The optimal management of the patient with COVID‐19 pneumonia: HFNC, NIV/CPAP or mechanical ventilation?
Main Article Content
Abstract
The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID‐19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient.
This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes.
On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet‐CPAP (continuous positive airway pressure) (although not widely available) may be superior to high‐flow nasal cannula (HFNC) therapy or facemask non‐invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces.
In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.
Downloads
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
How to Cite
References
Gorman E, Connolly B, Couper K, et al. Non‐invasive respiratory support strategies in COVID‐19. Lancet Respir Med 2021;9:553‐556. https://doi.org/10.1016/s2213‐ 2600(21)00168‐5
Papoutsi E, Giannakoulis VG, Xourgia E, et al. Effect of timing of intubation on clinical outcomes of critically ill patients with COVID‐19: A systematic review and meta‐analysis of non‐randomised cohort studies. Crit Care 2021;25(1):121. https:// doi.org/10.1186/s13054‐021‐03540‐6
Cammarota G, Esposito T, Azzolina D, et al. Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus‐19 disease: A systematic review and meta‐analysis. Crit Care 2021;25(1):268. https://doi. org/10.1186/s13054‐021‐03697‐0
Sen‐Crowe B, McKenney M, Elkbuli A. Disparities in global COVID‐19 vaccination rates & allocation of resources to countries in need. Ann Med Surg 2021;68:102620.
Biccard BM, Gopalan PD, Miller M, et al. Patient care and clinical outcomes for patients with COVID‐19 infection admitted to African high‐care or intensive care units (ACCCOS): A multicentre, prospective, observational cohort study. Lancet
;397:1885‐1894. https://doi.org/10.1016/s0140‐6736(21)00441‐4
Sim MA, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated.
Anaesthesia 2008;63(9):938‐940. https://doi.org/10.1111/j.1365‐2044.2008.05536.x
Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high‐flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intens Care 2011;39(6):1103‐1110. https://doi.
org/10.1177/0310057x1103900620
Wagstaff TA, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia 2007;62(5):492‐503. https://doi.org/10.1111/j.1365‐ 2044.2007.05026.x
Miller T, Saberi B, Saberi S. Computational fluid dynamics modeling of extrathoracic airway flush: Evaluation of high flow nasal cannula design elements. J Pulm Respir Med 2016;6(5):376.
Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle. Respir Care 2013;58(10):1621‐1624. https://doi. org/10.4187/respcare.02358
Nishimura M. High‐flow nasal cannula oxygen therapy devices. Respir Care 2019;20:64(6):735‐742. http://rc.rcjournal.com/lookup/doi/10.4187/respcare.06718
Arabi YM, Murthy S, Webb S. COVID‐19: A novel coronavirus and a novel challenge
for critical care. Intensive Care Med 2020;46(5):833‐866. https://doi.org/10.1007/
s00134‐020‐05955‐1
Calligaro GL, Lalla U, Audley G, et al. The utility of high‐flow nasal oxygen for severe COVID‐19 pneumonia in a resource‐constrained setting: A multi‐centre prospective observational study. E Clin Med 2020;28:100570. https://doi.org/10.1016/j. eclinm.2020.100570
Lewis SR, Baker PE, Parker R, Smith AF. High‐flow nasal cannulae for respiratory support in adult intensive care patients. Cochrane Database Syst Rev 2021;2021(3). 15. Ferreyro BL, Angriman F, Munshi L, et al. Association of noninvasive oxygenation
strategies with all‐cause mortality in adults with acute hypoxemic respiratory failure.
JAMA 2020;324(1):57. https://doi.org/10.1001/jama.2020.9524
DemouleA,VieillardBaronA,DarmonM,etal.High‐flownasalcannulaincritically ill patients with severe COVID‐19. Am J Respir Crit Care Med 2020;202(7):1039‐
https://doi.org/10.1164/rccm.202005‐2007le
Perkins GD, Ji C, Connolly BA, et al. Effect of noninvasive respiratory strategies on
intubation or mortality among patients with acute hypoxemic respiratory failure and COVID‐19: The RECOVERY‐RS randomised clinical trial. JAMA. Published online 24 January 2022.
