Louise Rose Martyn Hawkins Airway pressure release ventilation and biphasic positive airway pressure: a systematic review of definitional criteria Received: 1 April 2008 Accepted: 24 June 2008 Published online: 17 July 2008 Ó Springer-Verlag 2008 This work was performed at the Lawrence S. Bloomberg Faculty of Nursing, Toronto, Canada and the Intensive Care Unit of the Stirling Royal Infirmary, UK. L. Rose ( ) ) Lawrence S. Bloomberg Faculty of
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  Louise RoseMartyn Hawkins  Airway pressure release ventilationand biphasic positive airway pressure:a systematic review of definitional criteria Received: 1 April 2008Accepted: 24 June 2008Published online: 17 July 2008   Springer-Verlag 2008This work was performed at the LawrenceS. Bloomberg Faculty of Nursing, Toronto,Canada and the Intensive Care Unit of theStirling Royal Infirmary, UK.L. Rose ( ) )Lawrence S. Bloomberg Faculty of Nursing,University of Toronto, 155 College Street,Room 276, Toronto, ON M5T 1P8, Canadae-mail: louise.rose@utoronto.caTel.:  + 1-416-9783492Fax:  + 1-416-9460665M. HawkinsIntensive Care Unit,Stirling Royal Infirmary,Stirling, Scotland, UK  Abstract  Objective:  The objec-tive of this study was to identify thedefinitional criteria for the pressure-limited and time-cycled modes: air-way pressure release ventilation(APRV) and biphasic positive airwaypressure (BIPAP) available in thepublished literature.  Design:  Sys-tematic review.  Methods:  Medline,PubMed, Cochrane, and CINAHLdatabases (1982–2006) were searchedusing the following terms: APRV,BIPAP, Bilevel and lung protectivestrategy, individually and in combi-nation. Two independent reviewersdetermined the paper eligibility andabstracted data from 50 studies and18 discussion articles.  Measurementsand results:  Of the 50 studies, 39(78%) described APRV, and 11(22%) described BIPAP. Variousstudy designs, populations, or out-come measures were investigated.Compared to BIPAP, APRV wasdescribed more frequently as extremeinverse inspiratory:expiratory ratio[18/39 (46%) vs. 0/11 (0%), P  =  0.004] and used rarely as anoninverse ratio [2/39 (5%) vs. 3/11(27%),  P  =  0.06]. One (9%) BIPAPand eight (21%) APRV studies usedmild inverse ratio ( [ 1:1 to  B 2:1)( P  =  0.7), plus there was increaseduse of 1:1 ratio [7 (64%) vs. 12(31%),  P  =  0.08] with BIPAP. Inadult studies, the mean reported setinspiratory pressure (PHigh) was6 cm H 2 O greater with APRV whencompared to reports of BIPAP( P  =  0.3). For both modes, the meanreported positive end expiratorypressure (PLow) was 5.5 cm H 2 O.Thematic review identified inconsis-tency of mode descriptions. Conclusions:  Ambiguity exists inthe criteria that distinguish APRV andBIPAP. Commercial ventilatorbranding may further add to confu-sion. Generic naming of modes andconsistent definitional parametersmay improve consistency of patientresponse for a given mode and assistwith clinical implementation. Keywords  Airway pressure releaseventilation    Acute lung injury   Mechanical ventilation   Positive pressure respiration   Assisted spontaneous breathing   Biphasic positive airway pressure Introduction Airway pressure release ventilation (APRV) and bipha-sic positive airway pressure (BIPAP) are modes of mechanical ventilation that allow unrestricted spontane-ous breathing independent of ventilator cycling, using anactive expiratory valve [1–4]. Both modes are pressure- limited and time-cycled. Ventilation occurs via the time- Intensive Care Med (2008) 34:1766–1773DOI 10.1007/s00134-008-1216-3  REVIEW  cycled switching between two set pressure levels. In theabsence of spontaneous breathing, these modes resembleconventional pressure-limited, time-cycled ventilation(Table 1) [5]. A proposed advantage of APRV and BIPAP comparedto conventional pressure-controlled ventilation is theimproved distribution of gas to dependent lung regions asthe result of spontaneous breathing enabled during theinspiratory and expiratory time cycles. Radiologic