High-flow non-invasive ventilation (NIV) devices reduce the morbidity and mortality of COVID-19. The objective was to evaluate the use of the non-invasive ventilation device with high-flow helmet CPAP designed in Peru in patients with severe acute respiratory syndrome (COVID-19) hospitalized in the emergency services of five hospitals. Prospective multicenter and cross-sectional observational study from five hospitals from July to August 2020. 19 patients were recruited and divided into two groups (G-1 n = 10; G-2 n = 9) applying clinical and gasometric parameters as indicators of disease evolution upon hospital admission and within 24 hours. A progressive increase in these parameters was observed in those patients who used the NIV CPAP helmet within the first 24 hours. In G-01, improvement was evident in 90% (n = 9/10): PaO₂ (range 48–137; average: 82.49 ± 8.07; p-value = 0.008), CO₂ (25.2–51.0; 36.62 ± 2.62; p-value p = 0.327), and the PaO₂/FiO₂ coefficient (87–318; 191.5 ± 18.68). 10% of patients did not progress optimally, being subjected to endotracheal intubation and invasive mechanical ventilation. In G-02 the values ​​were %SatO₂ (range 92–98; 96 ± 0.76) and the SaO₂/FiO₂ coefficient (214–228; 223.2 ± 1.80), indicating significant improvement within 24 hours (p < 0.001). It is concluded that the use of the CPAP helmet non-invasive ventilation (NIV) device contributes to improving gasometric values ​​and clinical condition. Being an alternative to recover typical cases of COVID-19 in all hospitals in Peru.

COVID-19, respiratory failure, CPAP helmet, high-flow ventilation, ventilatory support

Severe acute respiratory syndrome (COVID-19) is an inflammatory process of the pulmonary capillary endothelium, with a decrease in the capillary lumen due to endothelial thickening and angiogenesis in response to severe local tissue hypoxia (Ackermann et al. 2020; Varga et al. 2020); additionally, endothelial inflammation of arterioles and capillaries-venules of the heart and necrosis of cardiac myocytes is observed (Agyeman et al. 2020; Fox et al. 2020; Bartra et al. 2021). The causal agent of COVID-19 is the type 2 coronavirus (SARS-CoV-2), made up of an outer membrane with accessory glycoproteins (protein E and M) and the main spike protein (S), inside which is located a nucleocapsid and single-stranded genomic RNA (Ackermann et al. 2020; Carsana et al. 2020; Liu et al. 2020). The spike protein has been described to bind to the angiotensin-converting enzyme 2 (ACE-2) receptor and to the immunoglobulin family proteins basigin (EMMPRIN) and CD147 on erythrocytes.

The Spike (S) protein binds to ACE-2, then the transmembrane protease serine 2 (TMPRSS2, which is located near ACE-2) cleaves the spike protein to form the dimeric Spike/ACE-2 complex that enters the cytoplasm (Hoffmann et al. 2020) and promotes the activation of metalloproteinase 17 (ADAM17), which is responsible for removing ACE-2 from the surface of vessels and epithelia (Fig. 1A) (Cumhur Cure et al. 2020; Kreutz et al. 2020). Additionally, ADAM17 activates macrophages, which release tumor necrosis factor (TNF-α) and leukocytes, including granulocytes (neutrophils, eosinophils, and basophils), monocytes (CD14+ and CD16+), and lymphocytes, responsible for releasing IL-1β, IL-7, IL-8, IL-9, IL-10, FGFb, CSF-G, CSF-GM, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, and VEGF; these cytokines are detected in plasma at high concentrations and are associated with the cytokine storm (Kreutz et al. 2020; Parra-Izquierdo et al. 2020).

Figure 1. 

Mechanism of destruction and elimination of the ACE-2 receptor and the molecular mechanism of action of COVID-19.

