COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)

INTRODUCTION — The major morbidity and mortality from coronavirus disease 2019 (COVID-19) is largely due to acute viral pneumonia that evolves to acute respiratory distress syndrome. As patients progress, increasing respiratory support is required, which often necessitates intensive care unit level of care, depending on the facility and patient characteristics. Respiratory support includes oxygenation with low-flow and high-flow systems, noninvasive ventilation, and the use of other adjunctive therapies (eg, nebulized medications) and rescue therapies (eg, prone positioning). While some patients improve and respiratory support can be de-escalated, a proportion continue to deteriorate, and a decision needs to be made regarding intubation and mechanical ventilation.

This topic discusses noninvasive respiratory support of the critically ill COVID-19 patient as well as the timing and procedure of intubation. Clinical features of the critically ill adult with COVID-19 and management of the hospitalized and the intubated patient with COVID-19 are discussed separately. (See "COVID-19: Clinical features" and "COVID-19: Management in hospitalized adults" and "COVID-19: Management of the intubated adult".) (Related Pathway(s): COVID-19: Anticoagulation in adults with COVID-19.)

GENERAL ISSUES FOR ALL HYPOXEMIC PATIENTS

Awake pronation — For hospitalized patients with hypoxemic respiratory failure due to COVID-19 who are receiving oxygen or noninvasive modalities of support (including low-flow oxygen, high-flow oxygen delivered via nasal cannulae [HFNC], or noninvasive ventilation [NIV]), we suggest attempting awake/nonsedated prone positioning. While an optimally beneficial amount of time has not been established, we typically encourage at least 6 to 8 hours prone in a 24-hour period in the appropriate patient. We encourage adherence but recognize that some patients have difficulty with this maneuver because of personal discomfort or preference (eg, face, neck, or arm pain; cannot fall asleep prone) or discomfort from external hardware (eg, mask and tubing). Patients with COVID-19 who have hypoxemic respiratory failure due to other conditions do not necessarily need to undergo pronation (eg, pulmonary edema, pulmonary embolism). Contraindications to pronation (table 1) are provided separately. (See "Prone ventilation for adult patients with acute respiratory distress syndrome", section on 'Contraindications'.)

Similar to ventilated patients, we monitor for any adverse effects of pronation (eg, pressure ulcers, retinal damage), although we typically observe fewer complications in those who undergo self-pronation presumably because they can self-adjust for ongoing comfort (table 1). (See "Prone ventilation for adult patients with acute respiratory distress syndrome", section on 'Complications'.)

The rationale for this approach is based on limited direct evidence in patients with COVID-19 that demonstrates transient improvement in oxygenation with this strategy [1-18] and indirect evidence of its efficacy in ventilated patients with acute respiratory distress syndrome. Consistent between trials is that awake pronation has not yet been shown to reduce mortality. However, data on its impact on intubation rates are conflicting but on balance suggest benefit. Future data are warranted to identify the optimal indications for and duration of pronation. (See "Prone ventilation for adult patients with acute respiratory distress syndrome" and "COVID-19: Management of the intubated adult", section on 'Low tidal volume ventilation in the prone position'.)

Several trials support awake pronation as an intervention to improve oxygenation and decrease intubation [8,9,14,19-22]:

●Several meta-analyses support awake pronation. As examples [14,19,22,23]:

•One meta-analysis of 17 randomized trials including 2931 patients reported that awake pronation reduced the need for intubation compared with supination (mean relative risk [RR] 0.83, 95% CI 0.70-0.97) [22]. Although a mortality benefit was suggested, the wide confidence interval limits reduce the certainty of this benefit (RR 0.90, 95% CI 0.73-1.13).

•In a meta-analysis of 29 trials (10 of which were randomized trials), awake pronation reduced the need for intubation compared with supination (RR 0.84, 95% CI 0.75-0.98), particularly among those who needed advanced respiratory support (RR 0.83, 95% CI 0.71-0.97) or ICU admission (RR 0.83, 95% CI 0.71-0.97) [19]. This meta-analysis was largely influenced by one meta-trial of six randomized open-label trials [14]. For the latter trial, several factors may have reduced the certainty of the effect, including issues such as stopping the trial early for benefit and the open-label nature of the study (which could have affected the threshold for intubation).

●A randomized trial of 430 patients with COVID-19 receiving HFNC found a similar effect of prone positioning on intubation rates (30 versus 43 percent; RR 0.70, 95% CI 0.54-0.90) [20]; features associated with intubation despite prone positioning included duration of awake pronation <7.7 hours, respiratory rate ≥25 breaths per minute (bpm) at enrollment, and a decrease in respiratory rate <3 bpm after the awake pronation session.

●Several prospective studies have consistently shown improved oxygenation parameters in response to awake pronation that is not always sustained upon resupination [8,9]. Most patients tolerated awake pronation for three hours or more (eg, two-thirds).

