APRV Review

Other approaches to open-lung ventilation: Airway pressure releaseventilation

Nader M. Habashi, MD, FACP, FCCP

Airway pressure release ventila-tion (APRV) was initially de-scribed by Stock and Downs (1,2) as continuous positive air-

way pressure (CPAP) with an intermittentpressure release phase. Conceptually,APRV applies a continuous airway pres-sure (Phigh) identical to CPAP to maintainadequate lung volume and promote alve-olar recruitment. However, APRV adds atime-cycled release phase to a lower setpressure (Plow). In addition, spontaneousbreathing can be integrated and is inde-pendent of the ventilator cycle (Fig. 1).CPAP breathing mimics the gas distribu-tion of spontaneous breaths as opposed tomechanically controlled, assisted, or sup-ported breaths, which produce less phys-iological distribution (3–6). Mechanicalbreaths shift ventilation to nondependentlung regions as the passive respiratorysystem accommodates the displacementof gas in to the lungs. However, sponta-neous breathing during APRV results in amore dependent gas distribution whenthe active respiratory system draws gasinto the lung as pressure changes and

flow follow a similar time course (7–9).As a result, by allowing patients to spon-taneously breathe during APRV, depen-dent lung regions may be preferentiallyrecruited without the need to raise ap-plied airway pressure.

APRV has been used in neonatal, pe-diatric, and adult forms of respiratoryfailure (1–4, 6, 10–22). Clinical studiesusing APRV are summarized in Table 1(1–4, 12, 18, 23–28).

In patients with decreased functionalresidual capacity (FRC), elastic work ofbreathing (WOB) is effectively reducedwith the application of CPAP. As FRC isrestored, inspiration begins from a morefavorable pressure/volume relationship,facilitating spontaneous ventilation andimproving oxygenation (29).

However, in acute lung injury/acuterespiratory distress syndrome (ALI/ARDS), the surface area available for gasexchange is significantly reduced. Despiteoptimal lung volume, CPAP mandatesthat unaided spontaneous breathingmanage the entire metabolic load or CO2

production. However, CPAP alone may beinadequate to accomplish necessary CO2

removal without producing excessiveWOB. In contrast to CPAP, APRV inter-rupts airway pressure briefly to supple-ment spontaneous minute ventilation.During APRV, ventilation is augmented

by releasing airway pressure to a lowerCPAP level termed Plow. The intermittentrelease in airway pressure during APRVprovides CO2 removal and partially un-loads the metabolic burden of pure CPAPbreathing.

By using a release phase for ventila-tion, APRV uncouples the traditional re-quirement of elevating airway pressure,lung volume, and distension during tidalventilation. Rather than generating atidal volume by raising airway pressureabove the set positive end-expiratorypressure (PEEP) (like in conventionalventilation), release volumes in APRV aregenerated by briefly releasing airwaypressure from Phigh to Plow. Because ven-tilation with APRV results as airway pres-sure and lung volume decrease (releasevolume), the risk of overdistension maybe reduced. In contrast, conventionalventilation raises airway pressure, elevat-ing lung volumes, potentially increasingthe threat of overdistension (Fig. 2).

Ventilation generated by the releasephase of APRV may have additional ad-vantages in ALI/ARDS. Increased elasticrecoil is common to restrictive lung dis-eases such as ALI/ARDS. With APRV, asairway pressure is briefly interrupted, therelease volume is driven by gas compres-sion and lung recoil (potential energy)stored during the Phigh time period or

From the Multi-trauma ICU, R Adams CowleyShock Trauma Center, Baltimore, MD.

Copyright © 2005 by the Society of Critical CareMedicine and Lippincott Williams & Wilkins

DOI: 10.1097/01.CCM.0000155920.11893.37

Objective: To review the use of airway pressure release ven-tilation (APRV) in the treatment of acute lung injury/acute respi-ratory distress syndrome.

Data Source: Published animal studies, human studies, andreview articles of APRV.

Data Summary: APRV has been successfully used in neonatal,pediatric, and adult forms of respiratory failure. Experimental andclinical use of APRV has been shown to facilitate spontaneousbreathing and is associated with decreased peak airway pres-sures and improved oxygenation/ventilation when compared withconventional ventilation. Additionally, improvements in hemody-namic parameters, splanchnic perfusion, and reduced sedation/neuromuscular blocker requirements have been reported.

Conclusion: APRV may offer potential clinical advantages forventilator management of acute lung injury/acute respiratorydistress syndrome and may be considered as an alternative“open lung approach” to mechanical ventilation. WhetherAPRV reduces mortality or increases ventilator-free days com-pared with a conventional volume-cycled “lung protective”strategy will require future randomized, controlled trials. (CritCare Med 2005; 33[Suppl.]:S228 –S240)

KEY WORDS: airway pressure release ventilation; airway pres-sure release ventilation; spontaneous breathing; lung protectivestrategies; acute lung injury; acute respiratory distress syndrome

S228 Crit Care Med 2005 Vol. 33, No. 3 (Suppl.)

Thigh. During conventional ventilation,inspiratory tidal volumes must overcomeairway impedance and elastic forces ofthe restricted lung from a lower baselineresting volume, increasing the energy orpressure required to distend the lung andchest wall. Furthermore, as thoraciccompliance decreases, the inspiratorylimb of the volume/pressure curve shiftsto the right, i.e., more pressure is re-quired to deliver a set tidal volume. How-ever, the expiratory limb remains unaf-fected by the prevailing volume/pressurerelationship and extends throughout allphases of injury (30). APRV uses the morefavorable volume/pressure relationship ofthe expiratory limb for ventilation by ap-plying a near-sustained inflation or re-cruitment state (31).

