assays [36], it may not be enough to rely on oropharyngeal swabs specimens alone for SARS-CoV-2 diagnosis due to their low negative predictive value.
On page 9
36. Chu DKW, Pan Y, Cheng SMS, Hui KPY, Krishnan P, Liu Y, Ng DYM, Wan CKC, Yang P, Wang Q, Peiris M, Poon LLM (2020) Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia. Clin Chem. https://doi.org/10.1093/clinchem/hvaa029
On
page 28
International Journal of Infectious Diseases (Elsevier BV)
Chunbao Xie et al. 2020
In a recent study, only 9 out of 19 (47%) oropharyngeal swabs from COVID-19 patients tested positive by RT-PCR [37].
On page 9
37. Xie C, Jiang L, Huang G, Pu H, Gong B, Lin H, Ma S, Chen X, Long B, Si G, Yu H, Jiang L, Yang X, Shi Y, Yang Z (2020) Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis. https://doi.org/10.1016/j.ijid.2020.02.050
On
page 28
Journal of Clinical Microbiology (American Society for Microbiology)
W. C. Yam et al. 2003
38. Yam WC, Chan KH, Poon LL, Guan Y, Yuen KY, Seto WH, Peiris JS (2003) Evaluation of reverse transcription-PCR assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus. J Clin Microbiol 41:4521–4524
On
page 28
Radiology (Radiological Society of North America (RSNA))
Tao Ai et al. 2020
Similarly, in a study accounting for CT scan findings among suspected COVID-19 cases, 48% with negative oropharyngeal or nasal swabs were considered highly likely cases, and 33% were considered probable cases [39].
On page 9
39. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, Tao Q, Sun Z, Xia L (2020) Correlation of chest CT and RT-PCR testing in Coronavirus Disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. https://doi. org/10.1148/radiol.2020200642
On
page 28
Emerging Infectious Diseases (Centers for Disease Control and Prevention (CDC))
Xiaojing Wu et al. 2020
Similarly, given that coinfection with other viral pathogens has been observed, a positive test for another respiratory virus does not rule out COVID-19, and should not delay testing if there is a high suspicion of COVID-19 [40].
On page 9
40. Wu X, Cai Y, Huang X, Yu X, Zhao L, Wang F, Li Q, Gu S, Xu T, Li Y, Lu B, Zhan Q (2020) Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis. https://doi. org/10.3201/eid2606.200299
On
page 28
Emerging Infectious Diseases (Centers for Disease Control and Prevention (CDC))
Paul K. S. Chan et al. 2004
Lower respiratory tract specimens are considered to give a higher diagnostic yield than upper respiratory specimens in patients with pneumonia, consistent with what was observed for SARS [41], and should therefore be obtained whenever possible.
On page 9
41. Chan PK, To WK, Ng KC, Lam RK, Ng TK, Chan RC, Wu A, Yu WC, Lee N, Hui DS, Lai ST, Hon EK, Li CK, Sung JJ, Tam JS (2004) Laboratory diagnosis of SARS. Emerg Infect Dis 10:825–831
On
page 28
The Lancet Respiratory Medicine (Elsevier BV)
Xiaobo Yang et al. 2020
In hospitalized patients, the incidence is likely higher [42] (Table 3), and may reach 20–35% among patients in the ICU [42, 43].
On page 9
Guan et al. [1] 1099 – – 1 5.1 2.3 1 Yang et al. [42] 52 100 23 35 55.8 42.3 62 Zhou et al. [45] 191 26 17 20 14 17 28
On page 9
Recent reports from China showed that 4–13% of COVID-19 patients in these studies received non-invasive positive pressure ventilation (NIPPV), and that 2.3–12% required invasive mechanical ventilation (Table 3) [1, 12, 42, 43, 65].
On page 14
Another study reported on 52 critically ill COVID-19 patients; 67% of these patients had ARDS, 33 (63.5%) received high-flow nasal cannula (HFNC), 56% invasive mechanical ventilation, and 42% NIPPV [42].
On page 14
Risk factors for respiratory failure Risk factors associated with respiratory failure requiring mechanical ventilation are not clearly described in published reports, although from the limited available data, risk factors associated with a critical illness/ICU admission included older age (> 60 years), male gender, and the presence of underlying comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 42, 43].
On page 14
A recent study that described the clinical course of COVID-19 in the ICU showed that prone ventilation was used in 11.5% of patients (6 out of 52) [42].
On page 19
A recent report from China suggested that 11.5% of COVID-19 cases in the ICU received ECMO [42], but the clinical courses and the outcomes of these patients have not been reported yet.
On page 21
The diagnostic difficulty is reflected in high rates of intravenous antibiotics administered in Wuhan: 53% with non-severe disease and > 90% of patients admitted to hospital or the ICU [1, 42, 43].
On page 23
42. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y (2020) Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. https://doi.org/10.1016/S2213-2600(20)30079-5
On
page 28
JAMA (American Medical Association (AMA))
Dawei Wang et al. 2020
In hospitalized patients, the incidence is likely higher [42] (Table 3), and may reach 20–35% among patients in the ICU [42, 43].
On page 9
Chen et al. [65] 99 23 – 4 13 4 11 Wang et al. [43] 138 26 7 9 11 12 – Guan et al. [1] 1099 – – 1 5.1 2.3 1
On page 9
Recent reports from China showed that 4–13% of COVID-19 patients in these studies received non-invasive positive pressure ventilation (NIPPV), and that 2.3–12% required invasive mechanical ventilation (Table 3) [1, 12, 42, 43, 65].
On page 14
Risk factors for respiratory failure Risk factors associated with respiratory failure requiring mechanical ventilation are not clearly described in published reports, although from the limited available data, risk factors associated with a critical illness/ICU admission included older age (> 60 years), male gender, and the presence of underlying comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 42, 43].
On page 14
However, these meta-analyses included studies focused on immunocompromised, acute cardiogenic pulmonary edema, or post-operative patients; their findings may therefore be less applicable to COVID-19 patients, in whom acute hypoxemic respiratory failure and ARDS are more common presentations. [43, 81–83] In acute hypoxemic respiratory failure with an etiology other than cardiogenic pulmonary edema, NIPPV has a high failure rate.
On page 15
The diagnostic difficulty is reflected in high rates of intravenous antibiotics administered in Wuhan: 53% with non-severe disease and > 90% of patients admitted to hospital or the ICU [1, 42, 43].
On page 23
43. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 Hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 45:50. https://doi.org/10.1001/ jama.2020.1585
On
page 28
The Lancet (Elsevier BV)
Chaolin Huang et al. 2020
Cardiac injury (elevation of cardiac injury biomarkers above the 99th percentile upper reference limit) has Table 3 Epidemiological characteristics in recent COVID-19 reports Study n ICU admission (%) Cardiac Injury (%) Shock (%) NIPPV (%) Invasive MV (%) CFR (%) Huang et al. [44] 41 32 12 7 24 5 15 Chen et al. [65] 99 23 – 4 13 4 11
On page 9
A recent study from China showed that COVID-19 is associated with a cytokine elevation profile that is reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH) [44].
On page 21
44. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497–506
On
page 28
The Lancet (Elsevier BV)
Fei Zhou et al. 2020
Yang et al. [42] 52 100 23 35 55.8 42.3 62 Zhou et al. [45] 191 26 17 20 14 17 28 CFR case fatality rate, ICU intensive care unit, NIPPV non-invasive positive pressure ventilation been reported in 7–23% of patients with COVID-19 in Wuhan, C
On page 9
Rationale The prolonged detection of SARS-CoV-2 RNA in the respiratory tract and sometimes other sites of seriously ill COVID-19 patients provides the rationale for administration of antiviral agents to reduce replication in efforts to improve clinical outcomes [45].
On page 24
45. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. https ://doi.org/10.1016/S0140-6736(20)30566-3
On
page 28
Intensive Care Medicine (Springer Science and Business Media LLC)
Qiurong Ruan et al. 2020
In a study of 150 patients from 2 hospitals in Wuhan, China, shock was a major reason for death in 40%, and may, at least in part, be due to fulminant myocarditis [46].
On page 10
The limited data available on COVID-19 show that cardiac failure, alone or in combination with respiratory failure, was the cause of 40% of COVID-19 deaths [46].
On page 19
Furthermore, the majority of patients with COVID-19 in the ICU are elderly, and may develop myocardial dysfunction that could limit their ability to handle large fluid volumes [46].
On page 19
46. Ruan Q, Yang K, Wang W, Jiang L, Song J (2020) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan. Intensive Care Med, China. https://doi.org/10.1007/s0013 4-020-05991-x
On
page 28
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Joseph M. Bednarczyk et al. 2017
In a systematic review and meta-analysis of 13 RCTs (n = 1652) examining the effect of dynamic assessment of fluid therapy on important patient outcomes in adult ICU patients requiring fluid resuscitation [47], the use of dynamic assessment to guide fluid therapy was found to reduce mortality (RR 0.59, 95% CI 0.42–0.83), ICU length of stay (MD − 1.16 days, 95% CI − 1.97 to − 0.36) and duration of mechanical ventilation (− 2.98 h, 95% CI − 5.08 to − 0.89).
On page 10
47. Bednarczyk JM, Fridfinnson JA, Kumar A, Blanchard L, Rabbani R, Bell D, Funk D, Turgeon AF, Abou-Setta AM, Zarychanski R (2017) Incorporating dynamic assessment of fluid responsiveness into goal-directed therapy: a systematic review and meta-analysis. Crit Care Med 45:1538–1545
On
page 28
JAMA (American Medical Association (AMA))
Peter Bentzer et al. 2016
Among the examined dynamic parameters, passive leg raising followed by PPV and SVV appears to predict fluid responsiveness with highest accuracy [48].
On page 10
48. Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT (2016) Will this hemodynamically unstable patient respond to a bolus of intravenous fluids? JAMA 316:1298–1309
On
page 28
JAMA (American Medical Association (AMA))
Glenn Hernández et al. 2019
In the ANDROMEDA-SHOCK trial, capillary refill testing (CRT) every 30 min was associated with a nonsignificant reduction in mortality (HR 0.75, 95% CI 0.55– 1.02) compared with serum lactate measurement every 2 h [50].
