Safety and efficacy of noninvasive ventilation for acute respiratory failure in general medical ward: a prospective cohort study

Introduction

Noninvasive ventilation (NIV) is widely used as first-line respiratory support in patients with acute respiratory failure of various etiologies. In a selected population, NIV can reduce the need for endotracheal intubation, hospital length of stay, and mortality (1). Large epidemiological studies demonstrated a significant increase in NIV use in the intensive care unit (ICU) from 5% in the 1998 cohort to 14% in the 2010 cohort (2,3). The overall intubation rate in these studies was approximately 30–35% and there was a trend towards a decrease in ICU mortality from 30% in the 1998 cohort to 24% in the 2004 cohort (4).

The recent clinical practice guideline of the European Respiratory Society and the American Thoracic Society recommends the use of NIV in several conditions, such as patients with hypercapnia from exacerbation of chronic obstructive pulmonary disease (COPD), cardiogenic pulmonary edema, immunocompromised patients, and prophylaxis for post-extubation respiratory failure (5). However, the application of NIV in patients with acute de novo hypoxemic respiratory failure, for example, pneumonia and acute respiratory distress syndrome (ARDS), should be carefully considered because of the lack of evidence to demonstrate the benefit of NIV in terms of improving clinical outcomes in such conditions. Additionally, delay in endotracheal intubation in patients with NIV failure can worsen outcomes (6,7).

The application of NIV requires close monitoring and experienced staff who are well trained and familiar with the use of NIV devices. Many published clinical studies on NIV were performed in the ICU. However, NIV is now also employed outside the ICU, such as in the emergency department and general wards. In our hospital, many patients with acute respiratory failure have been managed with NIV in the general medical wards due to a shortage of ICU beds during their admission. The objective of this study was to describe the indication for the use of NIV, clinical outcomes, and safety of patients with acute respiratory failure treated with NIV in the general medical wards of Siriraj Hospital and to identify the factors associated with NIV failure. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-732/rc).

Methods

Study designs and participants

A prospective cohort study was conducted from October 2017 to March 2018 in the general medical wards of the Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Adult patients (>18 years old) who were admitted to one of eight general medical wards and who had received NIV for at least 24 hours were enrolled in the study. Patients with “do-not-intubate” orders or obstructive sleep apnea were excluded. Due to the limitations of the ICU beds in our hospital, patients with acute respiratory failure and patients after extubation who have stable hemodynamics, a normal level of consciousness, and no need for organ support are considered for admission to the general medical wards. The indication and settings of NIV are considered by the attending physician. Each ward has a capacity of 20 beds located in one large room, where nurses can observe all patients from the nursing station, with a nurse-to-patient ratio of 1:4 during the day shift and 1:6 during the night shift. Patients are taken care of and continuously monitored their clinical status, vital signs, oxygen saturation, and arterial blood gas if necessary by a multidisciplinary team, including one attending staff, a third-year resident, and two first-year residents in the Department of Medicine, and nurses trained in and familiar with the NIV device. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Siriraj Institutional Review Board (certificate of approval No. Si 563/2017) and informed consent was taken from all the subjects or their relatives.

Data collection

Baseline characteristics and clinical data, including age, gender, comorbidity, Acute Physiology and Chronic Health Evaluation (APACHE) III and Sequential Organ Failure Assessment (SOFA) scores (using the worst variable within 24 hours before enrollment), cause of acute respiratory failure, and indication for NIV use, were collected and recorded. Other data collected included the type of NIV (dedicated NIV or ICU ventilator) and NIV interface, the duration of NIV use, the daily recorded vital signs, oxygen saturation by pulse oximetry (SpO₂), and the setting of the NIV device at 9:00 a.m. during the first 3 days of NIV use.

Outcomes

The primary outcome was the rate of failure of NIV at 48 hours, which was defined as a subsequent requirement for endotracheal intubation, reintubation, or death within 48 hours of NIV use. Secondary outcomes were cause of NIV failure and in-hospital mortality. We performed subgroup analysis to evaluate the outcomes of patients with success and failure of NIV, and the outcomes in each indication for NIV use. We also analyzed the factors associated with NIV failure.

Statistical analysis

Normally distributed variables are expressed as mean ± standard deviation, and were analyzed by an independent t-test. Nonnormally distributed variables are expressed as median (interquartile range) and were analyzed using the Mann-Whitney U test. The normality of the data distribution was tested using the Kolmogorov-Smirnov test. Categorical variables are presented as frequency and percentage, and were analyzed using the chi-square test. Univariate and multivariate backward stepwise logistic regression analyses were used to identify factors significantly associated with NIV failure. Factors associated with NIV failure in the univariate analysis (P<0.10) were put into the multivariate regression analysis, and these results are shown as odds ratio (OR) and 95% confidence interval (CI). Data were analyzed using PASW Statistics version 18 (SPSS, Inc., Chicago, IL, USA). A level of P<0.05 was considered statistically significant.