Alveolar recruitment is a pan-inspira-tory phenomenon. Successful recruitingpressure depends on the yield or thresh-old opening pressure (TOP) of lung units.ALI/ARDS may have a multitude of TOPdistributed throughout the lung (32–35).In addition to TOP, the time-dependentnature of recruitment should also be con-sidered. Although the exact mechanismsare not known, the lung is interdepen-dent and recruitment of air spaces resultsin radial traction of neighboring alveoli,producing a time-dependent ripple effectof recruitment (36–38).

As lung units recruit, the additionaltime (Thigh) at Phigh provides stability asan “avalanche” of lung units pop open(37, 38). Conceptually, superimposed

spontaneous breaths at a high lung vol-ume rather than brief and frequent tidalventilation between PEEP and end-inspiratory pressure may be more suc-cessful in achieving progressive and sus-tained alveolar recruitment.

Airway opening is dynamic as the lungcreeps to the recruited lung volume.Compliance and resistance (time con-stants) of recently recruited lung unitsdecrease the inflating or sustaining pres-sure requirements. Therefore, progres-sive extensions of Thigh may be critical forsustaining recruitment as time constantsevolve (38). Furthermore, the sustainedThigh period may encourage spontaneousbreathing at an upper and open lung vol-ume, improving efficiency of ventilation.

Although recruitment maneuvers maybe effective in improving gas exchangeand compliance, these effects appear tobe nonsustained, requiring repeated ma-neuvers (39, 40). Alternatively, APRV maybe viewed as a nearly continuous recruit-ment maneuver with the Phigh providing80% to 95% of the cycle time creating astabilized “open lung” while facilitatingspontaneous breathing. Fundamentally,assisted mechanical breaths cannot pro-vide the same gas distribution as sponta-neous breaths. Therefore, during a re-cruitment maneuver in a passiverespiratory system, the nondependentlung regions distend first until appliedairway pressure reaches and exceeds thehigh TOP of the dependent lung units,increasing the threat of overdistention.

Conversely, spontaneous breathing favorsdependent lung recruitment through theapplication of pleural pressure. Sponta-neous breaths at the CPAP level (Phigh)improve dependent ventilation throughpleural pressure changes rather than theapplication of additional applied airwaypressure (5, 6, 26). The recruited lungrequires less pressure than the recruitinglung. Therefore, maintaining lung vol-ume and allowing spontaneous breathingfrom the time of intubation by usingAPRV (CPAP with release) may reduce theneed for recurrent high CPAP recruit-ment maneuvers (41). If a recruitmentmaneuver is desired during APRV, thePhigh and Thigh can be adjusted to simu-late a conventional CPAP-type recruit-ment maneuver (e.g., Phigh 40–50 cmH2O and Thigh 30–60 secs).

Conventional volume ventilation lim-its recruitment to brief cyclic intervals atend-inspiration or plateau pressure. Lungregions that are recruited only duringbrief end-inspiratory pressure cycles pro-duce inadequate mean alveolar volume.Because alveolar volume is not main-tained, compliance does not improve, re-quiring the same inflation pressure onsubsequent breaths. Reapplication of thesame distending pressure without ade-quate lung recruitment is likely to pro-duce recurrent shear forces and does notattenuate potential lung injury (42). Con-versely, sustained recruitment is associ-ated with increased compliance allowingsuccessful, sequential airway pressure re-duction and improving gas exchange byincreasing alveolar surface area (4, 42–44). Increased alveolar surface area mayimprove stress distribution in the lung.

Gallagher and coworkers (45) demon-strated a direct correlation among meanairway pressure, lung volume, and oxy-genation. The use of APRV to optimizemean airway pressure/lung volume pro-vides a greater surface area for gas ex-change. Allowing sustained duration(Thigh) of Phigh and limiting duration andfrequency of the release phase (Tlow) ofPlow permits only partial emptying, lim-iting lung volume loss during ventilation.As lung recruitment is sustained, gas re-distribution and diffusion along concen-tration gradients have time to occur. Themixture of alveolar and inspired gaswithin the anatomic dead space results ina greater equilibration of gas concentra-tions in all lung regions, improved oxy-genation, and reduced dead-space venti-lation (26, 46) (Fig. 3).

Figure 1. Airway pressure release ventilation is a form of continuous positive airway pressure (CPAP).The Phigh is equivalent to a CPAP level; Thigh is the duration of Phigh. The CPAP phase (Phigh) isintermittently released to a Plow for a brief duration (Tlow) reestablishing the CPAP level on thesubsequent breath. Spontaneous breathing may be superimposed at both pressure levels and isindependent of time-cycling. Reprinted from ICON educational supplement 2004 with permission.

S229Crit Care Med 2005 Vol. 33, No. 3 (Suppl.)

In addition to FIO2 and slope, clini-cian-controlled APRV parameters are:Phigh, Thigh, Plow, and Tlow. Time parame-ters in APRV are independent rather thanan inspiratory:expiratory (I:E) ratio al-lowing precise adjustment.

