Annals of Thoracic Medicine
REVIEW ARTICLE
Year
: 2021  |  Volume : 16  |  Issue : 4  |  Page : 306--322

Bilevel positive airway pressure ventilation for non-COPD acute hypercapnic respiratory failure patients: A systematic review and meta-analysis


Bandar M Faqihi1, Samuel P Trethewey2, Julien Morlet2, Dhruv Parekh3, Alice M Turner4,  
1 Institute of Applied Health Research, University of Birmingham, Birmingham, UK; Respiratory Therapy Department, College of Applied Medical Sciences, King Saud bin Abdul Aziz University for Health Sciences, Saudi Arabia
2 University Hospitals Birmingham, NHS Foundation Trust, Birmingham, UK
3 University Hospitals Birmingham, NHS Foundation Trust; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
4 Institute of Applied Health Research, University of Birmingham; University Hospitals Birmingham, NHS Foundation Trust, Birmingham, UK

Correspondence Address:
Dr. Bandar M Faqihi
Department of Respiratory Therapy, College of Applied Medical Sciences, King Saud bin Abdul Aziz University for Health Sciences, Riyadh, Saudi Arabia

Abstract

The effectiveness of bi-level positive airway pressure (BiPAP) in patients with acute hypercapnic respiratory failure (AHRF) due to etiologies other than chronic obstructive pulmonary disease (COPD) is unclear. To systematically review the evidence regarding the effectiveness of BiPAP in non-COPD patients with AHRF. The Cochrane Library, MEDLINE, EMBASE, and CINAHL Plus were searched according to prespecified criteria (PROSPERO-CRD42018089875). Randomized controlled trials (RCTs) assessing the effectiveness of BiPAP versus continuous positive airway pressure (CPAP), invasive mechanical ventilation, or O2 therapy in adults with non-COPD AHRF were included. The primary outcomes of interest were the rate of endotracheal intubation (ETI) and mortality. Risk-of-bias assessment was performed, and data were synthesized and meta-analyzed where appropriate. Two thousand four hundred and eighty-five records were identified after removing duplicates. Eighty-eight articles were identified for full-text assessment, of which 82 articles were excluded. Six studies, of generally low or uncertain risk-of-bias, were included involving 320 participants with acute cardiogenic pulmonary edema (ACPO) and solid tumors. No significant differences were seen between BiPAP ventilation and CPAP with regard to the rate of progression to ETI (risk ratio [RR] = 1.49, 95% confidence interval [CI], 0.63–3.62, P = 0.37) and in-hospital mortality rate (RR = 0.71, 95% CI, 0.25–1.99, P = 0.51) in patients with AHRF due to ACPO. The efficacy of BiPAP appears similar to CPAP in reducing the rates of ETI and mortality in patients with AHRF due to ACPO. Further research on other non-COPD conditions which commonly cause AHRF such as obesity hypoventilation syndrome is needed.



How to cite this article:
Faqihi BM, Trethewey SP, Morlet J, Parekh D, Turner AM. Bilevel positive airway pressure ventilation for non-COPD acute hypercapnic respiratory failure patients: A systematic review and meta-analysis.Ann Thorac Med 2021;16:306-322


How to cite this URL:
Faqihi BM, Trethewey SP, Morlet J, Parekh D, Turner AM. Bilevel positive airway pressure ventilation for non-COPD acute hypercapnic respiratory failure patients: A systematic review and meta-analysis. Ann Thorac Med [serial online] 2021 [cited 2021 Dec 9 ];16:306-322
Available from: https://www.thoracicmedicine.org/text.asp?2021/16/4/306/329164


