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DOI: 10.1111/jan.13323
REVIEW
Zunjia Wen1,2,* | Wenting Wang1,* | Haiying Zhang2,* | Chao Wu2 | Jianping Ding1 |
Meifen Shen2
1
Nursing School of Soochow University, Su
Zhou, China Abstract
2
First Hospital Affiliated to Soochow Aims: To determine the effects of low-flow oxygen therapy with humidified or non-
University, Su Zhou, China
humidified oxygen in adult patients.
Correspondence Background: Although non-humidified oxygen in low-flow oxygen therapy is recom-
Meifen Shen, First Hospital Affiliated to
mended by many guidelines, humidifying oxygen regardless of oxygen flow has been
Soochow University, Su Zhou, Jiangsu
Province, China. routinely performed in China and Japan and further studies are needed to evaluate
Email: smf8165@126.com
the evidence.
Funding information Design: A systematic review and meta-analysis that comply with the recommenda-
This research received no specific grant from
tions of the Cochrane Collaboration were conducted.
any funding agency in the public, commercial
or not-for-profit sectors. Data sources: Studies (1980–2016) were identified by searching PUBMED,
EMBASE, Science Direct, Cochrane library, CNKI and Wanfang Database.
Methods: We performed a comprehensive, systematic meta-analysis of randomized
controlled trials on the efficacy of humidified and non-humidified low-flow oxygen
therapy. Summary risk ratios or weighted mean differences with 95% confidence
intervals were calculated using a fixed- or random-effects model.
Results: Twenty-seven randomized controlled trials with a total number of 8,876
patients were included. Non-humidified oxygen offers more benefits in reducing the
bacterial contamination of humidifier bottles, as shown by the mean operating time
for oxygen administration and the respiratory infections compared with humidified
oxygen therapy. No significant differences were found in dry nose, dry nose and
throat, nosebleed, chest discomfort, the smell of oxygen and SpO2 changes.
Conclusions: The routine humidification of oxygen in low-flow oxygen therapy is
not justifiable and non-humidified oxygen tends to be more beneficial. However,
considering that the quality of most included studies is poor, rigorously designed,
large-scale randomized controlled trials are still needed to identify the role of non-
humidified oxygen therapy.
KEYWORDS
care, humidification, meta-analysis, nurse, nursing, oxygen, review
1 | INTRODUCTION
2522 | © 2017 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/jan J Adv Nurs. 2017;73:2522–2533.
WEN ET AL. | 2523
Considering the significance of this issue, the review authors found • Rigorously designed and high-quality large-scale random-
that many randomized controlled trials (RCTs) on the superiority of ized controlled trials are needed to identify the efficacy
humidified and non-humidified oxygen in low-flow oxygen therapy and effectiveness of non-humidified and humidified oxy-
have been performed, yet a meta-analysis synthesizing these data to gen therapy in children and adults.
provide robust evidence is lacking. Two previous Chinese meta-ana- • Incorporating this evidence into related nursing guideli-
lyses (Chu & Chen, 2016; Ren, Wang, Liang, & Zhou, 2016) have nes and translating it to clinical applications should be
concluded that non-humidified oxygen appears to be more beneficial promoted.
