Update Alert 3: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19
Authors: Giovanna Elsa Ute Muti-Schüenemann, Wojciech Szczeklik, Karla Solo, Joanne Khabsa, Rebecca Thomas, Ewa Borowiack, Assem M. Khamis, Layal Hneiny, Andrea Darzi, Leila Harrison, Anna Bak, Antonio Bongnanni, Gian Paolo Morgano, Rosa Stalteri, Anisa Hajizadeh, Tamara Lotfi, Marge Reinap, Bram Rochwerg, Elie A. Akl, Holger J. Schünemann
Journal: Annals of Internal Medicine (2021)

LettersJanuary 2022Update Alert 3: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19FREEGiovanna Elsa Ute Muti-Schüenemann, MD, Wojciech Szczeklik, MD, PhD, Karla Solo, MSc, Joanne Khabsa, MPH, Rebecca Thomas, MPH, MBChB, Ewa Borowiack, MSc, Assem M. Khamis, MD, Layal Hneiny, MPH, MLIS, Andrea Darzi, MD, MPH, Leila Harrison, MPH, Anna Bak, PharmD, Antonio Bongnanni, MD, Gian Paolo Morgano, MSc, Rosa Stalteri, BSHc, Anisa Hajizadeh, MPH, Tamara Lotfi, MD, MPH, Marge Reinap, MA, Bram Rochwerg, MD, MSc†, Elie A. Akl, MD, MPH, PhD†, Holger J. Schünemann, MD, PhD, MSc†Giovanna Elsa Ute Muti-Schüenemann, MDMcMaster University, Hamilton, Ontario, Canada, Wojciech Szczeklik, MD, PhDJagiellonian University Medical College, Kraków, Poland, Karla Solo, MScMcMaster University, Hamilton, Ontario, Canada, Joanne Khabsa, MPHAmerican University of Beirut Medical Center, Beirut, Lebanon, Rebecca Thomas, MPH, MBChBLiverpool School of Tropical Medicine, Liverpool, United Kingdom, Ewa Borowiack, MScEvidence Prime, Kraków, Poland, Assem M. Khamis, MDHull York Medical School, University of Hull, Heslington, York, United Kingdom, Layal Hneiny, MPH, MLISAmerican University of Beirut Medical Center, Beirut, Lebanon, Andrea Darzi, MD, MPHMcMaster University, Hamilton, Ontario, Canada, Leila Harrison, MPHMcMaster University, Hamilton, Ontario, Canada, Anna Bak, PharmDEvidence Prime, Kraków, Poland, Antonio Bongnanni, MDMcMaster University, Milan, Italy, Gian Paolo Morgano, MScMcMaster University, Hamilton, Ontario, Canada, Rosa Stalteri, BSHcMcMaster University, Hamilton, Ontario, Canada, Anisa Hajizadeh, MPHMcMaster University, Hamilton, Ontario, Canada, Tamara Lotfi, MD, MPHMcMaster University, Hamilton, Ontario, Canada, Marge Reinap, MALondon School of Hygiene and Tropical Medicine, London United Kingdom, Bram Rochwerg, MD, MSc†McMaster University, Hamilton, Ontario, Canada, Elie A. Akl, MD, MPH, PhD†American University of Beirut, Beirut, Lebanon, Holger J. Schünemann, MD, PhD, MSc†McMaster University, Hamilton, Ontario, CanadaAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0424 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This is the third update of the living systematic review addressing ventilation techniques and risk for transmission of COVID-19 (1). We previously found that noninvasive ventilation (NIV) may have similar effects to invasive mechanical ventilation (IMV) on mortality in patients with COVID-19 and acute hypoxemic respiratory failure and that high-flow oxygen by nasal cannula (HFNC) may reduce mortality compared with no HFNC. In this update, which encompassed handsearching the bibliographies and searching ClinicalTrials.gov, we included only comparative studies published between 11 July 2020, the search date of our second update, and 21 June 2021.Supplement Figure 1 displays the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flow diagram for living systematic reviews (2). We included 10 new COVID-19 observational studies addressing NIV (3–12) and 1 randomized controlled trial comparing HFNC with no HFNC (13) (Supplement Tables 1 and 2). Most observational studies failed to provide adjusted effect estimates for the outcomes of interest.For continuous positive airway pressure (CPAP) versus oxygen alone, there was 1 new study with only 10 participants (4) that did not alter the conclusions for this comparison that CPAP