studiesindicate that gas is directed to dependent well-perfusedregions of the lungs during spontaneous breathing due tothe movement of the posterior muscular sections of thediaphragm [2]. Improved gas distribution to dependentlung regions prevents atelectasis and promotes alveolarrecruitment resulting in an improved ventilation–perfu-sion matching [6, 7]. Within the scientific literature, descriptions of APRVand BIPAP lack clarity. Various authors use the termAPRV to describe a range of ventilatory settings [8–11]. Others use the term BIPAP to describe settings that areindistinguishable from certain descriptions of APRV [12].In North America, the acronym BiPAP   is reserved fornoninvasive ventilation available on Respironics ventila-tors (Murrayville, PA, USA). With registration of thisacronym, ventilator companies have developed otherterms or acronyms to refer to modes with similarcharacteristics.Reports of the international utilization of ventilatormodes indicate limited clinical uptake of pressure-con-trol modes, which include APRV and BIPAP [13, 14]. Clarity of definitional criteria may assist in the clinicalunderstanding and application of these modes. The aimof this paper is to identify the criteria that define anddistinguish APRV and BIPAP within existing scientificliterature. Methods The following databases were electronically searched:Medline, PubMed, Cochrane Library, Cochrane Con-trolled Trials Registry, and CINAHL, from 1982 to 2006,using the terms APRV, BIPAP, Bilevel, and lung pro-tective strategy, individually and in combination. Twoindependent reviewers determined the eligibility of papersbased on appraisal of the article title and abstract,retrieved potentially relevant studies, and decided onstudy eligibility. Reference lists of those papers meetinginclusion criteria were also examined. All study designswere included. Studies were considered for inclusion if ventilator mode characteristics were identified, specifi-cally inspiratory and expiratory times or I:E ratio. Studiesthat contained enough data to calculate these variables,e.g., respiratory rate and expiratory time, were alsoincluded.No attempt was made to contact authors for unpub-lished data, as the objective was to identify distinguishingcriteria for APRV and BIPAP existent in the availableliterature. Studies published only in abstract form werenot included. Data on the study design and population,mode settings, mode of comparison (if any), and outcomemeasures were then abstracted from included experi-mental studies onto predesigned forms by each reviewerfollowing comprehensive review. Both reviewers tran-scribed mode descriptions from discussion articles ontodata collection forms independently.AnalysesContinuous variables describing mode characteristicsfrom experimental studies were summarized as mean and Table 1  Ventilator mode characteristicsAPRV BIPAP PCV (CMV) PCV (IMV) PCV (AC) PSVControl variable Pressure Pressure Pressure Pressure Pressure PressurePhase variablesTrigger Time/pressure Time Time Time Time Flow/pressure (patient triggered)Limit Pressure Pressure Pressure Pressure Pressure PressureCycle Time Time Time Time Time FlowBreath typesMandatory breaths a Yes Yes Yes Yes Yes NoAssisted breaths b No No c No No d Yes YesSpontaneous breaths e Yes Yes No Yes Yes YesActive expiratory valve Yes Yes No No No No  APRV   airway pressure release ventilation,  BIPAP  biphasic positiveairway pressure,  PCV   pressure-controlled ventilation,  CMV   con-trolled mechanical ventilation,  IMV   intermittent mandatoryventilation,  AC   assist control,  PSV   pressure support ventilation a Mandatory breath: machine triggering and/or cycling of thebreath b Assisted breath: patient triggers and cycles the breath but theventilator also does some work  c Exception would be the addition of pressure support availablewith Bilevel ventilation (Puritan Bennett, Pleasanton, CA) d Breaths are assisted if pressure support is applied betweenmandatory breaths e Spontaneous breath: breath in which the