Ospina‐Tascón GA, Calderón‐Tapia LE, García AF, et al. Effect of high‐flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID‐19: A randomised clinical trial. JAMA 2021;326(21):2161‐2171. https://doi.org/10.1001%2Fjama.2021.20714
Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS‐CoV‐2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020;323(16):1574‐1581. https://doi.org/10.1001/jama.2020.5394
Ehrmann S, Li J, Ibarra‐Estrada M, et al. Awake prone positioning for COVID‐19 acute hypoxaemic respiratory failure: A randomised, controlled, multinational, open‐ label meta‐trial. Lancet Respir Med 2021;9(12):1387‐1395. https://doi.org/10.1016/ S2213‐2600(21)00356‐8
Dogani B, Månsson F, Resman F, Hartman H, Tham J, Torisson G. The application of an oxygen mask, without supplemental oxygen, improved oxygenation in patients with severe COVID‐19 already treated with high‐flow nasal cannula. Crit Care 2021;25(1):319. https://doi.org/10.1186/s13054‐021‐03738‐8
Roca O, Caralt B, Messika J, et al. An index combining respiratory rate and oxygenation to predict outcome of nasal high‐flow therapy. Am J Respir Crit Care Med 2019;199(11):1368‐1376. https://doi.org/10.1164/rccm.201803‐0589oc
Zucman N, Mullaert J, Roux D, Roca O, Ricard JD. Prediction of outcome of nasal high flow use during COVID‐19‐related acute hypoxemic respiratory failure. Intensive Care Med 2020;46(10):1924‐1926. https://doi.org/10.1007/s00134‐020‐06177‐1
Crooks CJ, West J, Morling JR, et al. Pulse oximeters’ measurements vary across ethnic groups: An observational study in patients with Covid‐19 infection. Eur Respir J 2022; in press. https://doi.org/10.1183/13993003.03246‐2021
Hui DS, Chow BK, Lo T. Exhaled air dispersion during high‐flow nasal cannula therapy versus CPAP via different masks. Eur Respir J 2019;53(4):1802339. https:// doi.org/10.1183/13993003.02339‐2018
Li J, Fink JB, Ehrmann S. High‐flow nasal cannula for COVID‐19 patients: Low risk of bio‐aerosol dispersion. Eur Respir J 2020;55(5):2000892. https://doi.org/10.1183 %2F13993003.00892‐2020
Oranger M, Gonzalez‐Bermejo J, Dacosta‐Noble P, et al. Continuous positive airway pressure to avoid intubation in SARS‐CoV‐2 pneumonia: A two‐period retrospective case‐control study. Eur Respir J 2020;56(2):2001692. https://doi. org/10.1183/13993003.01692‐2020
Avdeev SN, Yaroshetskiy AI, Tsareva NA, et al. Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID‐19. Am J Emerg Med 2021;39:154‐157. https://doi.org/10.1016/j.ajem.2020.09.075
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(5). https://doi.org/10.1183/13993003.02130‐2020
Aliberti S, Radovanovic D, Billi F, et al. Helmet CPAP treatment in patients with COVID‐19 pneumonia: A multicentre cohort study. Eur Respir J 2020;56(4):2001935. https://doi.org/10.1183/13993003.01935‐2020
Raoof S, Nava S, Carpati C, Hill NS. High‐flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest 2020;158(5):1992‐2002. https://doi.org/10.1016/j.chest.2020.07.013
Rochwerg B, Brochard L, Elliott MW, et al. Official ERS/ATS clinical practice guidelines: Noninvasive ventilation for acute respiratory failure. Eur Respir J 2017;50(2):1602426. https://doi.org/10.1183/13993003.02426‐2016
Windisch W, Weber‐Carstens S, Kluge S, Rossaint R, Welte T, Karagiannidis C. Invasive und nichtinvasive beatmung bei COVID‐19‐patienten. Dtsch Arztebl Int 2020;117(31‐32):528‐533. https://doi.org/10.1007%2Fs15033‐021‐2711‐2
Wang Z, Wang YYY, Yang Z, et al. The use of non‐invasive ventilation in COVID‐19: A systematic review. Int J Infect Dis 2021;106:254‐261. https://doi.org/10.1016/j. ijid.2021.03.078
Azoulay E, De Waele J, Ferrer R, et al. International variation in the management of severe COVID‐19 patients. Crit Care 2020;24(1):1‐7. https://doi.org/10.1186/s13054‐020‐03194‐w
Grieco DL, Menga LS, Cesarano M, et al. 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 randomised clinical trial. JAMA 2021;325(17):1731‐1743. https://doi.org/10.1001/ jama.2021.4682
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalised with COVID‐19 in the New York City Area. JAMA 2020;323(20):2052. https://doi.org/10.1001/ jama.2020.6775
Lalla U, Allwood BW, Louw EH, et al. The utility of high‐flow nasal cannula oxygen therapy in the management of respiratory failure secondary to COVID‐19 pneumonia. S Afr Med J 2020;110(6):432.