Angiotensin II levels increase and bind to angiotensin II type 1 receptors (AT1R), coupling to the Gqα/11 protein, this activates phospholipase C (PLC) which cleaves phosphatidylinositol 4,5-bisphosphate (PIP₂), generating second messengers inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), responsible for activating protein kinase C (PKC), which activate myosin light chain kinase (MLCK), and these phosphorylate myosin to couple with actin, generating arteriolar vasoconstriction that leads to the elimination of nitric oxide (NO) derived from the endothelium, generating platelet aggregation, coagulation, microvascular thrombosis in pulmonary and heart vessels (Klok et al. 2020; Kreutz et al. 2020; Mehta et al. 2020); At the same time, mitogen-activated protein kinases (MAPK) and ERK are activated, releasing transforming growth factor-beta (TGF-β); additionally, heat shock protein 27 (HSP-27) and plasminogen activator inhibitor type 1 (PAl-1) are expressed, respectively. TGF-β increases collagen 1 and fibronectin, which are responsible for fibrosis, growth, and cell migration of vessels and heart (Fig. 1B) (Klok et al. 2020; Mehta et al. 2020). The cytokine storm, the high concentration of angiotensin II, the elimination and dysfunction of the ACE-2 receptor induce oxidative stress of the mitochondrial membrane and the cytoplasm, causing the elimination of nitric oxide (NO) derived from the endothelium, all of which generates the symptoms of COVID-19 (Klok et al. 2020; Kreutz et al. 2020; Mehta et al. 2020). Fig. 1 shows the entry of coronavirus type 2 (SARS-CoV-2) and the molecular mechanism of action of the disease.

To improve acute respiratory failure in patients with COVID-19, a non-invasive ventilation (NIV) device is used (Antonelli et al. 1998; Antonelli et al. 2007; Ferreyro et al. 2020), due to its easy handling and because it does not generate the complications of a conventional mechanical ventilator (Antonelli et al. 2007). A systematic review with meta-analysis concluded that timely use of NIV in adult patients with acute hypoxemic respiratory failure is associated with a lower risk of requiring mechanical ventilation and death compared to standard oxygen therapy (Garpestad and Hill 2006). Indications for NIV include chronic obstructive pulmonary disease (COPD), cardiogenic shock, and acute respiratory distress syndrome (ARDS) (Antonelli et al. 2007; Lazzeri et al. 2020).

In the context of the COVID-19 pandemic, the use of the NIV device has increased and represents a treatment alternative with a good response in European and American countries, since its use guarantees a lower rate of complications than invasive mechanical ventilation (IMV) (Lazzeri et al. 2020). NIV includes continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) mode, which can be delivered at different interfaces. The CPAP modality has the benefit of increasing the functional residual capacity of the lung, thus reducing both the work of breathing and the risk of opening and closing of the airways. Furthermore, the application of PEEP recruits non-aerated alveoli in dependent lung regions, stabilizing the airways; this modality is included in the recommendations for the treatment of mild to moderate ARDS by the WHO (World Health Organization 2020). The most used NIV devices are the facial or nasal mask and the helmet, which is the interface of choice. The selection of one of them is based on a risk/benefit analysis for both the patient and the healthcare staff, and helmets are recommended, as they have a lower range of aerosol dispersion, reducing the risk of contagion of COVID-19 (Ing et al. 2020). Given the need and shortage of non-invasive oxygen therapy alternatives in Peruvian hospitals, engineers from the National University of Engineering (UNI) designed, patented, and obtained permission to manufacture a “Helmet CPAP” helmet, which was called the “CONI CPAP helmet”; this device was inspired by and reproduced from Italian models and other European countries. Fig. 2 shows the correct use of the CPAP helmet non-invasive ventilation (NIV) device in two patients diagnosed with atypical pneumonia and COVID-19 infection.

Figure 2. 

Use of the CPAP helmet non-invasive ventilation (NIV) device in patients with a diagnosis of atypical pneumonia and COVID-19 infection.