The Phigh and Thigh regulate end-inspiratory lung volume and provide asignificant contribution to the mean air-way pressure. Mean airway pressure cor-relates to mean alveolar volume and iscritical for maintaining an increased sur-

face area of open air spaces for diffusivegas movement. As a result, these param-eters control oxygenation and alveolarventilation. Counterintuitive to conven-tional concepts of ventilation, the exten-sion of Thigh can be associated with a

Table 1. Clinical studies using airway pressure-release ventilation (APRV)

Author(yr Published) Study Measurements Findings Study design

Stock (1987) APRV vs. IPPV; dogs with ALI(n � 10)

Blood gases, hemodynamics,lung volume, airwaypressure, f, VT, VE

Hemodynamics were notdifferent at equivalent VE; withAPRV, PIP and physiologicaldead space were lower, meanairway pressure was higher,and oxygenation was better

Animal study, small n, andshort-term observations

Garner (1988) APRV vs. conventional ventilation,patients after cardiac surgery(n � 14)


Similar oxygenation andventilation at lower peakairway pressure

Observational, crossovertrial

Rasanen (1988) APRV vs. conventional ventilationvs. CPAP; anesthetized dogs(n � 10)


APRV had similar effects onblood gases but withsignificantly fewer adversehemodynamic effects

Animal studies, small n,and short-termobservations

Martin (1991) APRV vs. CPAP vs. conventionalventilation vs. spontaneousbreathing; neonatal sheep witholeic-acid lung injury (n � 7)


APRV increased VE more thanCPAP; APRV provided similargas exchange to conventionalventilation, but with feweradverse hemodynamic effects


Davis (1993) APRV vs. SIMV; surgery patientswith ALI(n � 15)


APRV provided similar gasexchange with lower PIP, butno hemodynamic advantagewas identified

Prospective, crossover trialwith short-termobservations

Putensen (1994) APRV (with and withoutspontaneous breathing) vs.PSV; anesthetized dogs(n � 10)

Blood gases, hemodynamics,lung volume, airwaypressure, f, VT, VE,ventilation/perfusiondetermined by multipleinert-gas-eliminationtechnique

PSV had highest VE; APRV hadhigher cardiac output, PaO2,and oxygen delivery; APRV hadbetter V/Q and less dead space


Sydow (1994) APRV vs. volume-controlledinverse-ratio ventilation;patients with ALI; 24-hrobservation periods (n � 18)


APRV provided 30% lower PIP,less venous admixture (14 vs.21%), and better oxygenation;no difference inhemodynamics

Prospective, randomized,crossover trial

Calzia (1994) BiPAP vs. CPAP; patients afterbypass surgery (n � 19)

WOB and PTP No difference Prospective, crossover trial

Rathgeber (1997) BiPAP vs. conventional ventilationvs. SIMV; patients after cardiacsurgery (n � 596)

Duration of intubation,sedation requirement,analgesia requirement

APRV had shorter duration ofintubation (10 hrs) than SIMV(15 hrs) or conventionalventilation (13 hrs);conventional ventilation wasassociated with greater dosesof midazolam; APRV wasassociated with less need foranalgesia

Prospective, randomized,controlled, open trialover 18 months, unevenrandomization

Kazmaier (2000) BiPAP vs. SIMV vs. PSV; pPatientsafter coronary artery bypass(n � 24)


No differences in blood gases orhemodynamics

Prospective, crossover trialwith short-termobservations

Putensen (2001) APRV vs. pressure controlledconventional ventilation;patients with ALI after trauma(n � 30)

Gas exchange,hemodynamics, sedationrequirement,hemodynamic support,duration of ventilation,ICU stay

APRV was associated with fewerICU days, fewer ventilatordays, better gas exchange,better hemodynamicperformance, better lungcompliance, and less need forsedation and vasopressors

Randomized controlled,prospective trial, smalln; the conventionalventilation groupreceived paralysis for thefirst 3 days, potentiallyconfounding results

Varpula (2003) Combined effects of proning andSIMV PC/PS vs. APRV; patientswith ALI (n � 45)

Blood gases, oxygenation(PaO2/FIO2 ratio),hemodynamic, sedationrequirement

Oxygenation was significantlybetter in APRV group beforeand after proning; sedation useand hemodynamics weresimilar

Prospective, randomizedintervention study

IPPV, intermittent positive-pressure ventilation; ALI, acute lung injury; f, respiratory frequency; VE, minute volume; VT, tidal volume; PIP, peakinspiratory pressure; CPAP, continuous positive airway pressure; PSV, pressure support ventilation; V/Q, ventilation/perfusion ratio; BiPAP, bilevel positiveairway pressure; SIMV, synchronized intermittent mandatory ventilation; WOB, work of breathing; PTP, pressure-time product; ICU, intensive care unit.

Reprinted with permission from Branson RD, Johannigman JA: What is the evidence base for the newer ventilation modes? Respir Care 2004;49:742–760.


decrease in PaCO2 as machine frequencydecreases. This has been previously de-scribed and is similar to improved CO2

clearance with increasing I:E ratios (47–51). Despite the intermittent nature ofventilation, CO2 delivery to the lung iscontinuous as cardiac output transfersCO2 into the alveolar space, provided air-ways remain open (52). During the briefTlow, released gas is exchanged with freshgas to regenerate the gradient for CO2

diffusion. In addition, cardiogenic mixingresults in CO2 movement toward centralairways during the Thigh or breathholdperiod (46, 53–55), improving the efficacyof the release for ventilation. The addi-tion of spontaneous breaths during theThigh period at Phigh (higher lung volume)further enhances recruitment and venti-lation efficiency (Fig. 3).

The risk of using APRV as a cyclicmode and attempting to increase the ma-chine frequency and minute ventilationby reducing Thigh may sacrifice alveolarventilation and oxygenation. Reducing

Thigh will lead to a reduction in meanairway pressure, potentially resulting inairway closure, decreasing alveolar sur-face area for gas exchange.

In addition to spontaneous breathing,ventilation is augmented during APRV asa result of the release phase. The releasephase is determined by the driving pres-sure differential (Phigh - Plow), inspiratorylung volume (Phigh), the potential energy(recoil or compliance of the thorax andthe amount of energy stored duringThigh), and downstream resistance (artifi-cial airway). Plow and Tlow regulate end-expiratory lung volume and should beoptimized to reduce airway closure/derecruitment and not as a primary ven-tilation adjustment. Generally, to main-tain maximal recruitment, the majorityof the time or Thigh (80–95% of the totalcycle time) occurs at the Phigh or CPAPlevel. To minimize derecruitment, thetime (Tlow) at Plow is brief (usually be-tween 0.2 and 0.8 secs in adults).