may reduce mortality but that the effect is very uncertain (Supplement Table 2). This latter study and 1 new study by Khalil and colleagues (8) also added very little evidence to the comparison of CPAP with IMV, suggesting similar effects on mortality with these methods, with very low-certainty evidence. Three studies (4, 9, 10) provided new information about the comparison of CPAP with HFNC without a clear difference in the effects, although the study by Franco and colleagues (10) showed higher unadjusted mortality in patients receiving CPAP. For CPAP compared with other NIV, we saw no clear difference in unadjusted effects on mortality in 2 studies (8, 10) and no clear difference on the need for IMV or length of hospital stay. For HFNC versus oxygen alone, only 1 new study was identified, but it contributed no events, and there is still too little data to identify an effect in favor of one or the methods (4). Since our last update, 2 new studies compared HFNC with other NIV (10, 13), and the only adjusted estimate for any of the critical outcomes suggested an increase in need for IMV with HFNC compared with other NIV (13). Two new studies (4, 12) compared HFNC with IMV, but there were no adjusted estimates that would allow for strong conclusions to be made. The better outcomes with HFNC in the study by Patel and colleagues (12) may be due to more favorable baseline characteristics in the group of patients receiving HFNC.For the comparison of NIV versus IMV, there are now a total of 13 studies, of which 6 were added since our last update (3, 5, 6, 8, 11, 14). A total of 4 studies in this living systematic review provided adjusted effect estimates for mortality (11, 14–16), with a pooled hazard ratio of 0.74 (95% CI, 0.46 to 1.18), but in the presence of high, unexplained heterogeneity (very low certainty of evidence) (Supplement Table 3 and Supplement Figure 2). The largest study by Grasselli and colleagues (14) of critically ill patients (n = 3988, Pao2 ranging from <76 to >127 mm Hg), found that NIV may have similar effects to IMV on mortality (hazard ratio, 0.81 [CI, 0.65 to 1]; high risk of bias). This study also contributed information to the new evidence base of 4 cohort studies comparing NIV with supplemental oxygen alone (3, 5, 11, 14). The adjusted estimates from the 2 studies reporting an effect estimate suggested no clear difference in mortality (hazard ratio, 1.07 [CI, 0.34 to 3.34]; very low-certainty evidence) (Supplement Table 4 and Supplement Figure 3).The included randomized controlled trial comparing NIV delivered via helmet interface with the use of HFNC in 109 patients with moderate to severe hypoxemia due to COVID-19 (Pao2–FIo2 ≤200 mm Hg) suggested no difference between the groups in mortality (24% for helmet NIV vs. 25% for HFNC) or days free of respirator support at 28 days (20 days [interquartile range {IQR}, 0 to 25 days] for helmet NIV vs. 18 days [IQR, 0 to 22 days] for HFNC), with a lower intubation rate in those receiving HFNC (30% vs. 51%; difference, −21 percentage points [CI, −38 to −3 percentage points]) (13). Furthermore, patients receiving helmet NIV had a higher number of IMV-free days at 28 days than those in the HFNC group (28 days [IQR, 13 to 28 days] vs. 25 days [IQR, 4 to 28 days]; P = 0.04). Nonetheless, the trial had few events and participants and was at high risk of bias because of imbalances of baseline covariates and crossover.In conclusion, this new evidence does not change our initial conclusions that NIV may have at least similar effects as IMV, and HFNC may reduce mortality. The low-certainty evidence suggests the need for high-quality studies. In addition, we have identified at least 6 ongoing trials on NIV (HiFlo-COVID [High-Flow Nasal Cannula in Severe COVID-19 With Acute Hypoxemic Respiratory Failure], COVID-NIV [Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome], Helmet-COVID [Helmet Non-Invasive Ventilation for COVID-19 Patients], PAP-COVID [Early CPAP in COVID-19 Confirmed or Suspected Patients], COVID HELMET [Helmet CPAP Versus HFNC in COVID-19], and COVID-HIGH [HFNT vs. COT in COVID-19]), which are registered, and their results should be monitored because they will build on the current evidence. Future reviews should focus on these randomized controlled trials to provide conclusions with more certainty. As originally reported, we will retire this living review after 1 year because of lack of dedicated funding for this work.References1. Schünemann HJ, Khabsa J, Solo K, et al. Ventilation techniques and risk for transmission of coronavirus disease, including COVID-19. A living systematic review of multiple streams of evidence. Ann Intern Med. 2020;173:204-216. [PMID: 32442035] doi:10.7326/M20-2306 LinkGoogle Scholar2. Kahale LA, Elkhoury R, El Mikati I, et al. Tailored PRISMA 2020 flow diagrams for living systematic reviews: a methodological survey and a proposal [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research. 2021;10:192. doi:10.12688/f1000research.51723.2 Google Scholar3. Gundem T, Olasveengen TM, Hovda KE, et al. Ventilatory support for hypoxaemic intensive care patients with COVID-19. Tidsskr Nor Laegeforen. 2020;140. [PMID: 32815344] doi:10.4045/tidsskr.20.0445 CrossrefMedlineGoogle Scholar4. Kanthimathinathan HK, Dhesi A, Hartshorn S, et al. COVID-19: a UK children's hospital experience. Hosp Pediatr. 2020;10:802-805. [PMID: 32518091] doi:10.1542/hpeds.2020-000208 CrossrefMedlineGoogle Scholar5. Mukhtar A, Lotfy A, Hasanin A, et al. Outcome of non-invasive ventilation in COVID-19 critically ill patients: a retrospective observational study [Letter]. Anaesth Crit Care Pain Med. 2020;39:579-580. [PMID: 32736030] doi:10.1016/j.accpm.2020.07.012 CrossrefMedlineGoogle Scholar6. Sivaloganathan AA, Nasim-Mohi M, Brown MM, et al; University Hospital Southampton Critical Care and Respiratory Medicine Teams and the REACT investigators. Noninvasive ventilation for COVID-19-associated acute hypoxaemic respiratory failure: experience from a single centre [Letter]. Br J Anaesth. 2020;125:e368-e371. [PMID: 32811662] doi:10.1016/j.bja.2020.07.008 CrossrefMedlineGoogle Scholar7. Zheng Y, Sun LJ, Xu M, et al. Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou, China. J Zhejiang Univ Sci B. 2020;21:378-387. [PMID: 32425003] doi:10.1631/jzus.B2000174 CrossrefMedlineGoogle Scholar8. Khalil K, Agbontaen K, McNally D, et al. Clinical characteristics and 28-day mortality of medical patients admitted with COVID-19 to a central London teaching hospital [Letter]. J Infect. 2020;81:e85-e89. [PMID: 32562795] doi:10.1016/j.jinf.2020.06.027 CrossrefMedlineGoogle Scholar9. Duan J, Chen B, Liu X, et al. Use of high-flow nasal cannula and noninvasive ventilation in patients with COVID-19: a multicenter observational study. Am J Emerg Med. 2021;46:276-281. [PMID: 33046296] doi:10.1016/j.ajem.2020.07.071 CrossrefMedlineGoogle Scholar10. Franco C, Facciolongo N, Tonelli R, et al. Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia. Eur Respir J. 2020;56. [PMID: 32747398] doi:10.1183/13993003.02130-2020 CrossrefMedlineGoogle Scholar11. Potalivo A, Montomoli J, Facondini F, et al. Sixty-day mortality among 520 Italian hospitalized COVID-19 patients according to the adopted ventilatory strategy in the context of an integrated multidisciplinary clinical organization: a population-based cohort study. Clin Epidemiol. 