Bellani G, Grasselli G, Cecconi M, et al. Noninvasive ventilatory support of patients with COVID‐19 outside the intensive care units (WARd‐COVID). Ann Am Thorac Soc 2021;18(6):1020‐1026. https://doi.org/10.1513/annalsats.202008‐1080oc
Battaglini D, Robba C, Ball L, et al. Noninvasive respiratory support and patient self‐ inflicted lung injury in COVID‐19: A narrative review. Br J Anaesth 2021;127(3):353‐ 364. https://doi.org/10.1016/j.bja.2021.05.024
Menga LS, Berardi C, Ruggiero E. Noninvasive respiratory support for acute respiratory failure. Curr Opin Crit Care 2022;28(1):25‐50. https://doi.org/10.1097/ mcc.0000000000000902
Carteaux G, Millán‐Guilarte T, De Prost N, et al. Failure of noninvasive ventilation for de novo acute hypoxemic respiratory failure: Role of tidal volume. Crit Care Med 2016;44(2):282‐290. https://doi.org/10.1097/ccm.0000000000001379
Yoshida T, Grieco DL, Brochard L, Fujino Y. Patient self‐inflicted lung injury and positive end‐expiratory pressure for safe spontaneous breathing. Curr Opin Crit Care 2020;26(1):59‐65. https://doi.org/10.1097/mcc.0000000000000691
Grieco DL, Menga LS, Raggi V, et al. Physiological comparison of high‐flow nasal cannula and helmet noninvasive ventilation in acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2020;201(3):303‐312. https://doi.org/10.1164/ rccm.201904‐0841oc
Hui DS, Chow BK, Lo T, et al. Exhaled air dispersion during noninvasive ventilation via helmets and a total facemask. Chest 2015;147(5):1336‐1343. https://doi. org/10.1378/chest.14‐1934
Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: A randomised clinical trial. JAMA 2016;315(22):2435‐2441. https://doi.org/10.1001/jama.2016.6338
Kyeremanteng K, Gagnon LP, Robidoux R, et al. Cost analysis of noninvasive helmet ventilation compared with use of noninvasive face mask in ARDS. Can Respir J 2018;2018:6518572. https://doi.org/10.1155/2018/6518572
Berbenetz N, Wang Y, Brown J, et al. Non‐invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev 2019;4. https://doi.org/10.1002/14651858.cd005351.pub4
Osadnik CR, Tee VS, Carson‐Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non‐ invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2017;7. https://doi.org/10.1002/14651858.cd004104.pub4
Xu X‐P, Zhang X‐C, Hu S‐L, et al. Noninvasive ventilation in acute hypoxemic nonhypercapnic respiratory failure: A systematic review and meta‐analysis. Crit Care Med 2017;45(7):e727‐e733. https://doi.org/10.1097/ccm.0000000000002361
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(3):204‐216. https://doi.org/10.7326/m20‐2306
Rochwerg B, Solo K, Darzi A, et al. Update alert: Ventilation techniques and risk for transmission of coronavirus disease, including COVID‐19. Ann Intern Med 2020;173(6):W122. https://doi.org/10.7326/l20‐0944
Thomas R, Lotfi T, Morgano GP, Darzi A, Reinap M, COVID‐19 systematic urgent review group effort (SURGE) study authors. Update alert 2: Ventilation techniques and risk for transmission of coronavirus disease, including COVID‐19. Ann Intern Med 2020;173(11):W152‐W153. https://doi.org/10.7326%2FL20‐1211