Full Text



Acute respiratory failure (ARF), which generally results from insufficient gas exchange by the respiratory system,[1] is a significant disorder that can require invasive mechanical ventilation (IMV) through endotracheal intubation (ETI) for its management.[2] In the 1990s, ARF was the most common indication for IMV among eight countries, accounting for more than 65% of ventilated patients.[2] Despite the high use of IMV due to improved survival rates,[3] IMV can cause many complications. ETI is associated with ventilator-associated pneumonia (VAP),[4] increased mortality rate,[4],[5] IMV weaning difficulties, and increased health-care costs.[5] Therefore, noninvasive ventilation (NIV) has been increasingly used for acutely ill patients. NIV has many advantages, including a reduction in the risk of infection, a greater degree of patient co-operation and an increased ability to communicate,[6] as well as improvement in dyspnea.[7] Compared with IMV, NIV can achieve the same physiological outcomes of improved gas exchange and reduced work in breathing.[8] Moreover, NIV has a reduced incidence of side effects related to ETI and IMV, such as VAP, upper airway injuries, and excessive sedation. Thus, NIV has the potential to provide better clinical outcomes in certain patient groups.[9]

For several decades, NIV has been regarded as an effective method for avoiding the use of ETI and decreasing mortality in patients with acute hypercapnic respiratory failure (AHRF). Evidence supports the suggestion that the inclusion of NIV in a standard care strategy may enhance the outcomes in both patients with chronic obstructive pulmonary disease (COPD) exacerbation and patients with hypoxemic acute cardiogenic pulmonary edema (ACPO).[10],[11] However, the effectiveness of bi-level positive airway pressure (BiPAP) in AHRF due to etiologies other than COPD is still questioned. For instance, some of the studies of pulmonary edema did not exclude COPD patients,[12],[13] so may not have proven NIV efficacy even in this group. Therefore, we performed a systematic review to determine the effectiveness of BiPAP in non-COPD patients with AHRF, using the need for ETI and the mortality rate after applying bi-level ventilation as the primary outcomes.

 Methods



Data sources and search strategy

The protocol for this systematic review was prospectively registered on PROSPERO (CRD42018089875). To identify the articles for the inclusion in this review, the Cochrane Central Register of Controlled Trials in the Cochrane Library (Wiley interface), MEDLINE (Ovid interface), EMBASE (Ovid interface), and CINAHL Plus (EBSCO interface) were searched for relevant studies. In addition, trial registries (clinicaltrials.gov and WHO ICTRP) were used to search for ongoing and completed, but not yet published clinical trials. The bibliographies of the retrieved articles were reviewed to identify and conduct searches on related articles. Search terms are shown in the supplementary file [Appendix 1]. In brief, the inclusion criteria were randomized controlled trials (RCTs) which compared the effectiveness of BiPAP ventilation versus continuous positive airway pressure (CPAP), IMV, or oxygen therapy in adults with non-COPD AHRF. Effectiveness was determined by the comparison of the rates of the primary outcomes of interest, ETI, and mortality, between treatment groups.[INLINE:1]

Study selection

The reviewers independently made study selections based on titles and abstracts, which were compared against the inclusion criteria (lead reviewer – B. M. F., second reviewers – D. P., A. M. T., J. M., S. P. T.). Full texts were obtained after screening the titles and abstracts of potentially includable studies and conducting a similar dual-review process. Discussion between two reviewers and consultation with a third reviewer was done to resolve any concerns regarding the study selections.

Data extraction and quality assessment

Two reviewers (B. M. F. and S. P. T.) independently extracted the data from the included studies. The lead supervisor was consulted to resolve any disagreement regarding data extraction. The extracted information included study participant demographic data, study setting, study methodology, details of NIV used, and outcome measures [Appendix 2] in the supplementary file].[INLINE:2]

The methodological quality of each study was assessed using the risk-of-bias tool in RevMan. This tool consists of the following six domains: Random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Each domain was graded “yes,” “no,” or “unclear” to reflect a high or low risk of bias and uncertain bias, respectively. One reviewer (B. M. F.) completed the risk of bias assessment which was checked by a second reviewer (A. M. T.).

Outcome measures

The primary outcomes of interest included the need for ETI and the mortality rate after applying BiPAP. The secondary outcomes of interest were length of intensive care unit (ICU) stay, length of hospital stay, complications from treatment, and blood gas following the start of NIV.

