Introduction

Airway pressure release ventilation (APRV) and biphasic positive airway pressure (BIPAP) are modes of mechanical ventilation that allow unrestricted spontaneous breathing independent of ventilator cycling, using an active expiratory valve [14]. Both modes are pressure-limited and time-cycled. Ventilation occurs via the time-cycled switching between two set pressure levels. In the absence of spontaneous breathing, these modes resemble conventional pressure-limited, time-cycled ventilation (Table 1) [5].

Table 1 Ventilator mode characteristics

A proposed advantage of APRV and BIPAP compared to conventional pressure-controlled ventilation is the improved distribution of gas to dependent lung regions as the result of spontaneous breathing enabled during the inspiratory and expiratory time cycles. Radiologic studies indicate that gas is directed to dependent well-perfused regions of the lungs during spontaneous breathing due to the movement of the posterior muscular sections of the diaphragm [2]. Improved gas distribution to dependent lung regions prevents atelectasis and promotes alveolar recruitment resulting in an improved ventilation–perfusion matching [6, 7].

Within the scientific literature, descriptions of APRV and BIPAP lack clarity. Various authors use the term APRV to describe a range of ventilatory settings [811]. Others use the term BIPAP to describe settings that are indistinguishable from certain descriptions of APRV [12]. In North America, the acronym BiPAP® is reserved for noninvasive ventilation available on Respironics ventilators (Murrayville, PA, USA). With registration of this acronym, ventilator companies have developed other terms or acronyms to refer to modes with similar characteristics.

Reports of the international utilization of ventilator modes indicate limited clinical uptake of pressure-control modes, which include APRV and BIPAP [13, 14]. Clarity of definitional criteria may assist in the clinical understanding and application of these modes. The aim of this paper is to identify the criteria that define and distinguish APRV and BIPAP within existing scientific literature.

Methods

The following databases were electronically searched: Medline, PubMed, Cochrane Library, Cochrane Controlled Trials Registry, and CINAHL, from 1982 to 2006, using the terms APRV, BIPAP, Bilevel, and lung protective strategy, individually and in combination. Two independent reviewers determined the eligibility of papers based on appraisal of the article title and abstract, retrieved potentially relevant studies, and decided on study eligibility. Reference lists of those papers meeting inclusion criteria were also examined. All study designs were included. Studies were considered for inclusion if ventilator mode characteristics were identified, specifically inspiratory and expiratory times or I:E ratio. Studies that contained enough data to calculate these variables, e.g., respiratory rate and expiratory time, were also included.

No attempt was made to contact authors for unpublished data, as the objective was to identify distinguishing criteria for APRV and BIPAP existent in the available literature. Studies published only in abstract form were not included. Data on the study design and population, mode settings, mode of comparison (if any), and outcome measures were then abstracted from included experimental studies onto predesigned forms by each reviewer following comprehensive review. Both reviewers transcribed mode descriptions from discussion articles onto data collection forms independently.

Analyses

Continuous variables describing mode characteristics from experimental studies were summarized as mean and SD and compared using Student t tests. Reported I:E ratios were categorized into four groups: noninverse, 1:1, mild inverse (>1:1 to ≤2.0), and extreme inverse (≥2.1), and compared using Fisher exact tests due to small expected values. Other categorical data including study population, study outcome, I:E ratio, and synchronization of the switching between set inspiratory pressure (PHigh) and positive end expiratory pressure (PLow) levels to spontaneous effort were summarized as proportions and also compared using chi square tests. Because of the substantial heterogeneity in study design, study population, comparative group, and primary outcome, no attempt was made to pool data for the purposes of meta-analysis. A two-tailed P value <0.05 was considered statistically significant. All analyses were performed using Minitab 14 [15]. Discussion articles were examined using content analysis to identify themes [16]. Article content was coded under theme headings such as ‘enables spontaneous breathing’ or ‘APRV uses short release time and long inspiratory times’ and then examined for repetition, characteristics and dimensions that identified and confirmed categories.

Results

Database searching yielded 501 citations, of which 81 were selected on review of the title and abstract. On further review, data was abstracted from 50 studies and 18 discussion articles. Both reviewers agreed in the selection of included studies (κ= 1). Excluded articles were those that contained editorial comment only (n = 8); the focus of the article was either APRV or BIPAP, but no description of the mode was provided (n = 2); or the main focus was not the mode of ventilation (n = 2).

Of the 50 studies, 31 (62%) were human clinical studies [811, 1743] and 19 (38%) [12, 4460] were experimental (either animal or bench) studies. The 31 human clinical studies included 14 (45%) interventional [8, 9, 17, 18, 22, 30, 32, 3640, 42, 43] and 17 (55%) observational studies [10, 11, 1921, 2329, 31, 3335, 41]. None of the human clinical studies were blinded; only two of the experimental studies were blinded. In these two studies reported by the same first author, investigators blinded to the mode of ventilation analyzed computed tomography images to determine aeration of lung tissue [59, 60].

