The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic, putting enormous strain on healthcare systems around the world. Depending on the admission criteria and available resources, 8–32 percent of patients presenting to hospital may require admission to the intensive care unit (ICU), with an ICU mortality rate of 34–50 percent.
Patients with COVID-19-related acute respiratory distress syndrome (ARDS) may present with significant hypoxia and a wide range of respiratory compliance, which distinguishes it from other causes of ARDS. Few randomised controlled trials (RCTs) on COVID-19-related acute respiratory failure (C-ARF) treatment have been published. As a result, there are clinical practice differences in the therapy of C-ARF, making the best therapeutic management unclear.
Given the scarcity of evidence, Delphi procedure was used to reach consensus on C-ARF respiratory care, generating statements with large agreement on the respiratory management of C-ARF. From these statements, 20 expert clinical practice statements were derived, addressing critical knowledge gaps in clinical management.
Expert clinical practice statements
Is COVID-19-related ARDS similar to other forms of ARDS?
Expert statement: COVID-19-related ARDS is clinically similar to other forms of ARDS.
Discussion: The pathophysiology of COVID-19 involves SARS-CoV-2 invasion of host cells using angiotensin converting enzyme 2 (ACE2) receptor present in lungs and other organs. The viral invasion is followed by replication in type II alveolar pneumocytes that induces a dysregulated host immune response which in turn causes alveolar damage and ARDS. In a cohort of 31 patients with COVID-19, higher lung compliance and volumes were found compared to patients with non-COVID-19 ARDS for a given PaO2/FiO2.
Though there may be some differences in the pathophysiology of COVID-19 and non-COVID-19 ARDS, the clinical presentation is similar. The respiratory mechanics of ventilated patients with C-ARF were noted to be similar to classical ARDS in larger observational multicentre studies. Further studies incorporating lung imaging and perfusion analysis will better address this important pathophysiological and clinical issue in future.
Expert statement: Systemic corticosteroids should be used in patients with critical COVID-19.Dexamethasone is the preferred choice of systemic corticosteroids in patients of C-ARF. The daily dose of dexamethasone should be 6 mg. The preferred duration of systemic corticosteroids is 5–10 days.
Discussion: There is a strong suggestion for the use of systemic corticosteroids in critical COVID-19 to reduce the need for invasive mechanical ventilation. Experts preferred the use of dexamethasone at a dose of 6 mg daily for a duration of 5–10 days, as used in the RECOVERY trial over other corticosteroids, higher dose and longer duration.
The RECOVERY trial and subsequent trials on corticosteroids in COVID-19 found a mortality benefit with its use. However, some questions remain unanswered, such as the type, duration of corticosteroid therapy, timing of initiation and role of a higher dose.
Expert statement: Awake self-proning may improve oxygenation when used in patients with C-ARF requiring supplemental oxygen to maintain oxygen saturation (SpO2) > 90%.
Discussion: Use of early prone position in patients with severe ARDS on invasive mechanical ventilation has been shown to significantly reduce mortality. Though small observational studies in non-COVID-19 and COVID-19 patients have reported improvements in oxygenation with awake self-proning, its impact on reducing tracheal intubation or mortality is unknown. Studies have shown either conflicting results or are difficult to interpret, as awake self-proning was used in combination with other non-invasive respiratory support.
High Flow Nasal Oxygen (HFNO)
Expert statement: HFNO therapy should be considered as an alternative strategy for oxygen support. HFNO should be used in patients who are unable to maintain SpO2 > 90% using oxygen delivery through a venturi mask or may be used in patients with increasing oxygen requirement. HFNO may avoid the need for tracheal intubation and invasive mechanical ventilation in patients with C-ARF.
Discussion: HFNO and non-invasive ventilation (NIV) were initially avoided in patients with C-ARF due to the concern around infectious aerosol generation. However, limited availability of invasive ventilators and ICU beds, favourable experience in small studies and increasing availability of personal protective equipment (PPE) have led to increased use of non-invasive therapies. Patients on non-invasive respiratory support need continuous monitoring to avoid any delays in tracheal intubation.
