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Article

A Brief Analysis of a New Device to Prevent Early Intubation in Hypoxemic Patients: An Observational Study

by
Luís Alberto Brêda Mascarenhas
1,
Bruna Aparecida Souza Machado
1,2,*,
Valter Estevão Beal
2,
Katharine Valéria Saraiva Hodel
1,
Luciana Moreira Nogueira
1,
Thayse Barreto
3,
Sérgio Fernandes de Oliveira Jezler
3,
Leonardo Redig Lisboa De Azevedo
3,
Uener Franklyn Teixeira da Silva
3,
Laiane Lopes da Cruz
3,
Lúcio Couto de Oliveira Júnior
4,
Vinicius Silva Oliveira
4 and
Roberto Badaró
1,3
1
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, Salvador 41650-010, Brazil
2
SENAI CIMATEC, National Service of Industrial Learning—SENAI, Computational Modeling and Industrial Technology, University Center SENAI/CIMATEC, Salvador 41650-010, Brazil
3
Espanhol Hospital COVID-19, Salvador 40140-110, Brazil
4
UNIMED Hospital, Feira de Santana 44052-064, Brazil
*
Author to whom correspondence should be addressed.
Appl. Sci. 2022, 12(12), 6052; https://doi.org/10.3390/app12126052
Submission received: 5 May 2022 / Revised: 9 June 2022 / Accepted: 10 June 2022 / Published: 14 June 2022
(This article belongs to the Special Issue COVID-19: Rehabilitation Needs, Therapeutic Development, and Impact on the Health System)
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Abstract

:

Featured Application

A new device to support oxygen therapy for patients diagnosed with severe COVID-19.

Abstract

The need for mechanical ventilation is one of the main concerns related to the care of patients with COVID-19. The aim of this study is to evaluate the efficacy of a bubble device for oxygen supplementation. This device was implemented for the selected patients hospitalized with severe COVID-19 pneumonia with persistent low oxygen saturation. Patients were selected in three major COVID-19 hospitals of Bahia state in Brazil from July to November 2020, where they remained with the device for seven days and were monitored for different factors, such as vital signs, oximetry evaluation, and arterial blood gasometry. Among the 51 patients included in the study, 68.63% successfully overcame hypoxemia without the necessity to be transferred to mechanical ventilation, whereas 31.37% required tracheal intubation (p value < 0.05). There was no difference of note on the analysis of the clinical data, chemistry, and hematological evaluation, with the exception of the SpO2 on follow-up days. Multivariate analysis revealed that the independent variable, male sex, SpO2, and non-inhaled mask, was associated with the necessity of requiring early mechanical ventilation. We concluded that this bubble device should be a prior step to be utilized before indication of mechanical ventilation in patients with persistent hypoxemia of severe COVID-19 pneumonia.

Graphical Abstract

1. Introduction

The outbreak caused by the new coronavirus 2019 disease (COVID-19) that began in Wuhan, China, in December 2019 has spread rapidly, and in the 21st century it has become one of the main challenges of modern medicine [1,2]. The pathogen responsible for COVID-19 is a positive-sense RNA virus member of the Coronaviridae family, later named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) due to its genomic similarities to the coronavirus of acute respiratory syndrome (SARS-CoV), that caused the coronavirus pandemic in Asia in 2002–2003 and Middle East respiratory syndrome (MERS) in 2016 [3,4]. Despite having a lower mortality rate than SARS-CoV [5], SARS-CoV-2 led to a higher number of total deaths because of the large number of cases, resulting until the beginning of May 2022 in an additional 6.23 million deaths worldwide since the first case reported in December 2019 [6,7]. Brazil is the third country in the number of confirmed cases of the disease, being the second in the number of deaths, which resulted in an overload of the health system due to the lack of beds inside the intensive care units (ICU) in different Brazilian states [7,8,9].
The clinical manifestations of individuals diagnosed with COVID-19 can vary between asymptomatic and those with critical disease development through severe symptoms [10,11]. It is widely demonstrated that the pathophysiology of the disease is quite complex and may affect organs such as the brain, liver, kidney, heart, coagulation system, and especially the lungs [12,13]. Thus, symptoms associated with COVID-19 range from fever, dry cough, diarrhea, myalgia, or fatigue to severe complications normally related to the respiratory system, such as viral pneumonia and acute respiratory distress syndrome [14]. Furthermore, it has been shown that the elderly and people of any age who have underlying medical conditions have had the worst disease prognosis through the development of a severe clinical condition [15,16]. The severe or critical manifestation of COVID-19 has been reported in 14% and 5% of patients, respectively [17]. Even so, despite most diagnosed patients presenting mild or medium symptoms (81%), the appearance of severe disease symptoms has been one of the main concerns of medical teams, because its development is associated with an increase in the fatality rate [18,19]. In addition, studies indicate that patients who present the most severe symptoms of the disease have impaired lung functions even after infection with SARS-CoV-2 [20,21].
Patients hospitalized with COVID-19 commonly present with hypoxemia (PaO2 < 60 mmHg) and are then treated symptomatically along with oxygen therapy, usually through non-invasive ventilation (NIV) [22,23]. In these cases, mechanical ventilation or invasive ventilation (IV) may become necessary when patients progress towards respiratory failure, making assistance necessarily provided within the ICUs through tracheal intubation [24]. Within this context, the mortality rate among patients with these conditions can vary between 20 and >90%, making it the most critical moment in the care of patients with COVID-19 [25,26]. Guidelines from different countries, such as the United States [27], China [28], and the United Kingdom [29], recommend that tracheal intubation be adopted early in the case of patients with COVID-19 in critical condition as a way to prevent induction of autoinflammatory lung lesions in spontaneously breathing patients who have sizeable transpulmonary pressure fluctuations [30].
However, it has been shown that NIV can effectively prevent the worsening of the clinical condition of patients diagnosed with COVID-19, causing many hospitals to adopt its use in clinical practice to avoid tracheal intubation and reduce hospital stay and mortality [31,32]. Another critical issue supporting early tracheal intubation to provide mechanical ventilation was the fears of health care workers spraying the SARS-CoV-2 virus aerosolized by the NIV [33]. For instance, the analysis of virus spreading by NIV revealed that air spreading could vary from less than 10 cm to 100 cm, depending on the non-invasive oxygen therapy method [34]. In addition, the use of mechanical ventilation can have critical outcomes, such as the occurrence of injuries to the airway, the increased possibility of the occurrence of nosocomial infections, and promoting significant physical discomfort, making patient sedation necessary [35,36].
Within this scenario, we noted that the outbreak caused by SARS-CoV-2 required unique solutions to mitigate the morbidity and mortality rates of the disease associated with lack of oxygenation necessary for the recovery of patients, especially to avoid the process of precocious tracheal intubation. Of particular interest, during the first wave of reported disease cases in Brazil, referring to the first half of 2020, there was an imbalance between supply and demand for specific activities and supplies, heightened by the difficulty in preparing the country for pandemic situations [37,38]. Thus, given the limited resources for treatment, particularly concerning mechanical ventilation, new approaches were needed to reduce the risk of morbidity and mortality at the time of hospitalization [24].
Therefore, the aim of this study is to evaluate the effectiveness of a device in the form of a capsule (bubble) in the feasibility of using non-invasive alternatives for oxygen supply in patients with hypoxemia without a risk of spreading the virus by NIV, thus avoiding early tracheal intubation.

