Non-invasive ventilation (NIV) vs High flow nasal oxygen (HFNO)

Definition of Severe illness

Pneumonia with ANY ONE of the following:

•  severe respiratory distress or respiratory rate >30/min
•  SpO2 <90% on room air •  NO invasive or non-invasive respiratory support needed Definition of critical:

•  Requirement for high-level respiratory support: noninvasive ventilation, high-flow oxygen (≥20 litres per minute) or invasive mechanical ventilation
•  OR acute respiratory distress syndrome (PaO2/FiO2 ratio of <300) •  OR sepsis •  OR shock

Non-invasive ventilation (NIV) can reduce endotracheal intubation and mortality in patients with acute respiratory distress syndrome (ARDS)while preventing nosocomial complications in COVID-19 infection. NIV can be delivered via a face mask or helmet interface (a transparent hood that covers the entire head of the patient with a soft collar neck seal ¹. High-flow oxygen therapy through a nasal cannula is a technique whereby heated and humidified oxygen is delivered to the nose at high flow rates. These high flow rates generate low levels of positive pressure in the upper airways, and the fraction of inspired oxygen (FIO₂) can be adjusted by changing the fraction of oxygen in the driving gas.

The evidence to answer the PICO question was very limited. There was only one randomized trial with 109 participants comparing NIV (delivered via helmet in the first 48 hours followed by HFNO), vs HFNO alone, as the initial ventilatory support for moderate to severe hypoxemic respiratory failure among COVID-19 patients. The study was small and the GRADING of the evidence very low, indicating that the research evidence is insufficient to recommend one over the other another as the initial ventilatory strategy.

The major issue with this trial was that patients in the NIV arm received NIV alone for only 48 hours; after which they also received HFNO in addition. However, the outcomes were recorded at 28 days. This makes it difficult to assess whether the outcomes reported in the NIV arm are related to NIV or the NIV followed by additional HFNO. The trial did not demonstrate a difference in the ‘number of days free of respiratory support’ within 28 days after enrolment. The number of ‘invasive ventilation free days’ was higher in the NIV group, but the overall rate of endotracheal intubation was lower in the NIV arm. No difference was demonstrated for mortality at 28 days, length of ICU stay, length of hospital stay, ICU acquired infection, and barotrauma in the two arms. Due to the methodological issue highlighted, and the small sample size, there is very uncertain evidence regarding the benefit of either modality over the other for these outcomes.

Date of latest search: 25^th June 2021.

Date of completion & presentation to Expert Working Group: 25 June 2021.

Date of planned review: 25^th December 2021.

Evidence synthesis team:  Jefferson Daniel J, Avinash A Nair, Richard Kirubakaran, Priscilla Rupali and Bhagteshwar Singh.

Problem

The key healthcare challenge of the COVID-19 pandemic has been the safe delivery of respiratory support on a large scale for management of the resultant acute respiratory distress syndrome (ARDS). Need for low technology and easily implementable oxygen delivery or respiratory support interventions to prevent further progression of ARDS has become the need of the hour. However, HFNO though used widely during this pandemic its efficacy vs NIV has been an area of equipoise and has led to much debate, with regard to the benefits with prevention of progression to invasive mechanical ventilation and harms to healthcare workers due to aerosol generation. NIV is resource intensive and needs a specific skill set which is not easy to come by, while HFNO is likely to be less resource and personnel intensive. Another important point to consider has been which intervention is likely to result in lower consumption of oxygen considering the acute urgency of the situation.

Desirable effects

The group considered the evidence presented. The previous meeting had considered evidence in the pre-covid era and with the results available from the HENIVOT trial the group decided to evaluate, evidence in the COVID era only. The evidence seemed to favour NIV in the outcomes of intubation at 28 days and various time to event outcomes like ventilation free days (invasive ventilation), length of ICU and hospital stay (by 1-14 days). It was not significant for outcomes like mortality, intubation at 4 and 8 days and adverse outcomes like ICU related nosocomial infections and barotrauma. The group also discussed at length the indirectness of this low certainty evidence there were many deviations from normal clinical practice (1) the various problems within the HENIVOT trial of NIV arm being given NIV only for 48 hours prior to switching to HFNO which may not again give a clear picture with regard to benefit of NIV over HFNO (2) Switching from HFNO directly to invasive mechanical ventilation without a trial of NIV (3) NIV was delivered by helmets which is not a common interface used in India. Hence the consensus in the group was that the evidence for desirable effects of NIV over HFNO was small.

Undesirable effects

The undesirable effects of NIV were thought to be trivial. NIV when delivered through a helmet did not seem to offer an advantage or cause a disadvantage when compared with HFNO for the outcomes of ICU infections or barotrauma. There was a concern regarding the possibility of nosocomial transmission of COVID-19 if given HFNO, though this risk is still not negligible if NIV delivered via mask rather than through a helmet.

