Impact of using non-rebreathing mask in patients with respiratory failure

doi:10.21203/rs.3.rs-27717/v1

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Impact of using non-rebreathing mask in patients with respiratory failure

https://doi.org/10.21203/rs.3.rs-27717/v1

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published 01 Apr, 2021

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Background

Liberal oxygen therapy might increase the mortality rate of patients. Non-rebreathing mask (NRM) is a high-flow, non-invasive oxygen device that can provide oxygen concentration up to 95%. This study aimed to determine the impact of using NRM in patients with respiratory failure.

Methods

This retrospective cohort study was conducted in four medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database between January 2010 and December 2016. The association between mortality and NRM use in patients with respiratory failure in the emergency department was analysed. Before receiving ventilator support, patients were divided into the NRM treatment and no NRM treatment groups. A 1:4 propensity score matching was conducted. Regarding the duration of NRM use, treatments were grouped as 0 hour, 0–1 hour, 1–2 hours, and > 2 hours.

Results

A total of 18749 patients were included, with 1074 using NRM. After the 1:4 propensity score matching, 1028 patients using NRM and 4112 patients not using NRM were analysed. The 72-hour and 30-day mortality rates were 14.8%, 14.1%, 10.4%, and 11.3% and 29.1%, 28.5%, 27.5%, and 35.5% in the 0 hour, 0–1 hour, 1–2 hour, and > 2 hour treatment groups, respectively. Patients with respiratory failure due to pulmonary disease using NRM (> 2 hours) for a prolonged period had a higher mortality rate than patients not using NRM (OR: 1.4, 95% CI: 1.06–1.74).

Conclusions

Prolonged use of NRM (> 2 hours) in patients with respiratory failure due to pulmonary disease possibly results in an increased mortality rate.

Pulmonology

mortality

non-rebreathing mask

high-concentration oxygen therapy

respiratory failure

Supplemental oxygen is a common therapy in clinical practice. Physicians started to use oxygen to treat patients since the nineteenth century.¹ Considering that supplemental oxygen had no adverse clinical effects, several clinicians used oxygen liberally in patients even without hypoxaemia.^2–4 However, several studies have indicated that liberal oxygen therapy is not safe considering the deleterious effects of hyperoxia such as increased levels of inflammatory cytokines and reactive oxygen species,^5,6 reduced cardiac output, and pulmonary vessel constriction.^3,7 A recent systematic review and meta-analysis study reported that liberal oxygen therapy increases the risk of mortality.⁸

High-concentration oxygen therapy is commonly used in critically ill patients.^9,10 Non-rebreathing mask (NRM) is a relatively high-flow and non-invasive oxygen device that can provide oxygen concentration up to 95% under a continuous oxygen flow of 10–15 L/minute.¹¹ NRM is usually used to preoxygenate patients before induction and intubation^12–14 and is not used as a long-term oxygen therapy because it might result in carbon dioxide retention and nasal and oral mucosa irritation.³

In emergency departments (EDs), patients experiencing shortness of breath are often treated with high-concentration oxygen.¹⁵ Emergency physicians (EPs) usually preoxygenate these patients with NRM before induction and intubation to increase the duration of safe apnoea.^16,17 However, excess supplemental oxygen could increase the mortality rate in critically ill patients because of oxygen toxicity.^18,19 The advantages and disadvantages of NRM in patients with respiratory failure are still unclear. Therefore, this study aimed to analyse the association between NRM use before intubation and mortality in patients with respiratory failure.

Study setting

The data were obtained from the largest healthcare system in Taiwan, the Chang Gung Memorial Hospital, which receives approximately 10–12% of the National Health Insurance budget according to government statistics. The Chang Gung Research Database (CGRD) is a multi-institutional and original medical record-based research database.²⁰ In this study, the data from Keelung, Linkou, Chiayi, and Kaohsiung branches located from northern to southern Taiwan were used.

Study participants

All patients aged older than 17 years who visited the ED for non-traumatic disease and who experienced respiratory failure with ventilator support between January 2010 and December 2016 were included in the study. Patients who experienced out-of-hospital cardiac arrest (OHCA) or had do-not-resuscitate (DNR) order were excluded. Patients were divided into the NRM group and the non-NRM group.