2. Materials and Methods

2.1. The Device

The bubble is a semi-spherical device capable of covering the patient’s head and upper chest through an opening in its lower part, in addition to having lateral openings to facilitate hygiene and procedures related to clinical care, such as the feeding process of the patient. All openings of the device allow the inclusion of curtains of different polymeric materials, such as polyvinyl chloride. The device was made in a single piece (without any joining or need for bonding) from a transparent polymer (acrylic), with a height greater than 45 cm, which reduces the sensation of claustrophobia. In its manufacturing process, the steps involved are mold making, heating of the polymeric material, forming to semi-spherical shape, cooling, and finishing. Thus, the finished product had approximate dimensions of 73 × 60 × 50 (±5) cm (depth, width, and height), with thicknesses ranging between 0.45 and 4 mm. The device’s internal space allows different NIV techniques to be used for patient treatment (Figure 1).

2.2. Study Design and Ethical Considerations

The experimental design applied was based on an observational and prospective study, with 1initiation visit (D0) and 3 monitoring visits (D1, D4, and D7) during 7 days of follow-up, when the period of execution was between July and November 2020. However, if the medical team considered that the patient had an excellent clinical evolution, they could remove the device on the 4th day of monitoring. The parameters established for this purpose were mainly related to the maintenance and/or increase in the level of consciousness, oxygenation (pulse and/or arterial saturation rate > 94%), and other parameters of arterial gasometry, as well as the respiratory effort conditions. We also highlight that the use of ventilatory support in patients diagnosed with acute respiratory failure, whether invasive or noninvasive, was determined based on clinical practice established by protocols from different healthcare organizations [39,40,41,42].
This study occurred after approval by the Ethics and Research Committee of the SENAI CIMATEC University Center (No. 4153349) and following all ethical principles for medical research of the International Declaration of Helsinki [43] and Brazilian legislation [44]. All participants voluntarily participated in the study and were informed of all their current rights. In addition, participants were informed of possible risks of the study, such as an adverse event while using the device. The personal information of each participant was kept anonymous.

2.3. Study Site and Team

We conducted the study in the two largest cities of the state of Bahia: the capital city Salvador and Feira de Santana, municipality of the state of Bahia, Brazil. We recruited the study participants from three hospitals: Espanhol Hospital, a field hospital specializing in the treatment of COVID-19 in Salvador, one of the primary references in the fight against the pandemic in the state of Bahia, together with Hospital Unimed Feira de Santana and the Clériston Andrade General Hospital, both located in the city of Feira de Santana, which also have areas dedicated to the treatment of patients with diagnostic of SARS-CoV-2 infection. The hospital’s medical team consisted of intensive care physicians, nurses, and physiotherapists. We trained them in the execution of the protocol and the operation of the device. All patients were admitted to the study hospitals with confirmed COVID-19 prior to inclusion in the study, monitored both during the day and at night by the medical team.