On page 10
50. Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J, The ASI, the Latin America Intensive Care N, Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Cavalcanti AB, Bakker J, Hernandez G, Alegria L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavez N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, Gonzalez H, Arancibia JM, Munoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Munoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpan B, Fasce F, Luengo C, Medel N, Cortes C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, Gonzalez MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudin A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, Garcia F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garces P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Perez V, Delgado G, Lopez A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderon A, Paredes G, Barberan JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernan Portilla A, Davila H, Mora JA, Calderon LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL (2019) Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: the ANDROMEDA- SHOCK randomized clinical trial. JAMA 321:654–664
On
page 28
Intensive Care Medicine (Springer Nature)
Jonathan A. Silversides et al. 2017
Correspondingly, in a 2017 meta-analysis of 11 RCTs (n = 2051 patients), adults and children with ARDS or sepsis managed according to a conservative fluid strategy in the post-resuscitation phase of critical illness had more ventilator-free days and shorter ICU stays than patients managed according to a liberal fluid strategy [52] (see section on respiratory support for more details).
On page 10
The risk of death was similar in both groups: 28% in the conservative fluid strategy group and 31.1% in the liberal strategy group (RR 0.91, 95% CI 0.77–1.07) [52].
On page 19
52. Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E (2017) Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med 43:155–170
On
page 28
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
Kathryn Maitland et al. 2011
In 2011, a large RCT of 3141 febrile African children (FEAST) found that children randomized to fluid boluses with saline or albumin had increased mortality compared with children not receiving fluid boluses [53].
On page 11
53. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM, Group FT (2011) Mortality after fluid bolus in African children with severe infection. N Engl J Med 364:2483–2495
On
page 28
Acta Anaesthesiologica Scandinavica (Wiley)
M. H. Møller et al. 2016
Guidelines in PubMed Central
A systematic review of 28 RCTs (n = 3497 patients) and a clinical practice guideline from 2016 summarized the available body of evidence on the best first-line vasopressor for patients with shock [56, 57].
On page 12
56. Moller MH, Claudius C, Junttila E, Haney M, Oscarsson-Tibblin A, Haavind A, Perner A (2016) Scandinavian SSAI clinical practice guideline on choice of first-line vasopressor for patients with acute circulatory failure. Acta Anaesthesiol Scand 60:1347–1366
On
page 29
Canadian Journal of Anesthesia/Journal canadien d'anesthésie (Springer Science and Business Media LLC)
Kimia Honarmand et al. 2020
In a recent clinical practice guideline, the use of vasopressin and vasopressin analogs in critically ill adults with distributive shock was assessed [58].
On page 13
58. Honarmand K, Um KJ, Belley-Cote EP, Alhazzani W, Farley C, Fernando SM, Fiest K, Grey D, Hajdini E, Herridge M, Hrymak C, Moller MH, Kanji S, Lamontagne F, Lauzier F, Mehta S, Paunovic B, Singal R, Tsang JL, Wynne C, Rochwerg B (2020) Canadian Critical Care Society clinical practice guideline: the use of vasopressin and vasopressin analogues in critically ill adults with distributive shock. Can J Anaesth 67:369–376
On
page 29
JAMA (American Medical Association (AMA))
William F. McIntyre et al. 2018
59. McIntyre WF, Um KJ, Alhazzani W, Lengyel AP, Hajjar L, Gordon AC, Lamontagne F, Healey JS, Whitlock RP, Belley-Cote EP (2018) Association of vasopressin plus catecholamine vasopressors vs catecholamines alone with atrial fibrillation in patients with distributive shock: a systematic review and meta-analysis. JAMA 319:1889–1900
On
page 29
Intensive Care Medicine (Springer Science and Business Media LLC)
François Lamontagne et al. 2018
A recent individual patient-data meta-analysis of 2 RCTs (n = 894 patients) comparing higher versus lower blood pressure targets for vasopressor therapy in adult patients with shock reported no significant difference in 28-day mortality (OR 1.15, 95% CI 0.87–1.52), 90-day mortality (OR 1.08, 95% CI 0.84–1.44), myocardial injury (OR 1.47, 95% CI 0.64–3.56), or limb ischemia (OR 0.92, 95% CI 0.36–2.10) [60].
On page 13
60. Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, Radermacher P, Chretien JM, Beaudoin N, Hebert P, D’Aragon F, Meziani F, Asfar P (2018) Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 44:12–21
On
page 29
JAMA (American Medical Association (AMA))
François Lamontagne et al. 2020
Correspondingly, the recently published 65 trial reports an absolute risk difference in mortality of 3% (RR 0.93, 95% CI 0.85–1.03) in favor of a MAP target of 60–65 mmHg (lower target), as compared to a standard of care MAP target (higher target) [61].
On page 13
61. Lamontagne F, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, Camsooksai J, Darnell R, Gordon AC, Henry D, Hudson N, Mason AJ, Saull M, Whitman C, Young JD, Rowan KM, Mouncey PR, trial i, (2020) Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2020.0930
On
page 29
Acta Anaesthesiologica Scandinavica (Wiley)
M. H. Møller et al. 2018
Guidelines in PubMed Central
62. Moller MH, Granholm A, Junttila E, Haney M, Oscarsson-Tibblin A, Haavind A, Laake JH, Wilkman E, Sverrisson KO, Perner A (2018) Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure. Acta Anaesthesiol Scand 62:420–450
On
page 29
Intensive Care Medicine (Springer Science and Business Media LLC)
Sofie Louise Rygård et al. 2018
Both a 2018 systematic review of 22 RCTs (n = 7297 patients) comparing low-dose corticosteroid therapy versus no corticosteroid therapy in adult patients with septic shock [63] and a clinical practice guideline [64] report no significant difference in short-term mortality (RR 0.96, 95% CI 0.91–1.02), long-term mortality (RR 0.96, 95% CI 0.90–1.02), or serious adverse events (RR 0.98, 95% CI 0.90–1.08).
On page 13
Recent systematic reviews and meta-analyses of RCTs in sepsis showed small improvements in mortality and faster resolution of shock with corticosteroid use, compared with not using corticosteroids [63, 149, 150] (see the previous section on hemodynamic support).
On page 22
63. Rygard SL, Butler E, Granholm A, Moller MH, Cohen J, Finfer S, Perner A, Myburgh J, Venkatesh B, Delaney A (2018) Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 44:1003–1016
On
page 29
BMJ (BMJ)
Francois Lamontagne et al. 2018
Both a 2018 systematic review of 22 RCTs (n = 7297 patients) comparing low-dose corticosteroid therapy versus no corticosteroid therapy in adult patients with septic shock [63] and a clinical practice guideline [64] report no significant difference in short-term mortality (RR 0.96, 95% CI 0.91–1.02), long-term mortality (RR 0.96, 95% CI 0.90–1.02), or serious adverse events (RR 0.98, 95% CI 0.90–1.08).
On page 13
64. Lamontagne F, Rochwerg B, Lytvyn L, Guyatt GH, Moller MH, Annane D, Kho ME, Adhikari NKJ, Machado F, Vandvik PO, Dodek P, Leboeuf R, Briel M, Hashmi M, Camsooksai J, Shankar-Hari M, Baraki MK, Fugate K, Chua S, Marti C, Cohen D, Botton E, Agoritsas T, Siemieniuk RAC (2018) Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ 362:k3284
On
page 29
The Lancet (Elsevier BV)
Nanshan Chen et al. 2020
n ICU admission (%) Cardiac Injury (%) Shock (%) NIPPV (%) Invasive MV (%) CFR (%) Huang et al. [44] 41 32 12 7 24 5 15 Chen et al. [65] 99 23 – 4 13 4 11 Wang et al. [43] 138 26 7 9 11 12 –
On page 9
Recent reports from China showed that 4–13% of COVID-19 patients in these studies received non-invasive positive pressure ventilation (NIPPV), and that 2.3–12% required invasive mechanical ventilation (Table 3) [1, 12, 42, 43, 65].
On page 14
65. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395:507–513
On
page 29
Chest (Elsevier BV)
Willem van den Boom et al. 2020
In critically ill patients, hypoxia can be detrimental and is associated with poor outcomes [66].
On page 14
66. van den Boom W, Hoy M, Sankaran J, Liu M, Chahed H, Feng M, See KC (2020) The search for optimal oxygen saturation targets in critically ill patients: observational data from large ICU databases. Chest 157:566–573
On
page 29
The Lancet (Elsevier BV)
Derek K Chu et al. 2018
A systematic review and meta-analysis of 25 RCTs (16,037 patients) showed that a liberal oxygen strategy is associated with increased risk of hospital mortality (RR1.21, 95% CI 1.03–1.43) in acutely ill patients [67].
On page 14
Furthermore, a meta-regression showed a linear association between risk of death and higher SpO 2 targets [67].
On page 14
67. Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, Szczeklik W, Schunemann HJ, Neary JD, Alhazzani W (2018) Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 391:1693–1705
On
page 29
BMJ (BMJ)
Reed A C Siemieniuk et al. 2018
A recent clinical practice guideline recommended that SpO 2 be maintained no higher than 96% [68].
On page 14
68. Siemieniuk RAC, Chu DK, Kim LH, Guell-Rous MR, Alhazzani W, Soccal PM, Karanicolas PJ, Farhoumand PD, Siemieniuk JLK, Satia I, Irusen EM, Refaat MM, Mikita JS, Smith M, Cohen DN, Vandvik PO, Agoritsas T, Lytvyn L, Guyatt GH (2018) Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ 363:k4169
On
page 29
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
Jean-Pierre Frat et al. 2015
In an RCT comparing HFNC with conventional oxygen therapy in patients with acute hypoxic respiratory failure, HFNC resulted in reduced 90-day mortality (OR 0.42, 95% CI 0.21–0.85), but did not reduce the risk of intubation [71].
On page 15
Finally, patients may find HFNC more comfortable than, or at least as comfortable as, conventional oxygen therapy [71, 74].
On page 15
In an RCT comparing HFNC with NIPPV in patients with acute hypoxic respiratory failure, HFNC resulted in reduced mortality at 90 days (HR 2.50, 95% CI 1.31–4.78), but did not significantly affect the need for intubation (50% failure rate in NIPPV vs 47% in conventional oxygen and 40% in HFNC groups; p = 0.18) [71].