Because patients can maintain theirnative respiratory drive during APRV,spontaneous inspiratory and expiratorytime intervals are independent of theThigh, Tlow cycle (56). Thus, the releasephase does not reflect the only expiratorytime during APRV when patients arebreathing spontaneously. Therefore,spontaneous expirations will occur at theupper pressure or Phigh phase. Active ex-halation during the Phigh phase may re-sult in additional recruitment and vol-ume redistribution analogous togrunting respiration in neonates, therebyimproving ventilation/perfusion (V/Q)matching (22, 57–61).

The release time (Tlow) may be titratedto maintain end-expiratory lung volume(EELV)/(end-release lung volume [ERLV]).The end-release lung volume can be ad-justed and continually assessed by usingthe expiratory flow pattern (Fig. 4). Theexpiratory gas flow is a result of the inspira-tory lung volume, the recoil or drive pres-sure of the lung, and downstream resis-tance (artificial airway, circuit, and PEEPvalve) (Fig. 5). Experimental data in a por-cine ALI model using dynamic computedtomography scanning shows that airwayclosure occurs rapidly (within 0.6 secs) (38,62). However, the rapid airway closure inpig models of ALI may be related to poorcollateral ventilation as opposed to humanlungs. Collateral ventilation may play a sig-nificant role in recruitment/derecruitmentin ALI (63).

Using a Plow of zero allows end-expiratory/release lung volume to be con-trolled by one parameter (time). The in-herent resistance of the artificial airwaybehaves as a flow resistor/limiter and, ifcoupled with a brief release time, caneffectively trap gas volume to maintainend-release or expiratory pressure(PEEP) (64, 65). During passive expira-tion or release in patients with ARDS,expiratory time constants are signifi-cantly modified (increased threefold) bythe flow-dependent resistance of the arti-ficial airway (66, 67).

Because the artificial airway produces anonlinear, flow-dependent resistive loadand the release results from a high lungvolume, flow resistance will be highest atthe initial portion of the release phase (67–69). The Tlow or release phase is terminatedT-PEFR rapidly before the flow-dependentexpiratory load is dissipated, resulting inend-expiratory volume and pressure.

The residual pressure and volume inthe lung during the brief release phasetypically yields end-release or end-

Figure 2. Ventilation during airway pressure release ventilation is augmented by release volumes andis associated with decreasing airway pressure and lung distension. Conversely, tidal volumes duringconventional ventilation are generated by increasing airway pressure and lung distension. Reprintedfrom ICON educational supplement 2004 with permission.

Figure 3. Gas exchange during airway pressure release ventilation. A, mean airway pressure (lungvolume) provides sustained mean alveolar volume for gas diffusion. B, alveolar gas volume combinedwith cardiac output provides continuous diffusive gas exchange between alveolar and blood compart-ments despite the cyclic nature of ventilation. C, CO2-enriched gas is released to accommodateoxygen-enriched gas delivered with the subsequent inspiratory cycle. New inspiratory volume isintroduced, regenerating diffusion gradients. Reprinted from ICON educational supplement 2004 withpermission.


expiratory pressure greater than the Plow

arbitrarily set at the machine’s peep valve(approximately 8 ft away). In fact, com-mercially available ventilators with tubecompensation algorithms for resistance

of artificial airways provide inadequateexpiratory compensation when PEEP isreduced to atmospheric pressure. The ad-dition of a negative pressure source tobriefly lower the end-expiratory pressure

to subatmospheric is required to fullycompensate the expiratory resistance im-posed by the artificial airway (70).

By using a Plow �0 cm H2O, peak expi-ratory flow rate (PEFR) is delayed, whereasa Plow of 0 cm H2O accelerates PEFR con-cluding the release phase earlier and en-abling the Phigh phase to be resumed earlierin the cycle. A greater percent of the cycletime at Thigh increases the potential forrecruitment, maintains lung volume, limitsderecruitment, and induces spontaneousbreathing. See Table 2 for goals, set up,oxygenation, ventilation, weaning, and pre-cautions during utilization of APRV.

Spontaneous Breathing DuringAirway Pressure ReleaseVentilation

During APRV, patients can control thefrequency and duration of spontaneousinspiration and expiration. Patients arenot confined to a preset I:E ratio, andspontaneous tidal volumes maintain a si-nusoidal flow pattern similar to normalspontaneous breaths. The ability of criti-cally ill patients to effectively augment

Figure 5. Patient interface to mechanical ventilator circuit and inherent resistance to expiratory flowfrom artificial airway (R1) and positive end-expiratory pressure (PEEP) valve (R2). Because the releaseoccurs from a high lung volume during airway pressure release ventilation, flow resistance developsat the distal end of R1 and R2. The proximal end of R1 decompresses more rapidly than the distal end.Despite zero end-expiratory pressure (ZEEP), flow resistance at R2 (typically measured approximately8 ft away) contributes to tracheal pressure elevation above end-expiratory pressure. Flow resistance ishighest at the onset of the release (�0.2 L/sec) and decreases as expiratory flow rate declines. Releasetime is terminated after a brief duration before flow resistance dissipates to maintain end-expiratorylung volume (67–69). Reprinted from ICON educational supplement 2004 with permission.