Measurements

Data of patients’ demographics and comorbidities were extracted from the CGRD database. Patients were divided into three diagnostic groups according to the causes of respiratory failure including pulmonary disease, cardiovascular disease, and other metabolic diseases. Diagnoses were grouped according to the diagnostic codes from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification. According to the duration of NRM use, patients using NRM were further grouped into the following treatment groups: 0 hour, 0–1 hour, 1–2 hours, and > 2 hours. Death in hospital within 30 days was defined as in-hospital mortality.

Data analysis

For continuous variables, age was summarised as means ± standard deviations. The distributions of categorical data were presented as numbers and percentages. Student’s t-test, one-way analysis of variance, and chi-square test were used.

Propensity score matching

Propensity score was calculated using logistic regression. Variables of age, sex, and co-morbidities (including myocardial infarction, heart failure, peripheral arterial disease, cerebrovascular accident, chronic obstructive pulmonary disease, peptic ulcer disease, liver cirrhosis, diabetes mellitus, chronic kidney disease, malignancy, and bedridden status) and main diagnoses were used to estimate the probability of receiving NRM before intubation. Main diagnoses, which were divided into other metabolic diseases, diseases of the circulatory system, and diseases of the respiratory system, were diseases considered to cause respiratory failure in a single episode. Propensity score matching (PSM) was performed using NCSS version 12.0.4 (NCSS statistical software, LLC, Kaysville, Utah, USA). The greedy method was used to create a 1:4 matched study groups with a 0.25 standard deviation width. The caliper half-width was 0.17579, and the average match Mahalanobis distance was 0.00014.

To determine the associations between the variables and NRM use, survival analysis using the Kaplan-Meier estimator and Cox regression was performed. The effects were estimated using adjusted odds ratios (aORs) and the corresponding 95% confidence intervals (CIs). Results were considered statistically significant for a two-tailed test at P < 0.05. In addition to PSM, the IBM Statistical Package for the Social Sciences for Windows version 22.0 (released 2013, IBM Corp., Armonk, NY) was used for statistical analyses.

After excluding patients with OHCA and DNR order, 18749 patients who developed respiratory failure in ED were enrolled. Among them, 1074 patients had used NRM (Fig. 1). After a 1:4 PSM, the age, sex, and distribution of co-morbidities between 1028 patients using NRM and 4112 patients not using NRM were similar. Tables 1 and 2 present the demographic characteristics of patients before and after PSM matching.

Table 1

Clinical characteristics of patients experienced respiratory failure
	Not used NRM before intubation n = 17675	Used NRM before intubation n = 1074	P-value
Male sex	11274 (63.8)	683 (63.6)	0.899
Age	66 ± 16.0	68 ± 14.8	< 0.001
Myocardial infarction	2119 (12.0)	222 (20.7)	< 0.001
Heart failure	1764 (10.0)	72 (6.7)	< 0.001
Peripheral arterial disease	291 (1.6)	16 (1.5)	0.695
Cerebrovascular accident	2428 (13.7)	59 (5.5)	< 0.001
Chronic obstructive pulmonary disease	2944 (16.7)	171 (15.9)	0.530
Peptic ulcer disease	954 (5.4)	44 (4.1)	0.065
Liver cirrhosis	1707 (9.7)	49 (4.6)	< 0.001
Diabetes mellitus	1559 (8.8)	80 (7.4)	0.122
Chronic kidney disease	2972 (16.8)	269 (25.0)	< 0.001
Malignancy	2042 (11.6)	178 (16.6)	< 0.001
Bedridden status	780 (4.4)	48 (4.5)	0.931
Main diagnosis			< 0.001
Pulmonary disease	5784 (32.7)	625 (58.2)
Cardiovascular disease	4843 (27.4)	153 (14.2)
Other metabolic problem	7048 (39.9)	296 (27.6)
72-hour mortality	3000 (17.0)	134 (12.5)	< 0.001
30-day mortality	5376 (30.4)	322 (30.0)	0.764