2020;12:1421-1431. [PMID: 33408529] doi:10.2147/CLEP.S278709 CrossrefMedlineGoogle Scholar12. Patel M, Gangemi A, Marron R, et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir Res. 2020;7. [PMID: 32847947] doi:10.1136/bmjresp-2020-000650 CrossrefMedlineGoogle Scholar13. Grieco DL, Menga LS, Cesarano M, et al; COVID-ICU Gemelli Study Group. Effect of helmet noninvasive ventilation vs high-flow nasal oxygen on days free of respiratory support in patients with COVID-19 and moderate to severe hypoxemic respiratory failure: the HENIVOT randomized clinical trial. JAMA. 2021;325:1731-1743. [PMID: 33764378] doi:10.1001/jama.2021.4682 CrossrefMedlineGoogle Scholar14. Grasselli G, Greco M, Zanella A, et al; COVID-19 Lombardy ICU Network. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med. 2020;180:1345-1355. [PMID: 32667669] doi:10.1001/jamainternmed.2020.3539 CrossrefMedlineGoogle Scholar15. Wang T, Tang C, Chen R, et al. Clinical features of coronavirus disease 2019 patients with mechanical ventilation: a nationwide study in China. Crit Care Med. 2020;48:e809-e812. [PMID: 32618693] doi:10.1097/CCM.0000000000004473 CrossrefMedlineGoogle Scholar16. Wang K, Zhang Z, Yu M, et al. 15-day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: an ambispective observational cohort study [Letter]. Intensive Care Med. 2020;46:1472-1474. [PMID: 32328724] doi:10.1007/s00134-020-06047-w CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, CanadaJagiellonian University Medical College, Kraków, PolandAmerican University of Beirut Medical Center, Beirut, LebanonLiverpool School of Tropical Medicine, Liverpool, United KingdomEvidence Prime, Kraków, PolandHull York Medical School, University of Hull, Heslington, York, United KingdomEvicence Prime, Kraków, PolandMcMaster University, Milan, ItalyLondon School of Hygiene and Tropical Medicine, London United KingdomAmerican University of Beirut, Beirut, Lebanon* Joint first authors.† Senior research team.Disclaimer: The systematic review was commissioned and in part paid for by the World Health Organization. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the World Health Organization.Acknowledgment: The authors wish to thank Lara Kahale for her assistance in preparing the living PRISMA flow diagram.Financial Support: The World Health Organization partially funded the first version of this systematic review but has not been funding further updates.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0424.Corresponding Author: Holger J. Schünemann, MD, PhD, MSc, McMaster University, HSC-2C, 1280 Main Street West, Hamilton, ON L8N 3Z5, Canada (e-mail, holger.[email protected]ca).This article was published at Annals.org on 14 December 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoVentilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 Holger J. Schünemann , Joanne Khabsa , Karla Solo , Assem M. Khamis , Romina Brignardello-Petersen , Amena El-Harakeh , Andrea Darzi , Anisa Hajizadeh , Antonio Bognanni , Anna Bak , Ariel Izcovich , Carlos A. Cuello-Garcia , Chen Chen , Ewa Borowiack , Fatimah Chamseddine , Finn Schünemann , Gian Paolo Morgano , Giovanna E.U. Muti-Schünemann , Guang Chen , Hong Zhao , Ignacio Neumann , Jan Brozek , Joel Schmidt , Layal Hneiny , Leila Harrison , Marge Reinap , Mats Junek , Nancy Santesso , Rayane El-Khoury , Rebecca Thomas , Robby Nieuwlaat , Rosa Stalteri , Sally Yaacoub , Tamara Lotfi , Tejan Baldeh , Thomas Piggott , Yuan Zhang , Zahra Saad , Bram Rochwerg , Dan Perri , Eddy Fan , Florian Stehling , Imad Bou Akl , Mark Loeb , Paul Garner , Stephen Aston , Waleed Alhazzani , Wojciech Szczeklik , Derek K. Chu , and Elie A. Akl Update Alert: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 Bram Rochwerg , Karla Solo , Andrea Darzi , Guang Chen , Assem M. Khamis , and Update Alert 2: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 Rebecca Thomas , Tamara Lotfi , Gian Paolo Morgano , Andrea Darzi , Marge Reinap , and Metrics January 2022Volume 175, Issue 1Page: W6-W7 ePublished: 14 December 2021 Issue Published: January 2022 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...