On page 15
71. Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage-Metreau C, Richard JC, Brochard L, Robert R, Group FS, Network R (2015) High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 372:2185–2196
On
page 29
The American Journal of Emergency Medicine (Elsevier BV)
Yue-Nan Ni et al. 2018
A systematic review and meta-analysis of 9 RCTs (2093 patients) showed that HFNC reduces intubation compared with conventional oxygen (RR 0.85, 95% CI 0.74– 0.99), but does not affect the risk of death or ICU length of stay [72–74].
On page 15
Another meta-analysis comparing HFNC with NIPPV showed HFNC to decrease the need for intubation of patients, yet without significantly reducing mortality or ICU length of stay [72].
On page 15
72. Ni YN, Luo J, Yu H, Liu D, Liang BM, Liang ZA (2018) The effect of highflow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation. A systematic review and meta-analysis. Am J Emerg Med 36:226–233
On
page 29
Intensive Care Medicine (Springer Science and Business Media LLC)
B. Rochwerg et al. 2019
A systematic review and meta-analysis of 9 RCTs (2093 patients) showed that HFNC reduces intubation compared with conventional oxygen (RR 0.85, 95% CI 0.74– 0.99), but does not affect the risk of death or ICU length of stay [72–74].
On page 15
Finally, patients may find HFNC more comfortable than, or at least as comfortable as, conventional oxygen therapy [71, 74].
On page 15
74. Rochwerg B, Granton D, Wang DX, Helviz Y, Einav S, Frat JP, Mekontso- Dessap A, Schreiber A, Azoulay E, Mercat A, Demoule A, Lemiale V, Pesenti A, Riviello ED, Mauri T, Mancebo J, Brochard L, Burns K (2019) High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and metaanalysis. Intensive Care Med 45:563–572
On
page 29
PLoS ONE (Public Library of Science (PLoS))
Janet Raboud et al. 2010
In addition, in SARS, there are reports of increased transmission of disease to healthcare workers, especially nurses, during endotracheal intubation (OR 6.6, 95% Cl 2.3–18.9) [29, 75, 76].
On page 15
In SARS, healthcare workers exposed to HFNC were not at increased risk of developing disease [75].
On page 15
75. Raboud J, Shigayeva A, McGeer A, Bontovics E, Chapman M, Gravel D, Henry B, Lapinsky S, Loeb M, McDonald LC, Ofner M, Paton S, Reynolds D, Scales D, Shen S, Simor A, Stewart T, Vearncombe M, Zoutman D, Green K (2010) Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada. PLoS ONE 5:e10717
On
page 29
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Robert A. Fowler et al. 2004
In addition, in SARS, there are reports of increased transmission of disease to healthcare workers, especially nurses, during endotracheal intubation (OR 6.6, 95% Cl 2.3–18.9) [29, 75, 76].
On page 15
Several other studies and meta-analyses of SARS have also highlighted the risk of nosocomial spread of the disease with NIPPV [76, 87].
On page 16
76. Fowler RA, Guest CB, Lapinsky SE, Sibbald WJ, Louie M, Tang P, Simor AE, Stewart TE (2004) Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation. Am J Respir Crit Care Med 169:1198–1202
On
page 29
Journal of Hospital Infection (Elsevier BV)
C.C.H. Leung et al. 2019
In studies evaluating bacterial environmental contamination, HFNC presented a contamination risk similar to that of conventional oxygen [77].
On page 15
77. Leung CCH, Joynt GM, Gomersall CD, Wong WT, Lee A, Ling L, Chan PKS, Lui PCW, Tsoi PCY, Ling CM, Hui M (2019) Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial. J Hosp Infect 101:84–87
On
page 29
The Lancet Respiratory Medicine (Elsevier BV)
Jonathan Chun-Hei Cheung et al. 2020
Although some authors advised avoiding the use of HFNC in patients with COVID-19 due to the fear of disease transmission, studies supporting this advice are lacking [78].
On page 15
78. Cheung JC, Ho LT, Cheng JV, Cham EYK, Lam KN (2020) Staff safety during emergency airway management for COVID-19 in Hong Kong. Lancet Respir Med. https://doi.org/10.1016/S2213-2600(20)30084-9
On
page 29
Influenza and Other Respiratory Viruses (Wiley)
Basem M. Alraddadi et al. 2019
However, any patients receiving HFNC or NIPPV should be monitored closely and cared for in a setting where intubation can be facilitated in the event of decompensation, as the failure rate may be high and emergency intubation in an uncontrolled setting may increase the risk of nosocomial infection of healthcare providers [79, 80].
On page 15
In a cohort of Middle East Respiratory Syndrome (MERS) patients, NIPPV was not associated with improved mortality or length of stay, compared with patients who were intubated without trying NIPPV [79].
On page 16
Patients who received NIPPV prior to intubation had increased inhaled nitric oxide requirements and increased mortality [79].
On page 16
However, because limited experience with NIPPV in pandemics suggests a high failure rate, we recommend that any patient receiving NIPPV be monitored closely and cared for in a setting where intubation can be facilitated in the event of decompensation [79, 80].
On page 16
79. Alraddadi BM, Qushmaq I, Al-Hameed FM, Mandourah Y, Almekhlafi GA, Jose J, Al-Omari A, Kharaba A, Almotairi A, Al Khatib K, Shalhoub S, Abdulmomen A, Mady A, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Balkhy HH, Al Harthy A, Sadat M, Tlayjeh H, Merson L, Hayden FG, Fowler RA, Arabi YM, Saudi Critical Care Trials G (2019) Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome. Influenza Other Respir Viruses 13:382–390
On
page 29
Annals of Internal Medicine (American College of Physicians)
Yaseen M. Arabi et al. 2014
However, any patients receiving HFNC or NIPPV should be monitored closely and cared for in a setting where intubation can be facilitated in the event of decompensation, as the failure rate may be high and emergency intubation in an uncontrolled setting may increase the risk of nosocomial infection of healthcare providers [79, 80].
On page 15
However, because limited experience with NIPPV in pandemics suggests a high failure rate, we recommend that any patient receiving NIPPV be monitored closely and cared for in a setting where intubation can be facilitated in the event of decompensation [79, 80].
On page 16
80. Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, Hawa H, Alothman A, Khaldi A, Al Raiy B (2014) Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med 160:389–397
On
page 29
European Respiratory Review (European Respiratory Society (ERS))
Antonio M. Esquinas et al. 2014
In China, the use of NIPPV for pandemic respiratory infection is common, whereas guidelines from Europe, Hong Kong, and the US advise against NIPPV as a first-line therapy in H1N1 [84].
On page 16
84. Esquinas AM, Egbert Pravinkumar S, Scala R, Gay P, Soroksky A, Girault C, Han F, Hui DS, Papadakos PJ, Ambrosino N, International NIVN (2014) Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review. Eur Respir Rev 23:427–438
On
page 29
Seminars in Respiratory and Critical Care Medicine (Georg Thieme Verlag KG)
Jean-Claude Lefebvre et al. 2014
There are additional concerns over the use of NIPPV in respiratory pandemics like COVID- 19: NIPPV may aggravate severe forms of lung injury as a result of injurious transpulmonary pressures and large tidal volumes [85, 86], and may delay initiation of invasive mechanical ventilation, leading to emergency or more unstable intubations that can increase the risk of transmission to the healthcare team [85].
On page 16
85. Brochard L, Lefebvre JC, Cordioli RL, Akoumianaki E, Richard JC (2014) Noninvasive ventilation for patients with hypoxemic acute respiratory failure. Semin Respir Crit Care Med 35:492–500
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
Arthur S. Slutsky et al. 2013
There are additional concerns over the use of NIPPV in respiratory pandemics like COVID- 19: NIPPV may aggravate severe forms of lung injury as a result of injurious transpulmonary pressures and large tidal volumes [85, 86], and may delay initiation of invasive mechanical ventilation, leading to emergency or more unstable intubations that can increase the risk of transmission to the healthcare team [85].
On page 16
While mechanical ventilation is a potentially life-saving intervention, it can worsen lung injury and, through ventilator-induced lung injury (VILI), contribute to multiorgan failure in patients with ARDS [86].
On page 17
86. Slutsky AS, Ranieri VM (2013) Ventilator-induced lung injury. N Engl J Med 369:2126–2136
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
Laurent Brochard et al. 1995
If, in certain COVID-19 patients, other forms of respiratory failure, such as acute hypercapnic respiratory failure or acute cardiogenic pulmonary edema, are known to be the cause of respiratory failure, NIPPV may be beneficial [88, 89].
On page 16
88. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F et al (1995) Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 333:817–822
On
page 30
Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure
European Respiratory Journal (European Respiratory Society (ERS))
Bram Rochwerg et al. 2017
If, in certain COVID-19 patients, other forms of respiratory failure, such as acute hypercapnic respiratory failure or acute cardiogenic pulmonary edema, are known to be the cause of respiratory failure, NIPPV may be beneficial [88, 89].
On page 16
89. Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, Navalesi PMOTSC, Antonelli M, Brozek J, Conti G, Ferrer M, Guntupalli K, Jaber S, Keenan S, Mancebo J, Mehta S, Raoof SMOTTF (2017) Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. https://doi.org/10.1183/13993003.02426-2016
On
page 30
JAMA (American Medical Association (AMA))
Bhakti K. Patel et al. 2016
A single-center RCT showed decreased intubation and improved mortality from NIPPV delivered by helmet in ARDS patients [90].
On page 16
90. Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP (2016) Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 315:2435–2441
On
page 30
Chest (Elsevier BV)
David S. Hui et al. 2015
Of particular importance in the setting of a pandemic such as COVID-19, NIPPV by helmet has also been shown to reduce exhaled air dispersion, whereas face masks were insufficient [91].
On page 16
91. Hui DS, Chow BK, Lo T, Ng SS, Ko FW, Gin T, Chan MTV (2015) Exhaled air dispersion during noninvasive ventilation via helmets and a total facemask. Chest 147:1336–1343
On
page 30
Annals of the American Thoracic Society (American Thoracic Society)
Allan J. Walkey et al. 2017
A systematic review and meta-analysis of RCTs found an inverse association between larger Vt gradient and mortality [92].