Table 2

Clinical characteristics of patients experienced respiratory failure after 1:4 propensity score matching
	Not used NRM before intubation n = 4112	Used NRM before intubation n = 1028	P-value
Male sex	2713 (66.0)	656 (63.8)	0.192
Age	68 ± 15.0	68 ± 14.9	0.976
Myocardial infarction	681 (16.6)	176 (17.1)	0.667
Heart failure	294 (7.1)	72 (7.0)	0.871
Peripheral arterial disease	47 (1.1)	16 (1.6)	0.281
Cerebrovascular accident	205 (5.0)	59 (5.7)	0.327
Chronic obstructive pulmonary disease	685 (16.7)	171 (16.6)	0.985
Peptic ulcer disease	148 (3.6)	43 (4.2)	0.376
Liver cirrhosis	178 (4.3)	49 (4.8)	0.541
Diabetes mellitus	320 (7.8)	78 (7.6)	0.835
Chronic kidney disease	909 (22.1)	237 (23.1)	0.513
Malignancy	698 (17.0)	167 (16.2)	0.576
Bedridden status	135 (3.3)	47 (4.6)	0.045
Main diagnosis			0.994
Pulmonary disease	2312 (56.2)	579 (56.3)
Cardiovascular disease	609 (14.8)	153 (14.9)
Other metabolic problem	1191 (29.0)	296 (28.8)
72-hour mortality	606 (14.7)	130 (12.6)	0.087
30-day mortality	1196 (29.1)	314 (30.5)	0.358

Figure 2 shows the 72-hour and 30-day mortality rates in patients using and not using NRM. Before PSM matching, patients not using NRM had a higher 72-hour mortality rate than those using NRM, but after PSM matching, there were no significant differences in 72-hour mortality rates between patients using NRM and patients not using NRM (Fig. 2a and 2b). The 30-day mortality rate was relatively higher in patients using NRM > 2 hours than in patients belonging to the remaining three treatment groups (i.e. 0 hour, 0–1 hour, 1–2 hours treatment groups) both before and after PSM matching. However, there was no significant difference in the 30-day mortality rate between patients using NRM and patients not using NRM (Fig. 2c and 2d).

Figure 3 shows the survival curve of patients not using NRM and patients using NRM for different durations. After performing a stratified analysis according to the cause of respiratory failure, patients with pulmonary disease and using NRM for more than 2 hours had a higher mortality rate than patients with pulmonary disease but without using NRM (p-value: 0.016) (Fig. 3b). There was no association between mortality and NRM use in patients with respiratory failure due to cardiovascular disease and other metabolic diseases.

Figure 4 shows the result of Cox regression analysis. Patients with respiratory failure due to pulmonary disease and who use NRM > 2 hours had a higher mortality rate than patients not using NRM (OR, 1.4; 95% CI, 1.06–1.74) (Fig. 4b).

A recent systematic review and meta-analysis showed that liberal oxygen therapy increases the mortality rate of patients and does not improve other important patient clinical outcomes.⁸ The study used different oxygen delivery devices including nasal prongs, face masks, and invasive mechanical ventilators. Different from a previous study, our study used a high-flow and non-invasive oxygen device, NRM, before providing ventilator support. In EDs, EPs usually preoxygenate patients with NRM before induction and intubation to increase the duration of safe apnoea.^16,17 EPs also use non-invasive but high-flow oxygen therapy in elderly patients considering the provision of hospice care rather than intensive resuscitation; however, this requires further communication and discussion among healthcare professionals.^21–23 In Taiwan, NRM is commonly used. Several patients hesitate to receive intubation considering the possibility of delayed weaning and tracheostomy, subsequently delaying the provision of ventilator therapy. Considering that excess supplemental oxygen causes oxygen toxicity in critically ill patients¹⁸, we determined whether NRM use in patients with respiratory failure could increase their mortality rate.