2.4. Study Population

Patients were included in the study after obtaining written consent to participate. Only individuals who met all of the inclusion criteria and none of the exclusion criteria were considered eligible for inclusion. For inclusion, the criteria established were: patient admitted to hospitals with diagnosis or suspicion of pneumonia or respiratory failure caused by COVID-19, patient of both genders aged ≥18 years, patient with laboratory diagnosis of SARS-CoV-infection 2 confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) or by IgM/IgG lateral flow test, patient with pulse oxygen saturation (SpO2) < 94% and mechanically ventilated patients in conditions of early extubation for alternative oxygenation by non-invasive method feasible to be used with the bubble device or patient with a recommendation to use supplemental oxygen therapy with the use of non-invasive mechanical ventilation. The exclusion criteria were: pregnant patients, patients with signs of acute respiratory failure/ventilatory effort, patients on invasive mechanical ventilation, and patients without early extubation conditions. We excluded those participating in other research protocols.
All study participants received pharmacological treatment, where patients who were on the wards were treated with corticoids, whereas those in the ICU were treated with corticoids and antibiotics. It is highlighted that the pharmacological treatment was recommended based on the guidelines of Brazilian health institutions and authorities [45]. The ideal sample size was 48 individuals. Furthermore, this value was calculated according to Equation (1), according to the sample calculation proposed by Moser and Kalton [46].
n = z 2 x ( p · q ) e ²
where: n = sample size; p = prevalence of SARS-CoV-2 infection in the population = 0.99% [47,48]; q = prevalence of non-infection by SARS-CoV-2 in the population = 99.01%; z = value of the standard normal distribution corresponding to the desired confidence level (z = 1.96 for 95% confidence Interval–95% CI); e = maximum acceptable error in the estimate = 2%.

2.5. Data Collection: Clinical Monitoring

Clinical monitoring for the clinical follow-up of each research participant: data regarding their vital signs: heart rate, respiratory rate, temperature, blood pressure, and oxygen saturation level measured by pulse oximetry (SpO2), along with the analysis of imaging (computed tomography or chest X-ray) before starting to use the device, mainly considering the predominant pulmonary findings, the distribution, the extent of pulmonary involvement, and the clinical opinion of the Laudist physician. In addition, patients admitted to the ICUs were also monitored using arterial blood gases to assess their hydrogen potential (pH), arterial oxygen saturation (SaO2), partial pressure of carbon dioxide (paCO2), partial pressure of oxygen (paO2), the concentration of bicarbonate anion (HCO3−), and the concentration of lactate (La−). All data were collected from source documents (electronic medical records) and transcribed to a restricted-access database.

2.6. Data Collection: Patients’ and Professionals’ Perception of the Device

In addition to clinical monitoring, this article considers the perception of the use of the device by the included patients, health professionals responsible for patient care, and professionals responsible for cleaning the device (three research groups). For this, each research group answered a specific questionnaire (Table S1 for included patients, Table S2 for health professionals, and Table S3 for cleaning professionals), with multiple-choice questions based on the satisfaction scale “great”, “good”, “bad”, or “terrible” and with subjective questions (open). We elaborated the questions considering the following general aspects associated with the experience of the use of the device, such as the easiness related to feeding, access to the patient’s arm, cleaning/sanitizing the device, interaction between the medical team and the patient, and the report of some discomfort while using the device. All recruited professionals had links with the participating research centers and had direct contact with the patient using the device or were responsible for cleaning the blister after its use. To reduce the potential bias introduced by the self-reported data in the questionnaires, the participants (patients, healthcare professionals, and those responsible for hygiene) assured the confidentiality and privacy of their responses. All professionals who answered the questionnaire provided written consent to participate in the study.

2.7. Outcomes

The study’s primary outcome was determined as the absence of the patient’s need for invasive ventilatory support during the period of use of the device. Secondary outcomes included the impact of device use on vital signs and blood gases for patients recruited from the ICU of study participants. It is important to emphasize that we exclude individuals with acute respiratory failure to avoid confounding biases in the primary outcome analysis, taking into account the medical evaluation of the participant’s respiratory conditions.

2.8. Statistical Analysis

We used GraphPad Prism 9 (San Diego, CA, USA) to perform the statistical analysis. The data found were reported as mean or median (25–75 percentiles), depending on the form of distribution. We tested continuous variables for normality using the Shapiro–Wilk test. In non-normal distribution, the Kruskal–Wallis test and the Mann–Whitney U test were used to analyze independent quantitative data and the Bonferroni correction to account for errors due to comparisons between the initiation day (D0) and the monitoring days (D1, D4, and D7). Comparison of categorical variables was performed using Fisher’s exact test or the chi-squared test, and their values were expressed as absolute (%) and relative (n) frequency. We performed a logistic regression using multivariate analysis to identify independent factors associated with the primary outcome (the need or not for invasive ventilatory support). For this, the independent variables analyzed were gender, age, type of NIV, presence of comorbidity, and SpO2 level.

