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Postgraduate Education Corner: CONTEMPORARY REVIEWS IN CRITICAL CARE MEDICINE |

Severe Hypoxemic Respiratory Failure: Part 1—Ventilatory Strategies FREE TO VIEW

Adebayo Esan, MD; Dean R. Hess, PhD, RRT, FCCP; Suhail Raoof, MD, FCCP; Liziamma George, MD, FCCP; Curtis N. Sessler, MD, FCCP
Author and Funding Information

From the New York Methodist Hospital (Drs Esan, Raoof, and George), Division of Pulmonary and Critical Care Medicine, Brooklyn, NY; Respiratory Care Services (Dr Hess), Massachusetts General Hospital, Boston, MA; and Pulmonary and Critical Care Medicine (Dr Sessler), Virginia Commonwealth University, Richmond, VA.

Correspondence to: Suhail Raoof, MD, FCCP, Division of Pulmonary and Critical Care Medicine, New York Methodist Hospital, 506 Sixth St, Brooklyn, NY 11215; e-mail: sur9016@nyp.org


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(5):1203-1216. doi:10.1378/chest.09-2415
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Approximately 16% of deaths in patients with ARDS results from refractory hypoxemia, which is the inability to achieve adequate arterial oxygenation despite high levels of inspired oxygen or the development of barotrauma. A number of ventilator-focused rescue therapies that can be used when conventional mechanical ventilation does not achieve a specific target level of oxygenation are discussed. A literature search was conducted and narrative review written to summarize the use of high levels of positive end-expiratory pressure, recruitment maneuvers, airway pressure-release ventilation, and high-frequency ventilation. Each therapy reviewed has been reported to improve oxygenation in patients with ARDS. However, none of them have been shown to improve survival when studied in heterogeneous populations of patients with ARDS. Moreover, none of the therapies has been reported to be superior to another for the goal of improving oxygenation. The goal of improving oxygenation must always be balanced against the risk of further lung injury. The optimal time to initiate rescue therapies, if needed, is within 96 h of the onset of ARDS, a time when alveolar recruitment potential is the greatest. A variety of ventilatory approaches are available to improve oxygenation in the setting of refractory hypoxemia and ARDS. Which, if any, of these approaches should be used is often determined by the availability of equipment and clinician bias.

Figures in this Article

The American-European Consensus Conference on ARDS1 standardized the definition of acute lung injury (ALI) and ARDS on the basis of the following clinical parameters: acute onset of severe respiratory distress; bilateral infiltrates on frontal chest radiograph; absence of left atrial hypertension, a pulmonary capillary wedge pressure ≤ 18 mm Hg, or no clinical signs of left heart failure; and severe hypoxemia (ALI, PaO2/FIO2 ratio ≤ 300 mm Hg; ARDS, PaO2/FIO2 ratio ≤ 200 mm Hg). The definition does not take into consideration, however, the etiology (pulmonary or extrapulmonary) or the level of positive end-expiratory pressure (PEEP) required. More than 80% of patients with ARDS require intubation and mechanical ventilation.2 A lung-protective ventilation strategy should be used with a tidal volume of 4 to 8 mL/kg ideal body weight (IBW), a plateau pressure (Pplat) of ≤ 30 cm H2O, and modest levels of PEEP. Such an approach affords a survival benefit and is standard care.3

Patients with ARDS who are placed on lung-protective mechanical ventilation may have an improvement in oxygenation and disease severity within 24 h; their mortality is 13% to 23%4,5; and they should be continued on lung-protective ventilator settings. In patients with little improvement in PaO2 /FIO2 ratio in the first 24 h after instituting mechanical ventilation, the observed mortality is significantly higher and varies from 53% to 68%.4,5 In one study, setting PEEP at 10 cm H2O allowed better differentiation of ARDS and ALI. After the PEEP trial, about one-third of patients initially classified as having ARDS were reclassified as having ALI, and 9% had a PaO2/FIO2 ratio of > 300 mm Hg. The mortality rates for reclassified categories were 45% for ARDS, 20% for ALI, and 6% for others.6

Another parameter that may identify patients with severe ARDS is a PEEP requirement of ≥ 15 cm H2O. to maintain adequate oxygenation. Indirect evidence for this parameter comes from Kallet and Branson,7 who reviewed data for 197 patients from 16 studies. They determined that 84% of patients with ARDS had a lower inflection point of ≤ 15 cm H2O on the pressure-volume curve, suggesting that a PEEP of ≥ 15 cm H2O may identify severe ARDS. In a series of 47 patients with ARDS, refractory hypoxemia was associated with a 16% mortality rate among ARDS deaths.8 In the same vein, Luhr et al2 reported that patients with a PaO2/FIO2 ratio of < 100 mm Hg required more aggressive therapy for oxygenation.

The oxygenation index (OI) incorporates the severity of oxygenation impairment (PaO2/FIO2 ratio) and mean airway pressure into a single variable:OI = (FIO2 × mPaw × 100)/PaO2
OI=(FIO2×mPaw×100)/PaO2 
(where mPaw = mean airway pressure). The OI is used more commonly in neonatal and pediatric patients but also has been used in adults with ARDS and may be a better predictor of poor outcome than the PaO2/FIO2 ratio.9-12 A high OI 12 to 24 h after the onset of ARDS and rising values of OI from persistent ARDS have been shown to be independent risk factors for mortality.10-12 An OI of > 30 is reported to represent failure of conventional ventilation and may be considered an indication for nonconventional modes of ventilation.9,13-16

For the purpose of this article, we have used the following definition of refractory hypoxemia: PaO2/FIO2 ratio of < 100 mm Hg or inability to maintain Pplat < 30 cm H2O despite a tidal volume of 4 mL/kg IBW or the development of barotrauma. An OI of > 30 also categorizes a patient as having refractory hypoxemic respiratory failure. We define high ventilator requirement as an FIO2 of ≥ 0.7 mm Hg and a PEEP of > 15 cm H2O or Pplat > 30 cm H2O with a tidal volume of < 6 mL/kg IBW. This requirement should be recognized early in the course of ARDS (< 96 h) when the potential for alveolar recruitment is greatest.17-20 Consideration also should be given to transferring patients with refractory hypoxemia to a center with established expertise in caring for such patients.21-23

What is the physiologic basis for rescue therapies in severe ARDS? In the lungs of patients with ARDS, there are alveoli that are relatively normal, that are collapsed but recruitable, and that are nonrecruitable.24 Rescue methods are used to recruit the collapsed, but potentially recruitable alveoli. Alveolar recruitment reduces the shunt fraction, reduces dead space, and improves compliance. Another important physiologic concept is optimally matching ventilation and perfusion.

The primary focus should be on prevention of refractory hypoxemia rather than on reversing it after it develops. If small tidal volumes and adequate levels of PEEP are used and careful attention given to fluid status and patient-ventilator synchrony, the need for rescue therapy may be obviated in many cases.25 Rescue therapies can be categorized arbitrarily as ventilatory and nonventilatory strategies. Nonventilatory interventions, such as neuromuscular blockade, inhaled vasodilator therapy, prone positioning, and extracorporeal life support, are discussed in a companion article forthcoming in the June 2010 issue of CHEST,26 whereas ventilatory approaches are addressed here. Use of rescue therapies is controversial, as, to our knowledge, none to date has been shown to reduce mortality when studied in large heterogeneous populations of patients with ARDS. However, some rescue therapies have been shown to improve oxygenation, which may be important as a short-term goal in the 16% of patients deteriorating with hypoxemic respiratory failure.8 When instituting rescue strategies, an attempt should be made to assess for alveolar recruitment. If alveolar recruitment is demonstrated, higher levels of PEEP should be considered.27-30 Other rescue therapies include airway pressure release ventilation (APRV),31 high-frequency oscillatory ventilation (HFOV),32 and high-frequency percussive ventilation (HFPV).33,34 In patients demonstrating very severe hypoxemic respiratory failure, defined as a PaO2/FIO2 ratio of < 60 mm Hg,27 consideration of extracorporeal life support,35 HFOV, or HFPV may be appropriate.

Because there are no data establishing the superiority of one rescue mode over another,36 the choice of rescue therapy is based on equipment availability and clinician expertise. Some clinicians may choose not to use a rescue therapy, which is legitimate on the basis of the level of available evidence. If a rescue therapy does not result in improved oxygenation or if complications from the therapy occur, that rescue therapy should be abandoned.

Thus, a reasonable evidence-based approach might be one in which lung-protective ventilation is used (volume and pressure limitation with modest PEEP). This approach may require permissive hypercapnia (ie, a higher-than-normal PaCO2)37 and permissive hypoxemia (ie, a lower-than-normal PaO2).38 If a clinical decision is made to implement rescue therapy for the patient with ARDS and refractory hypoxemia, one or more of the strategies described in this article can be used.

In this narrative review, we discuss ventilatory techniques that have been used in the setting of refractory hypoxemia in patients with ARDS. A PubMed search was conducted, with each strategy used as a key term. We narrowed the search to articles published in English and those that studied human subjects. We broadened the search to include additional articles, as appropriate, from the reference lists of those identified from our primary search.

Increasing the level of PEEP often is the first consideration when the clinician is faced with a patient with refractory hypoxemia. If PEEP results in alveolar recruitment, the shunt is reduced, and PaO2 increases. Three randomized controlled trials (RCTs) have evaluated modest vs high levels of PEEP in patients with ALI and ARDS (Table 1).27,28,39 Although none of these studies reported a survival advantage for use of higher PEEP, each reported a higher PaO2/FIO2 ratio in the higher PEEP group. Moreover, two of the studies reported lower rates of refractory hypoxemia, death with refractory hypoxemia, and use of rescue therapies.27,28 Gattinoni and Caironi40 argued for the use of higher PEEP on the basis of fewer pulmonary deaths and absence of reported complications with this strategy.