According to a previous study, the 30-day mortality rate in patients with respiratory failure ranged from 29.7–41.7%.²⁴ In this study, the mortality rates were 30.0% and 30.4% in patients using NRM and patients not using NRM, respectively, a result consistent with the results of the previous studies. However, according to clinical practice, patients using NRM as an alternative oxygen treatment are considered less critical than patients using ventilator support immediately. We found that the 72-hour mortality rate in patients using NRM was 4.5% lower than the mortality rate of patients not using NRM. This suggests that the initial conditions of patients using NRM were less critical than the initial conditions of patients not using NRM. Therefore, this study performed PSM and analysed the influence of NRM according to its duration of use. Patients using NRM for a prolonged period had a higher mortality rate than patients using NRM for a limited time. This is possibly attributed to the high oxygen toxicity as a result of high-concentration oxygen therapy reported in a previous study.¹⁸

Although liberal oxygen therapy has not been recommended considering that it results in an increased mortality rate, it is still unclear which groups of patients are evidently affected with the increase in mortality rate following liberal oxygen therapy. The recent systemic review enrolled patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest and patients undergoing emergency surgery.⁸ While liberal oxygen therapy might increase patients’ mortality rate, there was no association between liberal oxygen treatment and mortality in patients with sepsis, stroke, trauma, and myocardial infarction. In our study, after performing a stratified analysis, the influence of NRM use on mortality was observed only in patients with respiratory failure due to pulmonary disease. This result is relatively consistent with the results of a systemic review, although there was no clear definition of critically ill patients in the systemic review article. Clinically, high-concentration oxygen therapy was not recommended in patients with asthma and chronic obstructive pulmonary disease, as it might result in carbon dioxide retention and acidosis.^25–27 Several studies have also reported that prolonged breathing with a significantly high fraction of inspired oxygen (FIO₂) (FIO₂ ≥ 0.9) uniformly causes severe hyperoxic acute lung injury, and when the FIO₂ is not reduced, death may occur.²⁸ Hence, patients with pulmonary disease who prolonged use NRM have higher mortality rates than patients with pulmonary disease who are not using NRM.

This study has some limitations. First, the diagnoses that cause respiratory failure were divided into only three groups, namely, pulmonary disease, cardiovascular disease, and other metabolic diseases. However, these diseases are significantly different regardless of being in the same group. For example, respiratory failure caused by pneumonia and chronic pulmonary disease have different mechanisms, but are all grouped as pulmonary disease, possibly influencing the result of the study. Second, the four study settings belonged to the same medical system; this may limit the implications of the conclusions. Finally, considering the retrospective design of this study, there might be some confounding factors that were not measured in this analysis that could influence the outcome of the study. For example, ventilator setting is associated with mortality.²⁹ High-concentration oxygen ventilation and prolonged use of ventilator, which were not well controlled in the study, could also cause lung damage.^30,31 In this study, data regarding ventilator setting were unavailable; hence, the confounding effects of ventilator were not controlled. Thus, further prospective studies are required to determine the association between NRM use and patient mortality.

Prolonged use (> 2 hours) of NRM before ventilator treatment in patients with respiratory failure due to pulmonary disease might increase patients’ mortality rate.

Geolocation information

The study area included four medical institutions at Keelung, Linkou, Chiayi, and Kaohsiung branches located from northern to southern Taiwan.

Availability of data and materials

Not applicable.

Ethical Approval and Consent to participate

This retrospective study was approved by the Chang Gung Medical Foundation Institutional Review Board (IRB) (IRB No.: 202000073B0). All patients’ data were anonymised.

Consent for publication

We consent the article for publication.

Competing interests

None to be declared.

Funding

No funding sources to declare.

Authors’ contributions

Po-Chun Chuang concepted and designed the study Chao-Jui Li, Yan-Ren Lin, and Chien-Chih Chen analyzed and interpreted the data. Chao-Jui Li, Xin-Hong Lin, and Po-Chun Chuang wrote the manuscript. Chao-Jui Li revised the manuscript. The authors read and approved the final

Acknowledgements:

We thank Hsin-Yi Chien, Chih-Yun Lin, and the Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital for their statistics work.

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Journal Publication

published 01 Apr, 2021

Read the published version in The American Journal of the Medical Sciences →

Version 1

posted

You are reading this latest preprint version

Impact of using non-rebreathing mask in patients with respiratory failure

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Methods

Study setting

Study participants

Measurements

Data analysis

Propensity score matching

Results

Discussion

Limitations

Conclusion

Geolocation information

Declarations

Availability of data and materials

Ethical Approval and Consent to participate

Consent for publication

Competing interests

Funding

Authors’ contributions

Acknowledgements:

References

Status:

Journal Publication

Version 1