3. Results

3.1. Baseline Data of Participants

A total of 51 patients were included in the study. This is three more participants than expected in the sample size calculation to ensure the representativeness of the target population. Of the 51 patients included, 35 (68.63%) individuals remained with the device for 4 or 7 days without the need for invasive ventilatory support, whereas 16 (31.37%) patients discontinued its use because they needed tracheal intubation, with a significant difference between these two groups (p < 0.05). Considering the 35 patients who remained with the device, completing the study follow-up period, 18 (51.43%) used it for four days and 17 used it (48.57%) for seven days. The need for invasive ventilatory support we considered as one of the possible outcomes of patients’ progress to more severe stages of the disease.
Regarding the demographic data of the 51 study patients, 28 were male, whereas 23 were female. Of the 23 women who were included in the study, 12 (52.18%) did not need mechanical support for ventilation, whereas 11 women (47.82%) did (p > 0.05) (Table 1). However, in the case of males, 23 men (82.14%) were not intubated after inclusion in the study, whereas five men (17.86%) required invasive ventilation (p < 0.05) (Table 1). The average age of the two groups was similar: 65 years old. However, the age group was different, where patients who remained with the device for 4 or 7 days were between 41 and 97 years old, and the intubated group of patients was between 26 and 86 years (Table 1). The non-rebreathing mask and the high-flow nasal catheter were the oxygenation devices used by the patients in the study. The high-flow nasal catheter was the primary oxygenation device used by patients who did not require mechanical ventilation (n = 25 or 86.21%), whereas the non-rebreathing mask was the most used device among patients who were intubated (n = 12 or 54.55%) (Table 1).
Considering the symptoms presented by the study participants, difficult breathing, dry cough, and fever were the most frequent symptoms presented before admission, regardless of the participant’s clinical status (whether they needed mechanical ventilation) (Figure 2). In general, the frequency of symptoms reported by patients who remained on the device and those who required invasive ventilation was similar.
Figure 3 shows the analysis of comorbidities documented by the study patients. Approximately 74.28% (n = 26) of individuals who used the device for 4 or 7 days had some comorbidity. A value close to what we found for the intubated patients was 75% (n = 12). Hypertension and diabetes were the most frequent diseases, regardless of the analyzed group. Of the patients who did not need mechanical ventilation, 51.1% (n = 23) and 33.3% (n = 15) reported having hypertension and diabetes, respectively, whereas for patients who were intubated the frequency of hypertension was 47.6% (n = 17) and the frequency of diabetes was 33.3% (n = 7). Obesity and cardiovascular disease were also clinical conditions reported by study patients, with a relative frequency between 3 and 10%.

3.2. Clinical Data of the Participants

Figure 4 shows the results related to the vital signs of the 51 study patients, regardless of the type of outcome observed (the need for mechanical ventilation or not). Regarding heart rate (Figure 4a,b), temperature (Figure 4c,d), and respiratory rate (Figure 4e,f), we observed that there was no statistical difference between the mean values found for these parameters in D0 when compared to D1, D4, and D7 (p > 0.05). The mean respiratory rate on D0 during the monitoring days (D1, D4, and D7) of the patients who did not need intubation was the same, around 21 bpm, except for D1, which was 22 bpm (Table S4). However, intubated patients showed a different behavior, the average observed for this parameter on D0 was 28 bpm, a value higher than the monitoring days (25, 21, and 21 irpm for D1, D4, and D7, respectively) (Table S4). Considering SpO2, there was an increase in the mean values of this variable comparing D0 with all monitoring days (D1, D3, and D7) with a significant difference (p < 0.05) (Figure 4h). The mean SpO2 among patients who did not require intubation was 92% on D0 and went to 95% regardless of the monitoring day. Whereas for participants who needed intubation, the mean for this parameter was 90% (D0) to 91, 93, and 97%, considering D1, D4, and D7, respectively (Table S4).
Of the 51 study patients, 35 individuals were admitted to the ICUs of the Espanhol Hospital. Thus, Figure 5 presents the results of the blood gases of these patients during the monitoring days (D1, D4, and D7). The values found for the parameters evaluated in this exam, in this case, paCO2 (Figure 5a,b), paO2 (Figure 5c,d), SaO2 (Figure 5e,f), pH (Figure 5g,h), HCO3- (Figure 5i,j), and Lactate (Figure 5k,l), showed no significant difference (p < 0.05) compared to the monitoring days (D1, D4, and D7). The mean values for paCO2 of participants who did not need mechanical ventilation after using the device for 4 or 7 days were lower than the mean values found for patients who required intubation, regardless of the day of monitoring (D1, D4, or D7) (Table S4). More specifically, the paCO2 of patients who did not require intubation had mean values of 37.15, 39.71, and 36.00 mmHg on D1, D4, and D7, respectively, whereas participants who were intubated had mean values of 48.31 (D1), 48.67 (D4), and 42.00 (D7) mmHg (Table S4).
Concerning paO2, the mean values found for patients who did not need intubation were 115.38, 107.33, and 103.00 mmHg for D1, D4, and D7, respectively, whereas for patients who required intubation, the values obtained were 89.92, 106.91, and 123.00 for D1, D4, and D7, respectively, indicating an inverse trend to that found for paCO2 (Table S4). Regarding SaO2, unlike SpO2, there was no significant difference (p > 0.05) when comparing the 3 (three) days of monitoring (D1, D4, and D7) (Figure 5). It is noteworthy that the SaO2 level of both the patients who did not need intubation and those who needed the intervention was higher on D4 or D7 when compared to the level found on the first day of monitoring (D1); these values were higher than >90% (Table S4). Furthermore, we noted that the values found for SaO2 were higher than those found for SpO2, regardless of the monitoring day (Table S4).
The values referring to blood pH and the concentration of lactate and HCO3- remained stable during the use of the device. In both the patients who needed intubation and those who did not, except for the level of HCO3− among intubated patients, we observed a greater than 100% increase in blood buffer concentration, comparing day 4 (D4) (1.70 mmol·L−1) with day 7 (D7) (4.45 mmol·L−1) of monitoring (Table S4).
Figure 6, Figure 7 and Figure 8 show the analysis of the results of the imaging examination of the study patients before using the device, according to the observed primary outcome. No significant difference (p > 0.05) was found between the variables analyzed and the outcome primary (needing or not needing mechanical ventilation). The pulmonary findings (Figure 6), the patterns of lesion distribution (Figure 7a), and the degree of pulmonary involvement (Figure 7b) found were similar between the patients who required or who did not require mechanical ventilation after device usage. Predominant ground-glass opacity (amorphous and rounded) and thickening of intra/interlobular septa (mosaic paving) were the most frequent pulmonary findings among study participants (Figure 6).
Figure 8a,b show the result of computed tomography of one of the patients included in the study, where predominantly amorphous and rounded ground-glass opacities were the main pulmonary findings, with bilateral distribution and diffusely affecting several lobes, resulting in a moderate pulmonary impairment (between 25 and 50%). Whereas Figure 8c,d present the imaging exam of patient with severe pulmonary involvement (<50%), characterized by a bilateral distribution affecting several lobes, with ground-glass opacities, intra/interlobular (mosaic paving), air space consolidation foci, sometimes with perilobular morphology, suggestive of organizing pneumonia.