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Table 1 —Summary of Results of Three Randomized Controlled Trials of Lower vs Higher Levels of PEEP

ALVEOLI = Assessment of Low Tidal Volume and Elevated End-Expiratory Pressure to Obviate Lung Injury Trial; EXPRESS = Expiratory Pressure Trial; IBW = ideal body weight; LOV = Lung Open Ventilation Trial; PEEP = positive end-expiratory pressure; Pplat = plateau pressure; SpO2 = oxygenation by pulse oximetry; Vt = tidal volume.

The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network39 and Meade et al27 set individualized PEEP using a table of FIO2-PEEP combinations based on oxygenation. Mercat et al28 individualized PEEP to a level set to reach a plateau pressure of 28 to 30 cm H2O. Post hoc analysis of data from their study suggested that compared with ARDS, mild lung injury may be associated with less benefit and more adverse effects from higher levels of PEEP. Thus, a strategy of a higher PEEP and lower tidal volume with a plateau pressure target of 28 to 30 cm H2O should not be used in patients with ALI. Moreover, critics have argued that the low PEEP (5-9 cm H2O) used in the control group in Mercat et al may have been excessively conservative and a suboptimal control.

The benefit of PEEP in patients with refractory hypoxemia might depend on the potential for alveolar recruitment.24 If the recruitment potential is low, then an increase in PEEP will have a marginal effect on shunt and PaO2, and it may contribute to overdistension of already-open alveoli,41 which could lead to increased risk for ventilator-induced lung injury and increased dead space and might potentially result in redistribution of pulmonary blood flow to nonventilated regions of the lungs. If an increase in PEEP results in alveolar recruitment, then the strain (distribution of pressure) in the lungs is reduced. On the other hand, if an increase in PEEP increases transpulmonary pressure, then the stress (change in size of the lungs during inflation) on the lungs is increased. PEEP may adversely affect PaO2 in the presence of unilateral lung disease.42

The potential for recruitment can be identified in an individual patient by use of a short (30-min) trial of increased PEEP. If an increase in PEEP results in minimal improvement (or worsening) of PaO2, an increase in dead space (increased PaCO2) with stable minute ventilation, and worsening compliance, then alveolar recruitment is minimal.43 Conversely, if an increase in PEEP results in a large increase in PaO2, a decrease in PaCO2, and improved compliance, it suggests significant recruitment. Some have suggested a decremental rather than an incremental PEEP trial.44,45 With this approach, PEEP is set to ≥ 20 cm H2O and then decreased to identify the level that produces the best PaO2 and compliance.

The stress index was recently proposed to assess the level of PEEP to avoid overdistension.29 This approach uses the shape of the pressure-time curve during tidal volume delivery. Worsening compliance as the lungs are inflated (upward concavity; stress index, > 1) suggests overdistension, and the recommendation is to decrease PEEP (Fig 1). Improving compliance as the lungs are inflated (downward concavity; stress index, < 1) suggests tidal recruitment and potential for additional recruitment, thus a recommendation to increase PEEP.

Figure Jump LinkFigure 1. Graphic representation of the stress index. Flow and airway pressure vs time are displayed for three examples of stress index categories. The ventilator is set for constant-flow inflation. The stress index is derived from the airway pressure waveform between the dashed lines. For stress index values < 1, the airway pressure curve presents a downward concavity, suggesting a continuous decrease in elastance (or increase in compliance) during constant-flow inflation, and further recruitment of alveoli is likely. For stress index values > 1, the curve presents an upward concavity, suggesting a continuous increase in elastance (decrease in compliance), and excessive positive end-expiratory pressure may be present. Finally, for a stress index value = 1, the curve is straight, suggesting the absence of tidal variations in elastance. Pao = airway pressure. (Reprinted with permission from the American Thoracic Society.29)Grahic Jump Location

The use of an esophageal balloon to assess intrapleural pressure has been advocated to allow more precise setting of PEEP.30,46 If pleural pressure is high relative to alveolar pressure (ie, PEEP), there may be potential for alveolar derecruitment, which is most likely seen with a decrease in chest wall compliance, such as occurs with abdominal compartment syndrome, pleural effusion, or obesity. In this case, it is desirable to keep PEEP greater than pleural pressure. Unfortunately, artifacts in esophageal pressure, especially in supine patients who are critically ill, make it very difficult to measure absolute pleural pressure accurately.47-50 Although it is important to consider pleural pressure when setting PEEP, the use of an esophageal balloon may not be required. In patients with abdominal compartment syndrome, bladder pressure may be useful to assess intraabdominal pressure, the potential collapsing effect on the lungs, and the amount of PEEP necessary to counterbalance this effect.48

The available evidence does not clearly indicate the best method to select PEEP in patients with ARDS. Various options are listed in Table 2. A PEEP setting of 0 cm H2O generally is accepted to be harmful in the patient with ARDS. A PEEP setting of 8 to 15 cm H2O is appropriate in most patients with ARDS. Higher levels of PEEP should be used in patients for whom a greater potential for recruitment can be demonstrated. Care must be taken to avoid overdistension when PEEP is set. Higher PEEP settings may be required in patients with refractory hypoxemia; however, a PEEP of > 24 cm H2O seldom is required. In the decision-making for each patient, the potential benefit of high levels of PEEP should be balanced against the risk of harm (ventilator-induced lung injury, barotrauma, hypotension).

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Table 2 —Methods for Selecting PEEP

See Table 1 for expansion of the abbreviation.

A recruitment maneuver is a transient increase in transpulmonary pressure intended to promote reopening of collapsed alveoli 52-54 and has been shown to open collapsed alveoli, thereby improving gas exchange.17,18,55-58 However, to our knowledge, there have been no RCTs demonstrating a mortality benefit from this improvement in gas exchange.

A variety of techniques have been described as recruitment maneuvers (Table 3).52,54 One approach involves a sustained high-pressure inflation using pressures of 30 to 50 cm H2O for 20 to 40 s.51,56 A sustained inflation usually is achieved by changing to a continuous positive airway pressure (CPAP) mode and setting the pressure to the desired level. Pressure-controlled breaths can be applied in addition to the sustained high pressure.18,57 Another approach is to use intermittent sighs, using three consecutive sighs set at a pressure of 45 cm H2O.59 An extended sigh also has been used in which there is a stepwise increase in PEEP and a decrease in tidal volume over 2 min to a CPAP level of 30 cm H2O for 30 s.60 Another method applies an intermittent increase in PEEP for 2 breaths/min.55 Pressure-controlled ventilation (PCV) of 10 to 15 cm H2O with PEEP of 25 to 30 cm H2O to reach a peak inspiratory pressure of 40 to 45 cm H2O for 2 min also has been used as a recruitment maneuver.57 Prone positioning61 and HFOV62 also have been used to improve alveolar recruitment.

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Table 3 —Different Lung Recruitment Maneuvers

CPAP = continuous positive air pressure. See Table 1 legend for expansion of other abbreviation.

Just as it is unclear which, if any, recruitment maneuver is superior to another, the optimal pressure, duration, and frequency of recruitment maneuvers has not been established. Many patients require increased sedation, paralysis, or both during the application of a recruitment maneuver. Studies using a decremental PEEP trial after a recruitment maneuver have reported significant oxygenation benefits for at least 4 to 6 h.18,44 However, it is unclear whether this finding was due to the recruitment maneuver, the PEEP titration strategy, or both. An improvement in oxygenation with a recruitment maneuver may indicate that the level of PEEP is too low. A recruitment maneuver may be of limited benefit when higher levels of PEEP are used.63

A recent systematic review reported the acute physiologic effects of a recruitment maneuver in approximately 1,200 patients.52 Oxygenation was significantly increased after a recruitment maneuver (Fig 2). Hypotension (12%) and desaturation (8%) were the most common complications of recruitment maneuvers. Serious adverse events, such as barotrauma (1%) and arrhythmia (1%), were infrequent. The overall mortality was similar to observational studies of patients with ALI (38%). The finding of improved oxygenation was more common in the following subgroups: difference between pre- and post-recruitment maneuver PEEP (≤ 5 cm H2O vs > 5 cm H2O), baseline PaO2/FIO2 ratio (< 150 mm Hg vs ≥ 150 mm Hg), and baseline respiratory system compliance (< 30 mL/cm H2O vs ≥ 30 mL/cm H2O).

Figure Jump LinkFigure 2. The relationship between oxygenation (PaO2/FIO2 ratio) after the application of a recruitment maneuver (post-RM) with baseline (pre-RM) oxygenation in each individual study presented. Oxygenation was significantly increased post-RM (PaO2/FIO2 ratio, 139 mm Hg vs 251 mm Hg; P < .001). P/F = PaO2/FIO2. (Reprinted with permission from the American Thoracic Society.52)Grahic Jump Location

Many of the studies of recruitment maneuvers reported a rapid decline in oxygenation gains, some within 15 to 20 min of the maneuver.52 The application of higher levels of PEEP after a recruitment maneuver may affect the sustainability of the effect. Whether improvements in oxygenation associated with recruitment maneuvers result in reduced lung injury and improved outcomes remains to be determined. Some studies have shown a survival advantage with a lung-protective ventilation strategy incorporating recruitment maneuvers,51,64 whereas others have not.27 The potential for lung recruitment likely varies considerably among patients,24 which likely affects the response to a recruitment maneuver.

The routine use of recruitment maneuvers is not recommended at this time. Given that they pose little risk of harm if the patient is carefully monitored during their application and that some patients may have a dramatic improvement in oxygenation with their application,57 recruitment maneuvers may play a role in patients who develop life-threatening refractory hypoxemia. It is prudent to avoid the use of recruitment maneuvers in patients with hemodynamic compromise and those at risk for barotrauma.65 If the application of a recruitment maneuver results in an important improvement in oxygenation, higher levels of PEEP should be used to maintain recruitment. However, caution must be exercised to avoid overdistension with excessive levels of PEEP.