However, some trials [18,24] have not supported awake pronation as a tool to reduce intubation rates [18,21,24]:

●In one trial of 501 patients with COVID-19-associated hypoxemia who were assigned to awake pronation or usual care based upon an even or odd medical record number, there was no difference between groups in progression to mechanical ventilation, length of stay, and mortality at 14 or 28 days [24]. Pronation was associated with higher levels of oxygen support on day 5, although the clinical significance of this is uncertain given the lack of difference at subsequent timepoints.

●In another randomized open-label trial of 400 patients with COVID-19 who were receiving oxygen at an FiO₂ ≥0.4 or NIV, awake pronation did not significantly reduce the rate of intubation at 30 days compared with those who did not undergo proning (34 versus 41 percent; hazard ratio 0.81, 95% CI 0.59-1.12) [18]. Similarly, awake pronation had no impact on mortality, ventilator-free days, or ICU-free days. However, the effect estimates were imprecise suggesting that the possibility of benefit is not ruled out.

Oxygenation targets — The World Health Organization suggests titrating oxygen to a target peripheral oxygen saturation (SpO₂) of ≥94 percent during initial resuscitation and ≥90 percent for maintenance oxygenation. For most patients, we prefer the lowest possible FiO₂ necessary to meet oxygenation goals, ideally targeting an SpO₂ between 90 and 96 percent, if feasible. Hyperoxia should be avoided. If a higher SpO₂ is achieved during initial resuscitation and stabilization, supplemental oxygen should be weaned as soon as is safe to avoid prolonged hyperoxia. Individualization of the goal is important, as some patients may warrant a lower target (eg, patients with a concomitant acute hypercapnic respiratory failure from chronic obstructive pulmonary disease [COPD]) and others may warrant a higher target (eg, pregnancy). Data that support this target range are provided separately. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit", section on 'Fraction of inspired oxygen'.)

Using SpO₂ targets in patients with darkly pigmented skin warrants special attention because of the potential for pulse oximetry to overestimate arterial oxygenation and fail to identify hypoxemia in such individuals [25]. The US Food and Drug Administration and the Centers for Disease Control and Prevention have highlighted these concerns when risk-stratifying patients with COVID-19 [26,27]. We believe that in patients with darkly pigmented skin who have COVID-19, it is prudent to correlate the SpO₂ value with a saturation value derived from an arterial blood gas to ensure accuracy of the SpO₂ measurement. Of note, the SpO₂ to arterial oxygen saturation correlation may not be fixed over time in a given patient; thus, repeat correlation checks may be indicated, especially in acute situations, or at some regular interval. The potential for such discrepancy was illustrated by an analysis of over 1200 patients with COVID-19 who had oxygen saturation levels that were concurrently measured by pulse oximetry and arterial blood gas [28]. Pulse oximetry overestimated arterial oxygen saturation in Asian, Black, and Hispanic patients compared with White patients. Occult hypoxemia occurred in approximately one-third of Asian, Black, and Hispanic patients compared with 17 percent of White patients. Importantly, predicted overestimation of arterial oxygen saturation by pulse oximetry was associated with both a failure to identify Black and Hispanic patients who were qualified to receive COVID-19 therapy, and a delay in initiation of COVID-19-related therapy. Another study showed similar results [29].  (See "Pulse oximetry", section on 'Skin pigmentation'.)

Precautions with aerosol-generating procedures

Nebulized medications — Nebulizers are associated with aerosolization and potentially increase the risk of viral transmission. In spontaneously breathing patients with suspected or documented COVID-19, nebulized bronchodilator therapy should therefore be reserved for those with clear indications (eg, acute bronchospasm in the setting of asthma or COPD exacerbation; hypertonic saline, antibiotics, or DNase for cystic fibrosis).

Interventions that may decrease the risk of virus spread (eg, use of metered-dose inhalers, use of a mouthpiece rather than a mask, breath-synchronized nebulizer) are discussed separately. (See "Delivery of inhaled medication in adults", section on 'Infection control'.)

If nebulized therapy is used, patients should be in an airborne infection isolation room, health care workers should use contact and airborne precautions, and all nonessential personnel should leave the room during nebulization. Some experts also suggest not re-entering the room for two to three hours following nebulizer administration, unless clinically necessary. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Other — Potential for viral transmission should inform the use of other respiratory interventions in patients with documented or suspected COVID-19.

We restrict aerosol-generating procedures, such as chest physical therapy and oscillatory devices, oral and airway suctioning, and sputum induction to instances in which there is a clear clinical indication and expected benefit.

The performance of bronchoscopy should adhere to established guidelines. (See "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Bronchoscopy in COVID-19 patients' and "COVID-19: Management of the intubated adult", section on 'Bronchoscopy'.)

If any of these therapies are performed, similar personal protective equipment to that described for nebulizer therapy should be used. (See 'Nebulized medications' above.)