On page 17
In addition, authors found that using a protocolized low Vt strategy with high PEEP (9 RCTs and 1629 patients) reduced the risk of death (RR, 0.80, 95% CI, 0.66–0.98) [92].
On page 17
A systematic review and meta-analysis of RCTs found that using a lung protective strategy including protocolized low Vt and Pplat < 30 cmH 2 O (9 RCTs and 1629 patients) reduced the risk of death (RR, 0.80, 95% CI 0.66–0.98)[92].
On page 18
92. Walkey AJ, Goligher EC, Del Sorbo L, Hodgson CL, Adhikari NKJ, Wunsch H, Meade MO, Uleryk E, Hess D, Talmor DS, Thompson BT, Brower RG, Fan E (2017) Low tidal volume versus non-volume-limited strategies for patients with acute respiratory distress syndrome. a systematic review and meta-analysis. Ann Am Thorac Soc 14:S271–S279
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
Marcelo Britto Passos Amato et al. 1998
Our analysis of 5 RCTs (1181 patients) showed a reduction in hospital mortality with low Vt ventilation (RR 0.73, 95% CI 0.63–0.85) [93–98].
On page 17
93. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi- Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338:347–354
On
page 30
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Jesús Villar et al. 2006
Our analysis of 5 RCTs (1181 patients) showed a reduction in hospital mortality with low Vt ventilation (RR 0.73, 95% CI 0.63–0.85) [93–98].
On page 17
94. Villar J, Kacmarek RM, Perez-Mendez L, Aguirre-Jaime A (2006) A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 34:1311–1318
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
2000
Our analysis of 5 RCTs (1181 patients) showed a reduction in hospital mortality with low Vt ventilation (RR 0.73, 95% CI 0.63–0.85) [93–98].
On page 17
Practical considerations The ARDSNet study protocol set the initial Vt at 6 mL/kg which can be increased to 8 mL/kg if the patient is double triggering or if inspiratory airway pressure decreases below PEEP [95].
On page 17
Practical considerations The ARDSNet study protocol set the initial Vt at 6 mL/kg, and then measured Pplat (after a 0.5 s inspiratory pause) [95].
On page 18
95. Acute Respiratory Distress Syndrome N, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308
On
page 30
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Roy G. Brower et al. 1999
Our analysis of 5 RCTs (1181 patients) showed a reduction in hospital mortality with low Vt ventilation (RR 0.73, 95% CI 0.63–0.85) [93–98].
On page 17
96. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P Jr, Wiener CM, Teeter JG, Dodd-o JM, Almog Y, Piantadosi S (1999) Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 27:1492–1498
On
page 30
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
James Orme et al. 2003
Our analysis of 5 RCTs (1181 patients) showed a reduction in hospital mortality with low Vt ventilation (RR 0.73, 95% CI 0.63–0.85) [93–98].
On page 17
97. Orme J Jr, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, Crapo RO, Weaver LK (2003) Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 167:690–694
On
page 30
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Eddy Fan et al. 2017
American Association for Respiratory Care
On the basis of the available body of evidence, several guidelines recommended using low Vt (4–8 mL/kg of predicted body weight) in patients with ARDS [99, 100].
On page 17
On the basis of the available body of evidence, several guidelines recommended keeping Pplat < 30 cm H 2 O in patients with ARDS [99, 100].
On page 18
Guidelines published in 2017 were unable to provide specific guidance on the use of ECMO, and further research was recommended [99].
On page 21
99. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, Ferguson ND, Gajic O, Gattinoni L, Hess D, Mancebo J, Meade MO, McAuley DF, Pesenti A, Ranieri VM, Rubenfeld GD, Rubin E, Seckel M, Slutsky AS, Talmor D, Thompson BT, Wunsch H, Uleryk E, Brozek J, Brochard LJ, American Thoracic Society ESoICM, Society of Critical Care M (2017) An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 195:1253–1263
On
page 30
Intensive Care Medicine (Springer Science and Business Media LLC)
Arnaud W. Thille et al. 2006
Strict adherence to target Vt in spontaneously breathing patients with ARDS is a challenge; patient-ventilator dyssynchrony is not uncommon [101].
On page 17
101. Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L (2006) Patientventilator asynchrony during assisted mechanical ventilation. Intensive Care Med 32:1515–1522
On
page 30
BMJ Open (BMJ)
Hideto Yasuda et al. 2017
A subsequent meta-analysis of RCTs comparing ventilatory strategies with low and high Pplat in patients with ARDS (15 studies) found that short-term mortality was higher in patients with Pplat > 32 cmH 2 O during the first week in the ICU (Day 1: RR 0.77, 95% CI 0.66–0.89; Day 3: RR 0.76, 95% CI 0.64–0.90; Day 7: RR 0.78, 95% CI 0.65–0.93)[102].
On page 18
102. Yasuda H, Nishimura T, Kamo T, Sanui M, Nango E, Abe T, Takebayashi T, Lefor AK, Hashimoto S (2017) Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression. BMJ Open 7:e015091
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
2004
An individual patient data meta-analysis (IPDMA) of the 3 largest trials (2299 patients) of high PEEP [103–105] found no difference in in-hospital mortality in all patients (RR 0.94, 95% CI 0.86–1.04) [106].
On page 18
However, in patients Practical considerations Because the IPDMA combined different strategies to set higher PEEP, a reasonable starting point would be to implement a strategy used in the large RCTs that were included (i.e. ALVEOLI, LOV, and ExPRESS) [103–105].
On page 18
103. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT, National Heart L, Blood Institute ACTN (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351:327–336
On
page 30
JAMA (American Medical Association (AMA))
Maureen O. Meade et al. 2008
An individual patient data meta-analysis (IPDMA) of the 3 largest trials (2299 patients) of high PEEP [103–105] found no difference in in-hospital mortality in all patients (RR 0.94, 95% CI 0.86–1.04) [106].
On page 18
However, in patients Practical considerations Because the IPDMA combined different strategies to set higher PEEP, a reasonable starting point would be to implement a strategy used in the large RCTs that were included (i.e. ALVEOLI, LOV, and ExPRESS) [103–105].
On page 18
104. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE, Lung Open Ventilation Study I (2008) Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299:637–664
On
page 30
JAMA (American Medical Association (AMA))
Alain Mercat et al. 2008
An individual patient data meta-analysis (IPDMA) of the 3 largest trials (2299 patients) of high PEEP [103–105] found no difference in in-hospital mortality in all patients (RR 0.94, 95% CI 0.86–1.04) [106].
On page 18
However, in patients Practical considerations Because the IPDMA combined different strategies to set higher PEEP, a reasonable starting point would be to implement a strategy used in the large RCTs that were included (i.e. ALVEOLI, LOV, and ExPRESS) [103–105].
On page 18
105. Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Baudot J, Bouadma L, Brochard L, Expiratory Pressure Study G (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299:646–655
On
page 30
JAMA (American Medical Association (AMA))
Matthias Briel et al. 2010
with ARDS, a higher PEEP strategy resulted in lower ICU mortality (RR 0.85, 95% CI 0.76–0.95), lower in-hospital mortality (RR 0.90, 95% CI 0.81–1.0), and a reduction in the use of rescue therapies (RR 0.63, 95% CI 0.53–0.75), at the expense of a possible increase in the risk of pneumothorax [106].
On page 18
In the aforementioned IPDMA, the median PEEP level in the high PEEP arm was 15.3 and 13.3 cm H 2 O on days 1 and 3, respectively, compared with median values of 9 and 8.2 cm H 2 O on days 1 and 3 in the low PEEP arm [106].
On page 18
An individual patient data meta-analysis (IPDMA) of the 3 largest trials (2299 patients) of high PEEP [103–105] found no difference in in-hospital mortality in all patients (RR 0.94, 95% CI 0.86–1.04) [106].
On page 18
106. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303:865–873
On
page 30
New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS))
2006
The landmark trial in ARDS patients (FACTT) found a significant reduction in the duration of mechanical ventilation with a conservative fluid strategy [109].
On page 19
109. National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 354:2564–2575
On
page 30
The Lancet Infectious Diseases (Elsevier BV)
Heshui Shi et al. 2020
110. Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C (2020) Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. https://doi. org/10.1016/S1473-3099(20)30086-4
On
page 30
Effects of Prone Positioning on Lung Protection in Patients with Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Rodrigo A. Cornejo et al. 2013
Prone positioning theoretically makes ventilation more homogeneous by decreasing ventral alveolar distention and dorsal alveolar collapse [111].
On page 19
111. Cornejo RA, Diaz JC, Tobar EA, Bruhn AR, Ramos CA, Gonzalez RA, Repetto CA, Romero CM, Galvez LR, Llanos O, Arellano DH, Neira WR, Diaz GA, Zamorano AJ, Pereira GL (2013) Effects of prone positioning on lung protection in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 188:440–448
On
page 30
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
RICHARD K. ALBERT et al. 2000
This may reduce the difference between the dorsal and ventral transpulmonary pressures, in addition to reducing lung compression [112] and improving perfusion [113].
On page 19
112. Albert RK, Hubmayr RD (2000) The prone position eliminates compression of the lungs by the heart. Am J Respir Crit Care Med 161:1660–1665
On
page 30
Anesthesiology (Ovid Technologies (Wolters Kluwer Health))
Sven Nyrén et al. 2010
This may reduce the difference between the dorsal and ventral transpulmonary pressures, in addition to reducing lung compression [112] and improving perfusion [113].
On page 19
113. Nyren S, Radell P, Lindahl SG, Mure M, Petersson J, Larsson SA, Jacobsson H, Sanchez-Crespo A (2010) Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers. Anesthesiology 112:682–687
On
page 30
Medicina Intensiva (English Edition) (Elsevier BV)
J.A. Mora-Arteaga et al. 2015
116. Mora-Arteaga JA, Bernal-Ramirez OJ, Rodriguez SJ (2015) The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis. Med Intensiva 39:359–372
On
page 31
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Joo Myung Lee et al. 2014
117. Lee JM, Bae W, Lee YJ, Cho YJ (2014) The efficacy and safety of prone positional ventilation in acute respiratory distress syndrome: updated study-level meta-analysis of 11 randomized controlled trials. Crit Care Med 42:1252–1262
On
page 31
Nutrition in Clinical Practice (Wiley)
PHJ van der Voort et al. 2002
Enteral nutrition via nasogastric or nasoduodenal tube can be continued during proning [118, 119].