In patients with severe ARDS, some clinicians choose PCV as an alternative to volume-controlled ventilation (VCV) based on several lines of reasoning. First, the peak inspiratory pressure is lower on PCV, but this is related to the flow pattern during pressure control and, for the same tidal volume delivery, there is no difference in plateau pressure for PCV and VCV. Second, patient-ventilator synchrony is believed to be better with PCV. However, Kallet et al66 reported that the work of breathing is not better with PCV than with VCV during lung-protective ventilation in patients who are actively breathing. Moreover, the active inspiratory effort resulted in an increase in tidal volume such that lung-protective ventilation may have been violated in many patients.66 Third, some clinicians expect an improvement in gas exchange with PCV. With PCV, the pressure waveform approximates a rectangle, and flow decreases during the inspiratory phase. The resulting increased mean airway pressure and lower end-inspiratory flow theoretically should improve gas exchange. However, on many current-generation ventilators, a descending ramp of flow can be used with VCV, and this may result in similar findings with PCV and VCV with a descending ramp waveform.67-70 With careful attention to tidal volume, plateau pressure, PEEP, and inspiratory time, the differences between PCV and VCV are minor, and neither is clearly superior to the other. It is also worth pointing out that the ARDSNet trial was conducted with VCV.3

Following reports71-75 of improved oxygenation with pressure-controlled inverse-ratio ventilation (PCIRV) published 20 years ago, considerable enthusiasm for this method was generated. The approach to PCIRV is to use an inspiratory time greater than the expiratory time to increase mean airway pressure and, thus, improve arterial oxygenation. PCIRV most often is used with PCV, although VCV with inverse ratio also has been described.76 Following the initial enthusiasm for this ventilatory approach, a number of subsequent controlled studies reported no benefit or marginal benefit of PCIRV over more conventional approaches to ventilatory support in patients with ARDS.68,77-80 The elevated mean airway pressure and auto-PEEP that occur with PCIRV also may adversely affect hemodynamics. Because this approach can be very uncomfortable for the patient, sedation and paralysis often are required. On the basis of the available evidence, there is no clear benefit for PCIRV in the management of patients with ARDS. The likelihood of an improvement in oxygenation with PCIRV is small, and the risk of auto-PEEP and hemodynamic compromise is great.81-83

APRV is a mode of ventilation designed to allow patients to breathe spontaneously while receiving high airway pressure with an intermittent pressure release (Fig 3). The high airway pressure maintains adequate alveolar recruitment. Oxygenation is determined by high airway pressure and FIO2. The timing and duration of the pressure release (low airway pressure) as well as the patient’s spontaneous breathing determine alveolar ventilation (PaCO2). The ventilator-determined tidal volume depends on lung compliance, airway resistance, and the duration and timing of the pressure-release maneuver.

Figure Jump LinkFigure 3. Display of airway pressure and flow vs time during airway pressure-release ventilation. Spontaneous breaths occur at a high pressure level, leading to a pressure release to a lower pressure level, as seen in this figure. During this mode, ventilation occurs by intermittent switching between the two pressure levels while allowing spontaneous breathing to occur in either phase of the ventilator cycle. Because time at low airway pressure is brief, in practice, spontaneous breathing occurs primarily during the time of high airway pressure. Maintaining an adequate level of time during a high airway pressure enhances alveolar recruitment, whereas keeping time short prevents alveolar collapse during the release to low airway pressure. CPAP = continuous positive air pressure; Paw = airway pressure; T High = time at high airway pressure; T Low = time at low airway pressure; V˙  = flow. (Reprinted with permission from the Intensive Care On-line Network.89)Grahic Jump Location

An active exhalation valve allows the patient to breathe spontaneously throughout the ventilator-imposed pressures, although spontaneous breathing typically occurs only during high airway pressure due to the short time at low airway pressure. Diaphragmatic contraction associated with spontaneous breaths during APRV may recruit dependent (dorsal) juxtadiaphragmatic alveoli, thus reducing shunt and improving oxygenation. Because high airway pressure usually is much longer than low airway pressure, APRV is functionally the same as PCIRV in the absence of spontaneous breathing. Because the patient’s ability to breathe spontaneously is preserved, APRV allows for a prolonged inspiratory phase without the need for heavy sedation and paralysis.

Various time ratios for high-to-low airway pressure have been used with APRV, ranging from 1:1 to 9:1 in different studies.84-88 In order to sustain optimal recruitment, the greater part of the total time cycle (80%-95%) occurs at high airway pressure. In order to minimize derecruitment, the time spent at low airway pressure is brief (0.2-0.8 s in adults).89 Neumann et al88 demonstrated that spontaneous inspiratory and expiratory time intervals are independent of the time at high to low airway pressure cycle because patients who are breathing spontaneously can maintain their innate respiratory drive during high and low airway pressure; thus, the release phase does not reflect the only expiratory time. If the time at low airway pressure is too short, expiration may be incomplete, and intrinsic PEEP may result.88 However, creating intrinsic PEEP is, by design, required with some approaches to APRV in which low airway pressure is set to 0 cm H2O.89 With this approach, the time at low airway pressure is set such that the expiratory flow reaches 50% to 75% of the peak expiratory flow.

Crossover studies have reported improvements in physiologic end points with APRV.31,85,86,90-92 These studies reported that APRV required lower inflation pressure and less sedation and often produced better oxygenation than other forms of mechanical ventilation. Putensen et al87 randomized 30 trauma patients to APRV or PCV. With APRV, the inotropic support was lower, and the duration of ventilatory support and length of ICU stay were shorter. However, these findings are debatable because patients randomized to the conventional ventilation group were paralyzed for the initial 72 h of support. The largest RCT of APRV84 was terminated early for futility after recruiting 58 out of a targeted 80 subjects. At 28 days, there were no statistical differences in the number of ventilator-free days. In addition, mortality at 28 days and at 1 year was similar. However, the authors used prone positioning in both arms, which is known to improve the oxygenation in 60% to 70% of patients; thus, prone position may have eclipsed any oxygenation differences between the two groups. Additionally, the ventilator used to provide APRV in the test group is not designed to provide APRV and required modification to the expiratory limb.

Spontaneous breathing during high airway pressure has the potential to generate negative pleural pressures that may add to the stretch applied from the ventilator. This situation must be considered when evaluating the maximal stretch to which the lungs are exposed. Neumann et al88 reported tidal volumes of approximately 1 L and large pleural pressure swings with APRV. There is concern that these relatively large tidal volumes and transpulmonary pressures could contribute to the risk of ventilator-induced lung injury. The potential benefits of improved oxygenation and reduced need for sedation make APRV an attractive ventilator mode.89 However, without RCTs demonstrating improved patient outcomes, routine use of this mode cannot be recommended. If APRV is used, auto-PEEP and tidal volume must be closely monitored.

High-frequency ventilation is any application of mechanical ventilation with a respiratory rate of > 100 breaths/min. This can be achieved with a small tidal volume and rapid respiratory rate with conventional mechanical ventilation, various forms of external chest wall oscillation, HFPV, high-frequency jet ventilation, or HFOV, which currently is the form of high-frequency ventilation most widely used in adult critical care.62,93-95 It delivers a small tidal volume by oscillating a bias gas flow in the airway. The oscillator has an active inspiratory and expiratory phase. A frequency of 3 to 15 Hz can be used, although lower rates (3-6 Hz) are used in adults. Nevertheless, higher rates are feasible and may result in smaller tidal volumes and decreased risk for lung injury.96

HFOV oscillates the gas delivered to pressures above and below the mean airway pressure(mPaw). The mPaw and FIO2 are the primary determinants of oxygenation, whereas the pressure amplitude of oscillation (ΔP) and the respiratory frequency are the determinants of CO2 elimination. The tidal volume varies directly with ΔP and inversely with frequency.95 The mPaw is initially set to a level approximately 5 cm H2O above that with conventional ventilation, and ΔP is set to induce “wiggle,” which is visible to the patient’s mid-thigh.96,97 Much of the pressure applied to the airway is attenuated by proximal airways and does not reach the alveoli, resulting in a small tidal volume that may be less than dead space.98,99 The delivery of a small tidal volume and a high mPaw may result in improved alveolar recruitment with less risk of overdistension, thus providing improved gas exchange and lung protection. HFOV also has been combined with other strategies, such as recruitment maneuvers,100 inhaled nitric oxide,101 and prone positioning.102

Most of the evidence for HFOV has been from small observational studies,9,19,103,104 often in the setting of refractory hypoxemia. These studies have shown that HFOV is safe and effective, resulting in improvements in oxygenation and providing ample ventilation in adult patients with severe ARDS. There have been only two RCTs of HFOV in adult patients with ARDS.32,105 Derdak et al32 randomized 148 patients to receive either HFOV or conventional ventilation. The HFOV group showed an early improvement in the PaO2/FIO2 ratio, but this was not sustained beyond 24 h. There was a nonsignificant trend toward a lower 30-day mortality in the HFOV group (37% vs 52%; P = .102). A criticism of this trial is that patients in the conventional ventilation group were ventilated with relatively large tidal volumes, which may have contributed to the high mortality in the control group.93 Bollen et al105 reported no significant difference in mortality between patients randomized to HFOV and those to conventional ventilation. A post hoc analysis, however, suggested that HFOV might improve mortality in patients with a higher oxygenation index. Complications reported with HFOV are relatively infrequent and include barotrauma,19,32,100,104 hemodynamic compromise,9,104 mucus inspissations resulting in endo-tracheal tube occlusion or refractory hypercapnia,31 and increased use of sedation or neuromuscular blocking agents.9,19,32,102,106 In the two RCTs comparing HFOV with conventional ventilation, Derdak et al reported no significant effect of HFOV on hemodynamics, barotrauma, or mucus plugging, and Bollen et al did not report any increased risk of complications with HFOV.