PATIENTS WITH MINIMAL OXYGEN NEEDS

Low-flow oxygen — For patients with hypoxemic respiratory failure due to COVID-19, supplemental oxygenation with a low-flow system (ie, up to 6 L/minute) via nasal cannulae is appropriate as an initial strategy. The degree of viral aerosolization at low-flow rates is unknown but likely minimal. (See 'Oxygenation targets' above and "Continuous oxygen delivery systems for the acute care of infants, children, and adults".)

As flow increases, the risk of viral aerosolization may increase, potentially contaminating the surrounding environment and staff. However, the flow rate at which aerosolization risk increases is unknown. To address this issue, we typically have patients who wear nasal cannulae, low or high flow, also wear a droplet mask, especially during transport or when staff are in the room. Data to support this practice are largely non-peer-reviewed or derived from simulation experiments but make practical sense as a maneuver to reduce the infectious risk associated with potential aerosolization [30-32]. Additional information on infection precautions while using oxygen is provided below. (See 'Infection control precautions for noninvasive modalities' below.)

PATIENTS WITH REQUIREMENTS FOR ADVANCED RESPIRATORY SUPPORT — Once oxygen requirements start to increase over 6 to 15 L/minute or breathing becomes labored, options are high-flow oxygen via nasal cannulae (HFNC) and oxygen delivered via a noninvasive ventilation (NIV) device. Among these options, we prefer an initial trial of HFNC or NIV; either or both modalities can be trialed, unless there is a separate indication for one specific modality (eg, concomitant acute hypercapnia or heart failure requiring bilevel or continuous positive airway pressure, respectively). (See 'Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation' below.)

Noninvasive modalities — In patients with acute hypoxemic respiratory failure due to COVID-19 and higher oxygen needs than low-flow oxygen can provide, we suggest that noninvasive modalities be used. We believe that the decision to initiate noninvasive modalities, either HFNC or NIV, should be made by balancing the risks to and benefits for the patient, the risk of exposure to health care workers, best use of resources, and patient tolerance [33].

Both modalities, HFNC and NIV, have been used variably in critically ill patients with COVID-19. In retrospective cohorts, rates for HFNC use ranged from 14 to 63 percent, while 11 to 56 percent were treated with NIV [34-37]. While these modalities improve oxygenation and/or dyspnea, data demonstrating success at preventing progression to intubation have notable limitations and clear mortality reductions have not been found. However, reduced rates of mechanical ventilation have been reported after shifting to higher intubation thresholds during the pandemic, suggesting that some patients may not proceed to intubation if appropriately supported with noninvasive methods [38]. (See 'Timing' below.)

Support for advancing to HFNC in patients with increasing oxygen needs is derived from randomized trials that have demonstrated decreased intubation rates when compared with low-flow oxygen, even without mortality reductions and in the setting of a low-risk intervention [39,40]:

●In a randomized trial of 220 patients with COVID-19 and acute hypoxemic respiratory failure, intubation rates were lower with oxygen delivery through HFNC compared with standard low-flow delivery, with each adjusted to maintain peripheral oxygen saturation (SpO₂) ≥92 percent (43 versus 51 percent; hazard ratio 0.62, 95% CI 0.39-0.96; number needed to treat 7) [39]. HFNC also reduced the time to clinical recovery (11 versus 14 days), but the mortality difference was not statistically significant (8 versus 16 percent). However, the study excluded a number of medical comorbidities (eg, hypercapnia, heart failure, advanced chronic obstructive pulmonary disease, demyelinating disease, advanced cirrhosis, or imminent death), limiting interpretation of the trial.

●Another open-label randomized trial of 711 patients with acute hypoxemic respiratory failure due to COVID-19 reported lower intubation rates with HFNC compared with standard low-flow oxygen delivered through a nonrebreather mask (45 versus 53 percent), although the partial arterial oxygen tension was lower in the HFNC group (75 versus 80 mmHg) [40]. There was no difference in mortality (10 versus 11 percent) or ventilator-free days (28 versus 23 days). Limiting interpretation were several factors, including a change of inclusion criteria during the trial and the actual mortality rate was lower than that used to estimate the sample size.

●However, not all studies suggest that HFNC defers intubation, especially in those with mild hypoxemia [41].

Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation — The choice between NIV and HFNC in patients with COVID-19 is based largely upon the patient's comorbidities and the tolerability of the device:

●NIV should be used if the patient has a comorbidity for which there is proven efficacy of NIV (eg, acute hypercapnic respiratory failure from an acute exacerbation of chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, underlying sleep-disordered breathing [eg, obstructive sleep apnea or obesity hypoventilation], or respiratory muscle weakness). (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Patients likely to benefit'.)