Statistical analysis

The descriptive analyses are reported, and meta-analysis was performed using RevMan; pooled risk ratios (RRs) and 95% confidence intervals (CIs) were computed and Chi-square test and I2 statistics were used to assess the heterogeneity of the study results. The heterogeneity was defined as low, moderate, and high with I2 values of >25%, >50%, and >75%, respectively. In the analysis of heterogeneity, a P < 0.05 was considered to be statistically significant.

 Results



A total of 2485 records were identified through the database search after removing duplicates. Eighty-eight articles were identified for full-text assessment. Full-text reviews resulted in the exclusion of 82 studies for different reasons, as shown in [Figure 1]. The detailed included studies' characteristics and the reasons for excluded studies are shown in [Appendix 3] in the supplementary file.{Figure 1}[INLINE:3]

Study characteristics

The characteristics of the included studies are summarized in [Table 1]. Six articles were included in the study, involving 320 participants.[14],[15],[16],[17],[18],[19] These included four RCTs comparing BiPAP to CPAP[14],[15],[16],[17] and two comparing BiPAP to oxygen (O2) therapy.[18],[19] All of the studies were RCTs using a parallel-group design. The six studies occurred in Italy,[15],[18],[19] the United States,[14] France,[16],[17] Spain,[19] and Taiwan.[19] Four of the six articles were multicenter studies.[16],[17],[18],[19] All reported on adult patients with AHRF due to ACPO[14],[15],[16],[17],[18] and malignancy.[19] The number of patients recruited in each study ranged from 27 to 100 with an average age of participants of 74.3 years; males and females accounted for 52% and 48% of the participants, respectively. Five studies reported intervention failure, demonstrated by the need for an ETI outcome, four studies compared intubation between BiPAP and CPAP[14],[15],[16],[17] and one study compared intubation between BiPAP and O2.[18] In-hospital mortality was reported in almost all the studies; except for one study.[17] Three studies compared mortality between BiPAP and CPAP[14],[15],[16] and two studies between BiPAP and O2.[18],[19] [Table 2] shows the different IPAP, EPAP, and O2 levels and the choice of patient-ventilator interface. The risk of bias summary for the individual studies is shown in [Figure 2].{Table 1}{Table 2}{Figure 2}

Endotracheal intubation

The results from four trials in ACPO (156 patients) were available for examining the effects of BiPAP vs CPAP on the incidence of ETI. A low level of heterogeneity was found among the identified comparisons (I2 = 0%; P = 0.97). Pooled analysis showed that the use of BiPAP was as effective as the control (CPAP) group with regard to the rate of intubation in hypercapnic respiratory failure patients, with no statistically significant difference between treatment groups (RR = 1.49; 95% CI: 0.62–3.62; P = 0.37) [Figure 3]. One study reported the effect of BiPAP vs O2 with respect to ETI; this study showed that the percentage of patients with BiPAP needing intubation was significantly lower in a hypercapnic sub-group.[18]{Figure 3}

In-hospital mortality

In-hospital mortality was reported in three trials (120 patients) examining the effects of BiPAP versus CPAP on the incidence of in-hospital mortality in ACPO. A low level of heterogeneity was found (I2 = 0%; P = 0.75). Pooled analysis showed that BiPAP had no superior effect over CPAP with regard to the rate of in-hospital mortality (RR = 0.71; 95% CI: 0.25–1.99; P = 0.51) [Figure 4]. In hypercapnic patients with end-stage tumor, patients with BiPAP had a better expected survival than patients receiving O2 alone.[19]{Figure 4}

Other outcomes

Two studies of BiPAP vs CPAP reported hospital length of stay as an outcome.[14],[16] There were no significant differences in hospital length of stay observed between treatment groups in these studies. Bellone et al.[15] reported that there was a significant decrease in PaCO2 for both groups; however, other studies reported that the BiPAP group had greater reductions and significantly greater improvement in PaCO2 as compared to the control group.[14],[18],[19] Improvements in other physiological markers such as heart rate, blood pressure, pH, respiratory rate, and SpO2 were similar in trials comparing BiPAP to CPAP[15],[16],[17] and more significant in the BiPAP group when compared to O2 group.[18],[19]