patient determines boththe timing and size1767  SD and compared using Student  t   tests. Reported I:Eratios were categorized into four groups: noninverse, 1:1,mild inverse ( [ 1:1 to B 2.0), and extreme inverse ( C 2.1),and compared using Fisher exact tests due to smallexpected values. Other categorical data including studypopulation, study outcome, I:E ratio, and synchronizationof the switching between set inspiratory pressure (PHigh)and positive end expiratory pressure (PLow) levels tospontaneous effort were summarized as proportions andalso compared using chi square tests. Because of thesubstantial heterogeneity in study design, study popula-tion, comparative group, and primary outcome, noattempt was made to pool data for the purposes of meta-analysis. A two-tailed  P  value \ 0.05 was consideredstatistically significant. All analyses were performedusing Minitab 14 [15]. Discussion articles were examinedusing content analysis to identify themes [16]. Articlecontent was coded under theme headings such as ‘enablesspontaneous breathing’ or ‘APRV uses short release timeand long inspiratory times’ and then examined for repe-tition, characteristics and dimensions that identified andconfirmed categories. Results Database searching yielded 501 citations, of which 81were selected on review of the title and abstract. Onfurther review, data was abstracted from 50 studies and 18discussion articles. Both reviewers agreed in the selectionof included studies ( j = 1). Excluded articles were thosethat contained editorial comment only ( n  =  8); the focusof the article was either APRV or BIPAP, but nodescription of the mode was provided ( n  =  2); or themain focus was not the mode of ventilation ( n  =  2).Of the 50 studies, 31 (62%) were human clinicalstudies [8–11, 17–43] and 19 (38%) [12, 44–60] were experimental (either animal or bench) studies. The 31human clinical studies included 14 (45%) interventional[8, 9, 17, 18, 22, 30, 32, 36–40, 42, 43] and 17 (55%) observational studies [10, 11, 19–21, 23–29, 31, 33–35, 41]. None of the human clinical studies were blinded;only two of the experimental studies were blinded. Inthese two studies reported by the same first author,investigators blinded to the mode of ventilation analyzedcomputed tomography images to determine aeration of lung tissue [59, 60]. Airway pressure release ventilation was the namedmode in 39 (78%) studies [8, 9, 11, 17, 19–21, 23–27, 29, 31–33, 35, 36, 38–43, 46–53, 55–61], 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 enabledspontaneous breathing at two pressure levels. Themajority of reports involved either adult patients (21APRV and seven BIPAP studies) or animal studies (14APRV 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 conductedusing 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 respiratorydistress syndrome (ARDS), 5 (16%) reported the use of the ventilator mode in patients following coronary arterygraft surgery [18, 27, 30, 34, 40] and a further four (13%) studies were conducted in patients with acute respiratory Table 2  Reported outcomes according to comparator modeOutcome PCV( n  =  13)VCV( n  =  10)Spontaneous( n  =  10)More than onemode ( n  =  4)APRV a ( n  =  3)Other( n  =  3)Improved oxygenation/oxygen dynamics b 9 (69) 2 (20) 4 (40) 0 (0) 0 (0) 0 (0)No difference in oxygenation/oxygen dynamics 0 (0) 5 (50) 4 (40) 2 (50) 2 (67) 2 (67)Improved ventilation c 3 (23) 1 (10) 2 (20) 1 (25) 1 (33) 2 (67)No difference in ventilatory parameters 3 (23) 3 (30) 3 (30) 1 (25) 1 (33) 1 (33)Improved hemodynamic parameters d 8 (61) 0 (0) 6 (60) 0 (0) 0 (0) 0 (0)No difference in hemodynamic parameters 3 (23) 6 (60) 1 (10) 3 (75) 0 (0) 0 (0)Reduction in peak airway pressure 2 (15) 10 (100) 0 (0) 3 (75) 0 (0) 0 (0)Reduced sedation 2 (15) 1 (10) 0 (0) 0 (0) 0 (0) 0 (0)Other e 1 (8) 0 (0) 4 (40) 1 (25) 1 (33) 0 (0) PCV   pressure-controlled ventilation,  VCV   volume-controlled ven-tilation,  APRV   airway pressure release ventilationFigures reported are  n  (%). Percentages