●In the absence of such comorbidities, either modality is acceptable. The tolerability of the device and patient comfort are often the determining factors. HFNC is arguably associated with fewer adverse events and is a more comfortable and practical mode of support, during which patients can continue to converse and eat when compared with NIV.

In some cases, we may transition between HFNC and NIV for short periods (eg, during sleep, acute episodes of acute pulmonary edema, attempts at meals) and occasionally cycle between both modalities until the patient improves or deteriorates.

The available clinical trial data do not clearly demonstrate the benefit of one modality over the other:

●Evidence supporting NIV in this setting comes from randomized trials involving patients with COVID-19 . On balance, these data suggest that NIV may be associated with lower intubation rates compared with HFNC, though a mortality benefit has not been demonstrated [42,43]. These data have important limitations as summarized below.

●Indirect evidence supporting HFNC comes from randomized trials involving patients with non-COVID-19-related acute hypoxemic respiratory failure, which on balance favor HFNC over NIV. Data supporting HFNC over NIV in non-COVID-19 populations are discussed elsewhere. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Hypoxemic nonhypercapnic respiratory failure not due to ACPE'.)

Studies involving patients with COVID-19 and patients with non-COVID-19-related acute hypoxic respiratory failure suggest that compared with low-flow oxygen, noninvasive respiratory support (including HFNC, continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BPAP]) reduces intubation rates and may improve mortality [12,33,42-47]. However, data directly comparing NIV and HFNC in this setting are more limited:

●In a clinical trial involving 1273 patients with acute hypoxemic respiratory failure due to COVID-19 who required O₂ at a fraction of inspired oxygen (FiO₂) of at least 0.4, patients were randomly assigned to NIV (administered as CPAP), HFNC, or conventional oxygen therapy (via face mask or low-flow nasal cannula) [43]. NIV reduced tracheal intubation compared with conventional oxygen (33 versus 41 percent; odds ratio [OR] 0.71, 95% CI 0.53-0.96). By contrast, intubation rates were similar with HFNC and conventional oxygen (41 percent each). Mortality rates were similar in all three groups (17, 19, and 20 percent, respectively). In a post-hoc analysis comparing NIV and HFNC, intubation rates were lower in the NIV group (32 versus 41 percent; OR 0.68, 95% CI 0.46-0.99). This is an indirect comparison since some centers only offered one or the other modality. The findings of this trial should be interpreted with caution since the trial had several important limitations (ie, lack of blinding, substantial crossover between groups [17 percent], low recruitment, and no standardized criteria for intubation).

●Trials using helmet NIV have had conflicting results on rates of intubation:

•One randomized trial of 110 patients with moderate or severe acute hypoxemic respiratory failure due to COVID-19 reported that helmet NIV use resulted in lower rates of intubation (30 versus 51 percent) and more days free of invasive mechanical ventilation (28 versus 25 days) compared with HFNC [42]. Although encouraging, the trial was performed by experts in the delivery of helmet NIV and as such, may not be easily generalizable.

•Another randomized trial of 320 patients with acute hypoxemic respiratory failure due to suspected or confirmed COVID-19 reported no difference in the 28-day mortality or rates of intubation with helmet NIV versus "usual" respiratory support (mask NIV, HFNC, or low-flow oxygen) [48]. However, several limitations, including imprecise effect estimates, lack of blinding, and poor training in helmet NIV, also reduce confidence in the findings. In a follow-up analysis of long-term outcomes, there was no difference at 180 days in mortality or health-related quality of life between the helmet NIV group and the usual respiratory support group [49]. A smaller trial found no differences in rates of mechanical ventilation or death at 28 and 90 days between HFNC, mask NIV, and helmet NIV [50].

Further study is needed before helmet NIV can be routinely incorporated into the first-line menu of NIV-patient interfaces for the treatment of acute respiratory failure in patients with COVID-19, although it may remain an option for some patients. Data in non-COVID-19 patients that describe outcomes associated with helmet NIV are provided separately. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications", section on 'Medical patients with severe hypoxemic respiratory failure' and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation", section on 'Interface (mask)'.)

●Another randomized trial of 546 patients reported no difference in the 28-day cumulative need for mechanical ventilation among patients who received HFNC, NIV, or low flow oxygen [51].

●Retrospective studies have reached variable conclusions regarding the benefits of NIV in patients with acute COVID. Two Italian studies reported high NIV failure rates (38 to 44 percent) among patients with moderate-to-severe hypoxemia from COVID-19, most of whom were receiving NIV via a helmet interface [52,53]. One study reported reduced rates of intubation and mechanical ventilation with HFNC [47], while another reported similar intubation rates among patients treated with HFNC (29 percent), continuous positive airway pressure (25 percent), or other modes of NIV (28 percent) [45].

Data that have directly compared HFNC with conventional low-flow oxygen in patients with COVID-19 also support the use of HFNC as an effective modality that may prevent intubation. These data are discussed above. (See 'Noninvasive modalities' above.)