3.3. Independent Predictors of the Primary Outcome: A Multivariate Analysis

The multivariate analysis (Table 2) showed that male gender, SpO2, and type of NIV, in this case, the use of a non-rebreathing mask, were independent factors that affected the need or not for invasive mechanical ventilation (p < 0.05). The other factors analyzed, the absence of comorbidities and age, did not emerge as independent predictors of the need for intubation among the patients in this study (p > 0.05), as shown in Table 1. It is important to emphasize that hemodynamic conditions, blood gases, and the presence of comorbidities and CT findings are factors directly related to the need for mechanical ventilation in patients diagnosed with COVID-19 [49,50,51,52]. Thus, the use of the proposed device alone cannot be entirely associated with the outcome related to the absence of the need for tracheal ventilatory support. However, because of the analysis of the results, the use of the bubble device can contribute to maintaining the essential physiological parameters of respiration and optimizing pulmonary oxygenation. Consequently, it can positively interfere in the analysis of the primary outcome.

3.4. Perception of Patients and Professionals Regarding the Use of the Device

In addition to clinical monitoring, another critical assessment was regarding the perception of patients included in the study, health professionals, and professionals responsible for cleaning the device, regarding the use of the blister device in clinical practice. The experience with the device was “good” or “great” for 93.5% of patients (Figure 9a) and 90.65% of health professionals (n = 128) attributed the satisfaction levels as “good” and “great” for the utility of the blister device to support the treatment of patients diagnosed with COVID-19 (Figure 9b). Among health care workers responsible for cleaning the device, 17 (88.23%) reported that the degree of simplicity to cleaning the device was between 8 and 10, on a scale from 1 to 10 (Figure 9c). Figure 10 shows participants using the device in different activities during the follow-up period of the study. Thus, the results indicate that the device evaluated presented a positive perception among the three groups evaluated, which may facilitate its implementation in clinical practice.