than humidified oxygen in low-flow oxygen therapy, but the included
data were all from Chinese papers and the sample sizes of the
included RCTs were small. Recently, several related RCTs that inves-
2.3 | Search methods
tigated this issue have been performed and published, thereby war-
ranting a larger sized meta-analysis. We planned, performed and reported this meta-analysis in compliance
with the PRISMA guideline (Liberati et al., 2009). Related articles that
have been either published in English or Chinese (1980 – 2016) were
2 | THE REVIEW
identified and selected by searching PUBMED, EMBASE, Science Direct,
Cochrane Central Register of Controlled Trials, China National Knowl-
2.1 | Aims
edge Infrastructure (CNKI) and Wanfang Database using the following
We performed this systematic review and meta-analysis of RCTs search terms: “oxygen inhalation therapy,” “oxygen inhalation ”, “oxygen
with the following aims: (1) to review the current evidence on the therapy,” “humidification”, “humidified,” “non-humidified,” “dried,” “low
oxygen humidification in low-flow oxygen therapy; (2) to compare flow,” and “low concentration.” We combined these terms in accordance
the efficacy of humidified and non-humidified oxygen in low-flow with the instructions of the database (Wen, Wang and Zhang). In addi-
oxygen therapy; and (3) to analyse and conclude the appropriateness tion, the reference lists of the retrieved studies and previous reviews
of oxygen humidification in low-flow oxygen therapy. and meta-analyses were reviewed and manually searched (Wen and
Wu) and we made no attempts to identify unpublished reports.
Identification
Studies included in
qualitative synthesis
(n = 27)
Included
Studies included in
qualitative synthesis
(meta-analysis)
(n = 27)
Liu & Chen, 2015; Yuan, Zhu, & Zhang, 2013; Yue, He, &
3.2 | Main analysis
Chang, 2015; Zeng et al., 2009) reported the incidence of dry
3.2.1 | The incidence of dry nose nose and throat after oxygen administration; the summary OR
on the incidence of dry nose and throat was 0.93 (95% CI:
Four studies (Andres et al., 1997; Chen et al., 2012; Tian et al.,
0.78–1.10), with no evidence of heterogeneity (p = .35, I2 = 10%)
2012; Yang & Yu, 2015) reported the incidence of dry nose after
(Figure 4b).
oxygen administration; the summary OR on the incidence of dry
nose was 1.21 (95% CI: 0.76–1.93), with evidence of heterogeneity
(p = .07, I2 = 58%) (Figure 4a).
3.2.3 | The incidence of cough
Two studies (Andres et al., 1997; Franchini et al., 2016) reported the
3.2.2 | The incidence of dry nose and throat
incidence of cough after oxygen administration; the summary OR on
Nine studies (Cai, Dong, Lv, Tang, & Wu, 2013; Chen & Guo, the incidence of cough was 0.80 (95% CI: 0.42–1.52), with no evi-
2015; Han, 2011; Li, Wang, Wang, et al., 2010; Li et al., 2015; dence of heterogeneity (p = .17, I2 = 6%) (Figure 4c).
2526 | WEN ET AL.
NA, not available; SDW, sterile distilled water; a, non-humidified nose; b, non-humidified throat and non-humidified mouth; c, headache; d, chest discom-
fort; e, nosebleed; f, cough; g, sleep problems; h, nausea; i, the smell of oxygen during oxygen therapy; j, SpO2; k, bacteria contaminations of humidifier
bottles; l, the mean operating time for oxygen administration; m, respiratory infections; n, heart rate; o, respiratory rate; p, the cost of oxygen therapy.
Other bias
3.2.8 | The smell of oxygen
Four studies (Chen et al., 2012; Liu & Chen, 2015; Yuan et al., 2013;
Andres 1997 + + + + + + + Yue et al., 2015) reported the smell of oxygen after oxygen adminis-
tration; the summary OR on smell of oxygen was 1.35 (95% CI:
Cai 2013 ? ? ? + + + +
0.69–2.65), with no evidence of heterogeneity (p = .41, I2 = 0%)
Campbell 1988 ? ? ? + + + + (Figure 5c).
Chen 2012 + – ? – + + +
Franchini 2016 ? + ? ? + + + Two studies (Cai et al., 2013; Wu, 2016) reported SpO2 after oxygen
administration; the summary WMD on SpO2 was 0.60 (95% CI:
Han 2011 ? – ? – + + +
3.32–2.21), with evidence of heterogeneity (p < .01 I2 = 97%)
Huang J 2014 ? – ? – + + + (Figure 5d).