On page 19
118. van der Voort PH, Zandstra DF (2001) Enteral feeding in the critically ill: comparison between the supine and prone positions: a prospective crossover study in mechanically ventilated patients. Crit Care 5:216–220
On
page 31
Intensive Care Medicine (Springer Science and Business Media LLC)
Annika Reintam Blaser et al. 2017
Guidelines in PubMed Central
Enteral nutrition via nasogastric or nasoduodenal tube can be continued during proning [118, 119].
On page 19
119. Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, Fruhwald S, Hiesmayr M, Ichai C, Jakob SM, Loudet CI, Malbrain ML, Montejo Gonzalez JC, Paugam-Burtz C, Poeze M, Preiser JC, Singer P, van Zanten AR, De Waele J, Wendon J, Wernerman J, Whitehouse T, Wilmer A, Oudemans-van Straaten HM, Function EWGoG (2017) Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med 43:380–398
On
page 31
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Michael J. Murray et al. 2016
Rationale Several professional societies have issued recommendations on the use of NMBAs in ARDS [100, 120–123].
On page 20
120. Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, McGee W, McManus C, Meade M, Nix S, Patterson A, Sands MK, Pino R, Tescher A, Arbour R, Rochwerg B, Murray CF, Mehta S (2016) Clinical practice guidelines for sustained neuromuscular blockade in the adult critically Ill patient. Crit Care Med 44:2079–2103
On
page 31
Thorax (BMJ)
Mark Griffiths et al. 2019
Rationale Several professional societies have issued recommendations on the use of NMBAs in ARDS [100, 120–123].
On page 20
121. Griffiths M, Fan E, Baudouin SV (2019) New UK guidelines for the management of adult patients with ARDS. Thorax 74:931–933
On
page 31
Acta Anaesthesiologica Scandinavica (Wiley)
J. Claesson et al. 2016
Rationale Several professional societies have issued recommendations on the use of NMBAs in ARDS [100, 120–123].
On page 20
122. Claesson J, Freundlich M, Gunnarsson I, Laake JH, Moller MH, Vandvik PO, Varpula T, Aasmundstad TA (2016) Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome. Acta Anaesthesiol Scand 60:697–709
On
page 31
New England Journal of Medicine (Massachusetts Medical Society)
The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network 2019
The ROSE trial investigators randomized 1006 patients with moderate or severe ARDS to receive either an infusion of NMBA for 48 h or intermittent NMBA boluses on an as needed basis [125].
On page 20
125. National Heart L, Blood Institute PCTN, Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC (2019) Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 380:1997–2008
On
page 31
New England Journal of Medicine (Massachusetts Medical Society)
Luciano Gattinoni et al. 2006
RMs aim to improve oxygenation by increasing transpulmonary pressure to open atelectatic alveoli [127].
On page 20
127. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G (2006) Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 354:1775–1786
On
page 31
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Robert M. Kacmarek et al. 2016
128. Kacmarek RM, Villar J, Sulemanji D, Montiel R, Ferrando C, Blanco J, Koh Y, Soler JA, Martinez D, Hernandez M, Tucci M, Borges JB, Lubillo S, Santos A, Araujo JB, Amato MB, Suarez-Sipmann F, Open Lung Approach N (2016) Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial. Crit Care Med 44:32–42
On
page 31
JAMA (American Medical Association (AMA))
Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators et al. 2017
Incremental PEEP titration RMs are described as incremental increases in PEEP from 25 to 35 to 45 cm H 2 0 for 1–2 min each [130–133].
On page 21
130. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I, Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimaraes HP, Romano ER, Regenga MM, Taniguchi LNT, Teixeira C, Pinheiro de Oliveira R, Machado FR, Diaz-Quijano FA, Filho MSA, Maia IS, Caser EB, Filho WO, Borges MC, Martins PA, Matsui M, Ospina-Tascon GA, Giancursi TS, Giraldo-Ramirez ND, Vieira SRR, Assef M, Hasan MS, Szczeklik W, Rios F, Amato MBP, Berwanger O, Ribeiro de Carvalho CR (2017) Effect of lung recruitment and titrated positive endexpiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 318:1335–1345
On
page 31
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Carol L. Hodgson et al. 2019
Incremental PEEP titration RMs are described as incremental increases in PEEP from 25 to 35 to 45 cm H 2 0 for 1–2 min each [130–133].
On page 21
132. Hodgson CL, Cooper DJ, Arabi Y, King V, Bersten A, Bihari S, Brickell K, Davies A, Fahey C, Fraser J, McGuinness S, Murray L, Parke R, Paul E, Tuxen D, Vallance S, Young M, Nichol A (2019) Maximal recruitment open lung ventilation in acute respiratory distress syndrome (PHAR‐ LAP). A phase II, multicenter randomized controlled clinical trial. Am J Respir Crit Care Med 200:1363–1372
On
page 31
New England Journal of Medicine (Massachusetts Medical Society)
Alain Combes et al. 2018
Although the most recent RCT (EOLIA) was stopped early for futility [136], a re-analysis of this trial using a Bayesian approach provided a more favorable interpretation, suggesting lower mortality with ECMO in severe ARDS [137].
On page 21
136. Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A, Eolia Trial Group R, Ecmonet (2018) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 378:1965–1975
On
page 31
JAMA (American Medical Association (AMA))
Ewan C. Goligher et al. 2018
Although the most recent RCT (EOLIA) was stopped early for futility [136], a re-analysis of this trial using a Bayesian approach provided a more favorable interpretation, suggesting lower mortality with ECMO in severe ARDS [137].
On page 21
137. Goligher EC, Tomlinson G, Hajage D, Wijeysundera DN, Fan E, Juni P, Brodie D, Slutsky AS, Combes A (2018) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc bayesian analysis of a randomized clinical trial. JAMA 320:2251–2259
On
page 31
The Lancet Respiratory Medicine (Elsevier BV)
Laveena Munshi et al. 2019
A recent systematic review including two RCTs (429 patients) found a reduction in 60-day mortality with ECMO (RR 0.73, 95% CI 0.58–0.92), but the risk of major bleeding was higher with ECMO [138].
On page 21
138. Munshi L, Walkey A, Goligher E, Pham T, Uleryk EM, Fan E (2019) Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Lancet Respir Med 7:163–172
On
page 31
JAMA (American Medical Association (AMA))
Graeme MacLaren et al. 2020
Therefore, its use as a rescue therapy should be reserved for carefully selected patients [139].
On page 21
139. MacLaren G, Fisher D, Brodie D (2020) Preparing for the most critically ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation. JAMA. https://doi.org/10.1001/jama.2020.2342
On
page 31
Arthritis & Rheumatology (Wiley)
Laurence Fardet et al. 2014
Some authors even suggest that we screen critically ill COVID-19 patients for secondary HLH using the Hscore [140], and that corticosteroids and other immunosuppressive agents can be used in patients with a high likelihood of HLH [141].
On page 21
140. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G (2014) Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 66:2613–2620
On
page 31
The Lancet (Elsevier BV)
Puja Mehta et al. 2020
Some authors even suggest that we screen critically ill COVID-19 patients for secondary HLH using the Hscore [140], and that corticosteroids and other immunosuppressive agents can be used in patients with a high likelihood of HLH [141].
On page 21
141. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. https://doi.org/10.1016/S0140-6736(20)30628-0
On
page 31
medRxiv (Cold Spring Harbor Laboratory)
Yin Wang et al. 2020
142. Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P, Dong N, Tong Q, (2020) Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China. medRxiv: 2020.2003.2006.20032342
On
page 31
Annals of Internal Medicine (American College of Physicians)
Reed A.C. Siemieniuk et al. 2015
A systematic review and meta-analysis of RCTs showed that using corticosteroids may reduce the need for mechanical ventilation (5 RCTs; 1060 patients; RR 0.45, 95% CI 0.26–0.79), ARDS (4 RCTs; 945 patients; RR 0.24, 95% CI 0.10–0.56) and the duration of hospitalization (6 RCTs; 1499 patients; MD − 1.00 day, 95% CI, − 1.79 to − 0.21), but increase the risk of hyperglycemia requiring treatment [143].
On page 22
143. Siemieniuk RA, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, Alexander PE, Fei Y, Vandvik PO, Loeb M, Guyatt GH (2015) Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med 163:519–528
On
page 31
JAMA (American Medical Association (AMA))
V. Marco Ranieri et al. 2020
In a recent RCT (INTEREST trial), the use of recombinant interferon β1b (rIFN β1ba) did not reduce mortality in ARDS patients, but in the subgroup of patients receiving corticosteroids, rIFN β1ba use was associated with increased mortality (OR, 2.53, 95% CI 1.12–5.72) [147].
On page 22
147. Ranieri VM, Pettila V, Karvonen MK, Jalkanen J, Nightingale P, Brealey D, Mancebo J, Ferrer R, Mercat A, Patroniti N, Quintel M, Vincent JL, Okkonen M, Meziani F, Bellani G, MacCallum N, Creteur J, Kluge S, Artigas-Raventos A, Maksimow M, Piippo I, Elima K, Jalkanen S, Jalkanen M, Bellingan G, Group IS (2020) Effect of Intravenous Interferon beta-1a on death and days free from mechanical ventilation among patients with moderate to severe acute respiratory distress syndrome: a randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2019.22525
On
page 32
JAMA Internal Medicine (American Medical Association (AMA))
Chaomin Wu et al. 2020
148. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y (2020) Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus Disease 2019 pneumonia in Wuhan. JAMA Intern Med, China. https://doi.org/10.1001/jamainternmed.2020.0994
On
page 32
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Bram Rochwerg et al. 2018
Recent systematic reviews and meta-analyses of RCTs in sepsis showed small improvements in mortality and faster resolution of shock with corticosteroid use, compared with not using corticosteroids [63, 149, 150] (see the previous section on hemodynamic support).
