Invasive mechanical ventilation in COVID-19 associated ARDS

There is increasing worldwide experience in the management of ventilation in patients with COVID-19 associated acute respiratory distress syndrome (ARDS). Healthcare systems have been stretched to the limit with a relative lack of resources against the background of a rapid surge in patients who are critically ill. A large majority of critically ill patients with COVID-19 require respiratory support, including invasive mechanical ventilation. Is COVID-19 pneumonia distinctly different from other common causes of ARDS? Do we need to modify our ventilation strategy, particularly against the background of healthcare systems that are rapidly overwhelmed? 

When to intubate?

The question of when to initiate invasive mechanical ventilation in patients receiving non-invasive types of respiratory support has often bewildered clinicians over the ages. Harry Lassen was the chief physician at the Blegdam Hospital, Copenhagen, during the polio epidemic that ushered in the era of mechanical ventilation. He observed that in the US, respirators were being used too early among patients who did not actually require it; this appeared to improve survival among these patients. Non-invasive modalities of respiratory support are being extensively resorted to in patients with COVID-19, particularly in resource-limited settings. However, there is a dearth of literature regarding the clinical efficacy of prolonged non-invasive ventilation in COVID-19. 

Patients who generate vigorous spontaneous respiratory efforts and breathe large tidal volumes develop a high transpulmonary pressure gradient, leading to increased fluid leakage into the lungs. This phenomenon is similar to ventilator-associated lung injury observed in patients who receive injurious ventilation strategies.¹ Increased work of breathing associated with vigorous spontaneous respiratory efforts may be noted by the phasic contraction of the sternomastoid muscle on palpation.² In the LUNG-SAFE study, among 2813 patients with acute respiratory distress syndrome (ARDS), 436 (15%) patients received non-invasive ventilation (NIV). Intensive care mortality was higher in patients with a PaO₂/FiO₂ of less than 150 who received NIV.³

Delaying intubation to the point of acute decompensation usually results in disastrous consequences. Clearly, rapid progression of respiratory failure and lack of an early response to non-invasive support should trigger the requirement for expeditious intubation if aggressive supportive measures are otherwise appropriate. Hemodynamic instability and the presence of multiorgan failure would generally necessitate early invasive ventilation. Worsening hypercapnia and altered conscious level also suggest the requirement for invasive ventilation.

Ventilation parameters

Tidal volume and ventilation pressures 

Low tidal volume ventilation has been firmly established as a safe and effective strategy in improving clinical outcomes in ARDS.⁴ Cohort studies from several countries, including the US, UK, Italy, and China support the use of tidal volumes ranging between 4–8 ml/kg predicted body weight in patients with COVID-19.^5–7  Limitation of plateau pressure to 30 cm of H₂O and the driving pressure (Plateau pressure – PEEP) to 15 cm of H₂O or less⁸ are also an important facets of the ventilation strategy. 

PEEP and recruitment 

During the initial phase of the pandemic, two distinctive phenotypes were proposed. The low elastance (L) type was characterized by relatively less involvement of the lung parenchyma, less recruitable lung, and a poor response to PEEP. In contrast, the high elastance phenotype (H) was considered to result in more extensive parenchymal involvement, a more recruitable lung, and a greater response to PEEP.⁹ However, increasing experience suggests that these different phenotypes probably reflect a varying spectrum of disease severity.¹⁰ Early disease typically demonstrates the L phenotype and transitions to the H phenotype with disease progression.   

It is important to identify patients who have a high potential for alveolar recruitment. A higher level of PEEP may lead to improved gas exchange and a lower risk of ventilator-induced lung injury in patients with recruitable lung units. In contrast, patients with poorly recruitable lungs may suffer adverse hemodynamic consequences and ventilator-induced lung injury, including barotrauma from the injudicious application of high levels of PEEP. Hypoxemia with poor recruitability may arise due to thrombotic phenomena within the lung or inhibition of the hypoxic pulmonary vasoconstrictor response.

How to assess recruitability? 

The recruitment to inflation ratio is a convenient bedside tool to assess recruitability. On volume-controlled ventilation, the PEEP level is dropped abruptly by 10 cm H₂O (usually from 15 to 5 cm H₂O; the initial PEEP level must be set above the airway opening pressure). 

Dropping the PEEP level from 15 to 5 cm H₂O results in a large “exhaled release volume”. The difference between the “exhaled release volume” and the predicted volume at low PEEP provides an estimate of the recruited volume as the PEEP level increases from 5 to 15 cm H₂O. The recruited volume divided by pressure change denotes the compliance of the “recruited” lung. The recruitment to inflation ratio is the ratio of the compliance of the recruited lung at high PEEP to the compliance at low PEEP. Recruitment to inflation ratio of more than 0.5 suggests the potential for recruitment.¹¹Details of the procedure with video demonstration and a calculator for the recruitment to inflation ratio are available at https://crec.coemv.ca/. In a series of 25 patients with COVID-19 pneumonia, 64% were considered recruitable based on the recruitment to inflation ratio.¹²

In our experience, several patients who receive invasive mechanical ventilation and survive the initial phase of the disease develop progressive pulmonary fibrosis, often with recurrent episodes of bacterial superinfection. These patients have poorly compliant lungs and become progressively difficult to ventilate, with worsening hypoxia and hypercapnia; a significant number of these patients die after several weeks of ventilator support. However, some patients improve gradually to a variable level of function; continued home oxygen therapy may be required in those who eventually recover.  