Attaway AH, Scheraga RG, Bhimraj A, Biehl M, Hatipoğlu U. Severe covid‐19 pneumonia: Pathogenesis and clinical management. BMJ 2021;372:n436. https:// doi.org/10.1136/bmj.n436
Grieco DL, Menga LS, Eleuteri D, Antonelli M. Patient self‐inflicted lung injury: Implications for acute hypoxemic respiratory failure and ARDS patients on non‐invasive support. Minerva Anestesiol 2019;85(9):1014‐1023. https://doi. org/10.23736/s0375‐9393.19.13418‐9
Duan J, Han X, Bai L, Zhou L, Huang S. Assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients. Intensive Care Med 2017;43(2):192‐199. https://doi. org/10.1007/s00134‐016‐4601‐3
Guia M, Boleo‐Tome J, Imitazione P, et al. Usefulness of the HACOR score in predicting success of CPAP in COVID‐19‐related hypoxemia. Respir Med 2021;187:106550. https://doi.org/10.1016/j.rmed.2021.106550
International Consensus Conferences in Intensive Care Medicine: Noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001;163(1):283‐291. https://doi.org/10.1164/ajrccm.163.1.ats1000
Carron M, Freo U, BaHammam AS, et al. Complications of non invasive ventilation techniques: A comprehensive qualitative review of randomised trials. Br J Anaesth 2013;110(6):896‐914. https://doi.org/10.1093/bja/aet070
Lie J, Ehrmann S. High‐flow aerosol‐dispersing versus aerosol‐generating procedures. Am J Respir Crit Care Med 2020;202(8):1069‐1071. https://doi. org/10.1164%2Frccm.202008‐3317ED
Wu X, Li Z, Cao J, et al. The association between major complications of immobility during hospitalisation and quality of life among bedridden patients: A 3 month prospective multi‐center study. PLOS ONE 2018;13(10):e0205729. https://doi. org/10.1371/journal.pone.0205729
Gattinoni L, Chiumello D, Caironi P, et al. COVID‐19 pneumonia: Different respiratory treatments for different phenotypes? Intensive Care Med 2020;46(6):1099‐ 1102. https://doi.org/10.1007/s00134‐020‐06033‐2
Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. 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 2000;342(18):1301‐1308. https://doi.org/10.1056/nejm200005043421801
Lieuwe D, Martin‐Loeches BI, Schultz MJ. ARDS: Challenges in patient care and frontiers in research, Eur Respir Rev 2018;27(147):170107. https://doi. org/10.1183/16000617.0107‐2017
Arnold‐Day C, Zyl‐Smit R, Joubert I, et al. Outcomes of patients with COVID‐19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa. S Afr Med J 2022;112(1):13516. https://doi.org/10.21203/rs.3.rs‐603988/v1
Brochard L, Slutsky A, Pesenti A. Mechanical ventilation to minimise progression of lung injury in acute respiratory failure. Am J Respir Crit Care Med 2017;195(4):438‐ 442. https://doi.org/10.1164/rccm.201605‐1081CP
Matta A. Timing of intubation and its implications on outcomes in critically ill patients with coronavirus disease 2019 infection. Crit Care Explor 2020;2(10):e0262. 68. European Society of Intensive Care Medicine. https://academy.esicm.org/mod/ emodulepage/view.php?id=7939 (accessed 4 November 2021). At the time of publishing the present article, the cited course was not accessible or available. Please
contact ESICM for further information.
