Oxygenation and Ventilation
Last Updated: July 17, 2020
For hypoxemic patients, the recommendations below emphasize well-described and documented recommendations from the Surviving Sepsis Campaign Guidelines for adult sepsis, pediatric sepsis, and COVID-19, which provide more details about management and the data that support the recommendations.
- For adults with COVID-19 who are receiving supplemental oxygen, the COVID-19 Treatment Guidelines Panel (the Panel) recommends close monitoring for worsening respiratory status and that intubation, if it becomes necessary, be performed by an experienced practitioner in a controlled setting (AII).
- For adults with COVID-19 and acute hypoxemic respiratory failure despite conventional oxygen therapy, the Panel recommends high-flow nasal cannula (HFNC) oxygen over noninvasive positive pressure ventilation (NIPPV) (BI).
- In the absence of an indication for endotracheal intubation, the Panel recommends a closely monitored trial of NIPPV for adults with COVID-19 and acute hypoxemic respiratory failure for whom HFNC is not available (BIII).
- For patients with persistent hypoxemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated, the Panel recommends considering a trial of awake prone positioning to improve oxygenation (CIII).
- The Panel recommends against using awake prone positioning as a rescue therapy for refractory hypoxemia to avoid intubation in patients who otherwise require intubation and mechanical ventilation (AIII).
Hypoxemia is common in hospitalized patients with COVID-19. The criteria for hospital admission, intensive care unit (ICU) admission, and mechanical ventilation differ between countries. In some hospitals in the United States, >25% of hospitalized patients require ICU care, mostly due to acute respiratory failure.1-5
In adults with COVID-19 and acute hypoxemic respiratory failure, conventional oxygen therapy may be insufficient to meet the oxygen needs of the patient. Options include HFNC, NIPPV, or intubation and invasive mechanical ventilation.
HFNC and NIPPV are preferable to conventional oxygen therapy based on data from non-COVID-19 clinical trials and meta-analyses that showed reductions in the need for therapeutic escalation and the need for intubation in patients who received HFNC or NIPPV.6, 7
HFNC is preferred over NIPPV in patients with acute hypoxemic respiratory failure based on data from an unblinded clinical trial that was performed prior to the COVID-19 pandemic. This trial found more ventilator-free days with HFNC than with conventional oxygen therapy or NIPPV (24 days vs. 22 days vs. 19 days, respectively; P = 0.02) and lower 90-day mortality with HFNC than with either conventional oxygen therapy (hazard ratio [HR] 2.01; 95% confidence interval [CI], 1.01–3.99) or NIPPV (HR 2.50; 95% CI, 1.31–4.78).8
In the subgroup of more severely hypoxemic patients with PaO2/FiO2 ≤200, HFNC reduced the rate of intubation compared to conventional oxygen therapy or NIPPV (HRs 2.07 and 2.57, respectively). These findings were corroborated in a meta-analysis that showed a lower likelihood of intubation (odds ratio [OR] 0.48; 95% CI, 0.31–0.73) and ICU mortality (OR 0.36; 95% CI, 0.20–0.63) with HFNC than with NIPPV.9 In situations where the options for respiratory support are limited, reducing the need for intubation may be particularly important.
Prone positioning improves oxygenation and patient outcomes in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) that requires mechanical ventilation.10,11 Prone positioning is thought to improve oxygenation because it improves ventilation-perfusion matching and recruits collapsed alveoli in the dorsal lungs.12 Two case series that were published prior to the COVID-19 pandemic reported improved oxygenation and low intubation rates after placing spontaneously breathing patients with hypoxemia in the prone position,13,14 and several new case series reported similar results with awake prone positioning in patients with COVID-19 pneumonia who required supplemental oxygen.