 Discussion



This systematic review and meta-analysis demonstrates the effectiveness of using BiPAP in non-COPD patients with AHRF. The difference between BiPAP and CPAP or O2 was investigated, with regard to ETI and in-hospital mortality, and included studies generally showed little heterogeneity, perhaps due to our strict inclusion criteria. We were surprised to find that we were only able to meta-analyze studies of hypercapnic patients with ACPO, with a lack of RCTs for other hypercapnic non-COPD conditions. The number of studies using the treatment in ACPO was also lower than might be at first expected because many of the studies claiming to be treating a pulmonary edema population and included in prior systematic reviews,[20],[21] in fact included high numbers of patients with coexistent COPD.[22],[23],[24],[25],[26],[27],[28],[29],[30]

The European Society of Cardiology and the American Heart Association have recommended the use of NIV in the treatment of acute heart failure,[31] so it would be beneficial to identify which of the ventilation modalities offers the optimal therapeutic benefit in patients with AHRF. Physiologically, BiPAP has a potential advantage over CPAP in reducing dyspnea and exhaustion by assisting the respiratory muscles in ACPO patients.[32] However, these physiological benefits did not translate into improved primary outcomes in our meta-analysis, which did not find any differences between BiPAP and CPAP with regard to ETI or in-hospital mortality. Nevertheless, hypercapnic patients, due to physiological reasons, were expected to benefit from BiPAP based on favorable results in some of the studies using BiPAP.[18],[33] In hospitals where BiPAP is not available, however, CPAP would be a viable alternative based on the results.

Since the analysis was mainly based on an ACPO cohort, information on myocardial infarction (MI), which is an important cause of ACPO, was an important element to assess in our review. Overall, the incidence of MI was similar between the BiPAP and CPAP treatment groups in these studies. Although Mehta et al.'s study presented a higher rate of MI with BiPAP, Moritz et al.'s study also showed no significant differences in the incidence of MI when comparing BiPAP to CPAP. Moritz et al.'s findings were consistent with the other RCTs, as there were no differences between either technique on the incidence of MI.[22],[27],[34] This suggests that irrespective of the etiology of ACPO, whether it is due to MI or not, CPAP is equally effective as BiPAP and is safe to use.

The studies included in the review generally used IPAP, EPAP, and CPAP pressures that are not different from previous reviews on different hypercapnic conditions or the same condition but with different inclusion criteria. In addition, with regard to the NIV interfaces, most of the included studies used face mask interfaces which are consistent with the previous systematic reviews that reports the positive outcomes on hypercapnic respiratory failure patients.[20],[35],[36],[37]

This meta-analysis is strengthened by its robust exclusion of coexistent COPD patients, such that we can be confident of the results with respect to conditions other than COPD. It also used a broad search strategy and multiple data sources, with no language restrictions, hence all available evidence was considered. However, it also has limitations. First, the sample size of the trials included in the meta-analysis was small, which could have underpowered our analysis of BiPAP compared to CPAP with regard to ETI and mortality. Second, a publication bias test was not performed due to the low number of included trials, and so these results should be viewed with caution.

 Conclusion



Based on our systematic review and meta-analysis, we conclude that NIV reduces the incidence of intubation rate and mortality in hypercapnic patients with ACPO and that BiPAP appears equally effective as CPAP. This implies that patients with AHRF due to ACPO can be safely managed with CPAP, which is available in more non-ICU settings than BiPAP in most countries. For example, in the UK, CPAP is often available in coronary care units and acute medical units, whereas BiPAP is only available in specialized respiratory wards. This may aid patient flow through the hospital by opening up more locations in which such patients can be safely managed with taking in consideration healthcare providers' experience and confidence with the management of the ARF. Further research is needed in this area which includes various other conditions which can cause AHRF, in particular obesity-hypoventilation. No RCTs of NIV in obesity-hypoventilation-related AHRF were seen, yet cohort studies suggest a beneficial effect[38] and sufficiently good in-hospital mortality[39] such that management in a ward-based setting may be preferable to the more costly and resource intensive ICU setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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