are [ 100% as most studiesreported more than one outcome of interest a APRV with various release times b Indices of oxygenation included the following: PaO 2 , PaO 2  /FiO 2 ratio, mixed venous oxygen content, oxygen delivery, oxygenconsumption, shunt fraction, ventilation/perfusion ratio c Ventilatory parameters measured included the following: PaCO 2 ,pH, minute ventilation d Hemodynamic parameters measured included the following:heart rate, mean arterial pressure, cardiac output, cardiac index,stroke volume, pulmonary vascular resistance, global end diastolicvolume, right ventricular end diastolic volume, respiratory muscleblood flow, intestinal blood flow e ‘‘Other’’ includes the following: pressure time product; asyn-chrony of effort and ventilator cycling; increased aeration of dependant lung regions close to diaphragm, power of breathing,indirect calorimetry1768  failure distinct from ALI and ARDS [19, 23, 33, 36]. The remaining studies examined the use of APRV and BIPAPfor a variety of patient diagnoses.Forty-three studies compared the identified mode toanother style of ventilation. Pressure-controlled ventila-tion 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 mandatoryventilation (IMV), assist control (A/C), or through neu-romuscular blockade-induced apnoea with APRV orBIPAP. 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 airwaypressure (CPAP) or pressure support ventilation wereevaluated 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], trachealgas 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) andspontaneous modes.Table 2 shows the reported outcomes of studies thatcompared APRV or BIPAP with another mode of venti-lation. The majority of studies (30/43, 70%) examined anumber of variables including determinants of gasexchange, lung mechanics hemodynamic variables, andsedation use. Studies that compared APRV or BIPAP tovolume-control ventilation all found a reduction in thepeak inspiratory pressure. Improvement in oxygenationindices and hemodynamic parameters were the two mostfrequent findings when either APRV or BIPAP werecompared to a pressure-control mode (Table 2).Ventilator settingsIn adult studies, the mean reported set inspiratory pressure(PHigh) was 6 cm H 2 O higher with APRV when com-pared to reports of BIPAP ( P  =  0.3). The mean reportedpositive end expiratory pressure (PLow) was the same forboth modes (Fig. 1). Various descriptors for set inspira-tory pressure (PHigh) and positive end expiratorypressure (PLow) were identified (Table 3). The meanreported inspiratory time was 3.4  ±  1.7 s for APRVstudies conducted in adults compared to 2.4  ±  0.9 s forstudies BIPAP ( P  =  0.08). Conversely, the mean reportedexpiratory time was nearly three times longer in BIPAPstudies compared to APRV (3.4  ±  1.6 and 1.3  ±  0.4 s,respectively,  P  =  0.01).For analytical purposes, studies reporting I:E ratioswere categorised into the following: an extreme inverseratio ( [ 2:1), mild inverse ratio ( [ 1:1 to  B 2:0), 1:1 ratio,and a noninverse ratio. Extreme inverse I:E ratios wereused exclusively in APRV studies ( P  =  0.004), whereas1:1 and normal inverse ratios were used more frequentlyin BIPAP studies (Table 4).The majority (38/50, 76%) of identified experimentalstudies did not discuss the method of patient-ventilatorsynchronization. Of the remaining 12 studies, eight statedthe 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 thatdescribed synchronization stated that it was not available[9, 19, 38]. PHigh PLow05101520253035 APRVBIPAP Pressure Settings    c   m    H    2    O THigh TLow012345APRVBIPAP Inspiratory/Expiratory Times    S   e   c   o   n   d   s Fig. 1  Mode settings Table 3  Descriptors of pressure settingsDescriptorsSet inspiratory pressure PHighPinspHigh CPAP levelPeak inspiratory pressurePinflationInflation pressurePositive end expiratory pressure PLowLow CPAP levelPreleaseBaseline pressure CPAP  continuous positive airway pressure1769
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