Figure 4. End-expiratory lung volume. Expiratory flow pattern during the release phase of airway pressure release ventilation. Initial portion of expiratoryflow limb is the peak expiratory flow rate (PEFR) as a result of Phigh to Plow pressure reduction. Deceleration of gas flow occurs as driving pressure dissipatesproducing the decelerating limb. PEFR and rate of deceleration are affected by inspiratory lung volume, thoracic recoil, and downstream resistance(artificial airway resistance with Plow of zero). A, expiratory flow pattern demonstrating normal deceleration at 45° as airways empty sequentially (67).Release time is adjusted to regulate T-PEFR to 60% of PEFR. The flow/time beyond the T-PEFR correlates with the end-release lung volume (ERLV)(end-expiratory lung volume [EELV]). The angle of deceleration (ADEC) can suggest alterations in lung mechanics resulting in altered expiratory gas flow([a] Normal (45°), [b] restrictive, e.g., decrease thoracic compliance (�45°) [c] obstructive, e.g., OLD, small or obstructed artificial airway (�45°)]. B,expiratory flow pattern with lung changes indicating derecruitment. As lung compliance worsens (less end-inspiratory lung volume and increasing thoracicrecoil, e.g., increased lung water or decreased thoracic/abdominal compliance), the expiratory flow pattern will become more restricted (the deceleratinglimb will become steeper, i.e., ADEC �45°) and the set release time will result in a lower T-PEFR and less end-expiratory lung volume (or ERLV); lowerERLV with resulting airway closure/derecruitment. C, the release time can be adjusted to limit airway closure and prevent derecruitment. D, conversely,as respiratory mechanics improve (lung, thoracic, abdominal compliance), recruitment is reflected as the decelerating limb returns to a 45° angle and theset release time increases the T-PEFR regulating ERLV (EELV). E, the release time can be readjusted to maintain T-PEFR at 50% to 75%. Reprinted fromICON educational supplement 2004 with permission.


Table 2. Airway pressure release ventilation (APRV) clinical guide

GoalsAcute (recruitable) restrictive lung disease (RLD)

Increase (recruit) and maintain lung volume (Phigh and Thigh)Decrease elastic WOB with CPAP (Phigh and Thigh)ATC set at 100% to maximally compensate for artificial airway resistance and decrease resistive WOB imposed by the artificial airwaya

Minimize number of releases to supplement ventilation from spontaneous breathing (71)Limit derecruitment; Tlow set to ensure T-PEFR is �50 and �75%Allow spontaneous breathing within 24 hrs of APRV application

Acute obstructive lung disease (OLD)Decrease lung volumeMaintain Phigh at or 1–2 cm H2O above PEEPiMinimize number of releases to supplement ventilation from spontaneous breathing (71)Stint airways; Tlow set for 25–50% T-PEFR

Allow spontaneous breathing within 24 hrs of APRV application. May require a brief course of NMBA (�24 hrs) to control high spontaneousbreathing frequency and artificial airway contribution to dynamic hyperinflation.

Set-up—adultsNewly intubated

Phigh—set at desired plateau pressure (typically 20–35 cm H2O)Note: Phigh �35 cm H2O may be necessary in patients with decreased thoracic/abdominal compliance or morbid obesity (73, 74). With a Phigh

�25 cm H2O, use of noncompliant ventilator circuit is recommended to minimize circuit volume compression (75, 76).Plow—0 cm H2OThigh—4–6 secsTlow—0.2–0.8 secs (RLD)0.8–1.5 secs (OLD)

Transition from conventional ventilationPhigh—plateau pressure in volume-cycled mode or peak airway pressure in pressure-cycled modePlow—0 cm H2OThigh—4–6 secsTlow—0.2–0.8 secs (RLD)0.8–1.5 secs (OLD)

Transition from HFOVb—use noncompliant ventilator circuitPhigh—mPaw on HFOV plus 2–4 cm H2OPlow—0 cm H2OThigh—4–6 secsTlow—0.2–0.8 secs (RLD)0.8–1.5 secs (OLD)

Set-up—PediatricsNewly intubated

Phigh—set at desired plateau pressure (typically 20–30 cm H2O)Note: Phigh �30 cm H2O may be necessary in patients with decreased thoracic/abdominal compliance or morbid obesity (73, 74). With a Phigh

�25 cm H2O, use of noncompliant ventilator circuit is recommended to minimize circuit volume compression (75, 76).Plow—0 cm H2OThigh—3–5 secsTlow—0.2–0.8

Transition from conventional ventilationPhigh—plateau pressure in volume-cycled mode or peak airway pressure in pressure-cycled modePlow—0 cm H2OThigh—3–5 secsTlow—0.2–0.8

Transition from HFOVb

Phigh—mPaw on HFOV plus 2–4 cm H2OPlow—0 cm H2OThigh—3–5 secsTlow—0.2–0.8

Set-up—NeonatesNewly intubated

Phigh—set at desired plateau pressure (typically 10–25 cm H2O)Note: Phigh �25 cm H2O may be necessary in patients with decreased thoracic/abdominal compliance (73, 74). With a Phigh�25 cm H2O,

use of noncompliant ventilator circuit is recommended to minimize circuit volume compression (75, 76).Plow—0 cm H2OThigh—2–3 secsTlow—0.2–0.4

Transition from conventional ventilationPhigh—plateau pressure in volume-cycled mode or peak airway pressure in pressure-cycled modePlow—0 cm H2OThigh—2–3 secsTlow—0.2–0.4

Transition from HFOVb

Phigh—mPaw on HFOV plus 0–2 cm H2OPlow—0 cm H2OThigh—2–3 secsTlow—0.2–0.4

Continues


spontaneous ventilation in response tochanging metabolic needs may promotesynchrony during mechanical ventilationand improve V/Q matching (3–6, 10, 11).In contrast, patients transitioned fromspontaneous breathing to mechanicalventilation through the induction of an-esthesia exhibit worsening gas exchangeand dependent atelectasis on computedtomography scan within minutes (7–9,76–83). These studies suggest rapid al-teration of ventilation distribution whenthe respiratory system becomes passive.

