We explored the effectiveness of NIPPV in a cohort of patients with COVID-19-associated AHRF admitted to non-ICU wards, characterized by a mean age of 74.6 years, and a mean PaO2/FiO2 ratio before starting NIPPV of 130.1 mmHg. Overall, 44% (22/50) of patients were successfully weaned from NIPPV, avoiding ETI and transfer to ICU. The rate of success was substantially higher (64%) in the subgroup of patients without treatment limitations, whose in-hospital death rate was very low (12%). On the contrary, a high percentage (76%) of NIPPV failure and subsequent AHRF-related death was registered among older patients with a “do not intubate” order, whose in-hospital mortality reached 88%, due to the non-AHRF-related death of 3 patients who had been successfully weaned from NIPPV.
Delivery of NIPPV to COVID-19 patients in our study appeared safe for HCWs, as only 2 out of 124 individuals (1.6%) experienced a SARS-CoV-2 infection while on activity in the COVID-19 wards, in the absence of serious symptoms.
In general, the use of NIPPV in patients with AHRF is expected to improve oxygenation, decrease the work of breathing, and avoid intubation, reducing the complications associated with invasive MV, such as pneumonia, excessive sedation, delirium, and ICU–acquired weakness . Risks of NIPPV include large tidal volumes and injurious transpulmonary pressures, and delayed initiation of invasive MV in a rapidly decompensating patient, which can increase the risk of death and nosocomial spread of the infection [4, 13]. Previous studies on the use of NIPPV in patients with AHRF due to pandemic viral illnesses have yielded conflicting results, with failure rates ranging from 10 to 70% in patients with influenza, H1N1 and Severe Acute Respiratory Syndrome (SARS), and up to 92.4% in patients with Middle East Respiratory Syndrome (MERS) [4, 7, 14]. Furthermore, NIPPV is an aerosol generating procedure (AGP) with the potential to increase the risk of SARS-CoV-2 infection transmission to HCWs, as shown in previous studies on SARS epidemic [4, 11, 15, 16].
Despite controversies over the benefits and risks of NIPPV, reports from several countries have shown that 11 to 62% of patients hospitalized with severe to critical COVID-19 received NIPPV [17-21]. In Italy, NIPPV has been widely used, especially in non-ICU setting, since the huge number of patients with COVID-19-related AHRF outweighed the provision of ICU beds and ventilators [22, 23].
The results of our series seem to indicate that NIPPV, delivered via face mask, in a non-ICU setting, is considerably effective in the treatment of COVID-19-associated AHRF in patients without limited life expectancy. In addition, it is worth noting that the death rate of patients undergoing delayed ETI after an initial unsuccessful trial of NIPPV (33.3%) did not exceed the mortality reported for ARDS (35-45%) and death rates registered in series of mechanically ventilated COVID-19 patients . Our findings are corroborated by the recent metanalysis from Ferreyro et al., which found that NIPPV, delivered via face mask or helmet, reduces mortality and intubation rate compared to standard oxygen therapy in patients with AHRF from any cause .
The high mortality rate (88%) registered in our series among patients with limited life expectancy, seems to indicate a scarce utility of NIPPV in this subset of COVID-19 individuals. However, if intubation and MV appear as an inappropriate choice, NIPPV could still play a role in the therapeutic management of such frail patients, since it allows, with a limited resource investment, to cure a small but not negligible proportion of patients (12%) and deliver palliative care to dying subjects with COVID-19-related respiratory failure .
Regarding predictors of NIPPV success, the multivariable logistic regression model identified several factors independently associated with NIPPV outcome (table 3). The analysis showed that an increase of the PO2/FiO2 ratio 24-48 hours after NIPPV initiation was predictive of successful weaning: as a consequence, the results of blood gas analysis acquired the day after the start of NIPPV might be used to early identify patients needing a treatment escalation toward ETI and ICU transfer.