Results

A total of 86 subjects were enrolled in the study (Figure 1). The mean age of the subjects was 70±17 years and 47.7% of them were male. The mean APACHE III score and SOFA scores were 56±17 and 4±3, respectively. The other baseline characteristics are presented in Table 1.

Figure 1 Patient population flow diagram.

Characteristics of NIV use

According to the indication for NIV use, 34.9% of the subjects had cardiogenic pulmonary edema followed by prevention of post-extubation respiratory failure (25.6%), pneumonia (16.3%), exacerbation of COPD (14.0%), neuromuscular disease (7.0%), and extrapulmonary sepsis (2.3%) (Table 2). The dedicated NIV was used in 72.1% of the subjects and the oronasal mask was used in all subjects who received NIV (Table 2).

On day 1, pressure support ventilation was the most frequently used mode (52.3%), followed by pressure assist-control mode (27.9%), and pressure control ventilation (18.6%). Average volume-assured pressure support was used only in one subject (1.2%). The average pressure support level and the positive end-expiratory pressure were 13±4 and 5±1 cmH₂O, respectively. Other NIV settings are shown in Table 2.

Clinical outcomes and factors associated with NIV failure

The overall rate of NIV failure at 48 hours was 20.9% and all subjects were intubated. Among the 18 subjects who developed NIV failure, increased work of breathing was the most common cause of NIV failure at 48 hours (61.1%), followed by airway and/or secretion obstruction (16.7%) (Table 3). According to the indication for NIV use, the rate of failure of NIV in each indication is presented in Figure 2. The hospital mortality was 12.8%.

Figure 2 Rate of NIV failure in each indication of NIV use. NIV, noninvasive ventilation.

Patients who failed NIV had higher disease severity compared to patients with NIV success according to the APACHE III score (65±15 vs. 53±17, respectively; P=0.009) and the SOFA score (6±3 vs. 3±2, respectively; P=0.001). Hospital mortality was significantly higher in patients with NIV failure than in NIV success (33.3% vs. 7.4%, respectively; P=0.009) (Table 4).

We performed univariate and multivariate analyses to identify factors associated with NIV failure using the logistic regression model. Multivariate analysis demonstrated that the male gender and higher SOFA score were significantly associated with NIV failure (OR 4.59, 95% CI: 1.29–16.34; P=0.019 and OR 1.48, 95% CI: 1.16–1.89; P=0.002, respectively) (Table 5).

Discussion

In this prospective cohort study, we evaluated the characteristics, clinical outcomes, and safety of NIV use in 86 subjects who were admitted to general medical wards of the university hospital. The primary outcome demonstrated that the rate of NIV failure at 48 hours was 20.9%, and the secondary outcomes showed in-hospital mortality of 12.8%. In addition, male gender and higher SOFA score were associated with the failure of NIV. Cardiogenic pulmonary edema was the most common indication for the use of NIV, followed by the prevention of post-extubation respiratory failure and the exacerbation of COPD.

NIV is increasingly used in patients with acute respiratory failure. Data from large cohort studies demonstrated an overall increase in NIV used in the past decades (3,8). Potential physiological benefits of NIV have been proposed, including improved oxygenation, unloaded respiratory muscles, reduced patient work of breathing, and increased alveolar ventilation. Furthermore, several clinical studies demonstrated the advantages of NIV in avoidance of endotracheal intubation, a reduced incidence of nosocomial pneumonia, and a reduction in mortality in some specific populations (1,9). The recent clinical practice guideline of the European Respiratory Society and the American Thoracic Society recommends the use of NIV as first line treatment in patients with acute respiratory failure due to exacerbation of COPD, cardiogenic pulmonary edema, and prevention of post-extubation respiratory failure (5). However, patients receiving NIV is recommended to initiate in the ICU or within a care system capable of providing close monitoring and well-trained staff (10).

NIV has been used outside the ICU, such as in general wards, respiratory wards, or emergency departments due to limited ICU beds and financial limitations. Many studies demonstrated that NIV was implemented outside the ICU in a range of 18% to 70% (11-16). In our hospital, many patients with acute respiratory failure, who had stable hemodynamics, a normal level of consciousness, and no need for organ support, were admitted to the general medical wards of the Department of Medicine due to the shortage of beds in the ICU and NIV has been implemented in many patients with acute respiratory failure from various etiologies. Our study demonstrated that cardiogenic pulmonary edema was the most common cause of NIV use in this cohort followed by prevention of post-extubation respiratory failure and pneumonia that corresponded to the recommendation for NIV use according to the recent guideline (5). The overall rate of failure of NIV at 48 hours in the present study was 20.9% and the hospital mortality was 12.8%. We used the rate of NIV failure at 48 hours as the primary outcome because the previous studies demonstrated that late NIV failure, which defined as more than 48 hours after initiation of NIV, was associated with poor outcomes (17,18). Our study demonstrated that the use of NIV in general medical wards was effective and safe in selected patients with acute respiratory failure. The success rate of NIV and the mortality rate in the present study were similar to those in other studies (13,19,20).