The use of HFOV may improve oxygenation in patients with refractory hypoxemia. However, there is not sufficient evidence to conclude that HFOV reduces mortality or long-term morbidity in patients with ALI or ARDS.107

HFPV was introduced in the early 1980s as the Volumetric Diffusive Respirator (Percussionaire Corporation; Sandpoint, ID). Compared with HFOV, only a few studies have investigated the use of HFPV in adult patients with ARDS.33,108-112 HFPV is a flow-regulated, pressure-limited, and time-cycled ventilator that delivers a series of high-frequency (200-900 cycles/min) small volumes in a successive stepwise stacking pattern, resulting in the formation of low-frequency (upper limit, 40-60 cycles/min) convective pressure-limited breathing cycles (Fig 4).34,110,113 An interplay of the Volume Diffusive Respirator control variables, either singly or in combination, contribute to the determination of mean airway pressure and gas exhange.34,109,112,114 At high percussion frequencies (300-600 cycles/min), oxygenation is enhanced, whereas at low percussion frequencies (180-240 cycles/min), CO2 elimination is enhanced.34,109,113

Figure Jump LinkFigure 4. High-frequency percussive ventilation. An interplay of the percussive frequency, peak inspiratory pressure (indirectly modulated by altering the pulsatile flow rate), inspiratory and expiratory times (of both percussive and convective breaths), and the oscillatory and demand continuous positive air pressure (CPAP) levels either singly or in combination is involved in determining mean airway pressure as well as the degree of gas exchange. The percussions are of lower amplitude at oscillatory CPAP (baseline oscillations) during exhalation and are of higher amplitude during inspiration as a result of the selected pulsatile flow rate (see pressure-time display). During inspiration, the lung volumes progressively increase in a cumulative, stepwise manner by continually diminishing subtidal deliveries that result in stacking of breaths. The peak pressure is reached as a result of modulations in the flow rate of the percussive breaths. Once an oscillatory pressure peak is reached and sustained, periodic programmed interruptions occur at specific times for predetermined intervals to allow for the return of airway pressures to baseline oscillatory pressure levels (ie, oscillatory CPAP), thereby passively emptying the lungs. A = pulsatile flow during inspiration at a percussive rate of 655 cycles/min; B = convective pressure-limited breath with low-frequency cycle (14 cycles/min); C = demand CPAP (provides static baseline pressure); D = oscillatory CPAP (provides high-frequency baseline pressure as a mean of the peak and nadir of the oscillations during exhalation); E = single percussive breath; F = periodic programmed interruptions signifying the end of inspiration and subsequent onset of exhalation.Grahic Jump Location

HFPV has been reported to improve oxygenation and ventilation in patients with ARDS refractory to conventional ventilation, although these studies are small in size, few in number, and nonrandomized. In a prospective trial of seven patients with ARDS requiring increased ventilator support on conventional ventilation, Gallagher et al112 found that when the patients were switched to HFPV at the same level of airway pressure and FIO2, the patients had a significant increase in PaO2, a slight reduction in PaCO2, and no change in cardiac output. In another prospective study comparing HFPV and conventional ventilation in 100 adult patients with acute respiratory failure, no difference was found between the two groups in the time to reach the study end points of PaO2/FIO2 ratio > 225 or shunt < 20%.114 In the subgroup of patients with ARDS, HFPV provided equal oxygenation and ventilation at significantly lower airway pressures, although there was no difference in the incidence of barotrauma, ICU days, hospital days, or mortality.114 In a retrospective series of 32 adult medical and surgical patients with ARDS unresponsive to at least 48 h of conventional ventilation, Velmahos et al33 demonstrated improved oxygenation within 1 h of being switched to HFPV. Peak inspiratory pressure decreased with HFPV, but mPaw increased. Although the peak inspiratory pressure decreased, peak alveolar pressure was not reported. In 12 patients with ARDS following blunt trauma who were switched to HFPV after failure of conventional ventilation, there was an improvement in oxygenation within 12 to 24 h.108 However, these improvements were not due to a rise in mPaw because there was no significant change following the switch to HFPV. The mechanisms that contribute to gas exchange in HFPV and other high-frequency ventilatory techniques have been described in a review by Krishnan and Brower.98

An additional reported benefit of HFPV is the enhanced mobilization and drainage of secretions from the lung periphery to the larger airways, potentially decreasing pulmonary infections.33,109,115 Nonetheless, HFPV has not demonstrated improved outcomes. Unlike other ventilatory strategies that might be applied in the patient with refractory hypoxemia, both HFOV and HFPV require a ventilator that is not available in all hospitals as well as respiratory therapists and physicians skilled in its use.

Figure 5 summarizes a proposed algorithmic approach to ventilator management of refractory hypoxemia. We recommend that lung-protective ventilation (volume and pressure limitation with moderate levels of PEEP) be instituted in patients with ALI and ARDS requiring mechanical ventilation. Rescue therapies may be considered in patients who develop refractory hypoxemia, with the use of these therapies based on a variety of factors, such as the severity of hypoxemia, likelihood of alveolar recruitment, response to the intervention, and patient characteristics. Rescue strategies are aimed at improving alveolar recruitment (high PEEP, recruitment maneuvers, APRV, HFOV) and, thereby, oxygenation; however, none of these modalities have been consistently shown to improve outcome in a critically ill patient population. Before a trial of rescue therapy is initiated, the target outcome should be established. If the rescue strategy does not achieve this end point, it should be abandoned. Nonventilatory rescue strategies, such as inhaled vasodilators, prone positioning, and extracorporeal life support, may be considered in conjunction with the ventilatory strategies outlined in this article. They are discussed in detail in part 2 of this series, which will appear in the June 2010 issue of CHEST.26 Further research is needed to elucidate how these rescue strategies may be better used to provide an outcome benefit.

Figure Jump LinkFigure 5. Ventilatory strategies for the management of refractory hypoxemic respiratory failure, showing the alternative ventilator strategies that can be used in patients with acute lung injury or ARDS with refractory hypoxemia following evaluation of the recruitment potential of the lungs. In patients with recruitable lungs, higher levels of positive end-expiratory pressure (PEEP) or other methods of setting appropriate levels of PEEP may be used initially.* However, failure of the aforementioned techniques can result in the use of the alternative ventilatory strategies in centers familiar with their use. * = other methods of setting appropriate levels of PEEP include setting PEEP to reach a plateau pressure of 28 to 30 cm H2O using esophageal pressure monitoring or the stress index. ALI = acute lung injury; APRV = airway pressure-release ventilation; ECLS = extracorporeal life support; ETCO2 = end-tidal carbon dioxide; HFOV = high-frequency oscillatory ventilation; HFPV = high-frequency percussive ventilation. See Table 1 legend for expansion of other abbreviations.Grahic Jump Location

Financial/nonfinancial disclosures: The authors have reported to the CHEST the following conflicts of interest: Dr Hess has received royalties from Impact. He was a consultant for Respironics and Pari. He also discloses relationships with Cardinal (CaseFusion) and Ikaria. Dr George was a consultant to Eubien, Boehringer Ingelheim, from 2006 to 2007. She has received money from AstraZeneca, Pfizer, Penexel, and Talceda. Drs Esan, Raoof, and Sessler report that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

ALI

acute lung injury

APRV

airway pressure-release ventilation

CPAP

continuous positive airway pressure

HFOV

high-frequency oscillatory ventilation

HFPV

high-frequency percussive ventilation

IBW

ideal body weight

mPaw

mean airway pressure

OI

oxygenation index

ΔP

pressure amplitude of oscillation

PCIRV

pressure-controlled inverse-ratio ventilation

PCV

pressure-controlled ventilation

PEEP

positive end-expiratory pressure

Pplat

plateau pressure

RCT

randomized controlled trial

VCV

volume-controlled ventilation

Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;1493 Pt 1:818-824. [PubMed]
 
Luhr OR, Antonsen K, Karlsson M, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med. 1999;1596:1849-1861. [PubMed]
 
The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;34218:1301-1308. [CrossRef] [PubMed]
 
Villar J, Pérez-Méndez L, Kacmarek RM. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome. Intensive Care Med. 1999;259:930-935. [CrossRef] [PubMed]
 
Ferguson ND, Kacmarek RM, Chiche JD, et al. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med. 2004;306:1111-1116. [CrossRef] [PubMed]
 
Villar J, Pérez-Méndez L, López J, et al. HELP Network An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007;1768:795-804. [CrossRef] [PubMed]
 
Kallet RH, Branson RD. Respiratory controversies in the critical care setting. Do the NIH ARDS Clinical Trials Network PEEP/FIO2 tables provide the best evidence-based guide to balancing PEEP and FIO2 settings in adults? Respir Care. 2007;524:461-475. [PubMed]
 
Montgomery AB, Stager MA, Carrico CJ, Hudson LD. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1985;1323:485-489. [PubMed]
 
Fort P, Farmer C, Westerman J, et al. High-frequency oscillatory ventilation for adult respiratory distress syndrome—a pilot study. Crit Care Med. 1997;256:937-947. [CrossRef] [PubMed]
 
Monchi M, Bellenfant F, Cariou A, et al. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. Am J Respir Crit Care Med. 1998;1584:1076-1081. [PubMed]
 
Seeley E, McAuley DF, Eisner M, Miletin M, Matthay MA, Kallet RH. Predictors of mortality in acute lung injury during the era of lung protective ventilation. Thorax. 2008;6311:994-998. [CrossRef] [PubMed]
 
Trachsel D, McCrindle BW, Nakagawa S, Bohn D. Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med. 2005;1722:206-211. [CrossRef] [PubMed]
 
Bayrakci B, Josephson C, Fackler J. Oxygenation index for extracorporeal membrane oxygenation: is there predictive significance? J Artif Organs. 2007;101:6-9. [CrossRef] [PubMed]
 