On page 22
149. Rochwerg B, Oczkowski SJ, Siemieniuk RAC, Agoritsas T, Belley-Cote E, D’Aragon F, Duan E, English S, Gossack-Keenan K, Alghuroba M, Szczeklik W, Menon K, Alhazzani W, Sevransky J, Vandvik PO, Annane D, Guyatt G (2018) Corticosteroids in sepsis: an updated systematic review and meta-analysis. Crit Care Med 46:1411–1420
On
page 32
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Yaseen M. Arabi et al. 2018
In viral pneumonia in the ICU, several studies showed increase in viral shedding with corticosteroid use [151–153], potentially indicating viral replication, but the clinical implication of increased viral shedding is uncertain.
On page 22
151. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, 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 AM, Al-Raddadi R, Ragab A, Balkhy HH, Al Harthy A, Deeb AM, Al Mutairi H, Al-Dawood A, Merson L, Hayden FG, Fowler RA, Saudi Critical Care Trial G (2018) Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med 197:757–767
On
page 32
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
David S. Hui 2018
In viral pneumonia in the ICU, several studies showed increase in viral shedding with corticosteroid use [151–153], potentially indicating viral replication, but the clinical implication of increased viral shedding is uncertain.
On page 22
152. Hui DS (2018) Systemic corticosteroid therapy may delay viral clearance in patients with middle east respiratory syndrome coronavirus infection. Am J Respir Crit Care Med 197:700–701
On
page 32
Journal of Clinical Virology (Elsevier BV)
Nelson Lee et al. 2004
In viral pneumonia in the ICU, several studies showed increase in viral shedding with corticosteroid use [151–153], potentially indicating viral replication, but the clinical implication of increased viral shedding is uncertain.
On page 22
153. Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, Wong VW, Chan PK, Wong KT, Wong E, Cockram CS, Tam JS, Sung JJ, Lo YM (2004) Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 31:304–309
On
page 32
Clinical Infectious Diseases (Oxford University Press (OUP))
Timothy M Uyeki et al. 2019
This recommendation is therefore based upon extrapolation of data from other viral pneumonias, particularly influenza [154].
On page 23
Co-infection with Staphylococcus aureus is common with influenza pneumonia and can be especially virulent [154].
On page 23
Recent clinical practice guidelines recommend initiating empiric antibacterial therapy in adults with community-acquired pneumonia who test positive for influenza [154].
On page 23
154. Uyeki TM, Bernstein HH, Bradley JS, Englund JA, File TM, Fry AM, Gravenstein S, Hayden FG, Harper SA, Hirshon JM, Ison MG, Johnston BL, Knight SL, McGeer A, Riley LE, Wolfe CR, Alexander PE, Pavia AT (2019) Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa. Clin Inf Dis 68:895–902
On
page 32
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Yaseen M. Arabi et al. 2017
In critically ill patients with MERS, 18% had bacterial and 5% viral co-infections [155].
On page 23
155. Arabi YM, Al-Omari A, Mandourah Y, Al-Hameed F, Sindi AA, Alraddadi B, Shalhoub S, Almotairi A, Al Khatib K, Abdulmomen A, Qushmaq I, Mady A, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Al Mekhlafi GA, Al Harthy A, Kharaba A, Ahmadi MA, Sadat M, Mutairi HA, Qasim EA, Jose J, Nasim M, Al-Dawood A, Merson L, Fowler R, Hayden FG, Balkhy HH, Saudi Critical Care Trials G (2017) Critically ill patients with the middle east respiratory syndrome: a multicenter retrospective cohort study. Crit Care Med 45:1683–1695
On
page 32
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
Todd W. Rice et al. 2012
In patients with COVID-19 and hypoxic respiratory failure requiring mechanical ventilation, the panel suggest empiric antimicrobial treatment, on the basis that superinfection is reasonably common in this population and may to lead to a substantial increase in mortality, as in pandemic influenza [156–158].
On page 23
156. Rice TW, Rubinson L, Uyeki TM, Vaughn FL, John BB, Miller RR 3rd, Higgs E, Randolph AG, Smoot BE, Thompson BT, Network NA (2012) Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med 40:1487–1498
On
page 32
The American Journal of Pathology (Elsevier BV)
Wun-Ju Shieh et al. 2010
In patients with COVID-19 and hypoxic respiratory failure requiring mechanical ventilation, the panel suggest empiric antimicrobial treatment, on the basis that superinfection is reasonably common in this population and may to lead to a substantial increase in mortality, as in pandemic influenza [156–158].
On page 23
157. Shieh WJ, Blau DM, Denison AM, Deleon-Carnes M, Adem P, Bhatnagar J, Sumner J, Liu L, Patel M, Batten B, Greer P, Jones T, Smith C, Bartlett J, Montague J, White E, Rollin D, Gao R, Seales C, Jost H, Metcalfe M, Goldsmith CS, Humphrey C, Schmitz A, Drew C, Paddock C, Uyeki TM, Zaki SR (2010) 2009 Pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol 177:166–175
On
page 32
Clinical Microbiology and Infection (Elsevier BV)
J.A. McCullers 2013
In patients with COVID-19 and hypoxic respiratory failure requiring mechanical ventilation, the panel suggest empiric antimicrobial treatment, on the basis that superinfection is reasonably common in this population and may to lead to a substantial increase in mortality, as in pandemic influenza [156–158].
On page 23
158. McCullers JA (2013) Do specific virus-bacteria pairings drive clinical outcomes of pneumonia? Clin Microbiol Infect 19:113–118
On
page 32
Surgical Infections (Mary Ann Liebert Inc)
Carl I. Schulman et al. 2005
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
160. Schulman CI, Namias N, Doherty J, Manning RJ, Li P, Elhaddad A, Lasko D, Amortegui J, Dy CJ, Dlugasch L, Baracco G, Cohn SM (2005) The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 6:369–375
On
page 32
New England Journal of Medicine (Massachusetts Medical Society)
Paul Young et al. 2015
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
161. Young P, Saxena M, Bellomo R, Freebairn R, Hammond N, van Haren F, Holliday M, Henderson S, Mackle D, McArthur C, McGuinness S, Myburgh J, Weatherall M, Webb S, Beasley R, Investigators H, Australian, New Zealand Intensive Care Society Clinical Trials G (2015) Acetaminophen for fever in critically ill patients with suspected infection. N Engl J Med 373:2215–2224
On
page 32
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
MARILYN T. HAUPT et al. 1991
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
162. Haupt MT, Jastremski MS, Clemmer TP, Metz CA, Goris GB (1991) Effect of ibuprofen in patients with severe sepsis: a randomized, doubleblind, multicenter study. The Ibuprofen Study Group. Crit Care Med 19:1339–1347
On
page 32
New England Journal of Medicine (Massachusetts Medical Society)
Gordon R. Bernard et al. 1997
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
163. Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918
On
page 32
Archives of Internal Medicine (American Medical Association (AMA))
Valerio Gozzoli et al. 2001
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
164. Gozzoli V, Schottker P, Suter PM, Ricou B (2001) Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling. Arch Intern Med 161:121–123
On
page 32
American Journal of Respiratory and Critical Care Medicine (American Thoracic Society)
Frédérique Schortgen et al. 2012
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
167. Schortgen F, Clabault K, Katsahian S, Devaquet J, Mercat A, Deye N, Dellamonica J, Bouadma L, Cook F, Beji O, Brun-Buisson C, Lemaire F, Brochard L (2012) Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 185:1088–1095
On
page 32
Journal of Critical Care (Elsevier BV)
Daniel J. Niven et al. 2013
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
168. Niven DJ, Stelfox HT, Leger C, Kubes P, Laupland KB (2013) Assessment of the safety and feasibility of administering antipyretic therapy in critically ill adults: a pilot randomized clinical trial. J Crit Care 28:296–302
On
page 32
Critical Care Medicine (Ovid Technologies (Wolters Kluwer Health))
David R. Janz et al. 2015
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
170. Janz DR, Bastarache JA, Rice TW, Bernard GR, Warren MA, Wickersham N, Sills G, Oates JA, Roberts LJ 2nd, Ware LB, Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis Study G (2015) Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial. Crit Care Med 43:534–541
On
page 32
Intensive Care Medicine (Springer Science and Business Media LLC)
Frédérique Schortgen et al. 2015
We reviewed the literature and identified 12 RCTs (1785 patients) that examined the effect of fever control in the critically ill population, excluding neurological indication for temperature control [160–171]; active temperature management (pharmacologic or non-pharmacologic) did not reduce the risk of death (RR 1.03, 95% CI 0.81–1.31), ICU length of stay (MD − 0.07 days, 95% CI − 0.70– 0.56), but it was effective in reducing body temperature (MD − 0.36 °C, 95% CI − 0.42 lower to − 0.29).
On page 23
171. Schortgen F, Charles-Nelson A, Bouadma L, Bizouard G, Brochard L, Katsahian S (2015) Respective impact of lowering body temperature and heart rate on mortality in septic shock: mediation analysis of a randomized trial. Intensive Care Med 41:1800–1808
On
page 32
Clinical Infectious Diseases (Oxford University Press (OUP))
Jian Wu et al. 2020
Rationale The use of intravenous immunoglobulin (IVIG) has been reported in several series of COVID-19 patients, but no efficacy data are available [172].
On page 23
172. Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, Xu W, Zhang C, Yu J, Jiang B, Cao H, Li L (2020) Clinical characteristics of imported cases of COVID-19 in Jiangsu Province: a multicenter descriptive study. Clin Inf Dis. https:// doi.org/10.1093/cid/ciaa199
On
page 32
Transfusion Medicine Reviews (Elsevier BV)
E. Richard Stiehm 2013
While IVIG may have immunomodulatory actions, its use can, rarely, also be associated with an increased risk of serious adverse events including anaphylactic reactions, aseptic meningitis, renal failure, thromboembolism, hemolytic reactions, transfusion-related lung injury, and other late reactions [173].
On page 23
However, data from recent trials on the use of antibody-based therapies (immune plasma, hyperimmune globulin, monoclonal antibody to hemagglutinin stalk)[173] in hospitalized seasonal influenza patients did not demonstrate improvement in outcomes [174–176].