The SciELO database of Peru, PubMed-NCBI and ScienceDirect were searched for published designs and studies of non-invasive ventilation (NIV) CPAP helmet devices in patients diagnosed with atypical pneumonia and COVID-19 infection in Peru, and it is evidenced that these studies are limited or scarce, in this sense, it is justified to carry out NIV CPAP helmet studies designed by the authors for four reasons: First, to generate scientific evidence of the advantages of using the helmet CPAP device designed by the authors, such as lower risk of gas leaks and therefore lower risk of disease transmission (Whittle et al. 2020), lower mortality compared to standard oxygen therapy, decreased intubation rate, easy use, and better patient tolerance compared to face mask (Amirfarzan et al. 2021); Second, it shortens the length of stay in the Intensive Care Unit (ICU), and therefore, less risk of acquiring other hospital-acquired diseases; Third, demonstrate that its use is not only for atypical pneumonia and COVID-19 but could also be used in other respiratory diseases that require oxygen therapy, such as chronic obstructive pulmonary disease (COPD), cardiogenic shock, and acute respiratory distress syndrome (ARDS). Fourth, by demonstrating their usefulness with greater advantages over invasive devices, health authorities will make these devices available to hospitals in the Andean and jungle regions of the country, making them accessible to patients with low economic resources. Therefore, the objective was to evaluate the use of the non-invasive ventilation device with high-flow helmet CPAP designed in Peru in patients with severe acute respiratory syndrome (COVID-19) hospitalized in the emergency services of five hospitals, evaluated in the first 24 hours, applying clinical and gasometric parameters as indicators of disease evolution.

Data were collected from 19 patients in five COVID-19 hospitals according to the operational definition and data selection criteria. Hospitalized patients were over 18 years of age, male, with comorbidities such as type 2 diabetes mellitus and obesity in 40% of patients (4/10), who were between day 1 and day 10 of hospitalization (mean: 4 ± 3.19), receiving 90% (9/10) ventilatory support with the reservoir mask and 10% (1/10) with a binasal cannula at 5 L/min (Table 1).

The analysis of clinical and laboratory parameters will be analyzed in two groups, due to the affinity of the variables collected. Group 1 included patients with a diagnosis of atypical pneumonia and COVID-19 infection who used the helmet CPAP non-invasive ventilation device, and arterial gasometric and clinical condition were used as a method of monitoring and evolution of the patients, one being taken at baseline and the other 24 hours after treatment (Table 2). Under baseline conditions, it was observed that patients presented moderate to severe hypoxemia with PaO₂ in a range of 38.1–80 (mean: 57.49 ± 14.33) and CO₂ in a range of 25.1–42.3 (mean: 33.5 ± 4.99), with PaO₂ coefficient/FiO₂ between 45–164 (mean: 76.5 ± 34.94), all with Glasgow 15, conscious, oriented in time, space, and person. During follow-up and monitoring within the first 24 hours with the NIV device with a CPAP helmet as ventilatory support, improvement was observed in hypoxemia levels, achieving mild hypoxemia values ​​or reaching normal values. PaO₂ values ​​were found in a range of 48–137 (mean: 82.49 ± 8.07), indicating significant improvement (p = 0.008); CO₂ values ​​were between 25.2–51 (mean: 36.62 ± 2.62), not statistically significant (p = 0.327); and the value of the PaO₂/FiO₂ coefficient was from 87 to 318 (mean: 191.5 ± 18.68), indicating that the degree of respiratory failure was reversed from severe to moderate.

In this sense, based on the operational definition and the values ​​of the gasometric parameters, the results indicate success of NIV with a CPAP helmet (90%; n = 9/10). Only 10% of patients did not progress optimally, being subjected to endotracheal intubation and invasive mechanical ventilation. No deaths were observed during the follow-up and monitoring of the present study.

The PaO₂/FiO₂ coefficient indirectly measures lung injury, while the percentage of normal hemoglobin saturation with oxygen (%SatO₂) indicates what percentage of the hemoglobin in the blood is loaded with oxygen molecules, which must be higher at 95% breathing room air (FiO₂ 0.21) at sea level (1 atm or 760 mmHg). With normal pulmonary ventilation (12 breaths/min, moving 500 mL of air in each cycle) and a normal dead space (ventilation not used for exchange), alveolar ventilation greater than 4 L/min is delivered, achieving an alveolar PO₂ (PAO₂) and arterial (PaO₂) of about 100 mmHg (Mateos 2020).

The comparison of the PaO₂/FiO₂ coefficient between baseline and follow-up is represented in Fig. 3.

Figure 3. 

Comparison of the PaO₂/FiO₂ coefficient between baseline and follow-up in relation to the use of the CPAP helmet non-invasive ventilation device.