Among the explored medical treatments, use of corticosteroids was associated with a higher probability of NIPPV success; this result appears in line with recent evidence demonstrating a survival benefit, and a lower rate of progression towards invasive MV in hypoxemic COVID-19 patients receiving steroids .
Finally, the presence of a treatment limitation decision (“do not intubate” order), determined by a limited life expectancy, appeared as a strong predictor of NIPPV failure. As a consequence, a careful clinical assessment of patient’s life expectancy, based on age, comorbidities and performance status, might be used to precociously identify patients with poor prognosis whose primary goal is palliative care.
HCWs represent a category at high risk of COVID-19 infection: up to 3.8% (1.716 of 44.674 confirmed cases) of the reported cases in China, and up to 12% (30.225 of 250.973) of all cases of COVID-19 in Italy have been among healthcare personnel [27, 28]. These data point out the crucial need to protect healthcare professionals, by adopting effective infection prevention and control measures.
SARS-CoV-2 is transmitted from person to person directly through respiratory droplets, or indirectly, via contaminated fomites. Another potential mode of transmission is the airborne route, i.e. the inhalation of respiratory particles smaller than droplets, generated by procedures such as non-invasive ventilation, tracheal intubation, tracheotomy, manual ventilation before intubation (AGP) [8, 9]. Based on these assumptions, airborne precautions (wearing of a respirator mask), in addition to droplet and contact precautions, are universally recommended when AGP are performed on COVID-19 patients [4, 9-11]. Moreover, international guidelines suggest to perform AGP in negative pressure isolation rooms [4, 10, 11]. Previous studies have shown that the adoption of adequate airborne precautions, and the use of negative pressure systems can minimize the risk of infection among HCWs caring for SARS patients treated with NIPPV [15, 29]. In our institution, HCWs caring for COVID-19 patients treated with NIPPV were equipped with respirators, and full contact and droplet precautions, according to national and international guidelines [4, 9-11, 30]. The low rate of SARS-CoV-2 infection registered among HCWs (1.6%), confirms that the adopted PPE is highly effective in preventing coronavirus transmission during NIPPV delivering, even in the absence of negative pressure rooms or HEPA air filtering systems.
Some authors have recently advocated the use of helmet interface for NIPPV delivery in COVID-19 patients, in spite of face masks, as a better fitting and tolerable interface, which might minimize widespread dispersion of exhaled air and reduce the risk of airborne SARS-CoV-2 transmission to HCWs [22, 23, 31, 32]. Furthermore, evidence exists that NIPPV delivered by helmet in patients with AHRF presents an advantage in terms of decreased intubation and improved mortality with respect to face mask [25, 33]. To date, however, no direct evidence of benefit of helmet over face mask in the treatment of COVID-19-associated AHRF exists . At our institution, no helmet interfaces were available during the study period, and NIPPV was delivered exclusively via full-face or oro-nasal face masks. We attempted to limit SARS-CoV-2 spread into the ambient air by selecting non-vented masks and applying an antimicrobial filter to the exhalation port of the NIPPV circuits .
Our study presents several limitations. The limited number of enrolled patients and the retrospective design reduce generalizability of our results. Due to the retrospective nature of the study, we were unable to retrieve detailed settings of NIPPV (e.g., PEEP, driving pressure, FiO2), respiratory rate and blood gas analysis parameters in the first hours after NIPPV initiation, and data on patient tolerance. The absence of a control group does not allow direct comparison of the cure rate between patients treated with NIPPV and patients undergoing early intubation.
Regarding the safety assessment of the use of NIPPV in COVID-19 patients, we did not compare the rate of SARS-CoV-2 infection between HCWs caring for NIPPV-treated patients and HCWs caring for non-ventilated patients, since the entire healthcare staff cared for both patient subgroups. As a consequence, we do not know which is the specific contribution of NIPPV to nosocomial transmission of SARS-CoV-2.