Application of noninvasive modalities — The application of HFNC and NIV is similar to that for non-COVID-19 conditions, with an emphasis on the lowest effective inspiratory and expiratory pressure, typically with CPAP rather than BPAP, to reduce the theoretical risk of aerosolization. Technical details regarding initial settings and application of HFNC and NIV are provided separately. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications" and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)

Monitoring on noninvasive modalities — When receiving noninvasive support, we monitor the patient's respiratory, fluid, and nutritional status closely. Encouragement for pronation should continue while patients are receiving noninvasive respiratory support. (See 'Awake pronation' above.)

●Respiratory – For patients in whom HFNC or NIV is administered, vigilant monitoring of the patient's respiratory status is warranted for progression. We evaluate patients clinically every one to two hours and obtain an arterial blood gas (ABG) after the first two hours to ensure effective and safe ventilation (eg, frequent coughing may not be "safe"). ABG evaluation thereafter is often daily or when needed to ensure accurate oximetry (ie, good correlation between the saturation measured on the ABG and the peripheral oxygen saturation) (see 'Oxygenation targets' above). Once patients are on HFNC or NIV, we advocate a low threshold to intubation, particularly if they show any signs of rapid progression that is not due to an underlying rapidly reversible cause. (See 'Timing' below.)

●Fluid and nutrition – We pay attention to the daily oral intake of food and fluids, especially when prolonged periods of NIV and/or diuresis are used (eg, greater than three to four days). Patients should be monitored for signs of dehydration and malnutrition.

For patients receiving noninvasive modalities for prolonged periods, we consider the administration of nasogastric feeding despite the theoretical risk of aspiration due to aerophagia on NIV [54]. We are not proponents of extra protein supplementation, vitamin C or D supplementation, or trace element supplementation over and above the usual recommended daily doses.

Guidelines for the provision of feeding while on NIV can be found by a collaborative group in the United Kingdom. Additional information on the provision of nutrition to critically ill patients is provided separately. (See "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription" and "Nutrition support in intubated critically ill adult patients: Enteral nutrition" and "Nutrition support in intubated critically ill adult patients: Parenteral nutrition".)

Course and duration — There is no set duration for a trial period of either modality. In our experience, some patients deteriorate quickly (hours to a few days), while others tolerate either or both of these modalities for prolonged periods (eg, one week to 10 days).

There are no factors that reliably predict which course a patient will take. Invariably, patients who require noninvasive modalities for prolonged periods or patients who progress despite one or both modalities are at high risk of requiring intubation and mechanical ventilation. The optimal timing of intubation is discussed below. (See 'Timing' below.)

Infection control precautions for noninvasive modalities — HFNC and NIV are considered aerosol-generating procedures. Thus, when HFNC or NIV is used, airborne, in addition to standard precautions should be undertaken (ie, airborne infection isolation room [also known as a negative pressure room] and full personal protective equipment). High-quality data are scarce, and investigation to support this approach is ongoing. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

●HFNC – We advocate placing a surgical mask on the patient during HFNC when health care workers are in the room or the patient is being transported, but the exact value of this practice is unknown [55]. Additional precautions for HFNC that have potential to reduce risk include starting at and using the lowest effective flow rate (eg, 20 L/minute and 0.4 FiO₂).

●NIV – If NIV is initiated, an oronasal or full facemask may reduce particle dispersion. The mask should preferably have a good seal and not have an anti-asphyxiation valve or port.

Use of a helmet has been proposed for delivering NIV to patients with COVID-19 and may theoretically be associated with reduced aerosol dispersion compared with oronasal or full facemasks [56]. However, experience is limited with this delivery method, especially in the United States, although clinicians with expertise support helmet interfaces [57]. Studies of helmet NIV are described separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation", section on 'Interface (mask)' and 'Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation' above.)

If NIV is used, dual limb circuitry with a filter on the expiratory limb on a critical care ventilator may decrease dispersion compared with single limb circuitry on portable devices, although data to support this are lacking. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation", section on 'Ventilator circuit' and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation", section on 'Circuit'.)

As an additional attempt to reduce aerosolization, we typically start with CPAP using the lowest effective pressures (eg, 5 to 10 cm H₂O) and only use higher positive end-expiratory pressure (PEEP) or add inspiratory positive pressure (eg, BPAP) as needed.

There are few data regarding aerosolization during HFNC and NIV [31,58-63]. In a normal lung simulation study, dispersion of air during exhalation increased with increasing HFNC flow from 65 mm (at 10 L/minute) to 172 mm (at 60 L/minute) mostly along the sagittal plane (ie, above the nostrils) [58]. Similar distances were found when CPAP was delivered via nasal pillows (up to 332 mm with CPAP 20 cm H₂O). However, there was no significant leakage noted when CPAP was administered via an oronasal mask with good seal (picture 1 and picture 2). Air leak increased when connections on any device were loose. Dispersion seemed to be reduced when the simulator simulated injured lung. In vitro and clinical studies have also shown that a surgical mask placed on the patient may decrease the dispersion distance [64]. In another patient intensive care unit room simulation experiment, invasive ventilation and helmet ventilation with a PEEP valve were associated with the lowest concentrations of aerosolized microorganism, while HFNC and nasal prongs were associated with the highest concentrations [63].