Most mechanical ventilators monitorairway pressures; however, transpulmo-nary pressures ultimately determine lungvolume change. Although difficult tomonitor clinically, the effects of pleuralpressure on transpulmonary pressuresshould not be excluded from manage-ment principles. For example, patientswith reduced thoracic and abdominalcompliance demonstrate higher airwaypressure yet may have lower transpulmo-nary pressure (73, 74).

Spontaneous breathing, diaphrag-matic tone, and prone positioning modify

pleural pressure, improving transalveolarpressure gradients in dependent lung re-gions (7, 84–87). Increased dependentlung ventilation during spontaneousbreathing recruits alveoli improving V/Qmatching without raising applied airwaypressure (3–6, 10, 11).

APRV and prone positioning mayhave an additive effect on recruitmentand gas exchange. Varpula demon-strated greater improvement in gas ex-change when prone positioning wascombined with APRV rather than syn-chronized intermittent mandatory ven-tilation (10).

Hemodynamic Effects of AirwayPressure Release Ventilation

The descent of the diaphragm into theabdomen during a spontaneous breathingeffort simultaneously decreases pleuralpressures and increases abdominal pres-sure. This effectively lowers the right atrial(RA) pressure while compressing abdomi-nal viscera propelling blood (preload) intothe inferior vena cava (IVC). Increasing the

mean systemic pressure (MSP)/RA gradientcouples the thoracic and cardiac pumps,increasing venous return, improving car-diac output, and decreasing dead space ven-tilation (88, 89). Conversely, when sponta-neous breathing is limited or thediaphragm is paralyzed, the passive decentof the diaphragm is no longer linked withlower pleural/right atrial pressure, mini-mizing the IVC–right atrial pressure gradi-ent (MSP-RA) and limiting venous return/cardiac output.

Restoration of cardiopulmonary inter-action with spontaneous breathing dur-ing APRV produces improvements in sys-temic perfusion. Animal and humanstudies document improved splanchnicand renal perfusion during APRV withspontaneous breathing (13, 90)

Use of Pressure SupportVentilation with Airway PressureRelease Ventilation

Currently, some ventilator manufac-turers incorporate pressure support ven-tilation (PSV) above Phigh. The addition of

Table 2. Continued

OxygenationOptimize end-expiratory or release lung volume

Reassess release volume to ensure T-PEFR is �50 and �75%If oxygenation poor and T-PEFR �50%, decrease release time until T-PEFR 75%Optimize gas exchange surface area by adjusting mPaw

Increase Phigh or Phigh and Thigh simultaneouslyAdjustment of Phigh to recruit by achieving TOPAdjustment of Thigh increases gas mixing and recruits lung units with high resistance time constants

Assess hemodynamicsVentilation

Assess for oversedation; consider using sedation scale (77)Optimize end-expiratory or release lung volume; reassess release volume to ensure at 50–75% T-PEFRIf T-PEFR �75% and oxygenation is acceptable, consider increasing Tlow by 0.05–0.1 increments to achieve 50% T-PEFRIf T-PEFR �50%, decrease Tlow to achieve minimum T-PEFR of 50%Increase alveolar ventilation (preferred method)—increase Phigh or Phigh and Thigh simultaneouslyIncrease minute ventilation—decrease Thigh and increase Phigh simultaneously (see precautions below)

WeaningSimultaneously reduce Phigh and increase Thigh for a gradual reduction of mPaw and to increase the contribution of spontaneous to total minute

ventilation.Progress to CPAP with automatic tube compensation when Phigh �16 and Thigh �12–15 sec (APRV � 90% CPAP)Wean CPAP (with automatic tube compensation) and consider extubation when CPAP 5–10 cm H2O

PrecautionsAdjustment of Tlow differs with lung disease, lung volume and artificial airway size. Tlow values provided are typical but not absolute; see goals forOLD and RLDIf minute ventilation is increased by decreasing Thigh in an attempt to improve CO2 clearance, mPaw and gas exchanging surface area will be

reduced; more so if Phigh is not simultaneously increased as CO2 may paradoxically increase (see text for details). May need to decrease Tlow asThigh reduction may produce less mean alveolar volume (lung volume) and will result in shorter emptying time.

Tlow should not be extended solely to lower CO2 as this may lead to airway closure (derecruitment) (38, 56, 71). Additionally, Tlow should not beviewed as an expiratory time as the patient may exhale throughout the respiratory cycle if permitted (58).

ATC, automatic tube compensation; PEEPi, intrinsic PEEP; mPaw, mean airway pressure; PEFR, peak expiratory flow rate; T-PEFR, peak expiratory flowrate termination; HFOV, high-frequency oscillatory ventilation; WOB, work of breathing; APRV, airway pressure release ventilation; TOP, threshold openingpressure.

aIn vitro resistance may be greater than in vivo resistance calculations and measurements (commercial tube compensation algorithms) due todeformation, kinks and secretion in the artificial airway (64, 65, 72); bmPaw during HFOV is equal to CPAP; mPaw during APRV is typically 2–4 cm H2Oless than CPAP as a result of the release phase (airway pressure interruption) and proximal vs. distal mPaw measurement. Reprinted from ICON EducationalSupplement—2004 with permission.


PSV to APRV contradicts limiting airwaypressure and lung distension during ven-tilation by not restricting lung inflationto the Phigh level.