Airway pressure release ventilation was the named mode in 39 (78%) studies [8, 9, 11, 17, 1921, 2327, 29, 3133, 35, 36, 3843, 4653, 5561], and BIPAP in 11 (22%) studies [10, 12, 18, 22, 28, 30, 34, 37, 44, 45, 54]. All 50 studies described a ventilatory mode that enabled spontaneous breathing at two pressure levels. The majority of reports involved either adult patients (21 APRV and seven BIPAP studies) or animal studies (14 APRV studies and 4 BIPAP studies). Only three studies [25, 36, 41] were conducted in the paediatric population, all describing the use of APRV. One study was conducted using a lung model [61]. Eleven [8, 9, 11, 21, 24, 26, 28, 29, 38, 42, 43] of the 31 (35%) human studies involved patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), 5 (16%) reported the use of the ventilator mode in patients following coronary artery graft surgery [18, 27, 30, 34, 40] and a further four (13%) studies were conducted in patients with acute respiratory failure distinct from ALI and ARDS [19, 23, 33, 36]. The remaining studies examined the use of APRV and BIPAP for a variety of patient diagnoses.

Forty-three studies compared the identified mode to another style of ventilation. Pressure-controlled ventilation was the most frequent mode of comparison (13/43, 30% of comparative studies [9, 10, 28, 29, 32, 42, 44, 45, 52, 54, 59, 60]). Pressure-controlled ventilation was applied either through use of intermittent mandatory ventilation (IMV), assist control (A/C), or through neuromuscular blockade-induced apnoea with APRV or BIPAP. Volume-controlled modes were evaluated in 10 (23%) studies [11, 17, 19, 27, 30, 33, 34, 36, 38, 58] and spontaneous modes, either continuous positive airway pressure (CPAP) or pressure support ventilation were evaluated in a further 10 (23%) studies [8, 12, 18, 22, 37, 39, 47, 51, 55, 57]. Six (14%) studies looked at either different release times for APRV [31, 50, 54], comparison with high frequency oscillatory ventilation [48], tracheal gas insufflation [53] or automatic tube compensation [43]. A further four (9%) studies [20, 40, 49, 56] compared the mode of interest with both mandatory (IMV or A/C) and spontaneous modes.

Table 2 shows the reported outcomes of studies that compared APRV or BIPAP with another mode of ventilation. The majority of studies (30/43, 70%) examined a number of variables including determinants of gas exchange, lung mechanics hemodynamic variables, and sedation use. Studies that compared APRV or BIPAP to volume-control ventilation all found a reduction in the peak inspiratory pressure. Improvement in oxygenation indices and hemodynamic parameters were the two most frequent findings when either APRV or BIPAP were compared to a pressure-control mode (Table 2).

Table 2 Reported outcomes according to comparator mode

Ventilator settings

In adult studies, the mean reported set inspiratory pressure (PHigh) was 6 cm H2O higher with APRV when compared to reports of BIPAP (P = 0.3). The mean reported positive end expiratory pressure (PLow) was the same for both modes (Fig. 1). Various descriptors for set inspiratory pressure (PHigh) and positive end expiratory pressure (PLow) were identified (Table 3). The mean reported inspiratory time was 3.4 ± 1.7 s for APRV studies conducted in adults compared to 2.4 ± 0.9 s for studies BIPAP (P = 0.08). Conversely, the mean reported expiratory time was nearly three times longer in BIPAP studies compared to APRV (3.4 ± 1.6 and 1.3 ± 0.4 s, respectively, P = 0.01).

Fig. 1
figure 1

Mode settings

Table 3 Descriptors of pressure settings

For analytical purposes, studies reporting I:E ratios were categorised into the following: an extreme inverse ratio (>2:1), mild inverse ratio (>1:1 to ≤2:0), 1:1 ratio, and a noninverse ratio. Extreme inverse I:E ratios were used exclusively in APRV studies (P = 0.004), whereas 1:1 and normal inverse ratios were used more frequently in BIPAP studies (Table 4).

Table 4 Reported inspiratory:expiratory ratios

The majority (38/50, 76%) of identified experimental studies did not discuss the method of patient-ventilator synchronization. Of the remaining 12 studies, eight stated the identified mode synchronized with patient’s effort [10, 18, 20, 22, 31, 37, 39, 61]. These comprised 36% of those identifying BIPAP as the mode of interest and 10% of APRV studies. Three (43%) APRV studies that described synchronization stated that it was not available [9, 19, 38].

Discussion themes

The following themes describing the modes APRV and BIPAP were identified through content analysis of discussion papers: enables spontaneous breathing during two phases of the respiratory cycle [14, 58, 6273]; applies two levels of CPAP [1, 3, 4, 58, 63, 64, 6669, 7174]; the difference (between the two modes) is the I:E ratio; BIPAP implies conventional as well as inverse, APRV always implies inverse [64, 66, 68, 72]; modes are synonymous [71]; modes form a continuum [1, 2, 63]; APRV implies short release times and long inspiratory times [14, 6368, 70]; and a PLow of 0 cm H2O is recommended for APRV [4, 65, 66]. Commonalities in the descriptions of APRV and BIPAP were the ability for spontaneous breathing throughout both the inspiratory and expiratory phases of the respiratory cycle and the application of two levels of CPAP [set inspiratory pressure (PHigh) and positive end expiratory pressure (PLow)]. Inconsistency existed in the defining criteria to distinguish the two modes. Some authors acknowledged a distinction between APRV and BIPAP [64, 66, 68, 72]; others described the modes as a continuum [1, 2, 63] while the two modes are referred to synonymously elsewhere [71].