Novel devices targeting limitation of aerosol spread from patients receiving HFNC or NIV have been proposed but are not commercially available, and their impact on clinical outcomes has not been tested [65].

Supportive therapy — Critically ill patients with COVID-19 who are on noninvasive modalities should receive supportive care similar to the intubated patient (eg, venous thromboembolism and stress ulcer prophylaxis, optimal glucose control, and nutrition). (See "COVID-19: Management of the intubated adult", section on 'Supportive care'.)

Additional considerations — In all patients with escalating oxygen requirements, additional diagnoses should be considered. For example, a sudden increase in oxygen requirement should raise the suspicion for pulmonary embolism, acute cardiogenic pulmonary edema, or myocardial infarction, all of which are known complications of COVID-19. (See "COVID-19: Hypercoagulability" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "COVID-19: Cardiac manifestations in adults" and "COVID-19: Evaluation and management of cardiac disease in adults".)

THE DECISION TO INTUBATE

Timing — In critically ill patients with COVID-19, the question of "when to intubate" is challenging. For patients with escalating needs for respiratory support, we generally start with noninvasive modalities on a trial basis (eg, high-flow oxygen delivered via nasal cannulae [HFNC] or noninvasive ventilation [NIV]) and monitor clinical and gas exchange parameters every one to two hours. (See 'Patients with requirements for advanced respiratory support' above.)

Determining when patients are failing noninvasive modalities and require intubation involves judgement. Practice varies and the decision should be individualized. Importantly, we do not advise routinely delaying intubation until the patient has features of impending respiratory arrest (eg, accessory muscle use, abdominal paradox) while receiving maximum noninvasive supportive care (eg, HFNC 60 L/minute and a fraction of inspired oxygen [FiO₂] 1.0), since this approach is potentially harmful to both the patient and health care workers [66]. While there are no set criteria for intubation, we consider the following high-acuity patients to be at the greatest risk for requiring intubation (table 2):

●Patients with rapid progression over hours

●Patients with a persistent need for high flows/FiO₂ (eg, >60 L/minute and an FiO₂ >0.6)

●Patients with evolving hypercapnia, increasing work of breathing, decreasing tidal volume, worsening mental status, increasing duration and depth of desaturations

●Patients with hemodynamic instability or multiorgan failure

In this group of high-risk patients, we advocate for close and regular communication between health care staff, patients, and patients' caregivers about the potential need for intubation. We believe that using this approach leads to a smooth and rapid transition for intubation when indicated. However, decisions on intubation timing remain very patient-specific. For example, some patients in this group can be maintained for prolonged periods on HFNC with high FiO₂ (eg, 60 L/minute and FiO₂ 0.8 to 1.0) and be relatively comfortable, while others struggle and deteriorate quickly.

Early during the pandemic, some experts advocated for "early" intubation in patients with escalating oxygen needs beyond 6 L/minute or increased work of breathing, although the definition of what constitutes "early" is unclear. This strategy intended to avoid aerosolization associated with noninvasive modalities and was based on the perception that patients who needed noninvasive modalities would ultimately require mechanical ventilation (eg, within one to three days). However, in our opinion, using this as an absolute rule results in unnecessary intubations and places an undue load on ventilator demand during the peak of surges. In addition, the approach of avoiding noninvasive modalities is particularly problematic for patients who have chronic nocturnal NIV requirements, patients with chronic respiratory failure who have a high baseline oxygen requirement, and patients with do-not-intubate status but who might benefit otherwise from NIV or HFNC.

Procedural modifications to minimize aerosolization — Intubation is one of the highest risk procedures for droplet dispersion in patients with COVID-19 [67-69]. The magnitude of the risk has been poorly documented. At the beginning of the pandemic, one prospective study of health care workers reported a cumulative incidence of self-reported SARS-CoV-2 infection following tracheal intubation as 3.6 percent at 7 days, 6.1 percent at 14 days, and 8.5 percent at 21 days [69]; however strategies for risk reduction have likely since improved [70-72].

The process of intubation is similar to that in non-COVID-19 patients being intubated outside of the operating room (eg, intensive care unit and emergency department (see "Rapid sequence intubation in adults for emergency medicine and critical care")), but the following precautions should be taken into consideration during the procedure [73]:

●We are proponents of intubation kits and intubation checklists for performing rapid sequence intubation in this population (figure 1). In the hypoxic, agitated patient who cannot cooperate with preoxygenation efforts, delayed sequence intubation may be performed to ensure adequate preoxygenation.