On page 23
173. Stiehm ER (2013) Adverse effects of human immunoglobulin therapy. Transfus Med Rev 27:171–178
On
page 32
The Lancet Respiratory Medicine (Elsevier BV)
Richard T Davey et al. 2019
Smith K, Hoover M, Coyle EM, Munroe D, Aagaard B, Pearson M, Cursley A, Webb H, Hudson F, Russell C, Sy A, Purvis C, Jackson B, Collaco- Moraes Y, Carey D, Robson R, Sánchez A, Finley E, Conwell D, Losso MH, Gambardella L, Abela C, Lopez P, Alonso H, Touloumi G, Gioukari V, Anagnostou O, Avihingsanon A, Pussadee K, Ubolyam S, Omotosho B, Solórzano C, Petersen T, Vysyaraju K, Rizza SA, Whitaker JA, Nahra R, Baxter J, Coburn P, Gardner EM, Scott JA, Faber L, Pastor E, Makohon L, MacArthur RA, Hillman LM, Farrough MJ, Polenakovik HM, Clark LA, Colon RJ, Kunisaki KM, DeConcini M, Johnson SA, Wolfe CR, Mkumba L, Carbonneau JY, Morris A, Fitzpatrick ME, Kessinger CJ, Salata RA, Arters KA, Tasi CM, Panos RJ, Lach LA, Glesby MJ, Ham KA, Hughes VG, Schooley RT, Crouch D, Muttera L, Novak RM, Bleasdale SC, Zuckerman AE, Manosuthi W, Thaonyen S, Chiewcharn T, Suwanpimolkul G, Gatechumpol S, Bunpasang S, Angus BJ, Anderson M, Morgan M, Minton J, Gkamaletsou MN, Hambleton J, Price DA, Llewelyn MJ, Sweetman J, Carbone J, Arribas JR, Montejano R, Lobo Beristain JL, Martinez IZ, Barberan J, Hernandez P, Dwyer DE, Kok J, Borges A, Brandt CT, Knudsen LS, Sypsas N, Constantinou C, Markogiannakis A, Zakynthinos S, Katsaounou P, Kalomenidis I, Mykietiuk A, Alzogaray MF, Obed M, Macias LM, Ebensrtejin J, Burgoa P, Nannini E, Lahitte M, Perez-Patrigeon S, Martínez-Orozco JA, Ramírez-Hinojosa JP (2019) Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial. Lancet Respir Med 7:951–963
On
page 33
Antiviral Research (Elsevier BV)
John H. Beigel et al. 2019
However, data from recent trials on the use of antibody-based therapies (immune plasma, hyperimmune globulin, monoclonal antibody to hemagglutinin stalk)[173] in hospitalized seasonal influenza patients did not demonstrate improvement in outcomes [174–176].
On page 23
175. Beigel JH, Nam HH, Adams PL, Krafft A, Ince WL, El-Kamary SS, Sims AC (2019) Advances in respiratory virus therapeutics: a meeting report from the 6th isirv antiviral group conference. Antiviral Res 167:45–67
On
page 33
Intensive Care Medicine (Springer Science and Business Media LLC)
Yaseen M. Arabi et al. 2020
However, data from recent trials on the use of antibody-based therapies (immune plasma, hyperimmune globulin, monoclonal antibody to hemagglutinin stalk)[173] in hospitalized seasonal influenza patients did not demonstrate improvement in outcomes [174–176].
On page 23
176. Arabi YM, Fowler R, Hayden FG (2020) Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med 46:315–328
On
page 33
Journal of Clinical Investigation (American Society for Clinical Investigation)
Arturo Casadevall et al. 2020
Rationale Convalescent plasma obtained from patients who have recovered from COVID-19 has been suggested as a potential therapy that may provide passive immunity from SARS-CoV2-specific antibodies [177].
On page 24
177. Casadevall A, Pirofski L-a (2020) The convalescent sera option for containing COVID-19. J Clin Investig. https://doi.org/10.1172/JCI138003
On
page 33
Convalescent plasma has been used to treat several other viral infections, including those caused by SARS coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178–182].
On page 24
178. Hung IF, To KK, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CC, Liu SH, Chan KH, Lin CK, Yuen KY (2013) Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest 144:464–473
On
page 33
PLoS Medicine (Public Library of Science (PLoS))
Lauren J Stockman et al. 2006
Convalescent plasma has been used to treat several other viral infections, including those caused by SARS coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178–182].
On page 24
Rationale Recombinant interferon, often combined with ribavirin therapy, has been used in patients with MERS and SARS [179, 200–202].
On page 25
179. Stockman LJ, Bellamy R, Garner P (2006) SARS: systematic review of treatment effects. PLoS Med 3:e343
On
page 33
Clinical Infectious Diseases (Oxford University Press (OUP))
I. F. Hung et al. 2011
Convalescent plasma has been used to treat several other viral infections, including those caused by SARS coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178–182].
On page 24
180. Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY (2011) Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Inf Dis 52:447–456
On
page 33
Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?
Annals of Internal Medicine (American College of Physicians)
Thomas C. Luke et al. 2006
Convalescent plasma has been used to treat several other viral infections, including those caused by SARS coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178–182].
On page 24
181. Luke TC, Kilbane EM, Jackson JL, Hoffman SL (2006) Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 145:599–609
On
page 33
Journal of Infectious Diseases (Oxford University Press (OUP))
John Mair-Jenkins et al. 2015
A recent meta-analysis of observational studies using passive immunotherapy for the treatment of severe acute respiratory infections of viral etiology suggests that convalescent plasma therapy was associated with reduction in mortality (OR 0.25, 95% CI 0.14–0.45) [183].
On page 24
183. Mair-Jenkins J, Saavedra-Campos M, Baillie K, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR (2014) The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral aetiology: a systematic review and exploratory meta-analysis. J Infect Dis 211:80–90
On
page 33
Emerging Infectious Diseases (Centers for Disease Control and Prevention (CDC))
Yaseen M. Arabi et al. 2016
A study on MERS concluded that use of convalescent plasma might be feasible but was challenging due to a small pool of potential donors with sufficiently high antibody titers [185].
On page 24
185. Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al- Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M (2016) Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia. Emerg Infect Dis 22:1554–1561
On
page 33
New England Journal of Medicine (Massachusetts Medical Society)
Johan van Griensven et al. 2016
An RCT in patients with confirmed Ebola virus disease showed that convalescent plasma, with unknown levels of neutralizing antibodies, was not associated with improvement in survival [186].
On page 24
186. van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, Lomas C, Faye O, Sall AA, Fransen K, Buyze J, Ravinetto R, Tiberghien P, Claeys Y, De Crop M, Lynen L, Bah EI, Smith PG, Delamou A, De Weggheleire A, Haba N, Ebola-Tx C (2016) Evaluation of convalescent plasma for ebola virus disease in Guinea. N Engl J Med 374:33–42
On
page 33
The Lancet Respiratory Medicine (Elsevier BV)
John H Beigel et al. 2019
Another RCT in patients with seasonal influenza treated with high-titer versus low-titer anti-influenza immune plasma was terminated for futility because of the lack of effect on the primary outcome measured by a 6-point ordinal scale of clinical status on Day 7 [187].
On page 24
187. Beigel JH, Aga E, Elie-Turenne M-C, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, Holley HP Jr, Warner S, Chorley C, Lane HC, Hughes MD, Davey RT Jr, Beigel JH, Aga E, Elie-Turenne M-C, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, Holley HP Jr, Warner S, Chorley C, Lane HC, Hughes MD, Davey RT, Barron M, Bastani A, Bauer P, Borkowsky W, Cairns C, Deville J, Elie M-C, Fichtenbaum C, Finberg R, Jain M, Kaufman D, Lin M, Lin J, Maves R, Morrow L, Nguyen M-H, Park P, Polk C, Randolph A, Rao S, Rubinson L, Schofield C, Shoham S, Stalets E, Stapleton RD (2019) Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial. Lancet Respir Med. https://doi. org/10.1016/s2213-2600(19)30199-7
On
page 33
Thorax (BMJ)
C M Chu 2004
Because it was found to show in vitro activity against SARS-CoV, lopinavir/ritonavir was administered, in combination with high-dose oral ribavirin and a tapering course of systemic corticosteroids, in a cohort of 41 patients with SARS, and was found to be associated with significantly fewer adverse clinical outcomes (ARDS or death) compared with ribavirin alone used in 111 historical controls that received ribavirin and corticosteroids [189].
On page 24
189. Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, Kao RY, Poon LL, Wong CL, Guan Y, Peiris JS, Yuen KY, Group HUSS (2004) Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 59:252–256
On
page 33
Antimicrobial Agents and Chemotherapy (American Society for Microbiology)
Adriaan H. de Wilde et al. 2014
In a high-throughput screening for antiviral compounds, lopinavir inhibited replication of MERS-CoV in vitro [190].
On page 24
190. de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ (2014) Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 58:4875–4884
On
page 33
Journal of Infectious Diseases (Oxford University Press (OUP))
Jasper Fuk-Woo Chan et al. 2015
In an animal model of MERS- CoV infection, treatment with lopinavir/ritonavir or IFNβ1b was associated with virologic, histologic and clinical improvement versus placebo [191].
On page 24
191. Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, Li F, Xiao C, Gao H, Yu P, Cai JP, Chu H, Zhou J, Chen H, Qin C, Yuen KY (2015) Treatment With lopinavir/ritonavir or interferon-beta1b improves outcome of MERS- CoV infection in a nonhuman primate model of common marmoset. J Infect Dis 212:1904–1913
On
page 33
New England Journal of Medicine (Massachusetts Medical Society)
Bin Cao et al. 2020
A recent RCT compared the use of lopinavir/ritonavir to usual care in 199 hospitalized patients with COVID- 19 in China [194].
On page 24
194. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C (2020) A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. https:// doi.org/10.1056/nejmoa2001282
On
page 33
World Health Organization
It was considered the most promising drug in an informal consultation on research prioritization of candidate therapeutic agents by WHO [195].