Prone ventilation 

Mechanical ventilation in the prone position results in more optimal ventilation-perfusion matching and improved oxygenation, besides reducing the risk of ventilator-induced lung injury. Several decades of experience with prone ventilation in ARDS finally led to the PROSEVA trial that demonstrated improved survival in patients with a PaO₂/FiO₂ of less than 150 mm Hg.¹³ Conventional ventilation strategies must be optimized, including the titration of PEEP to an appropriate level, the use of neuromuscular blocking drugs, and diuretics if volume overload is likely. The prone position is usually maintained for a duration of 16–24 hours. A modified care plan is essential for the management of ventilation in the prone position. Care must be taken to prevent pressure-related injury, including adequate protection of the forehead and the eyes, change of limb position as much as possible, and gentle repositioning of the head from one side to the other. A reverse Trendelenburg position may help to reduce facial edema. Enteral feeds may be continued as usual during prone ventilation.¹⁴

Tracheostomy 

Early attempts to wean and extubate are generally unsuccessful in patients with COVID-19 associated ARDS. However, in our experience, weaning and eventual extubation have been possible in many of these patients. The optimal timing of tracheostomy in patients with COVID-19 who receive invasive mechanical ventilation is currently unknown. Although tracheostomy within 7–10 days is feasible in these patients, a more pragmatic approach would be to wait for a longer duration. Experience suggests that many COVID-19 patients may require ventilation for a longer duration, but may be successfully weaned and extubated. Bedside percutaneous dilatational tracheostomy is the preferred option, with due care to prevent aerosolization as much as possible. In a prospective observational study from the UK, 100 of 164 (61%) of COVID-19 patients underwent tracheostomy, while 27 (16%) of patients were extubated at 30 days. The mean time to the performance of tracheostomy was 13.9 (4.5) days after initiation of invasive ventilation. No difference in survival was observed between patients who underwent tracheostomy before vs. after 10 days. A shorter duration of mechanical ventilation and ICU stay was observed among patients who underwent tracheostomy within 14 days of intubation.¹⁵

Although earlier tracheostomy may be feasible, one needs to consider the potential benefit of performing an early tracheostomy if long-term ventilator support seems likely. In patients who continue to require a high level of ventilator support with a low PaO₂/FiO₂ ratio and continued requirement for sedatives and neuromuscular blocking agents, there is little benefit in performing a tracheostomy. Besides, the transient deterioration in oxygenation that may occur during tracheostomy may be detrimental in such patients. Furthermore, prone ventilation is more difficult to carry out in the tracheostomized patient. It may be more prudent to perform a tracheostomy for patients who need a longer duration of ventilator support once the PaO₂/FiO₂ ratios improve, with acceptable PEEP levels (< 10 cm H₂O) and when weaning down of ventilator support appears realistic. 

Summary

• There are no typical features that differentiate severe COVID-19 from the usual causes of ARDS
• Early disease is usually characterized by preserved compliance, recruitability, and good response to prone ventilation; later disease with the onset of fibrosis results in stiffer lungs, refractory hypoxemia, and poor response to the application of PEEP and prone ventilation 
• Although extensively employed in COVID-19 related ARDS, the clinical efficacy of prolonged non-invasive ventilation is unknown
• Patients who have vigorous respiratory efforts with the generation of high spontaneous tidal volumes and persisting hypoxemia usually require earlier invasive ventilation, depending on the local availability of resources 
• Low tidal volume ventilation between 4–8 ml/kg predicted body weight, the judicious application of PEEP based on the potential for recruitment, and early prone ventilation are important facets of invasive ventilation 
• Although early tracheostomy is feasible, many patients may still be weaned and extubated after a longer duration of intubation  
• It is more pragmatic to perform a tracheostomy once the PaO₂/FiO₂ ratios improve, and PEEP levels come down, with a realistic possibility of stopping or reducing the dose of sedative and neuromuscular blocking agents   

References

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3.         Bellani G, Laffey JG, Pham T, et al. Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study. Am J Respir Crit Care Med. 2017;195(1):67-77. doi:10.1164/rccm.201606-1306OC

4.         Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308. doi:10.1056/NEJM200005043421801

5.         Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8(12):1201-1208. doi:10.1016/S2213-2600(20)30370-2

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10.       Bos LDJ, Sinha P, Dickson RP. The perils of premature phenotyping in COVID-19: a call for caution. Eur Respir J. 2020;56(1):2001768. doi:10.1183/13993003.01768-2020

11.       Chen L, Del Sorbo L, Grieco DL, et al. Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial. Am J Respir Crit Care Med. 2020;201(2):178-187. doi:10.1164/rccm.201902-0334OC

12.       Beloncle FM, Pavlovsky B, Desprez C, et al. Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome. Annals of Intensive Care. 2020;10(1):55. doi:10.1186/s13613-020-00675-7

13.       Guérin C, Reignier J, Richard J-C, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103

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15.       Breik O, Nankivell P, Sharma N, et al. Safety and 30-day outcomes of tracheostomy for COVID-19: a prospective observational cohort study. British Journal of Anaesthesia. 2020;125(6):872-879. doi:10.1016/j.bja.2020.08.023