4. Discussion

The use of respiratory support has been found to be one of the main therapies related to patients diagnosed with COVID-19. We considered the need for invasive ventilatory support as one of the possible outcomes of patients’ progress to more severe stages of the disease. This progression is also evident when there is a failure in oxygenation or when there is a worsening in the condition of hypoxemia, even with the use of oxygen support through non-invasive devices [53,54]. Data related to the use of NIV in different parts of the world indicate that the rate among patients hospitalized with COVID-19 who need this intervention can vary between 2.3 and 33.1% [55,56,57,58], whereas in Brazil, the rate reported was 24.4% among patients admitted to the ICU [59]. The study by Mukhtar et al. [60] demonstrated that using NIV (oxygen mask) helped prevent tracheal intubation in 77% of 39 patients with severe COVID-19 disease admitted to the Cairo University Hospital ICU. This percentage was similar to that reported by Ferrer et al. [61], where the intubation rate among patients with severe hypoxemia using NIV (oxygen mask or nasal mask) was 13%. In the case of our study, the use of NIV associated with the bubble device contributed to avoiding tracheal intubation in 68.63% of patients admitted to the wards and ICU of three reference hospitals for the treatment of COVID-19 in the state of Bahia, in Brazil.
Another point to be evaluated is the presence of comorbidity among subjects affected with COVID-19, because it is considered an essential issue for hospitalization due to the correlation with certain diseases being a risk factor for the susceptibility to progress to a more severe infection condition by SARS-CoV-2 [62,63]. The study by Coppadoro et al. [64] evaluated the success in using therapy with continuous positive airway pressure (CPAP) provided through a helmet (“Helmet”) in order to avoid intubation of patients diagnosed with COVID-19 outside the ICU. The presence of concomitant illnesses was one of the risk factors that could lead to failures in using helmets for the provision of CPAP, where these failures implicate the composite result of death or admission to the ICU for intubation [64]. Our study observed that most participants had comorbidities, regardless of whether they needed invasive ventilatory support or not. Thus, even with the presence of a significant predictor for the development of the most severe degree of the disease [65,66,67], the use of the bubble device can be a vital alternative to avoid intubation of patients diagnosed with COVID-19 who present comorbidities.
Monitoring lung function through blood parameters is one of the main tools in the care of patients diagnosed and hospitalized with COVID-19. Different follow-up studies of patients infected with SARS-CoV-2 have shown that SpO2 levels <92% have frequently been associated with the need for hospitalization and, as these levels decrease, with the indication of tracheal intubation [68,69,70]. In the study by Oranger et al. [71], the authors indicate that CPAP use can delay intubation for seven days or 14 days, mainly due to its ability to maintain SpO2 ≥92%. The work by Azoulay et al. [72] reports that the use of NIV in patients with acute respiratory failure with a low level of SpO2 (about 88%) was able to prolong the survival of these individuals, thus avoiding an increase in the number of deaths. Therefore, the use of the device analyzed in this study may be an alternative to maintain the SpO2 level within ideal values, which may reduce the rate of tracheal intubation among patients affected by COVID-19, which may also be an indication of survival of these individuals.
PaO2 and paCO2 are essential variables in the follow-up of patients with COVID-19 because pO2 provides information on the oxygenation status, whereas paCO2 provides information on the ventilation status (possible conditions of chronic or acute respiratory failure) [73]. Amati et al. [74] demonstrated that the use of a helmet with CPAP by patients diagnosed with COVID-19 was able to maintain mean levels of paCO2 between 36 and 39 mmHg, values similar to those found in this study for patients who did not need mechanical ventilation. However, the mean values for paO2 reported in the study by Amati et al. [74] were 72 to 79 mmHg, values lower than those found in this study, regardless of the need for intubation. It is noteworthy that paO2 values >80 mmHg are desirable within the context of hypoxemia [75].
Oxygen saturation levels are also key parameters within this context. Mejia et al. [76] demonstrated that patients with a SaO2 rate <90% had a higher risk of death when compared to patients with values >90%. This study reinforces the potential of using the bubble device, because the results found for this parameter were >90%, regardless of the day of monitoring. However, an important finding was the difference between SaO2 and SpO2 values, which has been reported in other studies involving patients diagnosed with COVID-19, in which the authors also point out that the levels found for SaO2 are higher when compared to SpO2 [77,78,79]. The difference between the values may be related to different factors, including pathophysiological issues that may affect the oxyhaemoglobin dissociation curve and might further complicate the interpretation of the SpO2 [80].
In addition to analysis using blood samples, imaging is also seen as an important tool during the management of patients with COVID-19, especially because it is predictive of clinical outcome [81,82]. Regarding the results found in this study, the analysis of imaging exams is similar to the typical results of COVID-19 already described in the literature [83,84,85]. The results reported by Gresser et al. [86] demonstrated that patients diagnosed with COVID-19 who required non-invasive ventilation and those who required tracheal intubation had a similar pattern of pulmonary findings, and ground-glass opacities, consolidations, and mosaic paving were the most frequent in both the groups. Different authors have reported that the degree of pulmonary impairment identified during hospital admission can be a crucial predictor of the need for ICU admission or early death [87,88,89]. Ruch et al. [90] demonstrated that patients diagnosed with COVID-19 who have >50% pulmonary impairment are more likely to die early. However, in our study, among the 35 patients not intubated, 68.8% had pulmonary impairment >50%, indicating the importance of using the device to prevent the worsening of SARS-CoV-2 infection.
Finally, it is noteworthy that hemodynamic and hemogasometric conditions, as well as the presence of comorbidities and tomographic findings, are factors directly related to the need for mechanical ventilation in patients diagnosed with COVID-19; thus, the use of only the proposed device cannot be fully associated with the outcome related to the absence of the need for tracheal ventilatory support. However, the use of the bubble device can contribute to the maintenance of important physiological parameters of breathing and to the optimization of pulmonary oxygenation.

5. Conclusions

We conclude that using the bubble device to help the oxygen supplementation for patients with hypoxemia during the treatment of COVID-19 pneumonia could be an alternative in clinical practice aimed to reduce the number of mechanical ventilation through tracheal intubations. Of the 51 patients included in the study, 68.63% (n = 35) did not need invasive mechanical ventilation during the evaluated period (7 days), even in those patients with comorbidities and a pulmonary impairment >50% associated with SARS-CoV-2 pneumonia. The use of the bubble device caused a significant difference in the levels of SpO2 comparing the day of initiation (D0) with the days of monitoring (D1, D4 and D7) and may have contributed to the mean SaO2 of all study participants being >97%, as well as to the levels of paO2 and paCO2 being maintained in a controlled manner, according to the desirable values.
Nevertheless, the highly complex treatment should be saved to critically ill patients when an efficient alternative could be tried first. Indeed, mechanical ventilation is a necessary procedure to save the lives of patients with severe respiratory failure. The bubble device can contribute to the optimization of pulmonary oxygenation, making it an alternative to support the treatment of patients with COVID-19 in the condition of severe hypoxemia. Furthermore, it is noteworthy that this was the first clinical trial with this device, which opens up the possibility of conducting new clinical trials with a larger sample size and more trial sites involved.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/app12126052/s1, Table S1. Questionnaire for collecting data on the perception of devices by patients; Table S2. Questionnaire for collecting data on the perception of devices by health professionals; Table S3. Questionnaire for collecting data on the perception of devices by cleaning professionals (sanitization); Table S4. Baseline data, vital signs, and blood gases of the 51 patients who joined the study, considering the analysis of the primary outcome.