PSV above Phigh may lead to signifi-cant elevation in transpulmonary pres-sure (Fig. 6). When PSV is triggeredduring the Phigh phase, the higher base-line lung volume distends further as thesum of Phigh, PSV, and pleural pressureraises transpulmonary pressure. Theadditional lung distension above Phigh

and the transpulmonary pressure eleva-tion will not be completely reflected inthe airway pressure because the pleuralpressure remains unknown (91). Fur-thermore, the imposition of PSV toAPRV reduces the benefits of spontane-ous breathing by altering sinusoidalspontaneous breaths to decelerating as-sisted mechanical breaths as flow andpressure development are uncoupledfrom patient effort (Fig. 7). Ultimately,PSV during APRV defeats improvementsin distribution of ventilation and V/Qmatching associated with unassistedspontaneous breathing (4, 6, 26, 92–94). During weaning, even low levels ofPSV used to overcome tube resistancemay overcompensate and convert pa-tient-triggered efforts to assisted rather

than spontaneous breaths, especially ifadequate PEEP levels are used (95, 96).If patient efforts are more vigorous, thePSV will undercompensate artificial air-way resistance.

Artificial Airway CompensationAlgorithms and Airway PressureRelease Ventilation

Computerized ventilator algorithms,which attempt to match inspiratory flow tocalculated resistance of the artificial airwayduring APRV may reduce spontaneousWOB (14). Unlike PSV, tube compensationalgorithms apply inspiratory flow in pro-portion to the pressure drop across theartificial airway resulting from patienteffort or flow demands (95, 96). As aresult, the dynamic pressure applied tothe artificial airway is determinedwithin the breath cycle, limiting over-or undercompensation of artificial air-way resistance. Furthermore, as tubecompensation is coupled to patient ef-fort, flow and resulting applied airwaypressure do not exceed inspiratory pres-sure generated by the respiratory mus-cles (Pmus) (patient’s effort), preservingthe sinusoidal flow pattern of spontane-ous breathing (97) (Fig. 6). Conversely,

applying a fixed airway pressure likePSV may result in both over- and un-dercompensation of artificial airway re-sistance as patient effort (flow) varies.

Commercially available ventilators offerforms of tube compensation but vary in theefficiency of the algorithms applied. Al-though many ventilators may compensateinspiratory resistance effectively, expiratorycompensation by lowering PEEP levels toatmosphere or ZEEP (at the initial phase ofexpiration) may not unload expiratory re-sistance imposed by the artificial airway.The application of negative airway pressureduring the initial expiration phase may benecessary to negate the pressure dropacross the artificial airway (70).

Airway Pressure ReleaseVentilation and Use of Sedationand Neuromuscular-BlockingAgents

Sedation is essential when caring forcritically ill and injured patients re-quiring mechanical ventilation. In se-vere cases of patient–ventilator dys-synchrony, neuromuscular-blockingagents (NMBAs) are frequently used.Excessive sedation has been associatedwith increased duration of mechanicalventilation in patients with acute respi-ratory failure (98 –103). Reducing the

Figure 7. Gas flow pattern comparing pressuresupport ventilation (PSV) and spontaneousbreathing. PSV produces a decelerating gas flowpattern because the gas flow and patient effort (PMus) do not follow a similar time course. Typi-cally, patient effort is outpaced by applied flowand pressure development. Gas distribution dur-ing PSV is similar to an assisted breath ratherthan a spontaneous breath. Spontaneous or un-assisted continuous positive airway pressure(CPAP) breath producing a sinusoidal gas flowpattern as gas flow and patient effort (P Mus) arecoupled and follow a similar time course. Sponta-neous ventilation (unassisted) is associated withimproved ventilation/perfusion distribution, unlikePSV (4, 6, 26, 92–94). Reprinted from ICON educa-tional supplement 2004 with permission.

Figure 6. A, pressure tracing represents a pressure support ventilation (PSV) breath at the Phigh level.During passive efforts, once the PSV trigger threshold is reached, airway pressure elevates above thePhigh level. Alternatively, if the patient generates vigorous inspiratory efforts, the transpulmonary pressuredifferential (sum of PSV, Phigh, Pmus) can be significant and may result in overdistension. B, flow tracingdemonstrates a triggered PSV breath with resultant decelerating gas flow as opposed to sinusoidal gas flowtypical of spontaneous breathing (see D). C, pressure tracing represents airway pressure release ventilation(APRV) with automatic tube compensation; note minimal airway pressure elevation above Phigh. D,spontaneous breaths during APRV with automatic tube compensation, preserving a sinusoidal flow pattern.Reprinted from ICON educational supplement 2004 with permission.


duration of mechanical ventilation de-creases patient exposure to artificialairways, sedation, and NMBAs and thelikelihood of ventilator-associatedpneumonia (VAP) (101, 104 –106).

The negative impact of sedation andNMBAs on the duration of mechanicalventilation and the risk of VAP is likely tobe in part related to depression of thecough reflex, increasing the risk of aspi-ration of pharyngeal secretions (107).Watando suggested that improved coughreflex may limit aspiration pneumonia inhigh-risk groups (108). Furthermore, aneffective cough may be a predictor of hos-pital mortality and of successful extuba-tion (109).

Because APRV uses an open breathingsystem and requires less sedation, pa-tients can exhale or cough throughoutthe respiratory cycle. As a result, coughand secretion clearance can be facilitatedwithout significant intrathoracic pres-sure elevation or airway pressure-limit-ing as would occur with a closed expira-tory valve system.

APRV has been associated with a 70%reduction in NMBA requirements and a30% to 40% reduction in sedation re-quirements when compared with conven-tional ventilation (3, 4, 11, 12, 23, 25,110). In addition, some studies suggest adecrease in ventilator days and intensivecare unit and hospital length of stay as aresult of using APRV (4).

The ARDS Network (ARDSNet) re-ported a significant reduction of mortal-ity from 39.8% to 31.0% with a low tidalvolume strategy (6 mL/kg of ideal bodyweight) and a limited inspiratory plateaupressure (30 cm H2O) using a volume-cycled mode (111). However, patientsventilated using low tidal volumes mayexperience more dyssynchrony and re-quire additional sedation (Kallet RH, per-sonal communication) (112–118).