Cavalcanti AB, Suzumura EA, Laranjeira LN, et al. End‐expiratory pressure (PEEP)
vs low PEEP on mortality in patients with acute respiratory distress syndrome: A randomised clinical trial. JAMA 2017;318(14):1335‐1345. https://doi.org/10.1001/ jama.2017.14171
Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015;372(8):747‐755. https://doi. org/10.1056/NEJMsa1410639. PMID: 25693014
Andrews PL, Shiber JR, Jaruga‐Killeen E, et al. Early application of airway pressure release ventilation may reduce mortality in high‐risk trauma patients: A systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg 2013;75(4):635‐641. https://doi.org/10.1097/TA.0b013e31829d3504. PMID: 24064877
RoyS,HabashiN,SadowitzB,etal.Earlyairwaypressurereleaseventilationprevents ARDS ‐ a novel preventive approach to lung injury. Shock 2013;39(1):28‐38. https:// doi.org/10.1097/SHK.0b013e31827b47bb
Zhou Y, Jin X, Lv Y, et al. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med 2017;43(11):1648‐1659. https://doi.org/10.1007/ s00134‐017‐4912‐z
Habashi NM. Other approaches to open‐lung ventilation: Airway pressure release ventilation. Crit Care Med 2005;33(3 Suppl):S228‐S240. https://doi.org/10.1097/01. ccm.0000155920.11893.37
Fredericks AS, Bunker MP, Gliga LA, et al. Airway pressure release ventilation: A review of the evidence, theoretical benefits, and alternative titration strategies. Clin Med Insights Circ Respir Pulm Med 2020;14:1179548420903297. https//doi. org/10.1177/1179548420903297
Swindin J, Sampson C, Howatson A. Airway pressure release ventilation. BJA Educ 2020;20(3):80‐88. https://doi.org/10.1016/j.bjae.2019.12.001
Simmons RS, Berdine GG, Seidenfeld JJ, et al. Fluid balance and the adult respiratory distress syndrome. Am Rev Respir Dis 1987;135:924‐929. https://doi.org/10.1164/ arrd.1987.135.4.924
Sakr Y, Vincent JL, Reinhart K, et al. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest 2005;128:3098‐3108. https://doi.org/10.1378/chest.128.5.3098
Van Mourik N, Metske HA, Hofstra JJ, et al. Cumulative fluid balance predicts mortality and increases time on mechanical ventilation in ARDS patients.
An observational cohort study. PLoS ONE 2019;14:e0224563. https://doi.
org/10.1371%2Fjournal.pone.0224563
Rosenberg AL, Dechert RE, Park PK, Bartlett RH, Network NIHNHLBIARDS. Review of a large clinical series: Association of cumulative fluid balance on outcome in acute lung injury: A retrospective review of the ARDSnet tidal volume cohort.
J Intensive Care Med 2009;24:35‐46. https://doi.org/10.1177/0885066608329850
National Heart, Lung, and Blood Institute acute respiratory distress syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, et al. Comparison of two fluid‐management strategies in acute lung injury. N Engl J Med 2006;354:2564‐ 2575. https://doi.org/10.1056/nejmoa062200
Bissell BD, Laine ME, Bastin MLT, et al. Impact of protocolised diuresis for deresuscitation in the intensive care unit. Critical Care 2020;24:70. https://doi. org/10.1186/s13054‐020‐2795‐9
Cinotti R, Lascarrou J‐B, Azais M‐A, et al. Diuretics decrease fluid balance in patients on invasive mechanical ventilation: The randomised‐controlled single blind, IRIHS study. Crit Care 2021;25:98. https://doi.org/10.1186/s13054‐021‐03509‐5
Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368(23):2159‐2168.