Table 3 reports the comparative parameters of the SatO₂ percentage of the patients with the NIV CPAP helmet device and the p-values ​​from the beginning, during the follow-up, monitoring, and end of the experiment corresponding to group 2, which was made up of 9 patients of different sexes, male (age range 45–55 years) with a diagnosis of atypical pneumonia and COVID-19 infection, without comorbidity, and who were hospitalized for at least 1 day. In this group, the percentage of oxygen saturation (%SatO₂) was used as a monitoring method; for this, a baseline was carried out at the first and then at the second hour, and during the experiment it was measured at 12 and 24 hours. Under baseline conditions, gasometric and clinical parameters such as SatO₂ percentage were between 80–93 (mean: 87.6 ± 1.73), all with Glasgow 15, conscious, oriented in time, space, and person.

At the first 2 hours of follow-up with the NIV CPAP helmet used as ventilatory support, SatO₂ percentage values ​​between 87–96 (mean: 92.6 ± 0.76) were evident, indicating that the degree of desaturation is improving, reaching mild levels, while the %SatO₂/FiO₂ coefficient was observed in a range of 202 to 223 (mean: 215.6 ± 2.08). In the first 24 hours of using the NIV helmet CPAP as ventilatory support, SatO₂ values ​​were observed between 92–98 (mean: 96 ± 0.76) and the SaO₂/FiO₂ coefficient in a range of 214–228 (mean: 223.2 ± 1.80), indicating significant improvement within 24 hours (p < 0.001).

The comparison of the SatO₂ percentage between baseline and follow-up values ​​is seen in Fig. 4.

Figure 4. 

Comparison of the SatO₂ percentage between baseline and follow-up values ​​obtained from patients who used the CPAP helmet non-invasive ventilation device.

The results of the present study are consistent with various prospective observational studies that have been previously published, such as the study by Aliberti et al. (2020), who reported that hypoxemia improved in 52% of patients who used CPAP, with the values ​​of the PaO₂/FIO₂ ratio at the beginning of oxygen therapy being 142.9 (range: 96.7–203.2), without a helmet, and after 6 h of using the CPAP helmet, it was 205.6 (range: 140.0–271.1; p < 0.0001). The mean duration of helmet CPAP treatment was 6 (3–10) days. Only four patients discontinued helmet CPAP due to intolerance. CPAP failure was observed in 70 patients (44.6%): 34 (21.7%) were intubated, and 36 (22.9%) died during the ICU stay. A total of 87 patients (55.4%) improved during their stay in the ICU, were transferred to oxygen therapy, and were transferred to the general ward. Amirfarzan et al. (2021) indicate that the CPAP device is not intended to replace endotracheal intubation and mechanical ventilation in patients with acute respiratory failure due to COVID-19; however, it deserves to be considered for use during a pandemic. It is proposed that to discontinue the use of the CPAP device, one must first decrease PEEP and FiO₂, increase CPAP-free time, achieve improvement in respiratory distress, and have an ability to maintain SpO₂ > 96% and FiO₂ ≤ 40%. Mateos-Rodríguez et al. (2021) observed a progressive increase in oxygen saturation (range 98–99%) in patients who used a CPAP device as an alternative after 30 and 60 min, although this change was not significant (p = 0.058 and p = 0.122, respectively). A statistically significant improvement was observed in the SatO₂/FiO₂ variable (p = 0.040). Liu et al. (2020) have shown that the use of NIV CPAP mode is safe and effective for the treatment of patients with mild to moderate acute respiratory failure. The need for ventilatory support is based on reducing respiratory work, and this is favored with the CPAP helmet because it acts as a positive pressure system that prevents the collapse of non-oxygenated alveoli; therefore, high FiO₂ is not required in the early stages of the disease and thus avoids lameness of the respiratory system.

Clinical pharmacists and medical specialists participated in the study process, controlling the blood gas parameters (% SatO₂, PaO₂, PCO₂, FiO₂, and PaO₂/FiO₂). Additionally, the pharmacists provided personalized pharmaceutical care on the ingestion of the medication with 200 mL of water, drug administration interval considering the maximum plasma time (t_max) and the half-life time (t_1/2) to avoid interactions, and exercising pharmacovigilance to detect, report, and prevent adverse reactions to medications and vaccines used in COVID-19.