In a case series of 50 patients with COVID-19 pneumonia who required supplemental oxygen upon presentation to a New York City emergency department (ED), awake prone positioning improved overall median oxygen saturation. However, 13 of these patients still required intubation due to respiratory failure within 24 hours of presentation to the ED.15 Another case series from Jiangsu province used awake prone positioning as part of a treatment strategy in nonintubated patients with COVID-19 pneumonia and reported an intubation rate of less than 1%.16 In a report of 24 patients who required either a nasal cannula or HFNC and who had a chest computed tomography scan that was consistent with COVID-19 pneumonia, 25% of patients tolerated prone positioning for at least 3 hours and showed >20% improvement in the partial pressure of oxygen in arterial blood. No complications were reported with prone positioning.17 Another case series of 15 patients with ARDS due to COVID-19 pneumonia who received awake prone positioning while on noninvasive ventilation reported that all patients showed improvement in their oxygen saturation during prone positioning, with 80% of patients maintaining their improved oxygen saturation after resupination. Seven percent of patients required intubation.18
Appropriate candidates for awake prone positioning are those who are able to adjust their position independently and tolerate lying prone. Awake prone positioning is contraindicated in patients who are in respiratory distress and who require immediate intubation. Awake prone positioning is also contraindicated in hemodynamically unstable patients, patients who recently had abdominal surgery, and patients who have an unstable spine.19 Awake prone positioning is acceptable and feasible for pregnant patients and can be performed in the left lateral decubitus position or the fully prone position.20
It is essential that hypoxemic patients with COVID-19 be monitored closely for signs of respiratory decompensation. To ensure the safety of both the patient and health care workers, intubation should be performed in a controlled setting by an experienced practitioner.
Early intubation may be particularly appropriate when patients have additional acute organ dysfunction or chronic comorbidities, or when HFNC and NIPPV are not available. NIPPV has a high failure rate in both patients with non-COVID-19 viral pneumonia21,22 and patients with ARDS.23,24 NIPPV may generate aerosol spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus increase nosocomial transmission of the infection.25,26 It remains unclear whether HFNC results in a lower risk of nosocomial SARS-CoV-2 transmission.
The use of supplemental oxygen in adults with COVID-19 has not been studied, but indirect evidence from other critical illnesses suggests the optimal oxygen target is an SpO2 between 92% and 96%:
- A meta-analysis of 25 randomized controlled trials found that a liberal oxygen strategy (median SpO2 96%) was associated with an increased risk of hospital mortality (relative risk 1.21; 95% CI, 1.03–1.43).27
- The LOCO2 randomized controlled trial compared a conservative oxygen strategy (target SpO2 88% to 92%) to a liberal oxygen strategy (target SpO2 ≥96%).28 The trial was stopped early due to futility. Mortality increased among those who received the conservative oxygen therapy at Day 28 (risk difference +8%; 95% CI, -5% to +21%) and Day 90 (risk difference +14%; 95% CI, +0.7% to +27%). These differences would be important if they were real, but the study was too small to definitively confirm or exclude an effect.
- For mechanically ventilated adults with COVID-19 and ARDS:
- The Panel recommends using low tidal volume (VT) ventilation (VT 4–8 mL/kg of predicted body weight) over higher tidal volumes (VT >8 mL/kg) (AI).
- The Panel recommends targeting plateau pressures of <30 cm H2O (AII).
- The Panel recommends using a conservative fluid strategy over a liberal fluid strategy (BII).
- The Panel recommends against the routine use of inhaled nitric oxide (AI).
Currently, there is no evidence that ventilator management of patients with ARDS due to COVID-19 should differ from the management of patients with viral pneumonia due to influenza or other respiratory viruses.
- For mechanically ventilated adults with COVID-19 and moderate-to-severe ARDS:
- The Panel recommends using a higher positive end-expiratory pressure (PEEP) strategy over a lower PEEP strategy (BII).
- For mechanically ventilated adults with COVID-19 and refractory hypoxemia despite optimized ventilation, the Panel recommends prone ventilation for 12 to 16 hours per day over no prone ventilation (BII).