Huang S 2014 ? – ? – + + +
Li 2011 ? – ? – + + + Four studies (Huang et al., 2014; Yang et al., 2015; Yue et al., 2015;
Zhou et al., 2015) reported the respiratory infection after oxygen
Li 2015 ? – ? – + + +
administration; the summary OR on respiratory infection was 0.39
Liu 2015 ? – ? – + + + (95% CI: 0.21–0.73), with no evidence of heterogeneity (p = .14,
Ning 2014 + – ? – + + +
+ – – + + +
3.3 | Subgroup and sensitivity analyses
Tian 2012 ?
Yang T 2015 + – ? – + + +
Yuan 2013 ? – ? – + + +
Findings from our meta-analysis indicate that non-humidified and
Yue 2015 + – ? – + + + humidified oxygen in low-flow oxygen administration provide no
+ + – + – + effect differences on dry nose, dry nose and throat, nosebleed, chest
Zeng 2009 ?
discomfort, smell of oxygen and SpO2 after oxygen administration, but
Zheng 2015 ? – ? – + + + non-humidified oxygen provide more beneficial effects on the reduc-
Zhou 2015 ? – ? – + – + tion of the bacterial contamination of humidifier bottles, shortening
the mean operating time for oxygen administration and decreasing
FIGURE 2 The risk of bias summary for included studies respiratory infections. Therefore, the use of non-humidified oxygen
2528 | WEN ET AL.
seems to be better than humidified oxygen in low-flow oxygen ther- Our review revealed that non-humidified oxygen offers more
apy. However, considering the quality of most included RCTs is poor, advantages in reducing bacteria contaminations of humidifier bottles,
our results should be interpreted with caution. the mean nursing operating time and respiratory infection without
In the past decades, humidification of the inhaled oxygen in low- increasing the incidence of other complications. Respiratory infection
flow oxygen therapy was considered unnecessary given that oxygen leads the list of hospital-acquired infections. While bacteria contami-
is not readily soluble in water (Miyamoto, 2004). The routinely used nations of humidifier bottles are closely related to respiratory infec-
cold bubble humidification for oxygen administration may not actu- tion (Kobayashi, Yamazaki, & Maesaki, 2006), the wet condition of
ally work (Vargas & Esquinas, 2016). A recent critical study (Fran- humidifier bottles with water inside may be more adaptable to bac-
chini et al., 2016) demonstrated that the cold bubble humidification teria proliferation. A survey (Li, Wang, Zhong, et al., 2010) reported
does not humidify inspired oxygen at all and offers no benefits in that the bacteria contamination rate of humidifier bottles with water
the promotion of mucociliary clearance, mucus hydration and pul- inside after 24-h oxygen therapy reached 57.5%, yet the non-humi-
monary function. Therefore, many related guidelines (Aarc 2007; dified oxygen group is only 44.2%, with the top three bacteria being
O’Driscoll et al., 2008; O’Driscoll et al., 1995) have recommended Staphylococcus aureus, Escherichia coli and Bacillus. The contamination
the direct use of non-humidified oxygen in low-flow oxygen therapy. of humidifier bottles possibly increases the risk for respiratory infec-
This may explain why the recent studies on this issue are quite few tion with the inhalation of contaminated oxygen. Ideally, the non-
in European and American areas; however, in China and Japan, humidified oxygen requires no addition or change of sterile water,
humidification of oxygen in clinic is still routinely performed whether which can significantly reduce the operating time for oxygen ther-
the oxygen flow is low or high (Li, Wang, Zhong, et al., 2010; Miya- apy, thereby relieving the nursing workload and decreasing the medi-
moto, 2004). Many Chinese medical researchers have investigated cal expenditure. Our results on the bacterial contamination of
this issue in the past few years as this situation warrants changes. humidifier bottles and the mean nursing operating time are signifi-
Patients receiving low-flow oxygen therapy by nasal cannula cantly heterogeneous. These outcomes should be interpreted care-
actually only inhale 2.4–19% of provided oxygen because the upper fully as the possible causes of the heterogeneity may be the
respiratory tract can provide 75% heat and moisture to make the difference on the nursing intervention and operating time calcula-
inhaled air comfortable for us (Branson, 1998). Additionally, the rela- tion. Some of the included RCTs did not indicate the accurate oxy-
tive humidity of inhaled air is more important than absolute humid- gen flow in the inhalation therapy, possibly contributing to the
ity; the discomfort caused by non-humidified oxygen to patients is results’ heterogeneity.
