key: cord-0839397-tul7tphc
authors: Winck, João Carlos; Ambrosino, Nicolino
title: COVID-19 pandemic and non invasive respiratory management: every Goliath needs a David. An evidence based evaluation of problems.
date: 2020-04-27
journal: Pulmonology
DOI: 10.1016/j.pulmoe.2020.04.013
sha: b6370a094816fd942183e9e1525487ddf2451797
doc_id: 839397
cord_uid: tul7tphc

Abstract Background and aim The war against Covid-19 is far from won. This narrative review attempts to describe some problems with the management of Covid-19 induced acute respiratory failure (ARF) by pulmonologists. Methods We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and reviewed the references of retrieved articles for additional studies. The search was limited to the terms: Covid-19 AND: acute respiratory distress syndrome (ARDS), SARS, MERS, non invasive ventilation (NIV), high flow nasal cannula (HFNC), pronation (PP), health care workers (HCW). Results Protection of Health care workers should be paramount, so full Personal Protective Equipment and Negative pressure rooms are warranted. HFNC alone or with PP could be offered for mild cases (PaO2/FiO2 between 200-300); NIV alone or with PP may work in moderate cases (PaO2/FiO2 between 100-200). Rotation and coupled (HFNC/NIV) strategy can be beneficial. A window of opportunity of 1-2hours is advised. If PaO2/FIO2 significantly increases, Respiratory Rate decreases with a relatively low Exhaled Tidal Volume, the non-invasive strategy could be working and intubation delayed. Conclusion Although there is a role for non-invasive respiratory therapies in the context of COVID-19 ARF, more research is still needed to define the balance of benefits and risks to patients and HCW. Indirectly, non invasive respiratory therapies may be of particular benefit in reducing the risks to healthcare workers by obviating the need for intubation, a potentially highly infectious procedure.

While the world is racing to contain the spread of COVID-19 and updated/real time medical information has reached high ranked journals faster than ever, there are still a lot of questions unanswered. The huge efforts made by some countries have allowed us to gain critical time for better preparation and increase our awareness In fact some reflections could help pulmonologists tackle the current pandemic. Reports from China suggest that 81% of COVID-19 are mild, 14% are severe and that 5% require intensive care 1 . Mortality rate in the series published from China, Italy and US ( 2-16 , ranges from 1,4% in hospitalized 6 to 61,5% in critically ill patients 10 .

In this frame the role of pulmonologists is increasing. This narrative review tries to describe some problems with the management of Covid-19 induced acute respiratory failure (ARF) by pulmonologists, remaining aware that the overflow of new information may make all reports rapidly obsolete.

We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, from 2010 to April, 15th 2020, with no language restriction. We also reviewed the references of retrieved articles for additional The ERS/ATS clinical practice guidelines recommend (not firmly) NIV as a preventive strategy for avoiding intubation in hypoxaemic ARF 20 only when performed by experienced teams in highly selected cooperative patients with community-acquired pneumonia or early ARDS without any associated major organ dysfunction.

In patients with de novo ARF under NIV, large expiratory tidal volumes (VTE) may be generated in assisted pressure controlled modes by the ventilator pressure and the one generated by the respiratory muscles. Therefore reliable monitoring of VTE and unintentional leaks would be of outmost importance. When using an ICU ventilator driven by high pressures in the double limb configuration, leaks are computed as the difference between inspired tidal volume and VTE. As a consequence, the amount of tidal volume that the patient gets is usually quantified as VTE 21 . In the majority of patients with " de novo" moderate-to-severe hypoxaemia, a targeted VTE of 6-8 mL/kg was impossible to achieve by NIV with humidified masks and ICU ventilators 22 . A higher VTE was independently associated with NIV failure. In the subgroup of patients with an arterial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio up to 200, a mean VTE higher than 9.5 mL/kg over the first four cumulative hours of NIV accurately predicted NIV failure 22 . A higher VTE was independently associated with NIV failure. In the subgroup of patients with an arterial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio up to 200, a mean VTE higher than 9.5 mL/kg over the first four cumulative hours of NIV accurately predicted NIV failure.

In a recent randomized controlled trial, Patel et al 23 significantly, compared to NIV delivered via facial mask (from 61% to 18%, respectively). As the helmet seems a more effective and tolerable interface in this setting, it would make sense to evaluate how it stands compared to HFNC 24 . Indeed, very recently, a physiological randomized cross-over study 25 , concluded that in patients with PaO2/FiO2<200, high-PEEP helmet NIV could be preferred over HFNC to optimize oxygenation and mitigate the inspiratory effort, especially in most severely hypoxaemic patients and in those exhibiting intense inspiratory effort during HFNC. Caution is needed in patients with low inspiratory effort during HFNC, because they can experience increases in dynamic transpulmonary driving pressure while on NIV with the helmet.

A recent systematic review 26 shows that compared to conventional oxygen therapy HFNC decreases risk of requiring intubation without impacting mortality. The authors pointed out that flow rates were variable between the studies and also, duration of treatment was not analysed. A physiologic randomized controlled study 27 showed that the higher (60 L·min −1 ) the flow, the better the physiologic response.

Adding prone positioning to HFNC, Riera et al, Riera et al 28 demonstrated, in healthy subjects, that it leads to a more homogeneous distribution of endexpiratory lung impedance possibly translating into better oxygenation.

