Manuscript: In order to manage moderate to severe category COVID-19 patients in the ICU, institutional protocols are being regularly updated with the changing guidelines. Our hospital is a tertiary care dedicated COVID Centre with a significant ICU admission turnover. More than 200 sick COVID patients with SpO2 of 65-80% on admission have recovered and this experience has led us to develop “evidence guided, experience based and patient compatible 3-step protocol” for managing moderate to severe category of COVID19 infections. 

Emerging evidence has demonstrated that the initial lung involvement COVID-19 can be characterised more by a “pneumonia pattern” rather than a typical “ARDS pattern”. It therefore makes sense that the ventilation strategies applied should be different from the routine ARDS protocol [2]. ERS/ATS clinical practice guidelines recommend that NIV for community-acquired pneumonia or early ARDS as is seen in early COVID should be used in highly selected, cooperative patients [3].

The China experience has suggested that early intervention with HFNC and Non-invasive ventilation (NIV) associated with or without prone positioning can lead to lower mortality with less than 1% of cases needing intubation (versus 2.3% of National average) [4].

However, the success of NIV depends to a large extent on patient cooperation. In a COVID ICU, apart from being an intensivist, the anaesthesiologist is now also playing the role of a guidance counsellor, a psychologist and a physician. The isolation, related to disease management per se has led to a significant increase in morbidity and stress amongst the patients. Patient cooperation and an understanding of his/her own condition can greatly impact the management and outcome. These patients can be categorised into three types of behavioural stages

• Cooperative and alert – at the time of admission 

• Cooperative and apprehensive – after 2-3 days in ICU

• Disoriented and apprehensive – after 5 days in ICU

It therefore makes sense that NIV should be started early, since a delay may permit further deterioration and increase the likelihood of NIV failure [1].

Three Step COVID-19 Patient Management Protocol

Even with low levels of saturation, COVID19 patients are often comfortable (“happy hypoxia”) and cooperative during the initial course of admission. And, being able to see healthcare professionals is very reassuring for them [1]. 

The 3-step protocol was created keeping these evidence and experiences in mind. The protocol was applied on conscious patients with refractory hypoxia maintaining saturation of 92-94% on Non-Rebreathing Mask (NRM) with flows of 10-15l/min, respiratory rate <28/min on admission to the ICU and had X-Ray findings of >50% involvement of lung fields with no evidence of a pneumothorax.

• First Step: For early alveolar recruitment, applying Bipap (Bilevel positive airway pressure) support for 48 hours with Pressures and FiO2 titrated to maintain SpO2> 94% 

• Second Step: Wean off the Bipap support over 48 hours (by attempting Bipap free intervals with High Flow Nasal Oxygenation (HFNO)) and replace with 24-hour HFNO support for next 3-5 days. HFNO was initiated at a flow rate of 60-70L/min corresponding with a PEEP of 6-7cm of H2O and gradually stepped down to 30-20L/min. In case the patients continued to worsen on Bipap support, then elective intubation was planned

• Third Step: place on NRM with intermittent face mask trials to allow early shift out of the ICU

The aim of the 3-step protocol was to ensure that maximum benefit of alveolar recruitment was provided in the first two days of ICU admission. The turning point for the successful expansion of NIV is its ability to achieve the same physiological effects as invasive mechanical ventilation with the avoidance of the life-threatening risks correlated with the use of an artificial airway [1]. Keeping this in mind, the bilevel pressure support was started with an inspiratory pressure of 12-16 cm of H2O (maintained depending on the tidal volume generated) and expiratory pressure of 5-10 cm of H2O, to prevent alveolar collapse. The Bipap mask was removed only during meals with a staff standing close by, and nasal prongs were applied for this duration.

The patients were most cooperative in the initial few days of ICU stay. Traditionally Bipap is used after failure to maintain saturation with NRM and HFNC in most COVID ICUs. In our experience, a Bipap mask becomes uncomfortable and patient compliance is reduced if it is continued for a longer period of time. Hence, its application was best and most effective when used early in the course of the illness. 

We observed that early Bipap not only ensured greater compliance and patient cooperation but resulted in improved patient outcome. Following an improvement in the PaO2/FiO2 ratio with reduction in FiO2 requirements, the patients were subsequently placed on High Flow nasal cannula (HFNC). HFNC was started with 60-80L/min with FiO2 of 0.6 or above titrated to maintain a SpO2 of >94%. This aided in continued alveolar recruitment and improved oxygenation as HFNC has been shown to deliver up to 1 mm of Hg of PEEP for every 10L/min of flow delivered with closed mouth breathing [5]. Additionally, the patient was now more comfortable and cooperative. This technique was used for another 2-3 days, with interval NRM trials. 

Frat J.P. et al. studied the effect of sequential application of sessions of HFNC and NIV patients with PaO2/FiO2 <300 and were able to reduce intubation to 36% of patients with ARDS. The authors concluded that due to the good tolerance and efficacy on oxygenation, HFNC could be a good option to be used between NIV sessions to pursue a coupled non-invasive strategy of ventilation without a marked impairment of oxygenation [6]. 

A pertinent concern during HFNC use was the aerosol generated with the high flow and its impact on health care workers. Loh et al demonstrated that while wearing a well-fitting nasal cannula at 60L/min flow, cough generated droplets can spread up to a distance of 4.50 m [7]. In our ICU, we started the practice of placing N 95 masks over the HFNC to reduce aerosol exposure of the HCWs. It provided the additional advantage of improving the fitting of the cannula and reducing the oxygen dilution.

If more than 50% of the lung fields are involved, the use of Bipap for recruitment is a better technique than the HFNC, since we are able to generate higher positive airway pressures [8].

The clinical outcome was considered successful if:

• The patient’s oxygen requirements were gradually reduced 
• The saturation was improved to above 95%
• The patient overall became comfortable

Treatment of ARDS from COVID-19 remains an ongoing challenge. It is important to continuously adapt the treatment strategy to the emerging evidence and to tailor the approach with patient compliance Clinical strategies using a step-up approach of sequential application of Bipap and HFNC can be beneficial in patients with moderately severe hypoxemia. This 3-step protocol has provided us with good results in 12 ICU patients and we were able to successfully treat obese, geriatric and cachexic patients who presented with SARI due to COVID19.

1. Scala, R. and Pisani, L. "Non-invasive ventilation in acute respiratory failure: which recipe for success?" European Respiratory Review, vol. 27, 2018.

2. Marini, J. and Gattinoni, L. "Management of COVID-19 respiratory distress." JAMA, 2020.

3. Rochwerg, B. et al. "Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure." European Respiratory Journal, vol. 50, 2017.

4. Wang, K. et al. "The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China." Annals of Intensive Care, vol. 10, 2020, pp. 37.

5. Parke, R. et al. "Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle." Respiratory Care, 2013.

6. Frat, J.P. et al. "Sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study." Respiratory Care, vol. 60, 2015, pp. 170–178.

7. Loh, N.W. et al. "The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak." Canadian Journal of Anaesthesia, 2020.

8. Parke, R.L. et al. "Effect of very-high-flow nasal therapy on airway pressure and end-expiratory lung impedance in healthy volunteers." Respiratory Care, vol. 60, 2015, pp. 1397–1403.