Respiratory support of COVID-19: evolving strategies

At the onset of the COVID-19 pandemic, there was a considerable lack of information regarding the pathophysiology of lung involvement, with several implausible hypotheses being proposed.¹ With a better understanding of the disease, it is abundantly clear that COVID-19 related acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage with significant involvement of the pulmonary vasculature and thrombus formation.² It is also increasingly clear that COVID-19 related ARDS bears considerable resemblance to classical ARDS as we know it, with variable compliance and gas exchange depending on the severity of the disease. In light of our improved understanding of the disease, let us consider how best to optimize respiratory support in patients with COVID-19 pneumonia. 

Non-invasive respiratory support 

During the early stages of the pandemic, caution was advised regarding the use of non-invasive ventilation (NIV) and high flow nasal cannula (HFNC) due to concerns regarding aerosol spread and risk of transmission to healthcare workers. Several guidelines had recommended against the routine use of NIV in COVID-19 patients.³ However, as healthcare systems became rapidly overwhelmed with a large number of patients with respiratory failure, non-invasive strategies were extensively employed. The use of an interphase with an adequate seal minimizes aerosol dispersion and the risk of airborne transmission. Besides, the risk of disease transmission associated with endotracheal intubation also needs to be considered.⁴ Non-invasive respiratory support has been extensively used during the course of the pandemic in various countries. In an early report from China, among 318 patients with COVID-19, failure of high-flow nasal cannula (HFNC) was associated with a PaO₂/FiO₂ ratio of less than 200 mm Hg.⁵ Our experience from a 50-bedded dedicated COVID-19 intensive care unit suggests that non-invasive respiratory support may be effective as the initial treatment modality in most patients who present with respiratory failure. 

An important consideration is the evaluation of the efficacy of NIV therapy and early identification of patients who are likely to fail and require invasive ventilation. Clearly, adequate patient assessment requires bedside vigilance and close monitoring of patients. Patient non-compliance with the interphase often lead to failure; hence, it may be appropriate to intubate such patients instead of persistence with ineffectual therapy.  

Generation of tidal volumes of more than 9.5 ml/kg has been demonstrated to be an independent predictor of NIV failure in patients with moderate to severe degree of hypoxemia. Hence, it may be appropriate to consider invasive ventilation in patients who continue to generate forceful inspiratory efforts with high tidal volumes during NIV.⁶ Besides, endotracheal intubation needs to be strongly considered in patients who continue to be tachypneic with failure to improve oxygenation, requiring progressively higher FiO₂ levels. Delaying intubation in patients who struggle to maintain oxygen saturation despite increasing FiO₂ requirements often leads to catastrophic outcomes. 

Prone positioning

Patients with severe COVID-19 pneumonia appear to be exquisitely responsive to prone positioning with a consistent improvement in oxygenation. Ziehr et al. studied 31 patients who were ventilated in the prone position. The PaO₂:FiO₂ratio improved from a median of 150 to 232 mm Hg, with an increase in compliance from 33 to 36 ml/cm H₂O after assuming the prone position. Prone ventilation was carried out for a median duration of 18 hours; the favorable effect on oxygenation persisted even after return to the supine position.⁷ The salutary effect of prone ventilation in COVID-19 appears to be consistent with previous studies in acute respiratory distress syndrome. We have observed a few patients in our unit who required prone ventilation over several days; the beneficial effect persisted even in the late stages of the disease. 

Awake prone positioning 

Prone positioning of patients receiving non-invasive respiratory support through HFNC or NIV is being increasingly resorted to in COVID-19 associated respiratory failure. In a cohort study from Canada, 17 non-intubated patients with COVID-19 associated respiratory failure underwent prone positioning. The duration of prone positioning ranged from 1 to 7 days with 1 to 6 sessions per day. Each session of prone positioning lasted between 30 to 480 minutes. The median oxygenation saturation improved from 91 to 98% with prone positioning. Invasive ventilation was required in 7 (41%) patients; the majority of patients remained comfortable in the prone position. In our unit, most patients who fail to improve with the initiation of non-invasive respiratory support undergo a trial of prone positioning.  

Timing of intubation

Two phenotypes of COVID-19 pneumonia have been postulated. Type L, with low elastance and preserved compliance, is characterized by lower lung weight and less recruitability and may be seen in the early stage of the disease. As the disease progresses, it evolves into the type H phenotype with high elastance, poor compliance, higher lung weight, and increased recruitability. The proponents of this hypothesis argue that higher tidal volumes with lower PEEP levels may be appropriate with the type L disease, while the conventional low-tidal volume strategy with higher PEEP levels may be beneficial in type H disease.⁸ Patient self-inflicted lung injury, characterized by vigorous spontaneous inspiratory efforts and the generation of pronounced negative pleural pressures may worsen lung injury and lead to progression from the type L to the type H phenotype. It was suggested that “early” intubation may be safer in patients who generate an esophageal pressure difference of more than 15 cm of H₂O during a respiratory cycle.⁹ Considering that the measurement of esophageal pressure may not be feasible in most healthcare setups in the setting of the pandemic, clinical assessment may be more practicable by the bedside. Refractory hypoxemia, the development of hypercapnia, and clinical features suggesting a high work of breathing, including phasic contraction of the sternomastoid muscle on palpation, may be more appropriate indicators for the requirement for intubation.¹⁰