On page 25
195. World Health Organization (2020) Informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection. Jan 24 2020. https://apps.who.int/iris/bitstream/handl e/10665/330680/WHO-HEO-RDBlueprint%28nCoV%29-2020.1-eng.pdf. Accessed 10 March 2020
On
page 33
Cell Research (Springer Science and Business Media LLC)
Manli Wang et al. 2020
Remdesivir demonstrated effective inhibition of SARS-CoV-2, MERS-CoV, and SARS-CoV in in vitro studies [196].
On page 25
Rationale Chloroquine and its metabolite, hydroxychloroquine, are antimalarial agents that have demonstrated antiviral effects on SARS-CoV and SARS-CoV-2 in vitro [196, 207, 208].
On page 25
An in vitro study showed that both nafamostat and nitazoxanide inhibited SARS-CoV-2 [196].
On page 26
196. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30:269–271
On
page 33
Proceedings of the National Academy of Sciences (Proceedings of the National Academy of Sciences)
Emmie de Wit et al. 2020
Furthermore, studies in animal models of MERS-CoV showed that it was more effective than control and superior to lopinavir/ritonavir combined with systemic IFN-β [197, 198].
On page 25
198. de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H (2020) Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Nat Acad Sci USA. https://doi.org/10.1073/pnas.1922083117
On
page 33
New England Journal of Medicine (Massachusetts Medical Society)
Sabue Mulangu et al. 2019
Although intravenous remdesivir appears to adequately tolerated, a recent RCT showed that it was less effective than several antibody therapies in Ebola virus disease [199].
On page 25
199. Mulangu S, Dodd LE, Davey RT Jr, Tshiani Mbaya O, Proschan M, Mukadi D, Lusakibanza Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC, Grais R, Diaz J, Lane HC, Muyembe-Tamfum JJ, Group TW, Sivahera B, Camara M, Kojan R, Walker R, Dighero-Kemp B, Cao H, Mukumbayi P, Mbala-Kingebeni P, Ahuka S, Albert S, Bonnett T, Crozier I, Duvenhage M, Proffitt C, Teitelbaum M, Moench T, Aboulhab J, Barrett K, Cahill K, Cone K, Eckes R, Hensley L, Herpin B, Higgs E, Ledgerwood J, Pierson J, Smolskis M, Sow Y, Tierney J, Sivapalasingam S, Holman W, Gettinger N, Vallee D, Nordwall J, Team PCS (2019) A randomized, controlled trial of ebola virus disease therapeutics. N Engl J Med 381:2293–2303
On
page 34
Nature Medicine (Springer Nature)
Darryl Falzarano et al. 2013
Rationale Recombinant interferon, often combined with ribavirin therapy, has been used in patients with MERS and SARS [179, 200–202].
On page 25
Different preparations of recombinant rIFNs (rIFN-α2a, rIFN-α2b, rIFN-β1a and rIFN-β1b) have shown activity against MERS-CoV in Vero and LLC- MK2 cells, and in a rhesus macaque model of MERS-CoV infection [200, 201, 203].
On page 25
201. Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H (2013) Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 19:1313–1317
On
page 34
Journal of General Virology (Microbiology Society)
B. J. Hart et al. 2014
Different preparations of recombinant rIFNs (rIFN-α2a, rIFN-α2b, rIFN-β1a and rIFN-β1b) have shown activity against MERS-CoV in Vero and LLC- MK2 cells, and in a rhesus macaque model of MERS-CoV infection [200, 201, 203].
On page 25
In vitro data showed that rIFN-β displayed the strongest MERS-CoV inhibition among different rIFN preparations (rIFN-α2b, rIFN-γ, rIFN-universal, and rIFN-α2a, rIFN-β), at 41 times lower than the previously reported 50% inhibitory concentration (IC50) of rIFN-α2b [203, 205].
On page 25
203. Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, Johnson RF, Olinger GG Jr, Frieman MB, Holbrook MR, Jahrling PB, Hensley L (2014) Interferon-beta and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J Gener Virol 95:571–577
On
page 34
Clinical Infectious Diseases (Oxford University Press (OUP))
Yaseen M Arabi et al. 2020
204. Arabi YM, Shalhoub S, Mandourah Y, Al-Hameed F, Al-Omari A, Al Qasim E, Jose J, Alraddadi B, Almotairi A, Al Khatib K, Abdulmomen A, Qushmaq I, Sindi AA, Mady A, Solaiman O, Al-Raddadi R, Maghrabi K, Ragab A, Al Mekhlafi GA, Balkhy HH, Al Harthy A, Kharaba A, Gramish JA, Al-Aithan AM, Al-Dawood A, Merson L, Hayden FG, Fowler R (2019) Ribavirin and interferon therapy for critically ill patients with middle east respiratory syndrome: a multicenter observational study. Clin Inf Dis 45:50. https://doi.org/10.1093/cid/ciz544
On
page 34
Journal of Infection (Elsevier BV)
Jasper F.W. Chan et al. 2013
In vitro data showed that rIFN-β displayed the strongest MERS-CoV inhibition among different rIFN preparations (rIFN-α2b, rIFN-γ, rIFN-universal, and rIFN-α2a, rIFN-β), at 41 times lower than the previously reported 50% inhibitory concentration (IC50) of rIFN-α2b [203, 205].
On page 25
205. Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY (2013) Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Inf 67:606–616
On
page 34
Clinical Infectious Diseases (Oxford University Press (OUP))
Xueting Yao et al. 2020
Rationale Chloroquine and its metabolite, hydroxychloroquine, are antimalarial agents that have demonstrated antiviral effects on SARS-CoV and SARS-CoV-2 in vitro [196, 207, 208].
On page 25
A recent study in China explored various dosing regimens of chloroquine and hydroxychloroquine using physiologicallybased pharmacokinetic models [208].
On page 25
models, a hydroxychloroquine loading dose of 400 mg twice daily followed by 200 mg twice daily for 4 days was recommended [208].
On page 26
208. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D (2020) In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Clin Infect Dis. https://doi.org/10.1093/cid/ciaa237
On
page 34
Viruses (MDPI AG)
Pierre Roques et al. 2018
In one non-human primate model of chikungunya infection, it was shown that chloroquine’s immunomodulatory effects were associated with delayed immune responses, higher levels of viral replication, and worse illness [210].
On page 25
210. Roques P, Thiberville SD, Dupuis-Maguiraga L, Lum FM, Labadie K, Martinon F, Gras G, Lebon P, Ng LFP, de Lamballerie X, Le Grand R (2018) Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection. Viruses. https://doi.org/10.3390/v10050268
On
page 34
BioScience Trends (International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA))
Jianjun Gao et al. 2020
A news briefing suggested that its use in more than 100 patients showed “that it was superior to the control in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course”, but the data have not been published yet [211].
On page 25
211. Gao J, Tian Z, Yang X (2020) Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 4:72–73
On
page 34
Annals of the Rheumatic Diseases (BMJ)
Hermine I Brunner et al. 2015
It has been approved for CRS and other inflammatory conditions related to IL-6 related inflammation, such as rheumatoid arthritis and juvenile idiopathic arthritis [214–217].
On page 26
214. Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Perez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gamir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F, Paediatric Rheumatology International Trials Organisation P, Pediatric Rheumatology Collaborative Study G (2015) Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis 74:1110–1117
On
page 34
Rheumatology (Oxford University Press (OUP))
Mark C Genovese et al. 2018
It has been approved for CRS and other inflammatory conditions related to IL-6 related inflammation, such as rheumatoid arthritis and juvenile idiopathic arthritis [214–217].
On page 26
215. Genovese MC, van Adelsberg J, Fan C, Graham NMH, van Hoogstraten H, Parrino J, Mangan EK, Spindler A, Huizinga TWJ, van der Heijde D, Investigators Es (2018) Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Rheumatology (Oxford) 57:1423–1431
On
page 34
The Lancet (Elsevier BV)
Shumpei Yokota et al. 2008
It has been approved for CRS and other inflammatory conditions related to IL-6 related inflammation, such as rheumatoid arthritis and juvenile idiopathic arthritis [214–217].
On page 26
216. Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, Iwata N, Umebayashi H, Murata T, Miyoshi M, Tomiita M, Nishimoto N, Kishimoto T (2008) Efficacy and safety of tocilizumab in patients with systemiconset juvenile idiopathic arthritis: a randomised, double-blind, placebocontrolled, withdrawal phase III trial. Lancet 371:998–1006
On
page 34
Rheumatology (Oxford University Press (OUP))
L. Campbell et al. 2011
From the rheumatoid arthritis literature, a systematic review and meta-analysis of 6 RCTs (3 with 8/mg dose and 3 with 4 mg/kg dose) showed an increased risk of adverse events compared with control treatment (OR 1.53, 95% CI 1.26–1.86), and an increased risk of infections (OR 1.30, 95% CI 1.07–1.58) [219].
On page 26
219. Campbell L, Chen C, Bhagat SS, Parker RA, Ostor AJ (2011) Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford) 50:552–562
On
page 34
The Lancet Infectious Diseases (Elsevier BV)
Jason Haffizulla et al. 2014
An RCT in patients with acute uncomplicated influenza demonstrated that the use of nitazoxanide reduced the duration of symptoms [221].
On page 26
221. Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF, Group USNICS (2014) Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a doubleblind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Inf Dis 14:609–618
On
page 34
Clinical Infectious Diseases (Oxford University Press (OUP))
Ana E Gamiño-Arroyo et al. 2019
However, in hospitalized patients with severe acute respiratory infection in Mexico, nitazoxanide was not found to be superior to placebo [222].
On page 26
222. Gamino-Arroyo AE, Guerrero ML, McCarthy S, Ramirez-Venegas A, Llamosas-Gallardo B, Galindo-Fraga A, Moreno-Espinosa S, Roldan-Aragon Y, Araujo-Melendez J, Hunsberger S, Ibarra-Gonzalez V, Martinez-Lopez J, Garcia-Andrade LA, Kapushoc H, Holley HP Jr, Smolskis MC, Ruiz- Palacios GM, Beigel JH, Mexico Emerging Infectious Diseases Clinical Research N (2019) Efficacy and safety of nitazoxanide in addition to standard of care for the treatment of severe acute respiratory illness. Clin Inf Dis 69:1903–1911
On
page 34