●Attention should be paid to donning full contact and airborne personal protective equipment (PPE) (figure 2 and figure 3) [67]. Appropriate PPE includes a fit-tested disposable N95 respirator mask (picture 3) with eye protection or a powered air-purifying respirator, also known as an isolation suit (picture 4 and picture 5). Also included are gown, caps and beard covers, protective footwear, neck covering, and gloves (using the double-glove technique). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

●Intubation should be performed in an airborne infection isolation room, if possible.

●Intubation should be performed by the most qualified individual (eg, anesthesiologist) since delayed intubation with multiple attempts may prolong dispersion and place the patient at risk of a respiratory arrest.

●Most experts suggest optimizing preoxygenation with nonaerosol-generating means, if possible (eg, avoiding very HFNC rates or transient noninvasive positive pressure ventilation), and intubating using video laryngoscopy. In patients previously on high-flow oxygen, some experts switch to 100 percent nonrebreather masks for preoxygenation.

●When feasible, manual bag mask ventilation (BMV) should be minimized before and after intubation, and a bacterial/viral high efficiency hydrophobic filter should be placed between the facemask and breathing circuit or resuscitation bag. Having a pre-prepared bag mask with filter attached in every room with a COVID-19 patient is prudent. Using a two-person technique for an adequate facemask seal is also reasonable (ie, one person to hold the mask in place and one to perform bag ventilation). When manual BMV is needed, switching the mask to a supraglottic device for manual bagging is reasonable.

●Clamping the endotracheal tube (ETT) for connections and disconnections (eg, capnography testing following intubation) is only appropriate if the patient is not spontaneously breathing (inhaling or exhaling against a closed valve can have major pulmonary and cardiovascular consequences).

●In advance, the ventilator and ventilator circuitry should be ready with preplanned settings already entered, so that it can be connected directly to the ETT without additional manual bag ventilation as soon as the ETT is placed and confirmed with capnography. In addition, if feasible, in-line suction devices and in-line adapters for bronchoscopy should be prepared and attached to the ventilator tubing in advance, in order to avoid unnecessary disconnection for their placement at a later point in time. The expiratory limb on the ventilator should have a high-efficiency particulate air (HEPA) filter to decrease contamination of the ventilator and environment and protect staff when changing limb circuitry.

●To minimize exposure, bundling intubation with other procedures is appropriate as is bundling the chest radiograph for ETT and central venous catheter placement.

●Doffing should follow strict procedure, and some experts also use viricidal wipes on areas of exposed skin (eg, neck) during intubation (figure 3).

Rates of success for emergency intubations appear to be similar to that in the general population. One prospective study reported successful first-attempt tracheal intubation was achieved in 90 percent of intubation episodes and <1 percent required four or more attempts [74]. Successful first attempt was more likely during rapid sequence induction, when operators used powered air-purifying respirators and were experienced in intubating patients with COVID-19 and when intubation was performed in resource-abundant countries.

Novel passive barrier protection intubation devices for use during intubation have been proposed, but we do not recommend their use [75,76]. However, concern about the potential for viral spread and impeded performance for one of these devices has led the US Food and Drug Administration to revoke the umbrella emergency use authorization for passive protective barrier enclosures without negative pressure [77]. In addition, subsequent simulation studies suggested significant delays in intubation and breaches in PPE for some devices [78,79].

Detailed guidance regarding intubation in the operating room, optimal PPE, and procedural details regarding intubation itself are discussed separately. (See "Direct laryngoscopy and endotracheal intubation in adults" and "Rapid sequence intubation in adults for emergency medicine and critical care" and "The decision to intubate" and "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care" and "Overview of infection control during anesthetic care", section on 'Infectious agents transmitted by aerosol (eg, COVID-19)'.)

Discussing end-of-life care — For patients with COVID-19 who do not have advance directives in place, discussing the patient's values and preferences with the patients (if feasible) and caregivers is prudent prior to intubation. For those who choose not to proceed with intubation, comprehensive palliation is appropriate. This and other issues pertinent to end-of-life discussions are provided separately. (See "COVID-19: Management of the intubated adult", section on 'End-of-life issues'.)

COVID-19-SPECIFIC THERAPIES — In patients with hypoxemic respiratory failure due to COVID-19, specific therapies targeted at treating SARS-CoV-2 should be considered (algorithm 1). These therapies are discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'COVID-19-specific therapy'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (See "Patient education: COVID-19 overview (The Basics)" and "Patient education: COVID-19 vaccines (The Basics)".)

SUMMARY AND RECOMMENDATIONS

●Self-pronation – For patients hospitalized with hypoxemic respiratory failure due to COVID-19 who are receiving supplemental oxygen or noninvasive respiratory support, we suggest prone positioning (Grade 2C). The optimal duration of proning is uncertain, but we encourage patients to spend as much time as is feasible (eg, 6 to 8 hours in a 24-hour period). (See 'Awake pronation' above.)