In awake, non-intubated, spontaneously breathing patients with hypoxaemic ARF (majorly immunocompromised) Scaravilli et al 29 , showed a significant improvement in PaO2/FiO2 with prone positioning. More recently, early prone positioning added to HFNC or NIV avoided the need for intubation in up to half of the patients with moderate to severe ARDS including those with viral pneumonia 30 . No health care professional was infected during this study carried out in isolation negative pressure rooms. Other authors report similar results 31 and a randomized controlled trial is ongoing 32 .

Frat JP et al 33 , in patients with PaO2/FiO2 < 300, studied the effect of sequential application of sessions of HFNC and NIV. Intubation was required in 36% of patients, including individuals with ARDS. 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. 

Before choosing the best respiratory support for patients with ARF, we need to understand the risks of different interventions. A systematic review concluded that the most consistent association with increased risk of SARS transmission to professionals was tracheal intubation; mask ventilation was also positively associated (only 2 studies) but data were not considered sufficiently robust to establish firm conclusions 41 .

As shown in Table 1 , bench studies showed that dispersion of exhaled air is different depending on the respiratory therapies and interfaces (nasal cannula, oro-nasal mask or helmet) [42] [43] [44] [45] [46] . Oxygen delivered at 6 L/min in a mild lung injury This increase in large droplets was not seen using the NIV circuit modification (with non-vented mask and exhalation filter). Oxygen therapy did not increase droplet count in any size range.

From these studies, we might conclude that NIV through the helmet with double limb circuit and a good seal at the neck-helmet interface would be a safe option for managing infectious patients with hypoxaemic ARF. As alternative, the 

Studies coming from the above mentioned laboratory 43 , showed that with HFNC (model Airvo 2; Fisher & Paykel®) exhaled air mean distances increased from 65 to 172 mm when flow was increased from 10 to 60 L·min−1, a shorter distance than that from application of CPAP through the commonly used nasal pillows.

Moreover air leakage to 620 mm occurred laterally when HFNC and the interface tube became loose 43 

Analyzing current trends in NIV and HFNC usage in all published series in major journals shows the following [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] 15, 16 , mean NIV usage in hospitalized patients in China was 20,1% ( from 4,9 to 56%; higher in series including only critically ill 10 , moderate to severe 14 and in one series of Pneumonia cases 11 ); in Italy 11% 15 ; and in USA from 0 to 19% 12, 13 . Mean HFNC usage in China was 22,8% (raging Page 9 of 25 J o u r n a l P r e -p r o o f from 0 to 63,5% and higher in series including only critically ill 10 and moderate to severe 14 ) , in Italy 15 0%, and in the USA from 4,8% to 42% (higher in Critically ill in Seattle 13 than in Washington-12 ). In a real world study in two Chongqing hospitals in China 53 52 of the patients experiencing severe ARF, 63% of patients were treated with HFNC as first-line therapy, 33% were treated with NIV and 4%

were treated with invasive ventilation. Of the HFNC patients, 41% experienced failure, failure rate being 0 in patients with PaO2/FiO2 > 200 and 63% in those with PaO2/FiO2 ≤ 200.

One important issue about HFNC is that the amount of condensation in the circuit increases when the ambient temperature decreases. At present, the condensed water can become an important source of infection for COVID-19 so, avoidance or reduction in condensation may be very important when HFNC is used. Bacterial contamination of the inner surface of circuits after termination of HFNC has been shown in 16.1% of cases, mainly occurring at the interface end.

This figure is as high as for anesthetic breathing circuits, but can be decreased by circuits fitted with heating wires, which greatly reduce condensation 54 .

Although the evidence from the recent series is lacking (with no single mention of transmission to professionals through these techniques), there are authors that do not recommend NIV or HFNC until the patients is cleared of COVID-19 55 . However some other experiments from China suggest that early intervention with HFNC and NIV associated or not with prone positioning can lead to lower mortality, less than 1% of cases needing intubation (versus 2.3% of National average) 53 .

Options differ between Scientific Societies [56] [57] [58] [59] [60] [61] [62] [63] (Table 2) Non invasive ventilation and HFNC can be reserved for patients with mild ARDS, with close monitoring, airborne precautions, and preferably in single rooms. In patients with suspected or diagnosed COVID-19 requiring NIV, helmets may be the best solution for CPAP or NIV, because of minimal or no dispersion from leaks, easy to filter/scavenge exhausted gas. Due to the scarcity of this interface it is probable that traditional oro-nasal masks will be the most commonly used. In this case suboptimal NIV set-up, with interface with inappropriate seals and improper circuitry will not be tolerable. If NIV is the option, try "protective-NIV" with lower tidal volumes between 6 and 8 mL/kg 69 .

This simple description of some problems of this narrative review elicits the need for innovative strategies 70 in addition to medical therapy and vaccination campaigns.

All respiratory therapies represent a risk of aerosol generating procedures during the care of patients with COVID-19. Personal Protective Equipment and Environmental Control/Engineering should be the initial concern and consideration when managing patients with COVID-19. Given the current circumstances it is not likely that there will be randomized controlled trials to confirm which non invasive respiratory support is better to reduce the need for intubation in the context of COVID-19 pandemic. Manufacturers should be urged to create safer interfaces, viral proof circuitry and "new generation" non invasive ventilators with integration of different therapies, specific monitoring and necessary safety features. It is our impression, that this will be a marathon not a sprint, and like David we must beat Goliath. Table 1 Exhaled air dispersion according with modalities and interfaces [43] [44] [45] [46] Interfaces and Pressures (in cmH20)

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