Taccone P, Pesenti A, Latini R, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: A randomised controlled trial. JAMA 2009;302(18):1977‐1984. https://doi.org/10.1001/jama.2009.1614
Gattinoni L, Taccone P, Carlesso E, Marini JJ. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Respir Crit Care Med 2013;188(11):1286‐1293. https://doi.org/10. 1164/rccm.201308‐1532CI
Gupta S, Hayek SS, Wang W, et al: Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA 2020;180:1‐12. https://doi. org/10.1001%2Fjamainternmed.2020.3596
Mathews KS, Soh H, Shaefi S, Wang W, Bose S, Coca S. Prone positioning and survival in mechanically ventilated patients with coronavirus disease 2019‐related respiratory failure. Crit Care Med 2021;49:1026‐1037. https://doi.org/10.1097/ CCM.0000000000004938
Langer T, Brioni M, Guzzardella A, et al. Prone position in intubated, mechanically ventilated patients with COVID‐19: A multi‐centric study of more than 1000 patients. Crit Care 2021;25:128. https://doi.org/10.1186/s13054‐021‐03552‐2
Scaramuzzo G, Gamberini L, Tonetti T, et al. Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID‐19 patients: A cohort study. Ann Intensive Care 2021;11(1):63. https://doi.org/10.1186/s13613‐021‐00853‐1
Lee HY, Cho J, Kwak N, et al. Improved oxygenation after prone positioning may be a predictor of survival in patients with acute respiratory distress syndrome. Crit Care
Med 2020;48(12):1729‐1736.
Papazian L, Forel J‐M, Gacouin A, et al., for the ACURASYS Study Investigators.
Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med
;363:1107‐1116. https://doi.org/10.1056/nejmoa1005372
The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early
neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med
;380:1997‐2008. https://doi.org/10.1056/NEJMoa1901686
Ho ATN, Patolia S, Guervilly C. Neuromuscular blockade in acute respiratory distress
syndrome: A systematic review and metaanalysis of randomised controlled trials.
J Intensive Care 2020;8:12. https://doi.org/10.1186/s40560‐020‐0431‐z
Capellier G, Panwar R. Is it time for permissive hypoxaemia in the intensive care unit?
Crit Care Resusc 2011;13(3):139‐141.
He H‐W, Liu DW. Permissive hypoxemia/conservative oxygenation strategy: Dr. Jekyll
or Mr. Hyde? J Thorac Dis 2016; 8(5):748‐750. https://doi.org/10.21037/jtd.2016.03.58 97. Taban E, Richards GA. Observational study of therapeutic bronchoscopy in critical hypoxaemic ventilated patients with COVID‐19 at Mediclinic Midstream Private Hospital in Pretoria, South Africa. Afr J Thoracic Crit Care Med 2020;26(4):138‐142.
https://doi.org/10.7196/AJTCCM.2020.v26i4.119
Carter C, Thi Lan Anh N, Notter J. COVID‐19 disease: Perspectives in low‐ and middle‐ income countries. Clin Integr Care 2020;1:100005. https://doi.org/10.1016%2Fj. intcar.2020.100005
Deng D, Naslund JA. Psychological impact of COVID‐19 pandemic on frontline health workers in low‐ and middle‐income countries. Harv Public Health Rev (Camb) 2020 Fall:28. http://harvardpublichealthreview.org/wp‐content/uploads/2020/10/Deng‐ and‐Naslund‐2020‐28.pdf. PMID: 33409499; PMCID: PMC7785092
Patel LN, Kozikott S, Ilboudo R, et al. Safer primary healthcare facilities are needed to protect healthcare workers and maintain essential services: Lessons learned from a multicountry COVID‐19 emergency response initiative. BMJ Global Health 2021;6:e005833. https://doi.org/10.1136/ bmjgh‐2021‐005833
Cobb N, Papali A, Pisani L, Schultz MJ, Ferreira JC; COVID‐LMIC Task Force and the Mahidol‐Oxford Research Unit (MORU). Pragmatic recommendations for infection prevention and control practices for healthcare facilities in low‐ and middle‐ income countries during the COVID‐19 Pandemic. Am J Trop Med Hyg 2021;104(3_ Suppl):25‐33. https://doi.org/10.4269/ajtmh.20‐1009. PMID: 33410392; PMCID: PMC7957238