A recent clinical practice guideline gave a strong recommendation for the use of HFNO over conventional oxygen therapy in patients with acute hypoxemic respiratory failure (AHRF) to prevent tracheal intubation. Though there has been conflicting evidence regarding the use of HFNO to prevent invasive mechanical ventilation in C-ARF, experts recommended its use.
Non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP)
Expert statement: NIV should be considered in patients with mixed respiratory failure and may be used in patients with increased work of breathing which is observed subjectively.
Discussion: NIV failure and higher ICU mortality were observed in patients with moderate-to-severe ARDS in a sub-analysis of the LUNG SAFE study including 2813 non-COVID patients receiving NIV. Continuous positive airway pressure (CPAP) was used in small retrospective studies with some benefit in reducing tracheal intubation in mild-to-moderate COVID-19-related ARDS. Helmet CPAP is also used for management of C-ARF and recommended over HFNO to limit the exposure of healthcare workers (HCW) to aerosols. However, the evidence on effectiveness of helmet CPAP in C-ARF in reducing the need of tracheal intubation is conflicting.
Expert statement: The appropriate triggers for tracheal intubation include altered mental status, hemodynamic instability and failure to maintain SpO2 > 90% with non-invasive respiratory interventions.
Discussion: The decision for tracheal intubation in patients receiving non-invasive respiratory support is challenging, requiring a fine balance between early intubation and risks of invasive mechanical ventilation versus the adverse effects of delaying intubation. The impact of early versus delayed tracheal intubation has not been compared in patients with C-ARF. The decision for tracheal intubation in COVID-19 patients may be best determined using a combination of factors that include clinical acumen, oxygen saturation, dyspnoea and respiratory rate. Experts recommended the use of clinical criteria to be preferred over the use of arterial blood gas or imaging findings to determine the need for tracheal intubation.
Lung protective ventilation
Expert statement: Lung protective ventilation (LPV) should be used for patients with C-ARF on IMV. The targets for LPV in C-ARF include tidal volume of 4–6 ml/kg of predicted body weight, plateau pressure ≤ 30 cm of H2O and driving pressure ≤ 15 cm of H2O.
Discussion: Experts agreed that the COVID-19-related ARDS is clinically similar to other forms of ARDS. Hence, there was a full agreement for the use of lung protective ventilatory strategies (tidal volume 4–6 mL/kg of predicted body weight and plateau pressure ≤ 30 cm of H2O). Severe hypoxaemia with near normal respiratory system compliance, a combination rarely seen in ARDS, had been noted in small studies. However, in large observational multicentre studies, the respiratory mechanics of ventilated patients with COVID-19-related ARDS were noted to be similar to non-COVID-19 ARDS.
Expert statement: Recruitment manoeuvres may be considered only in selected patients with C-ARF on invasive mechanical ventilation, in view of their potential deleterious effects.
Discussion: Diffuse alveolar damage, endotheliitis and microthrombi in pulmonary microvasculature have been reported in small autopsy studies of COVID-19 patients. Microthrombi causing hypoxaemia will not respond to PEEP or a recruitment manoeuvre. The experts suggested that recruitment manoeuvres, if ever used should be individualised, in view of the potential harmful effects as seen in non-COVID-19-related ARDS.
Neuromuscular blocking agents (NMBA)
Expert statement: NMBA may be considered during the early phase of invasive mechanical ventilation in case of patient-ventilator dyssynchrony.
Discussion: Recent meta-analyses have not demonstrated unambiguous benefits on important patient outcomes with the use of NMBA in non-COVID ARDS. It is possible that the impact of NMBA infusion on mortality depends on the strategy used in the control arm. The strong suggestion in favour of the use of NMBA by our experts, in case of patient-ventilator dyssynchrony contrasts with this lack of certainty and may be supported by the relative safety demonstrated so far. However, recent guidelines recommend the use of an NMBA infusion for 48 h in patients with refractory hypoxemia despite deep sedation to facilitate lung protective ventilation strategy or prone positioning and/or when there is high respiratory drive despite optimal sedation.
Expert statement: Prone position in patients with C-ARF on invasive mechanical ventilation should be used for a duration of 16–24 h per session to improve oxygenation.