far lower than the indoor air brings (Sottiaux, 2006). This may Although our results support the non-humidified oxygen applica-
explain the results that non-humidified and humidified oxygen pro- tion in the low-flow oxygen therapy, several details should be taken
duce no significant difference on the complications, such as the inci- into consideration. No significant change in airway humidity was
dence of non-humidified nose, non-humidified throat, nosebleed and observed when oxygen was given pre-nasally without humidification
chest discomfort. However, these outcomes are rather subjective as (Dellweg, Wenze, Hoehn, Bourgund, & Haidl, 2013). The room air
the measurements on these outcomes are not accurate enough. Sev- humidity may act as an important factor. A Chinese survey in Xin-
eral studies (Campbell, Baker, & Crites-Silver, 1988; Ning et al., jiang, northwest area with dry climate of China found that non-humi-
2014; Xia, Gu, Zhang, Liu, & Lv, 2014; Yang et al., 2014; Zheng dified oxygen leads to more complications when compared with the
et al., 2015) conducted classified evaluation on the severity of these humidified oxygen in low-flow oxygen therapy (Yang et al., 2014).
symptoms, but due to the criteria requirements, we did not include Hence, we should take air humidity into account when performing
these data in the meta-analysis. Besides, non-humidified and humidi- oxygen therapy. Besides, more studies are needed to address other
fied oxygen inhalation exerted similar effects on SpO2, indicating possible effects achieved with humidified oxygen administration,
similar therapeutic values. However, we only included two RCTs on such as the clarification of the effect of humidified oxygen on the
this outcome. Further studies are needed to elucidate the differ- recovery of patients with chest disease. Also, as the relative risks/
ences in efficacy. benefits of high vs. low oxygen therapy and humidified vs. non-
WEN ET AL. | 2529
humidified oxygen therapy in child and adult remain different (Nath, design (randomization, allocation, blinding, outcomes evaluation and
Ponnusamy, Willis, Bissett, & Clarke, 2010), more individual factors interpretation) to provide more insights and evidence into this issue.
should be considered.
Considering that only three fair-quality RCTs (Andres et al., 1997;
CONFLICT OF INTEREST
Franchini et al., 2016; Yang et al., 2014) were included, sensitivity
analysis of those better quality studies should be performed. Those No conflict of interest has been declared by the authors.
studies that used sound designs for the method of randomization and
blinding are likely to have less risk of bias. Andres et al. (1997) recom-
AUTHOR CONTRIBUTIONS
mended that accepting non-humidification as the standard method for
delivering low-flow oxygen therapy may decrease the patient’s risk of All authors have agreed on the final version and meet at least one
developing nosocomial pneumonia, reduce expenditures for oxygen of the following criteria [recommended by the ICMJE (http://www.ic
therapy and eliminate one source of biomedical waste. However, the mje.org/recommendations/)]:
study of Franchini et al. (2016) showed that unheated bubble humidi-
fication does not humidify inspired oxygen to prevent deterioration of • substantial contributions to conception and design, acquisition of
data or analysis and interpretation of data;
mucociliary clearance, mucus hydration and pulmonary function; this
may support the finding that humidification performed no better than • drafting the article or revising it critically for important intellectual
content.
non-humidification, which is consistent with Andres’s results (Andres
et al., 1997). Yang et al. (2014) found that the dryness of oropharyn-
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