HiFO Study Group Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. J Pediatr. 1993;1224:609-619. [CrossRef] [PubMed]
 
Clark RH, Yoder BA, Sell MS. Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation. J Pediatr. 1994;1243:447-454. [CrossRef] [PubMed]
 
Schwendeman CA, Clark RH, Yoder BA, Null DM Jr, Gerstmann DR, Delemos RA. Frequency of chronic lung disease in infants with severe respiratory failure treated with high-frequency ventilation and/or extracorporeal membrane oxygenation. Crit Care Med. 1992;203:372-377. [CrossRef] [PubMed]
 
Grasso S, Mascia L, Del Turco M, et al. Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy. Anesthesiology. 2002;964:795-802. [CrossRef] [PubMed]
 
Borges JB, Okamoto VN, Matos GF, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;1743:268-278. [CrossRef] [PubMed]
 
Mehta S, Lapinsky SE, Hallett DC, et al. Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome. Crit Care Med. 2001;297:1360-1369. [CrossRef] [PubMed]
 
Mancebo J, Fernández R, Blanch L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;17311:1233-1239. [CrossRef] [PubMed]
 
Kahn JM, Goss CH, Heagerty PJ, Kramer AA, O’Brien CR, Rubenfeld GD. Hospital volume and the outcomes of mechanical ventilation. N Engl J Med. 2006;3551:41-50. [CrossRef] [PubMed]
 
Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;35316:1685-1693. [CrossRef] [PubMed]
 
Kahn JM, Linde-Zwirble WT, Wunsch H, et al. Potential value of regionalized intensive care for mechanically ventilated medical patients. Am J Respir Crit Care Med. 2008;1773:285-291. [CrossRef] [PubMed]
 
Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006;35417:1775-1786. [CrossRef] [PubMed]
 
Yilmaz M, Keegan MT, Iscimen R, et al. Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med. 2007;357:1660-1666. [CrossRef] [PubMed]
 
Sessler CN, Goulet K, Esan A, Hess DR, Raoof S. Severe hypoxemic respiratory failure: part 2—nonventilatory strategies. Chest. 2010; In press.
 
Meade MO, Cook DJ, Guyatt GH, et al; Lung Open Ventilation Study Investigators Lung Open Ventilation Study Investigators Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. J Amer Med Assoc. 2008;2996:637-645. [CrossRef]
 
Mercat A, Richard JC, Vielle B, et al; Expiratory Pressure (Express) Study Group Expiratory Pressure (Express) Study Group Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. J Amer Med Assoc. 2008;2996:646-655. [CrossRef]
 
Grasso S, Stripoli T, De Michele M, et al. ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure. Am J Respir Crit Care Med. 2007;1768:761-767. [CrossRef] [PubMed]
 
Talmor D, Sarge T, O’Donnell CR, et al. Esophageal and transpulmonary pressures in acute respiratory failure. Crit Care Med. 2006;345:1389-1394. [CrossRef] [PubMed]
 
Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation. Am J Respir Crit Care Med. 1994;1496:1550-1556. [PubMed]
 
Derdak S, Mehta S, Stewart TE, et al. Multicenter Oscillatory Ventilation For Acute Respiratory Distress Syndrome Trial (MOAT) Study Investigators High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med. 2002;1666:801-808. [CrossRef] [PubMed]
 
Velmahos GC, Chan LS, Tatevossian R, et al. High-frequency percussive ventilation improves oxygenation in patients with ARDS. Chest. 1999;1162:440-446. [CrossRef] [PubMed]
 
Lucangelo U, Fontanesi L, Antonaglia V, et al. High frequency percussive ventilation (HFPV). Principles and technique. Minerva Anestesiol. 2003;6911:841-848. [PubMed]
 
Schuerer DJ, Kolovos NS, Boyd KV, Coopersmith CM. Extracorporeal membrane oxygenation: current clinical practice, coding, and reimbursement. Chest. 2008;1341:179-184. [CrossRef] [PubMed]
 
Girard TD, Bernard GR. Mechanical ventilation in ARDS: a state-of-the-art review. Chest. 2007;1313:921-929. [CrossRef] [PubMed]
 
Laffey JG, O’Croinin D, McLoughlin P, Kavanagh BP. Permissive hypercapnia—role in protective lung ventilatory strategies. Intensive Care Med. 2004;303:347-356. [CrossRef] [PubMed]
 
Abdelsalam M. Permissive hypoxemia: is it time to change our approach? Chest. 2006;1291:210-211. [CrossRef] [PubMed]
 
National Heart, Lung, and Blood Institute ARDS Clinical Trials NetworkNational Heart, Lung, and Blood Institute ARDS Clinical Trials Network Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;3514:327-336. [CrossRef] [PubMed]
 
Gattinoni L, Caironi P. Refining ventilatory treatment for acute lung injury and acute respiratory distress syndrome. J Amer Med Assoc. 2008;2996:691-693. [CrossRef]
 
Grasso S, Fanelli V, Cafarelli A, et al. Effects of high versus low positive end-expiratory pressures in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;1719:1002-1008. [CrossRef] [PubMed]
 
Kanarek DJ, Shannon DC. Adverse effect of positive end-expiratory pressure on pulmonary perfusion and arterial oxygenation. Am Rev Respir Dis. 1975;1123:457-459. [PubMed]
 
Ramnath VR, Hess DR, Thompson BT. Conventional mechanical ventilation in acute lung injury and acute respiratory distress syndrome. Clin Chest Med. 2006;274:601-613 abstract viii.. [CrossRef] [PubMed]
 
Girgis K, Hamed H, Khater Y, Kacmarek RM. A decremental PEEP trial identifies the PEEP level that maintains oxygenation after lung recruitment. Respir Care. 2006;5110:1132-1139. [PubMed]
 
Hickling KG. Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med. 2001;1631:69-78. [PubMed]
 
Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008;35920:2095-2104. [CrossRef] [PubMed]
 
Owens RL, Stigler WS, Hess DR. Do newer monitors of exhaled gases, mechanics, and esophageal pressure add value? Clin Chest Med. 2008;292:297-312. [CrossRef] [PubMed]
 
Hess DR, Bigatello LM. The chest wall in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care. 2008;141:94-102. [CrossRef] [PubMed]
 
Hager DN, Brower RG. Customizing lung-protective mechanical ventilation strategies. Crit Care Med. 2006;345:1554-1555. [CrossRef] [PubMed]
 
Brower RG, Hubmayr RD, Slutsky AS. Lung stress and strain in acute respiratory distress syndrome: good ideas for clinical management? Am J Respir Crit Care Med. 2008;1784:323-324. [CrossRef] [PubMed]
 
Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;3386:347-354. [CrossRef] [PubMed]
 
Fan E, Wilcox ME, Brower RG, et al. Recruitment maneuvers for acute lung injury: a systematic review. Am J Respir Crit Care Med. 2008;17811:1156-1163. [CrossRef] [PubMed]
 
Hess DR, Bigatello LM. Lung recruitment: the role of recruitment maneuvers. Respir Care. 2002;473:308-317. [PubMed]
 
Lapinsky SE, Mehta S. Bench-to-bedside review: Recruitment and recruiting maneuvers. Crit Care. 2005;91:60-65. [CrossRef] [PubMed]
 
Foti G, Cereda M, Sparacino ME, De Marchi L, Villa F, Pesenti A. Effects of periodic lung recruitment maneuvers on gas exchange and respiratory mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS) patients. Intensive Care Med. 2000;265:501-507. [CrossRef] [PubMed]
 
Lapinsky SE, Aubin M, Mehta S, Boiteau P, Slutsky AS. Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure. Intensive Care Med. 1999;2511:1297-1301. [CrossRef] [PubMed]
 
Medoff BD, Harris RS, Kesselman H, Venegas J, Amato MB, Hess D. Use of recruitment maneuvers and high-positive end-expiratory pressure in a patient with acute respiratory distress syndrome. Crit Care Med. 2000;284:1210-1216. [CrossRef] [PubMed]
 
Tugrul S, Akinci O, Ozcan PE, et al. Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms. Crit Care Med. 2003;313:738-744. [CrossRef] [PubMed]
 
Pelosi P, Cadringher P, Bottino N, et al. Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;1593:872-880. [PubMed]
 
Lim CM, Koh Y, Park W, et al. Mechanistic scheme and effect of “extended sigh” as a recruitment maneuver in patients with acute respiratory distress syndrome: a preliminary study. Crit Care Med. 2001;296:1255-1260. [CrossRef] [PubMed]
 
Galiatsou E, Kostanti E, Svarna E, et al. Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med. 2006;1742:187-197. [CrossRef] [PubMed]
 
Chan KP, Stewart TE. Clinical use of high-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome. Crit Care Med. 2005;3 suppl:S170-S174
 
Villagrá A, Ochagavía A, Vatua S, et al. Recruitment maneuvers during lung protective ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;1652:165-170. [PubMed]
 
Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med. 2006;345:1311-1318. [CrossRef] [PubMed]
 
Kacmarek RM, Kallet RH. Respiratory controversies in the critical care setting. Should recruitment maneuvers be used in the management of ALI and ARDS? Respir Care. 2007;525:622-631. [PubMed]
 
Kallet RH, Campbell AR, Dicker RA, Katz JA, Mackersie RC. Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes. Respir Care. 2005;5012:1623-1631. [PubMed]
 
Ravenscraft SA, Burke WC, Marini JJ. Volume-cycled decelerating flow. An alternative form of mechanical ventilation. Chest. 1992;1015:1342-1351. [CrossRef] [PubMed]
 
Muñoz J, Guerrero JE, Escalante JL, Palomino R, De La Calle B. Pressure-controlled ventilation versus controlled mechanical ventilation with decelerating inspiratory flow. Crit Care Med. 1993;218:1143-1148. [CrossRef] [PubMed]
 