Discussion: Prone position for ventilated patients with C-ARF was strongly suggested by experts, for a duration of 16–24 h per session, similar to the indication in non-COVID-19-related ARDS.
Veno-Venous extracorporeal membrane oxygenation (V-V ECMO)
Expert statement: V-V ECMO may be considered in patients with refractory hypoxemia on invasive mechanical ventilation, who do not respond to other adjuvant therapies.
Discussion: These recommendations are in agreement with COVID-19 guidelines. Though higher mortality was reported during initial days of the pandemic, there is increasing experience and evolving evidence showing favourable outcomes with ECMO in COVID-19 patients. In a recent meta-analysis, the 90-day mortality was lower in non-COVID-19-related ARDS patients on ECMO as compared to conventional ventilation. Experts recommend V-V ECMO for patients with refractory hypoxemia when lung protective ventilation and prone ventilation have failed or the latter is contraindicated.
Expert statement: Bag mask ventilation, HFNO, NIV, tracheal intubation, open suctioning, bronchoscopy, tracheal extubation and tracheostomy may be considered as aerosol-generating procedures in and outside the ICU. Airborne infection isolation rooms and video laryngoscopes may be considered during tracheal intubation; a closed suction system should be considered to reduce cross-transmission of SARS-CoV-2 in the ICU.
Discussion: There is limited evidence regarding the use of airborne infection isolation rooms, use of video laryngoscopes during tracheal intubation and closed suction systems to mitigate aerosol generation in COVID-19 patients. Simulation studies on aerosol production during tracheal intubation and extubation have provided divergent results. There is conflicting evidence on aerosol generation with NIV or HFNO. The experts have taken a conservative approach, labelling procedures as aerosol generating, until robust evidence is generated to the contrary.
Weaning from invasive mechanical ventilation
Expert statement: Weaning should not be delayed, for the threat of the risk of reintubation. A pressure support ventilation trial for 30 min to 2 h may be preferred over other weaning strategies.
Discussion: Weaning and extubation are very relevant to COVID-19 patients, due to concerns of the increased risk of aerosol exposure to the healthcare worker, if there is failure of tracheal extubation and need for a reintubation. Nevertheless, the experts were strongly against delaying extubation in order to potentially reduce risks of later reintubation, suggesting the use of similar criteria as in non-COVID-19 patients. The recommendation regarding the weaning strategy is consistent with recent evidence supporting pressure support ventilation for 30 min over T-piece for two hours, although this is not universally accepted.
Expert statement: Early mobilization may be beneficial in patients on respiratory support for C-ARF.
Discussion: Experts suggested that early mobilisation may be beneficial in patients with C-ARF receiving respiratory support; given the evidence that early mobilisation of ICU patients has significant benefits.
Expert statement: The timing of tracheostomy to facilitate weaning from mechanical ventilation should be the same as in non-COVID-19 patients. Percutaneous dilatational tracheostomy (PDT) with or without guidance (using ultrasound or bronchoscopic) may be preferred over other techniques.
Discussion: The safe period for performing a tracheostomy in COVID-19 patients is recommended to be 10–21 days after tracheal intubation to reduce infectious risk. However, no increased risk of infection to healthcare workers was observed, when clinical judgment-based instead of fixed timing tracheostomy was performed with appropriate PPE use. Modifications to tracheostomy techniques are recommended in COVID-19 patients to reduce aerosolisation risk. Although surgical tracheostomy was recommended over PDT, based on experiences from the SARS epidemic, the use of PDT in COVID-19 patients has not shown any increased risk to healthcare workers till date.
Using a Delphi method, an agreement among experts was reached for 27 statements on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Strong evidence from high-quality clinical trials is needed to clarify the remaining uncertainties.
While these expert clinical practice statements provide clinical direction with C-ARF, some of these general principles may help with the management of other viral pneumonias or future variants of the SARS-CoV-2 strain.
Source: Nasa, Prashant et al. “Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.” Critical care (London, England) vol. 25,1 106. 16 Mar. 2021, doi:10.1186/s13054-021-03491-y