PEEP is beneficial in patients with ARDS because it prevents alveolar collapse, improves oxygenation, and minimizes atelectotrauma, a source of ventilator-induced lung injury. A meta-analysis of individual patient data from the three largest trials that compared lower and higher levels of PEEP found lower rates of ICU mortality and in-hospital mortality with higher PEEP in patients with moderate (P/F ratio of 100–200) and severe ARDS (P/F ratio <100).29
Though there is no clear standard as to what constitutes a high level PEEP, one conventional threshold is >10 cm H2O.30 Recent reports have suggested that, in contrast to other causes of ARDS, some patients with moderate or severe ARDS due to COVID-19 have normal static compliance; higher PEEP levels may cause harm in this group by compromising hemodynamics and cardiovascular performance.31,32 However, this finding has not been confirmed in other studies. Several observational studies reported that patients with moderate to severe ARDS due to COVID-19 had low compliance, similar to the lung compliance seen in patients with conventional ARDS.33-36 In patients with ARDS due to COVID-19, assessment for responsiveness to higher PEEP may be individualized based on oxygenation and lung compliance. Clinicians should monitor patients for known side effects of higher PEEP, such as barotrauma and hypotension.
- The Panel recommends using, as needed, intermittent boluses of neuromuscular blocking agents (NMBA) or continuous NMBA infusion, to facilitate protective lung ventilation (BIII).
- In the event of persistent patient-ventilator dyssynchrony, which places the patient at risk for ventilator-induced lung injury, or in cases where a patient requires ongoing deep sedation, prone ventilation, or persistently high plateau pressures, the Panel recommends using a continuous NMBA infusion for up to 48 hours as long as patient anxiety and pain can be adequately monitored and controlled (BIII).
The recommendation for intermittent boluses of NMBA or continuous infusion of NMBA to facilitate lung protection may require a health care provider to enter the patient’s room more frequently for close clinical monitoring. Therefore, in some situations, the risks of COVID-19 exposure and the use of personal protective equipment for each entry may outweigh the benefit of NMBA treatment.
For mechanically ventilated adults with COVID-19, severe ARDS, and hypoxemia despite optimized ventilation and other rescue strategies:
- The Panel recommends using recruitment maneuvers rather than not using recruitment maneuvers (CII).
- If recruitment maneuvers are used, the Panel recommends against using staircase (incremental PEEP) recruitment maneuvers (AII).
- The Panel recommends using an inhaled pulmonary vasodilator as a rescue therapy; if no rapid improvement in oxygenation is observed, the treatment should be tapered off (CIII)
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32109013.
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32091533.
- Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32191259.
- Alhazzani W, Moller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32224769.
- Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32031570.
- Xu XP, Zhang XC, Hu SL, et al. Noninvasive ventilation in acute hypoxemic nonhypercapnic respiratory failure: a systematic review and meta-analysis. Crit Care Med. 2017;45(7):e727-e733. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28441237.
- Zhao H, Wang H, Sun F, Lyu S, An Y. High-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy but not to noninvasive mechanical ventilation on intubation rate: a systematic review and meta-analysis. Crit Care. 2017;21(1):184. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28701227.
- Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25981908.
- Ni YN, Luo J, Yu H, Liu D, Liang BM, Liang ZA. The effect of high-flow 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. 2018;36(2):226-233. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28780231.
- Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23688302.
- Fan E, Del Sorbo L, Goligher EC, et al. 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. 2017;195(9):1253-1263. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28459336.
- Nyren S, Mure M, Jacobsson H, Larsson SA, Lindahl SG. Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans. J Appl Physiol (1985). 1999;86(4):1135-1141. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10194194.
- Scaravilli V, Grasselli G, Castagna L, et al. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study. J Crit Care. 2015;30(6):1390-1394. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26271685.
- Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020;24(1):28. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32000806.
- Caputo ND, Strayer RJ, Levitan R. Early self-proning in awake, non-intubated patients in the emergency department: a single ED's experience during the COVID-19 pandemic. Acad Emerg Med. 2020;27(5):375-378. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32320506.
- Sun Q, Qiu H, Huang M, Yang Y. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care. 2020;10(1):33. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32189136.
- Elharrar X, Trigui Y, Dols AM, et al. Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failure. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32412581.
- Sartini C, Tresoldi M, Scarpellini P, et al. Respiratory parameters in patients with COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32412606.
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- Society for Maternal Fetal Medicine. Management Considerations for Pregnant Patients With COVID-19. 2020. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2336/SMFM_COVID_Management_of_COVID_pos_preg_patients_4-30-20_final.pdf. Accessed: May 20, 2020.
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