Author Contributions

Conceptualization, L.A.B.M., B.A.S.M., L.C.d.O.J., V.S.O. and R.B.; Data curation, L.M.N., L.L.d.C., L.C.d.O.J., V.S.O. and R.B.; Formal analysis, L.A.B.M., B.A.S.M., K.V.S.H., S.F.d.O.J., L.R.L.D.A., U.F.T.d.S. and L.L.d.C.; Funding acquisition, L.A.B.M.; Investigation, L.A.B.M., B.A.S.M., V.E.B., L.M.N., S.F.d.O.J., L.R.L.D.A., U.F.T.d.S., V.S.O. and R.B.; Methodology, B.A.S.M., V.E.B., K.V.S.H., L.M.N., S.F.d.O.J., L.R.L.D.A., U.F.T.d.S., L.L.d.C., L.C.d.O.J., V.S.O. and R.B.; Project administration, B.A.S.M., T.B., S.F.d.O.J. and L.R.L.D.A.; Software, K.V.S.H.; Supervision, L.A.B.M., B.A.S.M., T.B., L.R.L.D.A., U.F.T.d.S., L.C.d.O.J., V.S.O. and R.B.; Validation, L.A.B.M., T.B. and L.C.d.O.J.; Visualization, B.A.S.M. and T.B.; Writing–original draft, L.A.B.M., B.A.S.M., V.E.B., K.V.S.H. and R.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of SENAI CIMATEC University Center (No. 4,153,349 and date of approval was 14 July 2020).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

We are indebted to the medical staff team of all three hospitals: Espanhol Hospital, Hospital Clériston Andrade, and Hospital Unimed of Feira de Santana. Without their involvement in this study, it would be impossible to achieve this vital knowledge to help patients with respiratory failure. The authors are also grateful to CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) (BAMS is a Technological fellow from CNPq 306041/2021-9) and SEPLAN (Secretaria do Planejamento do Estado da Bahia).

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Device used in the study: (1) hard plastic bubble; (2) side openings; (3) flexible transparent plastic curtain; and (4) flexible plastic extension blanket. As shown in (1), this device has a semi-spherical shape that provides ease of disinfection by the specialized teams in hospitals. Structures (1), (2), and (3) point to a suitable shape, a transparent structure, and an opening selected to avoid the feeling of claustrophobia in patients suffering from respiratory insufficiency (the object of study of this experimental project). In (4), a structure designed to provide greater protection to the patient and to the healthcare worker can be observed.
Figure 1. Device used in the study: (1) hard plastic bubble; (2) side openings; (3) flexible transparent plastic curtain; and (4) flexible plastic extension blanket. As shown in (1), this device has a semi-spherical shape that provides ease of disinfection by the specialized teams in hospitals. Structures (1), (2), and (3) point to a suitable shape, a transparent structure, and an opening selected to avoid the feeling of claustrophobia in patients suffering from respiratory insufficiency (the object of study of this experimental project). In (4), a structure designed to provide greater protection to the patient and to the healthcare worker can be observed.
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Figure 2. Symptomatology reported by study patients before hospitalization: (a) patients who remained with the device for 4 or 7 days and (b) patients who required invasive ventilation (intubation).
Figure 2. Symptomatology reported by study patients before hospitalization: (a) patients who remained with the device for 4 or 7 days and (b) patients who required invasive ventilation (intubation).
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Figure 3. Comorbidity of study patients: (a) patients who remained with the device for 4 or 7 days and (b) patients who required invasive ventilation (intubation).
Figure 3. Comorbidity of study patients: (a) patients who remained with the device for 4 or 7 days and (b) patients who required invasive ventilation (intubation).
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Figure 4. Study patients’ vital signs (n = 51) considering heart rate (a,b), body temperature (c,d), respiratory rate (e,f), and pulse O2 saturation (g,h). *** indicates the persistence of statistically significant differences after Bonferroni correction for multiple comparisons (p < 0.05).
Figure 4. Study patients’ vital signs (n = 51) considering heart rate (a,b), body temperature (c,d), respiratory rate (e,f), and pulse O2 saturation (g,h). *** indicates the persistence of statistically significant differences after Bonferroni correction for multiple comparisons (p < 0.05).
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Figure 5. Blood gas analysis of study patients admitted to the ICU (n = 35) considering the partial pressure of CO2 (a,b), partial pressure of O2 (c,d), arterial O2 saturation (e,f), blood pH (g,h), the concentration of bicarbonate (i,j), and the lactate concentration (k,l).
Figure 5. Blood gas analysis of study patients admitted to the ICU (n = 35) considering the partial pressure of CO2 (a,b), partial pressure of O2 (c,d), arterial O2 saturation (e,f), blood pH (g,h), the concentration of bicarbonate (i,j), and the lactate concentration (k,l).
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Figure 6. Main pulmonary findings on imaging exams (computed tomography and chest X-ray) considering the patients who needed or who did not need mechanical ventilation.
Figure 6. Main pulmonary findings on imaging exams (computed tomography and chest X-ray) considering the patients who needed or who did not need mechanical ventilation.
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Figure 7. Patterns of lesion distributions and the level of lung involvement found in imaging exams (CT scan and chest X-ray) before using the device: (a) pattern of lesion distribution among patients who needed or who did not need mechanical ventilation required intubation and (b) level of pulmonary impairment among patients who needed or who did not need mechanical ventilation.
Figure 7. Patterns of lesion distributions and the level of lung involvement found in imaging exams (CT scan and chest X-ray) before using the device: (a) pattern of lesion distribution among patients who needed or who did not need mechanical ventilation required intubation and (b) level of pulmonary impairment among patients who needed or who did not need mechanical ventilation.
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Figure 8. Image examination result (computed tomography) of two study patients: (a,b) represent the frontal and lateral images, respectively, of a patient with moderate pulmonary impairment, and the main pulmonary findings were opacities in ground glass predominantly amorphous and rounded, with bilateral distribution and diffusely affecting several lobes; (c,d) represent the frontal and lateral images, respectively, of a patient with severe pulmonary involvement, with ground-glass opacities, intra/interlobular septal thickening (mosaic paving), foci of consolidation of the lung as pulmonary findings. Air space, sometimes with perilobular morphology, suggestive of organizing pneumonia, with bilateral distribution.
Figure 8. Image examination result (computed tomography) of two study patients: (a,b) represent the frontal and lateral images, respectively, of a patient with moderate pulmonary impairment, and the main pulmonary findings were opacities in ground glass predominantly amorphous and rounded, with bilateral distribution and diffusely affecting several lobes; (c,d) represent the frontal and lateral images, respectively, of a patient with severe pulmonary involvement, with ground-glass opacities, intra/interlobular septal thickening (mosaic paving), foci of consolidation of the lung as pulmonary findings. Air space, sometimes with perilobular morphology, suggestive of organizing pneumonia, with bilateral distribution.
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Figure 9. Analysis of the perception of patients and professionals regarding the use of the bubble device: (a) perception of patients regarding the experience with the bubble device, classifying it as “terrible”, “bad”, “good”, and “great”; (b) perception of health professionals regarding the usefulness of the bubble to support the treatment of diagnosed patients, classifying it as “terrible,” “bad,” “good”, and “great”; and (c) perception of professionals responsible for cleaning the device as to the level of ease of cleaning it, considering a scale from 1 to 10.
Figure 9. Analysis of the perception of patients and professionals regarding the use of the bubble device: (a) perception of patients regarding the experience with the bubble device, classifying it as “terrible”, “bad”, “good”, and “great”; (b) perception of health professionals regarding the usefulness of the bubble to support the treatment of diagnosed patients, classifying it as “terrible,” “bad,” “good”, and “great”; and (c) perception of professionals responsible for cleaning the device as to the level of ease of cleaning it, considering a scale from 1 to 10.
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Figure 10. Study participants used the device (a) during feeding and (b) during the response to the assessment questionnaire.
Figure 10. Study participants used the device (a) during feeding and (b) during the response to the assessment questionnaire.
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Table
Table 1. Characteristics of the study patients (n = 51), comparing patients who needed invasive ventilation (n = 16) and those who did not need this intervention (n = 35).
Table 1. Characteristics of the study patients (n = 51), comparing patients who needed invasive ventilation (n = 16) and those who did not need this intervention (n = 35).
VariablesAll Participants
n = 51		Primary Outcomep Value
Patients Who Did Not Need Invasive Ventilation
n = 35		Patients Who Needed Invasive Ventilation
n = 16
Female, n (%)2312 (52.17)11 (47.83)0.0951
(>0.05)
Male, n (%)2823 (82.14)5 (17.86)0.0169
(<0.05)
Age, average (interval)6665 [IQR 53–81]
(41–97)		65 [IQR 55–74.5]
(26–86)		0.4871
(>0.05)
Type of NIV, Nasal catheter, n (%)2925 (86.21)4 (13.79)0.1296
(<0.05)
NIV Type, Non-Reinhalant Mask, n (%)2210 (45.45)12 (54.55)0.3679
(>0.05)
IQR: interquartile range.
Table
Table 2. Multivariate analysis for analysis of independent factors associated with the need or not for intubation after starting to use the device.
Table 2. Multivariate analysis for analysis of independent factors associated with the need or not for intubation after starting to use the device.
Factorp-Value│z│Odds Ratio [95% C.I.]
Age (years)0.15401.4250.9870 to 1.145
Male (n)0.01452.4441.858 to 79.24
Absence of comorbidity0.61650.50080.01984 to 9.036
SpO2 (%)0.01312.4820.01543 to 0.5497
NIV Type: Non-Rebreathing Mask0.04771.9801.047 to 2.028
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MDPI and ACS Style