Ozsancak Ugurlu et al. (14) reported the outcomes of 499 patients with acute respiratory failure who received NIV. Eighteen percent of these patients were treated in general wards and the success rate and the hospital mortality rate were 68% and 17%, respectively. A prospective observational study in 76 subjects who received NIV on regular floors by Farha and colleagues (21) demonstrated that the rate of NIV failure (defined as the need to transfer to the ICU) was 31% and the mortality rate was 13%. In addition, exacerbation of COPD and congestive heart failure were the most common causes of NIV use in this study. Furthermore, they found that patients with pneumonia had a high rate of NIV failure (26%) that was similar to our study (28.6%). This finding emphasizes that using NIV in patients with acute de novo hypoxemic respiratory failure, such as pneumonia or ARDS, should be taken with caution. A multicenter randomized study by Frat et al. (22) to compare high-flow nasal cannula, standard oxygen therapy, and NIV in subjects with acute hypoxemic respiratory failure demonstrated that subjects who received NIV in this study had the worst clinical outcomes in terms of intubation rate and survival compared to the other two groups. Furthermore, a post-hoc analysis of the LUNG SAFE study by Bellani and colleagues also showed that 15% of patients with ARDS were treated with NIV and was associated with a higher mortality rate in patients with an arterial partial pressure of oxygen/oxygen fraction ratio lower than 150 mmHg (7). Failure of NIV and poor outcome in patients with acute de novo hypoxemic respiratory failure may be explained by higher tidal volume and minute ventilation as a result of high respiratory drive and potentially injurious transpulmonary pressure so-called patient self-inflicted lung injury (23,24).

The delivery of NIV with a helmet which is a transparent plastic hood covering the entire head and sealed with a neck collar may be an alternative method for the administration of NIV in patients with acute hypoxemic respiratory failure. A single center, randomized study by Patel et al. (25) in 83 patients with ARDS comparing NIV administered by helmet and face mask for at least 8 hours demonstrated that helmet NIV treatment significantly resulted in a reduction in the rate of endotracheal intubation and 90-day mortality. In addition, Liu and colleagues demonstrated that NIV with a helmet significantly improved oxygenation and tolerance and decreased NIV-related complications compared to NIV with face mask in patients with chest trauma (26). A systematic review and meta-analysis also confirmed that helmet NIV was associated with a reduction in intubation rate and hospital mortality compared to NIV or CPAP delivered by face mask (27). However, our study did not use a helmet during NIV application and the use of helmet NIV outside the ICU should be studied in the future.

Many severity scores such as APACHE II, SOFA, or Simplified Acute Physiology Score (SAPS) II scores can be used to predict the outcome of NIV in critically ill patients. Two previous studies demonstrated that higher SOFA score was a significant risk factor for NIV failure in patients after extubation (28,29). A prospective cohort study by Corrêa and colleagues (30) found that higher APACHE II score was a predictor of NIV failure in 85 patients with acute respiratory failure who received NIV. Furthermore, Carron et al. (31) demonstrated that patients with severe community-acquired pneumonia who failure NIV had significantly higher SAPS II score. Our study also found that higher SOFA score was associated with NIV failure. Thus, illness severity is an important predictor of NIV failure and this finding was consistent across several severity scores and in various conditions for NIV use.

Limitations

The present study had several limitations that may limit the generalizability of our findings. First, this is a single center, non-randomized study, and small sample size. Second, we did not compare the outcome with other respiratory support strategies, such as standard oxygen therapy or high-flow nasal cannula. Third, data was collected before the 2019 coronavirus pandemic that noninvasive respiratory support techniques including NIV and HFNC were implemented outside the ICU during the pandemic phase and the outcomes may differ from our study. Forth, we did not use the helmet interface that has been shown to be beneficial in patients with acute hypoxemic respiratory failure. Last, the severity scores including APACHE III and SOFA are routinely used in ICU to predict the mortality; however, we used these scores in the present study because our enrolled subjects were critically ill patients. In addition, many studies have already used these scores in critically ill patients who were managed at general wards (17,32-34). Further well-designed studies are needed to evaluate the benefits of the use of NIV outside the ICU.

Conclusions

NIV was safe and effective for use in general medical wards. Cardiogenic pulmonary edema was the most common indication for the application of NIV. Patients who failed NIV had a higher mortality rate than those who had succeeded with NIV. The male gender and SOFA score are associated with NIV failure at 48 hours.

Acknowledgments

The authors would like to thank Miss Khemajira Karaketklang (Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand) and Mr. Suthipol Udompunthurak (Clinical Epidemiology Unit, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand) for their assistance with the statistical analysis.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-732/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-732/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-732/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-732/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Siriraj Institutional Review Board (certificate of approval No. Si 563/2017) and informed consent was obtained from all individual participants or their relatives.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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