Discussion

The aim of this systematic review was to determine the defining characteristics of the two ventilator modes, APRV and BIPAP, existent in the published scientific literature. A moderate number of scientific investigations and educational or opinion articles were identified in which APRV was the named mode for the majority. The major distinction found in the description of the two modes was the mean duration of set expiratory time; nearly three times longer in BIPAP studies compared to reports of APRV. Conversely, set inspiratory pressure (PHigh) and positive end expiratory pressure (PLow) settings were similar in reports of either mode.

Another key finding was the lack of consistent parameters to describe or distinguish these two modes. In some studies, the ventilator settings used to apply APRV were indistinguishable from those used for BIPAP [54, 55]. Moreover, summary descriptions reported for educational purposes depicted APRV and BIPAP as either distinct modes, belonging to a continuum of ventilator styles, or as synonymous. The application of APRV, however, was more frequently described as a prolonged inspiratory time and shortened expiratory time resulting in an extreme inverse ratio. In contrast, no BIPAP studies described this type of ventilatory settings.

The original work conducted on these two modes of ventilation was undertaken by separate groups in different countries and published within two years of each other. Airway pressure release ventilation originated from North America and was initially described by Stock and Downs as CPAP with an intermittent release phase [58]. Subsequently, BIPAP was described by the European team, Baum and colleagues, as a mode that combined pressure-controlled ventilation and spontaneous breathing [7, 75].

In the original description of APRV, a mild inverse ratio was applied (1.3:1 in normal lungs and 1.4:1 in injured lungs) [58]. In subsequent studies, the applied inspiratory time for APRV was extended to 4 s or greater [9, 29, 38, 57]. Conversely, in the initial description of BIPAP, an inverse ratio of greater than 1:1 was distinguished as inverse ratio (IR) BIPAP and described as a variation of the mode [62]. Only one identified study has examined the use of BIPAP with an I:E ratio greater than 1:1 [28].

Commercial ventilator branding has imposed restrictions on the naming of modes and possibly contributed to the existing ambiguity in mode terminology. In North America, the term BiPAP® is reserved for noninvasive, pressure-controlled ventilation available on Respironics ventilators (Respironics Inc., Murraysville, PA, USA). This led ventilator companies to develop terms such as BiLevel (Puritan Bennett, Pleasanton, CA, USA; GE Healthcare, Madison, WI, USA), Bivent (Maquet, Solna, Sweden), DuoPaP (Hamilton Medical, Rhäzüns, Switzerland), PCV+ (Dräger Medical, Lübeck, Germany), or BiPhasic (Viasys, Conshocken, PA, USA).

Consistency in the parameters that define APRV and BIPAP is needed to enable clinicians to decide on an appropriate style of ventilation based on a patient’s clinical condition. Reports of the benefits of these modes demonstrate improvements in gas exchange [25, 26], hemodynamic parameters [10, 29, 46, 51], and a reduction in overall sedation requirements [29]. Some of these benefits may be attributable to the maintenance of spontaneous breathing common to both ventilator modes [2, 6, 7]. Further improvements in gas exchange, however, may be the result of an extended inspiratory time and shortened expiratory time that promote recruitment of alveoli with longer time constants [4]. These improvements may be dependent on the extreme inverse ratio advocated by some APRV studies [25, 26, 29]. There is the potential that expected improvements in gas exchange might not occur without use of an extreme inverse ratio, which may deter clinicians new to the mode from using an unfamiliar style of ventilation. Anecdotally, some clinicians perceive APRV as an extreme form of ventilatory support that may pose risk to patients. This perception may prevent clinical uptake of APRV, and by association BIPAP, used with a more conventional I:E ratio.

Conclusions

Ambiguity exists in the criteria that distinguish APRV and BIPAP. When applied with the same I:E ratio, no difference exists between the two modes. APRV as opposed to BIPAP, however, is more frequently described with an extreme inverse ratio and advocated as a method to improve oxygenation in refractory hypoxemia. This application of APRV warrants the consistent use of a distinguishing acronym similar to that used when differentiating the use of an inverse ratio in pressure-controlled ventilation (PCV-IRV).

Uncertainty concerning the correct style of application for APRV and BIPAP may obstruct the clinical adoption of these modes. Generic naming of ventilator modes, as with drug prescribing, combined with consistent definitions of the parameters that define and distinguish APRV and BIPAP, would help standardise research designed to investigate the effect of these modes of mechanical ventilatory support. This may improve the consistency of patient response and assist with future implementation into clinical practice.