In most instances, COVID-19 related ARDS may be akin to classical ARDS. Conventional ventilation strategies used in classical ARDS may be appropriate, with the use of tidal volumes ranging between 4–8 ml/kg and driving pressures of less than 15 cm of H₂O. Patients with PaO₂/FiO₂ ratios below 150 should undergo early prone ventilation.¹¹

Timing of tracheostomy in COVID-19 

The ideal time to perform a tracheostomy in COVID-19 patients is shrouded in controversy. Contrasting views have emerged, with some European guidelines recommending an early approach,¹² while British and North American guidelines suggest performing tracheostomy after a minimum of 14 days, or when the RT-PCR becomes negative.¹³ There is a glaring lack of controlled data on the timing of tracheostomy in COVID-19. Extubation may be possible in patients with improving respiratory and hemodynamic parameters who undergo a successful spontaneous breathing trial. However, considering the long-term nature of more severe disease, premature extubation to rescue strategies such as NIV may often lead to extubation failure and may lead to the urgent requirement for reintubation with associated risks to patients and caregivers. 

In a British study, tracheostomy was performed in 100 patients with COVID-19 and compared with 64 who did not undergo tracheostomy.¹⁴ Patients were clinically improving with reducing oxygen requirements, an FiO₂ of less than 0.4, and a PEEP of less than 10 cm H₂O. Tracheostomy was performed at 13.9 (4.5) days of intubation. The APACHE-II scores were similar between groups. The 30-day survival was significantly higher among patients who underwent tracheostomy compared to those who did not (85% vs. 42%; p <0.0001). Furthermore, tracheostomy within 14 days of intubation was associated with a significantly shorter duration of ventilator support and ICU length of stay.    

Tracheostomy may be appropriate in mechanically ventilated patients who show early signs of recovery from severe disease. However, patients who still require high levels of FiO₂ and PEEP are unsuitable for early tracheostomy. Patients who are likely to require prone positioning are better off with an endotracheal tube compared to tracheostomy, which leads to the inability to visualize the airway with the risk of accidental tube displacement. 

Summary

• The pathophysiology of COVID-19 related ARDS may not be significantly different from classical ARDS
• Different phenotypes with variable lung compliance depending on the disease stage have been proposed; however, the phenotypical difference is also seen with classical ARDS
• Non-invasive respiratory support is efficacious and may reduce the requirement for invasive ventilation; in contrast to earlier recommendations, NIV and HFNC are often effectively employed as the initial modality of respiratory support 
• COVID-19 related ARDS responds well to prone positioning, both in intubated and non-intubated patients. Response to prone positioning occurs even in the later stage of disease
• The decision regarding the timing of intubation and invasive mechanical ventilation needs to be individualized. It is important to diligently monitor patients who are on non-invasive support. Patients who show signs of deterioration must be identified early with the initiation of invasive ventilation 
• The time-tested ventilation strategy of low tidal volumes and titrated PEEP with limitation of driving pressures is appropriate in COVID related ARDS  
• The timing of tracheostomy also needs individualization. Tracheostomy needs to be considered in patients who may require long-term ventilation and carry a high risk of extubation failure. The FiO₂ requirement should come down to 0.4 or less with a PEEP requirement of 10 cm H₂O or less before tracheostomy is contemplated. 

References

1.         Wenzhong L, Hualan L. COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. Published online July 13, 2020. doi:10.26434/chemrxiv.11938173.v9

2.         Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432

3.         ANZICS-COVID-19-Guidelines-Version-1.pdf.

4.         Fowler RA, Guest CB, Lapinsky SE, et al. Transmission of Severe Acute Respiratory Syndrome during Intubation and Mechanical Ventilation. Am J Respir Crit Care Med. 2004;169(11):1198-1202. doi:10.1164/rccm.200305-715OC

5.         Wang K, Zhao W, Li J, Shu W, Duan J. The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China. Ann Intensive Care. 2020;10(1):37. doi:10.1186/s13613-020-00653-z

6.         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. doi:10.1097/CCM.0000000000001379

7.         Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE

8.         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. doi:10.1007/s00134-020-06033-2

9.         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. doi:10.1007/s00134-020-06033-2

10.       Fan E, Beitler JR, Brochard L, et al. COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Lancet Respir Med. 2020;8(8):816-821. doi:10.1016/S2213-2600(20)30304-0

11.       Trahtemberg U, Slutsky AS, Villar J. What have we learned ventilating COVID-19 patients? Intensive Care Med. Published online October 12, 2020:s00134-020-06275-0. doi:10.1007/s00134-020-06275-0

12.       Schultz P, Morvan J-B, Fakhry N, et al. French consensus regarding precautions during tracheostomy and post-tracheostomy care in the context of COVID-19 pandemic. Eur Ann Otorhinolaryngol Head Neck Dis. 2020;137(3):167-169. doi:10.1016/j.anorl.2020.04.006

13.       139939. Tracheotomy Recommendations During the COVID-19 Pandemic. American Academy of Otolaryngology-Head and Neck Surgery. Published March 27, 2020. Accessed October 17, 2020. https://www.entnet.org/content/tracheotomy-recommendations-during-covid-19-pandemic

14.       Breik O, Nankivell P, Sharma N, et al. Safety and 30-day outcomes of tracheostomy for COVID-19: a prospective observational cohort study. Br J Anaesth. 2020;0(0). doi:10.1016/j.bja.2020.08.023