The results of this study must be considered in the context of several limitations. One of them is the number of patients included (n = 19); the results cannot be extrapolated, and the cases must be analyzed individually. The collapse of hospital centers and health personnel cannot cope with personalized monitoring of patients, which is why we do not have clinical parameters that could help support the information. Other biases that can lead to confusion are the inequity of the Peruvian health system, given that many hospitals do not have basic laboratory tests to adequately monitor patients, as was evident in this study since the Hospital de Huánuco does not have AGA available, not allowing adequate monitoring; therefore, the health team decided to monitor the patient with non-invasive methods such as pulse oximeters, which give us approximate values ​​of the patient’s oxygenation. However, this is the first study that evaluates the use of a non-invasive high-flow helmet CPAP ventilation device designed by Peruvian researchers in patients with severe acute respiratory syndrome (COVID-19) in a multicenter prospective study that may be used in other respiratory diseases.

Based on the results, it is concluded that the use of the non-invasive ventilation (NIV) CPAP helmet device contributes to improving the values ​​of PaO₂, SatO₂, and SaO₂/FiO₂, which is considered useful and should be an alternative to recover typical cases of COVID-19 in all hospitals in Peru.

We thank the researchers from UTEC, UNI, and the company D+Imac Lab SAC, who developed the “CONI” CPAP helmet non-invasive ventilation (NIV) device, and the researchers from the hospitals, San Ignacio de Loyola University, and San Luis Gonzaga National University of Ica for their fine contributions.

Conflict of interest

The authors have declared that no competing interests exist.

Ethical statements

The authors declared that no clinical trials were used in the present study.

The authors declared that no experiments on humans or human tissues were performed for the present study.

The authors declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study.

The authors declared that no experiments on animals were performed for the present study.

The authors declared that no commercially available immortalised human and animal cell lines were used in the present study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

Conceptualization, methodology and research: José Luis Mantari, Diego Bonifacio, Fany Ponce Hinostroza, Roy Panduro, José Oliden, Lizbeth Mónica Cuba, José Luis Salazar, Jenny Tito, Jorge A. García, María R. Bendezú, Ricardo Pariona-Llanos, Priscilia AguilarRamirez, Angel T. Alvarado.

Literature analysis, writing of the manuscript-draft: José Luis Mantari, Diego Bonifacio, Fany Ponce Hinostroza, Angel T. Alvarado.

Review, writing and editing of the original manuscript: José Luis Mantari, Roy Panduro, José Oliden, Lizbeth Mónica Cuba, José Luis Salazar, Jenny Tito, Jorge A. García, María R. Bendezú, Ricardo Pariona-Llanos, Priscilia Aguilar-Ramirez.

Final review and approval of the manuscript: José Luis Mantari, Diego Bonifacio, Fany Ponce Hinostroza, Roy Panduro, José Oliden, Lizbeth Mónica Cuba, José Luis Salazar, Jenny Tito, Jorge A. García, María R. Bendezú, Ricardo Pariona-Llanos, Priscilia AguilarRamirez, Angel T. Alvarado.

Author ORCIDs

José Luis Mantari https://orcid.org/0000-0002-3621-3425

Fany Ponce Hinostroza https://orcid.org/0000-0002-0321-7876

Roy Panduro https://orcid.org/0000-0002-3479-4406

José Oliden https://orcid.org/0000-0003-2643-327X

Lizbeth Mónica Cuba https://orcid.org/0000-0001-7897-3054

José Luis Salazar https://orcid.org/0000-0002-0161-0172

Jenny Tito https://orcid.org/0009-0003-3524-7732

Jorge A. García https://orcid.org/0000-0001-9880-7344

María R. Bendezú https://orcid.org/0000-0002-3053-3057

Ricardo Pariona-Llanos https://orcid.org/0000-0001-9836-6526

P. Aguilar-Ramirez https://orcid.org/0000-0002-4830-8720

Angel T. Alvarado https://orcid.org/0000-0001-8694-8924

Data availability

All of the data that support the findings of this study are available in the main text.