Davis K Jr, Branson RD, Campbell RS, Porembka DT. Comparison of volume control and pressure control ventilation: is flow waveform the difference? J Trauma. 1996;415:808-814. [CrossRef] [PubMed]
 
Campbell RS, Davis BR. Pressure-controlled versus volume-controlled ventilation: does it matter? Respir Care. 2002;474:416-424. [PubMed]
 
Cole AG, Weller SF, Sykes MK. Inverse ratio ventilation compared with PEEP in adult respiratory failure. Intensive Care Med. 1984;105:227-232. [CrossRef] [PubMed]
 
Gurevitch MJ, Van Dyke J, Young ES, Jackson K. Improved oxygenation and lower peak airway pressure in severe adult respiratory distress syndrome. Treatment with inverse ratio ventilation. Chest. 1986;892:211-213. [CrossRef] [PubMed]
 
Tharratt RS, Allen RP, Albertson TE. Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Chest. 1988;944:755-762. [CrossRef] [PubMed]
 
Abraham E, Yoshihara G. Cardiorespiratory effects of pressure controlled inverse ratio ventilation in severe respiratory failure. Chest. 1989;966:1356-1359. [CrossRef] [PubMed]
 
Lain DC, DiBenedetto R, Morris SL, Van Nguyen A, Saulters R, Causey D. Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation. Chest. 1989;955:1081-1088. [CrossRef] [PubMed]
 
Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Rationale and implementation. Chest. 1991;1002:494-504. [CrossRef] [PubMed]
 
Mercat A, Graïni L, Teboul JL, Lenique F, Richard C. Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. Chest. 1993;1043:871-875. [CrossRef] [PubMed]
 
Lessard MR, Guérot E, Lorino H, Lemaire F, Brochard L. Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology. 1994;805:983-991. [CrossRef] [PubMed]
 
Mercat A, Titiriga M, Anguel N, Richard C, Teboul JL. Inverse ratio ventilation (I/E = 2/1) in acute respiratory distress syndrome: a six-hour controlled study. Am J Respir Crit Care Med. 1997;1555:1637-1642. [PubMed]
 
Zavala E, Ferrer M, Polese G, et al. Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome. Anesthesiology. 1998;881:35-42. [CrossRef] [PubMed]
 
Shanholtz C, Brower R. Should inverse ratio ventilation be used in adult respiratory distress syndrome? Am J Respir Crit Care Med. 1994;1495:1354-1358. [PubMed]
 
Kacmarek RM, Hess D. Pressure-controlled inverse-ratio ventilation: Panacea or auto-PEEP? Respir Care. 1990;3510:945-948
 
Duncan SR, Rizk NW, Raffin TA. Inverse ratio ventilation. PEEP in disguise? Chest. 1987;923:390-392. [CrossRef] [PubMed]
 
Varpula T, Valta P, Niemi R, Takkunen O, Hynynen M, Pettilä VV. Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome. Acta Anaesthesiol Scand. 2004;486:722-731. [CrossRef] [PubMed]
 
Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome. Crit Care. 2001;54:221-226. [CrossRef] [PubMed]
 
Räsänen J, Cane RD, Downs JB, et al. Airway pressure release ventilation during acute lung injury: a prospective multicenter trial. Crit Care Med. 1991;1910:1234-1241. [CrossRef] [PubMed]
 
Putensen C, Zech S, Wrigge H, et al. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001;1641:43-49. [PubMed]
 
Neumann P, Golisch W, Strohmeyer A, Buscher H, Burchardi H, Sydow M. Influence of different release times on spontaneous breathing pattern during airway pressure release ventilation. Intensive Care Med. 2002;2812:1742-1749. [CrossRef] [PubMed]
 
Habashi NM. Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med. 2005;333suppl:S228-S240. [CrossRef] [PubMed]
 
Cane RD, Peruzzi WT, Shapiro BA. Airway pressure release ventilation in severe acute respiratory failure. Chest. 1991;1002:460-463. [CrossRef] [PubMed]
 
Dart BW 4th, Maxwell RA, Richart CM, et al. Preliminary experience with airway pressure release ventilation in a trauma/surgical intensive care unit. J Trauma. 2005;591:71-76. [CrossRef] [PubMed]
 
Schultz TR, Costarino AT Jr, Durning SM, et al. Airway pressure release ventilation in pediatrics. Pediatr Crit Care Med. 2001;23:243-246. [CrossRef] [PubMed]
 
Fessler HE, Hess DR. Respiratory controversies in the critical care setting. Does high-frequency ventilation offer benefits over conventional ventilation in adult patients with acute respiratory distress syndrome? Respir Care. 2007;525:595-605. [PubMed]
 
Hess D, Mason S, Branson R. High-frequency ventilation design and equipment issues. Respir Care Clin N Am. 2001;74:577-598. [CrossRef] [PubMed]
 
Chan KP, Stewart TE, Mehta S. High-frequency oscillatory ventilation for adult patients with ARDS. Chest. 2007;1316:1907-1916. [CrossRef] [PubMed]
 
Fessler HE, Hager DN, Brower RG. Feasibility of very high-frequency ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2008;364:1043-1048. [CrossRef] [PubMed]
 
Ritacca FV, Stewart TE. Clinical review: high-frequency oscillatory ventilation in adults—a review of the literature and practical applications. Crit Care. 2003;75:385-390. [CrossRef] [PubMed]
 
Krishnan JA, Brower RG. High-frequency ventilation for acute lung injury and ARDS. Chest. 2000;1183:795-807. [CrossRef] [PubMed]
 
Hager DN, Fessler HE, Kaczka DW, et al. Tidal volume delivery during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2007;356:1522-1529. [CrossRef] [PubMed]
 
Ferguson ND, Chiche JD, Kacmarek RM, et al. Combining high-frequency oscillatory ventilation and recruitment maneuvers in adults with early acute respiratory distress syndrome: the Treatment with Oscillation and an Open Lung Strategy (TOOLS) Trial pilot study. Crit Care Med. 2005;333:479-486. [CrossRef] [PubMed]
 
Mehta S, MacDonald R, Hallett DC, Lapinsky SE, Aubin M, Stewart TE. Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2003;312:383-389. [CrossRef] [PubMed]
 
Demory D, Michelet P, Arnal JM, et al. High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation. Crit Care Med. 2007;351:106-111. [CrossRef] [PubMed]
 
David M, Weiler N, Heinrichs W, et al. High-frequency oscillatory ventilation in adult acute respiratory distress syndrome. Intensive Care Med. 2003;2910:1656-1665. [CrossRef] [PubMed]
 
Mehta S, Granton J, MacDonald RJ, et al. High-frequency oscillatory ventilation in adults: the Toronto experience. Chest. 2004;1262:518-527. [CrossRef] [PubMed]
 
Bollen CW, van Well GT, Sherry T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]. Crit Care. 2005;94:R430-R439. [CrossRef] [PubMed]
 
Sessler CN. Sedation, analgesia, and neuromuscular blockade for high-frequency oscillatory ventilation. Crit Care Med. 2005;333suppl:S209-S216. [CrossRef] [PubMed]
 
Wunsch H, Mapstone J, Takala J. High-frequency ventilation versus conventional ventilation for the treatment of acute lung injury and acute respiratory distress syndrome: a systematic review and cochrane analysis. Anesth Analg. 2005;1006:1765-1772. [CrossRef] [PubMed]
 
Eastman A, Holland D, Higgins J, et al. High-frequency percussive ventilation improves oxygenation in trauma patients with acute respiratory distress syndrome: a retrospective review. Am J Surg. 2006;1922:191-195. [CrossRef] [PubMed]
 
Salim A, Martin M. High-frequency percussive ventilation. Crit Care Med. 2005;3 suppl:S241-S245
 
Paulsen SM, Killyon GW, Barillo DJ. High-frequency percussive ventilation as a salvage modality in adult respiratory distress syndrome: a preliminary study. Am Surg. 2002;6810:852-856 discussion 856.. [PubMed]
 
Salim A, Miller K, Dangleben D, Cipolle M, Pasquale M. High-frequency percussive ventilation: an alternative mode of ventilation for head-injured patients with adult respiratory distress syndrome. J Trauma. 2004;573:542-546. [CrossRef] [PubMed]
 
Gallagher TJ, Boysen PG, Davidson DD, Miller JR, Leven SB. High-frequency percussive ventilation compared with conventional mechanical ventilation. Crit Care Med. 1989;174:364-366. [CrossRef] [PubMed]
 
Lucangelo U, Zin WA, Antonaglia V, et al. High-frequency percussive ventilation during surgical bronchial repair in a patient with one lung. Br J Anaesth. 2006;964:533-536. [CrossRef] [PubMed]
 
Hurst JM, Branson RD, Davis K Jr, Barrette RR, Adams KS. Comparison of conventional mechanical ventilation and high-frequency ventilation. A prospective, randomized trial in patients with respiratory failure. Ann Surg. 1990;2114:486-491. [CrossRef] [PubMed]
 