Mascarenhas, L.A.B.; Machado, B.A.S.; Beal, V.E.; Hodel, K.V.S.; Nogueira, L.M.; Barreto, T.; de Oliveira Jezler, S.F.; De Azevedo, L.R.L.; da Silva, U.F.T.; da Cruz, L.L.; et al. A Brief Analysis of a New Device to Prevent Early Intubation in Hypoxemic Patients: An Observational Study. Appl. Sci. 2022, 12, 6052. https://doi.org/10.3390/app12126052

AMA Style

Mascarenhas LAB, Machado BAS, Beal VE, Hodel KVS, Nogueira LM, Barreto T, de Oliveira Jezler SF, De Azevedo LRL, da Silva UFT, da Cruz LL, et al. A Brief Analysis of a New Device to Prevent Early Intubation in Hypoxemic Patients: An Observational Study. Applied Sciences. 2022; 12(12):6052. https://doi.org/10.3390/app12126052

Chicago/Turabian Style

Mascarenhas, Luís Alberto Brêda, Bruna Aparecida Souza Machado, Valter Estevão Beal, Katharine Valéria Saraiva Hodel, Luciana Moreira Nogueira, Thayse Barreto, Sérgio Fernandes de Oliveira Jezler, Leonardo Redig Lisboa De Azevedo, Uener Franklyn Teixeira da Silva, Laiane Lopes da Cruz, and et al. 2022. "A Brief Analysis of a New Device to Prevent Early Intubation in Hypoxemic Patients: An Observational Study" Applied Sciences 12, no. 12: 6052. https://doi.org/10.3390/app12126052

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