●Oxygen targets – For most patients, we use the lowest possible fraction of inspired oxygen (FiO₂) necessary to meet oxygenation goals. The ideal goal is uncertain, but we typically target a peripheral oxygen saturation (SpO₂) between 90 and 96 percent. Hyperoxia should be avoided. In patients with darkly pigmented skin, it is prudent to correlate SpO₂ with arterial blood gas (ABG) results to avoid occult hypoxemia. (See 'Oxygenation targets' above and "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Low tidal volume ventilation: Initial settings' and "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit", section on 'Fraction of inspired oxygen'.)

●Patients with low oxygen requirements (ie, <6 L/minute) – Supplemental oxygenation with a low-flow system via nasal cannulae is generally sufficient. We typically apply a droplet mask, especially during transport or when staff are in the room to reduce aerosolization. (See 'Patients with minimal oxygen needs' above and "Continuous oxygen delivery systems for the acute care of infants, children, and adults".)

●Patients with more advanced respiratory needs – Options for patients who need more advanced support than low-flow oxygen, but who do not yet require intubation, include noninvasive ventilation (NIV, including continuous positive airway and bilevel positive airway ventilation) and high-flow oxygen via nasal cannulae (HFNC). (See 'Patients with requirements for advanced respiratory support' above.)

•Choice between NIV and HFNC – The choice between NIV and HFNC is based largely upon the patient's comorbidities and the tolerability of the device. In practice, either or both modalities can be trialed, unless there is a separate indication for one specific modality (eg, concomitant acute hypercapnia or heart failure requiring bilevel or continuous positive airway pressure, respectively).

-NIV via an oronasal or full facemask (with a good seal) is appropriate if the patient has a comorbidity for which there is proven efficacy of NIV (eg, acute hypercapnic respiratory failure from an acute exacerbation of chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, underlying sleep-disordered breathing [eg, obstructive sleep apnea or obesity hypoventilation], or respiratory muscle weakness), as discussed separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Patients likely to benefit'.)

-In the absence of such comorbidities, either modality is acceptable. The tolerability of the device and patient comfort are often the determining factors. In practice, either or both modalities can be trialed. Studies involving patients with COVID-19 and patients with non-COVID-19-related acute hypoxic respiratory failure suggest that compared with low-flow oxygen, noninvasive respiratory support (including HFNC, continuous positive airway pressure, and bilevel positive airway pressure) reduces intubation rates and may improve mortality. The available clinical trial data do not clearly demonstrate a benefit of one modality over the other. (See 'Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation' above and "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications", section on 'Medical patients with severe hypoxemic respiratory failure' and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Patients less likely to benefit'.)

•Monitoring and duration – Vigilant monitoring for progression during HFNC or NIV use is warranted. We evaluate patients every one to two hours and obtain an ABG after the first two hours to ensure efficacy and safe ventilation. (See 'Monitoring on noninvasive modalities' above.)

There is no set duration for a trial period of either modality. In our experience, some patients deteriorate quickly (hours to a few days), while others tolerate noninvasive support for prolonged periods (eg, one week to 10 days). (See 'Course and duration' above.)

•Precautions – As potentially aerosol-generating therapies, HFNC and NIV warrant airborne in addition to standard precautions (ie, airborne infection isolation room [negative pressure room] and full personal protective equipment [PPE]), although high-quality data are scarce. With HFNC, we use the lowest effective flow rate (eg, 20 L/minute and 0.4 FiO₂). For NIV, we use an oronasal or full facemask with a good seal and generally start with continuous positive airway pressure rather than other modes (eg, bilevel positive airway pressure). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection" and 'Infection control precautions for noninvasive modalities' above.)

●The decision to intubate – Determining when patients are failing noninvasive modalities and require intubation involves judgement, and the decision should be individualized. Intubation should not be routinely delayed until the patient has features of impending respiratory arrest or is on maximum noninvasive support, since this is potentially harmful to both the patient and health care workers. In general, we use the following criteria to indicate a high risk of requiring intubation (see 'The decision to intubate' above and 'Timing' above):

•Rapid progression over hours

•Persistent need for high flows (eg, >60 L/minute) and FiO₂ (eg, >0.6)

•Evolving hypercapnia, increasing work of breathing, decreasing tidal volume, worsening mental status, increasing duration and depth of desaturations

•Hemodynamic instability or multiorgan failure

Intubation is a high-risk procedure for viral aerosolization. Full PPE with airborne precautions (figure 2 and figure 3), approaches that minimize dispersion (eg, video laryngoscopy, limiting bag mask ventilation), and use of procedural protocols (figure 1) are strategies to mitigate the risk. (See 'Procedural modifications to minimize aerosolization' above.)