Lucangelo U, Antonaglia V, Zin WA, et al. High-frequency percussive ventilation improves perioperatively clinical evolution in pulmonary resection. Crit Care Med. 2009;375:1663-1669. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Graphic representation of the stress index. Flow and airway pressure vs time are displayed for three examples of stress index categories. The ventilator is set for constant-flow inflation. The stress index is derived from the airway pressure waveform between the dashed lines. For stress index values < 1, the airway pressure curve presents a downward concavity, suggesting a continuous decrease in elastance (or increase in compliance) during constant-flow inflation, and further recruitment of alveoli is likely. For stress index values > 1, the curve presents an upward concavity, suggesting a continuous increase in elastance (decrease in compliance), and excessive positive end-expiratory pressure may be present. Finally, for a stress index value = 1, the curve is straight, suggesting the absence of tidal variations in elastance. Pao = airway pressure. (Reprinted with permission from the American Thoracic Society.29)Grahic Jump Location
Figure Jump LinkFigure 2. The relationship between oxygenation (PaO2/FIO2 ratio) after the application of a recruitment maneuver (post-RM) with baseline (pre-RM) oxygenation in each individual study presented. Oxygenation was significantly increased post-RM (PaO2/FIO2 ratio, 139 mm Hg vs 251 mm Hg; P < .001). P/F = PaO2/FIO2. (Reprinted with permission from the American Thoracic Society.52)Grahic Jump Location
Figure Jump LinkFigure 3. Display of airway pressure and flow vs time during airway pressure-release ventilation. Spontaneous breaths occur at a high pressure level, leading to a pressure release to a lower pressure level, as seen in this figure. During this mode, ventilation occurs by intermittent switching between the two pressure levels while allowing spontaneous breathing to occur in either phase of the ventilator cycle. Because time at low airway pressure is brief, in practice, spontaneous breathing occurs primarily during the time of high airway pressure. Maintaining an adequate level of time during a high airway pressure enhances alveolar recruitment, whereas keeping time short prevents alveolar collapse during the release to low airway pressure. CPAP = continuous positive air pressure; Paw = airway pressure; T High = time at high airway pressure; T Low = time at low airway pressure; V˙  = flow. (Reprinted with permission from the Intensive Care On-line Network.89)Grahic Jump Location
Figure Jump LinkFigure 4. High-frequency percussive ventilation. An interplay of the percussive frequency, peak inspiratory pressure (indirectly modulated by altering the pulsatile flow rate), inspiratory and expiratory times (of both percussive and convective breaths), and the oscillatory and demand continuous positive air pressure (CPAP) levels either singly or in combination is involved in determining mean airway pressure as well as the degree of gas exchange. The percussions are of lower amplitude at oscillatory CPAP (baseline oscillations) during exhalation and are of higher amplitude during inspiration as a result of the selected pulsatile flow rate (see pressure-time display). During inspiration, the lung volumes progressively increase in a cumulative, stepwise manner by continually diminishing subtidal deliveries that result in stacking of breaths. The peak pressure is reached as a result of modulations in the flow rate of the percussive breaths. Once an oscillatory pressure peak is reached and sustained, periodic programmed interruptions occur at specific times for predetermined intervals to allow for the return of airway pressures to baseline oscillatory pressure levels (ie, oscillatory CPAP), thereby passively emptying the lungs. A = pulsatile flow during inspiration at a percussive rate of 655 cycles/min; B = convective pressure-limited breath with low-frequency cycle (14 cycles/min); C = demand CPAP (provides static baseline pressure); D = oscillatory CPAP (provides high-frequency baseline pressure as a mean of the peak and nadir of the oscillations during exhalation); E = single percussive breath; F = periodic programmed interruptions signifying the end of inspiration and subsequent onset of exhalation.Grahic Jump Location
Figure Jump LinkFigure 5. Ventilatory strategies for the management of refractory hypoxemic respiratory failure, showing the alternative ventilator strategies that can be used in patients with acute lung injury or ARDS with refractory hypoxemia following evaluation of the recruitment potential of the lungs. In patients with recruitable lungs, higher levels of positive end-expiratory pressure (PEEP) or other methods of setting appropriate levels of PEEP may be used initially.* However, failure of the aforementioned techniques can result in the use of the alternative ventilatory strategies in centers familiar with their use. * = other methods of setting appropriate levels of PEEP include setting PEEP to reach a plateau pressure of 28 to 30 cm H2O using esophageal pressure monitoring or the stress index. ALI = acute lung injury; APRV = airway pressure-release ventilation; ECLS = extracorporeal life support; ETCO2 = end-tidal carbon dioxide; HFOV = high-frequency oscillatory ventilation; HFPV = high-frequency percussive ventilation. See Table 1 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Summary of Results of Three Randomized Controlled Trials of Lower vs Higher Levels of PEEP

ALVEOLI = Assessment of Low Tidal Volume and Elevated End-Expiratory Pressure to Obviate Lung Injury Trial; EXPRESS = Expiratory Pressure Trial; IBW = ideal body weight; LOV = Lung Open Ventilation Trial; PEEP = positive end-expiratory pressure; Pplat = plateau pressure; SpO2 = oxygenation by pulse oximetry; Vt = tidal volume.

Table Graphic Jump Location
Table 2 —Methods for Selecting PEEP

See Table 1 for expansion of the abbreviation.

Table Graphic Jump Location
Table 3 —Different Lung Recruitment Maneuvers

CPAP = continuous positive air pressure. See Table 1 legend for expansion of other abbreviation.

References

Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;1493 Pt 1:818-824. [PubMed]
 
Luhr OR, Antonsen K, Karlsson M, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med. 1999;1596:1849-1861. [PubMed]
 
The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;34218:1301-1308. [CrossRef] [PubMed]
 
Villar J, Pérez-Méndez L, Kacmarek RM. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome. Intensive Care Med. 1999;259:930-935. [CrossRef] [PubMed]
 
Ferguson ND, Kacmarek RM, Chiche JD, et al. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med. 2004;306:1111-1116. [CrossRef] [PubMed]
 
Villar J, Pérez-Méndez L, López J, et al. HELP Network An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007;1768:795-804. [CrossRef] [PubMed]
 
Kallet RH, Branson RD. Respiratory controversies in the critical care setting. Do the NIH ARDS Clinical Trials Network PEEP/FIO2 tables provide the best evidence-based guide to balancing PEEP and FIO2 settings in adults? Respir Care. 2007;524:461-475. [PubMed]
 
Montgomery AB, Stager MA, Carrico CJ, Hudson LD. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1985;1323:485-489. [PubMed]
 
Fort P, Farmer C, Westerman J, et al. High-frequency oscillatory ventilation for adult respiratory distress syndrome—a pilot study. Crit Care Med. 1997;256:937-947. [CrossRef] [PubMed]
 
Monchi M, Bellenfant F, Cariou A, et al. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. Am J Respir Crit Care Med. 1998;1584:1076-1081. [PubMed]
 
Seeley E, McAuley DF, Eisner M, Miletin M, Matthay MA, Kallet RH. Predictors of mortality in acute lung injury during the era of lung protective ventilation. Thorax. 2008;6311:994-998. [CrossRef] [PubMed]
 
Trachsel D, McCrindle BW, Nakagawa S, Bohn D. Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med. 2005;1722:206-211. [CrossRef] [PubMed]
 
Bayrakci B, Josephson C, Fackler J. Oxygenation index for extracorporeal membrane oxygenation: is there predictive significance? J Artif Organs. 2007;101:6-9. [CrossRef] [PubMed]
 
HiFO Study Group Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. J Pediatr. 1993;1224:609-619. [CrossRef] [PubMed]
 
Clark RH, Yoder BA, Sell MS. Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation. J Pediatr. 1994;1243:447-454. [CrossRef] [PubMed]
 
Schwendeman CA, Clark RH, Yoder BA, Null DM Jr, Gerstmann DR, Delemos RA. Frequency of chronic lung disease in infants with severe respiratory failure treated with high-frequency ventilation and/or extracorporeal membrane oxygenation. Crit Care Med. 1992;203:372-377. [CrossRef] [PubMed]
 
Grasso S, Mascia L, Del Turco M, et al. Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy. Anesthesiology. 2002;964:795-802. [CrossRef] [PubMed]
 
Borges JB, Okamoto VN, Matos GF, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;1743:268-278. [CrossRef] [PubMed]
 
Mehta S, Lapinsky SE, Hallett DC, et al. Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome. Crit Care Med. 2001;297:1360-1369. [CrossRef] [PubMed]
 
Mancebo J, Fernández R, Blanch L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;17311:1233-1239. [CrossRef] [PubMed]
 
Kahn JM, Goss CH, Heagerty PJ, Kramer AA, O’Brien CR, Rubenfeld GD. Hospital volume and the outcomes of mechanical ventilation. N Engl J Med. 2006;3551:41-50. [CrossRef] [PubMed]
 
Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;35316:1685-1693. [CrossRef] [PubMed]
 
Kahn JM, Linde-Zwirble WT, Wunsch H, et al. Potential value of regionalized intensive care for mechanically ventilated medical patients. Am J Respir Crit Care Med. 2008;1773:285-291. [CrossRef] [PubMed]
 
Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006;35417:1775-1786. [CrossRef] [PubMed]
 
Yilmaz M, Keegan MT, Iscimen R, et al. Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med. 2007;357:1660-1666. [CrossRef] [PubMed]
 
Sessler CN, Goulet K, Esan A, Hess DR, Raoof S. Severe hypoxemic respiratory failure: part 2—nonventilatory strategies. Chest. 2010; In press.
 