Airway Pressure ReleaseVentilation for Trauma-Associated Acute RespiratoryDistress Syndrome: ClinicalExperience

APRV has been used at R Adams Cow-ley Shock Trauma Center (STC) in Balti-more, MD, since 1994 and has become astandard of care. In the early 1990s, STCestablished a regional advanced respira-tory failure service, including the devel-opment of ventilation protocols aimed toreduce airway pressure with APRV, pronepositioning, and an extracorporeal lung

assist technique (119). The STC haslogged over 50,000 patient-hours annu-ally on APRV since 1994, developing sig-nificant clinical experience with APRV. AtSTC, the 2-yr period post-APRV imple-mentation for the management of ad-vanced respiratory failure was studiedand documented a reduction in ARDSmortality and multisystem organ failure.The mortality rates after the implemen-tation of APRV in patients meeting crite-ria for ARDS were lower than reported inthe ARDSNet trial, 21.4% vs. 31% (120).In addition, sedation requirements werereduced and NMBA use essentially elimi-nated from routine practice at STC.

Weaning from Airway PressureRelease Ventilation

Patients with improved oxygenationon APRV (e.g., FIO2 �40% with SpO2

�95%) can be progressively weaned bylowering the Phigh and extending theThigh. By decreasing the number of re-leases, the minute ventilation output ofthe ventilator is reduced while simulta-neously (if permitted) the patient’s spon-taneous minute ventilation increases,enabling a progressive spontaneousbreathing trial (99) (Fig. 8). The total andspontaneous minute ventilation shouldbe carefully monitored during weaning toanticipate changes in PaCO2. Eventually,the ventilator’s minute ventilation outputis significantly reduced or eliminated andthe patient has gradually transitioned topure CPAP. CPAP, when combined withtube compensation, can be used to effec-tively overcome artificial airway resis-tance during the final phase of weaning.When used in the final weaning phase,tube compensation may be a useful pre-dictor of successful extubation, particu-larly in the difficult-to-wean patient whofails PSV and T-piece weaning methods(96). This author believes that progres-sive extension of Thigh during APRV wean-ing increases spontaneous breathingthrough a gradual transition to pureCPAP (with tube compensation). There-fore, transitioning the weaning APRV pa-tient to PSV (a form of assisted breathing)may be counterproductive and unneces-sary (121).

Airway Pressure ReleaseVentilation and High-FrequencyOscillatory Ventilation

Fundamentally APRV and high-fre-quency oscillatory ventilation (HFOV)

have similar goals. Both techniques focuson maintaining lung volume while limit-ing the peak ventilating pressure. Main-taining lung volume optimizes V/Qmatching, improves gas exchange, andimproves stress distribution, minimizingshear forces. During HFOV, the continu-ous, high-flow gas pattern facilitates aconstant airway pressure profile mini-mizing derecruitment. In contrast toHFOV, APRV actively promotes spontane-ous breathing.

In addition, APRV does not require asingle-purpose ventilator, effectively usesconventional humidification systems,and is associated with reduced sedationand NMBA use. Furthermore, becauseALI can develop in 24% of patients receiv-ing mechanical ventilation who did nothave ALI at the onset (122), APRV as alung protective strategy, may be used ear-lier rather than at advanced stages ofrespiratory failure. APRV can be appliedas the initial ventilator mode for respira-tory failure or typically before HFOV cri-teria are reached. For patients showingimprovement on HFOV, APRV may rep-resent an ideal transition/weaning modal-ity because Phigh on APRV can be matchedto the mean airway pressure (mPaw) dur-ing HFOV, permitting continued gradualreduction of lung volume (123).

Noninvasive Ventilation withAirway Pressure ReleaseVentilation

APRV may also be applied noninva-sively pre- or postintubation (124). Non-invasive APRV has the advantage of anadjustable degree of mandatory ventila-tion without the need for a trigger (onlyforms of APRV that do not use pressuresupport), decreasing the likelihood of au-tocycling from leaks common to nonin-vasive ventilation.

Future clinical research with APRVshould test different algorithms for oxy-genation, ventilation, and weaning. In ad-dition, hemodynamic and systemic perfu-sion during APRV should be assessed.Animal studies should be performed withAPRV (coupled with spontaneous breath-ing) to compare histologic and biomarkerevidence of VILI/VALI compared withother mechanical ventilation approaches.The delivery of aerosol medications to thelung is poorly understood during APRVand should be studied. Ultimately, clini-cal studies should be conducted using avalidated, protocolized approach to APRV


compared with a protective conventionalventilation strategy.

CONCLUSION

Clinical and experimental studieswith APRV demonstrate improvementsin physiological end points such as gasexchange, cardiac output, and systemicblood flow (3, 4, 6, 11, 13, 26, 90). APRVfacilitates spontaneous breathing andimproves patient tolerance to mechan-ical ventilation by decreasing patient–ventilator dyssynchrony. Additionalstudies document reduction in sedationand NMBAs with APRV, and some, butnot all (10), studies suggest less venti-lator days and shorter length of inten-sive care unit stay (3, 4, 11, 12, 23, 25,111). An adequately designed and pow-ered study to demonstrate a reductionin mortality or ventilator days withAPRV compared with optimal lung pro-tective conventional ventilation has notyet been performed. APRV (combinedwith tube compensation software) re-mains unique among potential “open

lung” approaches to lung protectivemechanical ventilation with the abilityto facilitate spontaneous breathing.

ACKNOWLEDGMENTS

We thank John Downs for review ofthe manuscript and Penny Andrews forreview and assistance with the manu-script; Ulf Borg for review of the manu-script; and Alastair A. Hutchison for ob-servation and contribution on neonatalbreathing pattern during airway pressurerelease ventilation.

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