Certainty of evidence

This was agreed upon as “very low” based on the evidence presented.

Values

The group agreed that there was no important uncertainty or variability with regard to the outcomes studied. These were valid outcomes which were clinically relevant.

Balance of effects

The magnitude of desirable effects being small and undesirable effects being very low for the intervention of NIV and comparison of HFNO with very low certainty of evidence the group voted that the balance of effects did not favour either the intervention or the comparison.

Resources required

The group discussed that the costs varied depending on the interface, skill set of personnel involved, amount of oxygen utilised and the setting that it was used in. Helmets use far more oxygen as compared to the masks used for NIV, however the group agreed that some of that could be balanced by using air rather than oxygen. Masks are also a less expensive alternative as compared to helmets. There may be small savings if we use helmet with air rather than oxygen.

Certainty of evidence of required resources

The group considered this as low but cautioned that this was based on clinical experience rather than studies.

Cost effectiveness

Cost effectiveness would depend on resources like the interfaces, oxygen flow rate, devices and capital infrastructure and in addition will differ based on provider and health care setting. In lower resource settings, the costs are significantly in favour of NIV use. However, equipment is different and the flow rates can vary from 30L to 70L of oxygen/minute. Masks can also vary in cost. They felt that though HFNO was probably technically easier to administer through specialised devices, NIV may require ventilators suited to delivering this modality of oxygen along with the required setting and skilled personnel to deliver this. However, it would indeed be ideal to have studies which answer this question of cost effectiveness. Hence the group voted for no included studies for this section.

Equity

The group felt unable to comment on the impact for equity. The panel discussed that HFNO requires less expertise, but requires a specific device to implement. Capital costs differ if NIV used via ventilator/dedicated NIV machine. Hence the group voted “don’t know” for the impact on equity.

Acceptability

The group agreed that NIV would indeed acceptable. However, there are likely to be some differences with regard to implementation, experience and comfort level at each of the centres. NIV via any interface would be acceptable to clinicians, if resources and expertise were available. However, for patients or hospital administrators this is less clear, but some pre-covid studies suggest acceptability to patients.

Feasibility

The panel felt that in health facilities with a physician or anaesthetist, and the requisite devices and medical oxygen/air at required flow rates, this is feasible. This may vary between settings, but patients being considered for this intervention are likely to be in an appropriate setting. Members of the panel have used NIV in lower resource/remote settings.

Adequate training and devices are needed to implement either of these interventions. HFNO often considered as first step up from low-flow O2 with then NIV considered as the next step, but group acknowledged that O2 availability can be an issue. The group concluded that the use of NIV and HFNO are quite dependent on the end user as well as resources available. Majority of clinicians are familiar with NIV, and its use may be preferred when oxygen availability is a concern. HFNO is a newer respiratory support therapy which may not be available at most centres. In addition, it utilizes more oxygen especially at higher flow rates and is easier to use (needs less training than NIV). Often these therapies can be combined for a patient, with HFNO as a step up from low flow O2 and step down from NIV.  Overall, NIV seemed the option that is familiar and beneficial. However, if equipment and trained personnel are not in place, High Flow Nasal Oxygen may be used.

Mild (PF ratio 200-300) vs moderate ARDS (PF 100- 200): No subgroup analysis was done in the only RCT evaluated. Given that the use of NIV or HFNO did not result in statistically different outcomes, either can be used for moderate ARDS. In mild COVID-19 ARDS, no specific recommendation can be made based on current evidence. Perhaps decisions need to be taken based on individual patient’s condition and response to therapy, resources and experience of clinicians attending to the patient.

No specific recommendations can be made with regard to the following disease states based on available evidence-

• Pre-existing COPD
• Obesity
• Co-existing cardiac failure (acute/chronic)
• Age > 65 years

Although currently there is no evidence to support NIV over HFNO or vice versa as the initial mode of respiratory support in mild or moderate ARDS, this will be revisited as new evidence emerges. Large randomised studies where patients received exclusively one of these interventions against the other will be monitored periodically. In addition, studies which use oronasal masks as the interface in the non-invasive ventilation group will be more practically applicable in India, due to lower cost, lower oxygen use and ease of administration. Evidence of side effects of both these modalities needs monitoring in studies with larger number of patients, to see if one is safer than the other.

The group felt that we needed randomized controlled trials with regard to the following

•  RCT comparing NIVwith HFNO with clearly defined outcomes like mortality and requirement of IMV in early ARDS.

•  RCT comparing different interfaces face mask, helmets are also research priorities as there are no head to head comparisons available.

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Covid Management Guidelines India Group - Respiratory Therapy Working Group. Non-Invasive Ventilation (NIV) Vs High Flow Nasal Oxygen (HFNO). Covid Guidelines India; Published online on July 27, 2021; URL :- https://indiacovidguidelines.org/niv-vs-hfno/ (accessed ).