Meade MO, Cook DJ, Guyatt GH, et al; Lung Open Ventilation Study Investigators Lung Open Ventilation Study Investigators Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. J Amer Med Assoc. 2008;2996:637-645. [CrossRef]
 
Mercat A, Richard JC, Vielle B, et al; Expiratory Pressure (Express) Study Group Expiratory Pressure (Express) Study Group Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. J Amer Med Assoc. 2008;2996:646-655. [CrossRef]
 
Grasso S, Stripoli T, De Michele M, et al. ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure. Am J Respir Crit Care Med. 2007;1768:761-767. [CrossRef] [PubMed]
 
Talmor D, Sarge T, O’Donnell CR, et al. Esophageal and transpulmonary pressures in acute respiratory failure. Crit Care Med. 2006;345:1389-1394. [CrossRef] [PubMed]
 
Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation. Am J Respir Crit Care Med. 1994;1496:1550-1556. [PubMed]
 
Derdak S, Mehta S, Stewart TE, et al. Multicenter Oscillatory Ventilation For Acute Respiratory Distress Syndrome Trial (MOAT) Study Investigators High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med. 2002;1666:801-808. [CrossRef] [PubMed]
 
Velmahos GC, Chan LS, Tatevossian R, et al. High-frequency percussive ventilation improves oxygenation in patients with ARDS. Chest. 1999;1162:440-446. [CrossRef] [PubMed]
 
Lucangelo U, Fontanesi L, Antonaglia V, et al. High frequency percussive ventilation (HFPV). Principles and technique. Minerva Anestesiol. 2003;6911:841-848. [PubMed]
 
Schuerer DJ, Kolovos NS, Boyd KV, Coopersmith CM. Extracorporeal membrane oxygenation: current clinical practice, coding, and reimbursement. Chest. 2008;1341:179-184. [CrossRef] [PubMed]
 
Girard TD, Bernard GR. Mechanical ventilation in ARDS: a state-of-the-art review. Chest. 2007;1313:921-929. [CrossRef] [PubMed]
 
Laffey JG, O’Croinin D, McLoughlin P, Kavanagh BP. Permissive hypercapnia—role in protective lung ventilatory strategies. Intensive Care Med. 2004;303:347-356. [CrossRef] [PubMed]
 
Abdelsalam M. Permissive hypoxemia: is it time to change our approach? Chest. 2006;1291:210-211. [CrossRef] [PubMed]
 
National Heart, Lung, and Blood Institute ARDS Clinical Trials NetworkNational Heart, Lung, and Blood Institute ARDS Clinical Trials Network Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;3514:327-336. [CrossRef] [PubMed]
 
Gattinoni L, Caironi P. Refining ventilatory treatment for acute lung injury and acute respiratory distress syndrome. J Amer Med Assoc. 2008;2996:691-693. [CrossRef]
 
Grasso S, Fanelli V, Cafarelli A, et al. Effects of high versus low positive end-expiratory pressures in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;1719:1002-1008. [CrossRef] [PubMed]
 
Kanarek DJ, Shannon DC. Adverse effect of positive end-expiratory pressure on pulmonary perfusion and arterial oxygenation. Am Rev Respir Dis. 1975;1123:457-459. [PubMed]
 
Ramnath VR, Hess DR, Thompson BT. Conventional mechanical ventilation in acute lung injury and acute respiratory distress syndrome. Clin Chest Med. 2006;274:601-613 abstract viii.. [CrossRef] [PubMed]
 
Girgis K, Hamed H, Khater Y, Kacmarek RM. A decremental PEEP trial identifies the PEEP level that maintains oxygenation after lung recruitment. Respir Care. 2006;5110:1132-1139. [PubMed]
 
Hickling KG. Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med. 2001;1631:69-78. [PubMed]
 
Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008;35920:2095-2104. [CrossRef] [PubMed]
 
Owens RL, Stigler WS, Hess DR. Do newer monitors of exhaled gases, mechanics, and esophageal pressure add value? Clin Chest Med. 2008;292:297-312. [CrossRef] [PubMed]
 
Hess DR, Bigatello LM. The chest wall in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care. 2008;141:94-102. [CrossRef] [PubMed]
 
Hager DN, Brower RG. Customizing lung-protective mechanical ventilation strategies. Crit Care Med. 2006;345:1554-1555. [CrossRef] [PubMed]
 
Brower RG, Hubmayr RD, Slutsky AS. Lung stress and strain in acute respiratory distress syndrome: good ideas for clinical management? Am J Respir Crit Care Med. 2008;1784:323-324. [CrossRef] [PubMed]
 
Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;3386:347-354. [CrossRef] [PubMed]
 
Fan E, Wilcox ME, Brower RG, et al. Recruitment maneuvers for acute lung injury: a systematic review. Am J Respir Crit Care Med. 2008;17811:1156-1163. [CrossRef] [PubMed]
 
Hess DR, Bigatello LM. Lung recruitment: the role of recruitment maneuvers. Respir Care. 2002;473:308-317. [PubMed]
 
Lapinsky SE, Mehta S. Bench-to-bedside review: Recruitment and recruiting maneuvers. Crit Care. 2005;91:60-65. [CrossRef] [PubMed]
 
Foti G, Cereda M, Sparacino ME, De Marchi L, Villa F, Pesenti A. Effects of periodic lung recruitment maneuvers on gas exchange and respiratory mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS) patients. Intensive Care Med. 2000;265:501-507. [CrossRef] [PubMed]
 
Lapinsky SE, Aubin M, Mehta S, Boiteau P, Slutsky AS. Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure. Intensive Care Med. 1999;2511:1297-1301. [CrossRef] [PubMed]
 
Medoff BD, Harris RS, Kesselman H, Venegas J, Amato MB, Hess D. Use of recruitment maneuvers and high-positive end-expiratory pressure in a patient with acute respiratory distress syndrome. Crit Care Med. 2000;284:1210-1216. [CrossRef] [PubMed]
 
Tugrul S, Akinci O, Ozcan PE, et al. Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms. Crit Care Med. 2003;313:738-744. [CrossRef] [PubMed]
 
Pelosi P, Cadringher P, Bottino N, et al. Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;1593:872-880. [PubMed]
 
Lim CM, Koh Y, Park W, et al. Mechanistic scheme and effect of “extended sigh” as a recruitment maneuver in patients with acute respiratory distress syndrome: a preliminary study. Crit Care Med. 2001;296:1255-1260. [CrossRef] [PubMed]
 
Galiatsou E, Kostanti E, Svarna E, et al. Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med. 2006;1742:187-197. [CrossRef] [PubMed]
 
Chan KP, Stewart TE. Clinical use of high-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome. Crit Care Med. 2005;3 suppl:S170-S174
 
Villagrá A, Ochagavía A, Vatua S, et al. Recruitment maneuvers during lung protective ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;1652:165-170. [PubMed]
 
Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med. 2006;345:1311-1318. [CrossRef] [PubMed]
 
Kacmarek RM, Kallet RH. Respiratory controversies in the critical care setting. Should recruitment maneuvers be used in the management of ALI and ARDS? Respir Care. 2007;525:622-631. [PubMed]
 
Kallet RH, Campbell AR, Dicker RA, Katz JA, Mackersie RC. Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes. Respir Care. 2005;5012:1623-1631. [PubMed]
 
Ravenscraft SA, Burke WC, Marini JJ. Volume-cycled decelerating flow. An alternative form of mechanical ventilation. Chest. 1992;1015:1342-1351. [CrossRef] [PubMed]
 
Muñoz J, Guerrero JE, Escalante JL, Palomino R, De La Calle B. Pressure-controlled ventilation versus controlled mechanical ventilation with decelerating inspiratory flow. Crit Care Med. 1993;218:1143-1148. [CrossRef] [PubMed]
 
Davis K Jr, Branson RD, Campbell RS, Porembka DT. Comparison of volume control and pressure control ventilation: is flow waveform the difference? J Trauma. 1996;415:808-814. [CrossRef] [PubMed]
 
Campbell RS, Davis BR. Pressure-controlled versus volume-controlled ventilation: does it matter? Respir Care. 2002;474:416-424. [PubMed]
 
Cole AG, Weller SF, Sykes MK. Inverse ratio ventilation compared with PEEP in adult respiratory failure. Intensive Care Med. 1984;105:227-232. [CrossRef] [PubMed]
 
Gurevitch MJ, Van Dyke J, Young ES, Jackson K. Improved oxygenation and lower peak airway pressure in severe adult respiratory distress syndrome. Treatment with inverse ratio ventilation. Chest. 1986;892:211-213. [CrossRef] [PubMed]
 
Tharratt RS, Allen RP, Albertson TE. Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Chest. 1988;944:755-762. [CrossRef] [PubMed]
 
Abraham E, Yoshihara G. Cardiorespiratory effects of pressure controlled inverse ratio ventilation in severe respiratory failure. Chest. 1989;966:1356-1359. [CrossRef] [PubMed]
 
Lain DC, DiBenedetto R, Morris SL, Van Nguyen A, Saulters R, Causey D. Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation. Chest. 1989;955:1081-1088. [CrossRef] [PubMed]
 
Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Rationale and implementation. Chest. 1991;1002:494-504. [CrossRef] [PubMed]
 
Mercat A, Graïni L, Teboul JL, Lenique F, Richard C. Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. Chest. 1993;1043:871-875. [CrossRef] [PubMed]
 
Lessard MR, Guérot E, Lorino H, Lemaire F, Brochard L. Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology. 1994;805:983-991. [CrossRef] [PubMed]
 
Mercat A, Titiriga M, Anguel N, Richard C, Teboul JL. Inverse ratio ventilation (I/E = 2/1) in acute respiratory distress syndrome: a six-hour controlled study. Am J Respir Crit Care Med. 1997;1555:1637-1642. [PubMed]
 
Zavala E, Ferrer M, Polese G, et al. Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome. Anesthesiology. 1998;881:35-42. [CrossRef] [PubMed]
 
Shanholtz C, Brower R. Should inverse ratio ventilation be used in adult respiratory distress syndrome? Am J Respir Crit Care Med. 1994;1495:1354-1358. [PubMed]
 
Kacmarek RM, Hess D. Pressure-controlled inverse-ratio ventilation: Panacea or auto-PEEP? Respir Care. 1990;3510:945-948
 
Duncan SR, Rizk NW, Raffin TA. Inverse ratio ventilation. PEEP in disguise? Chest. 1987;923:390-392. [CrossRef] [PubMed]
 
Varpula T, Valta P, Niemi R, Takkunen O, Hynynen M, Pettilä VV. Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome. Acta Anaesthesiol Scand. 2004;486:722-731. [CrossRef] [PubMed]
 
Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome. Crit Care. 2001;54:221-226. [CrossRef] [PubMed]
 
Räsänen J, Cane RD, Downs JB, et al. Airway pressure release ventilation during acute lung injury: a prospective multicenter trial. Crit Care Med. 1991;1910:1234-1241. [CrossRef] [PubMed]
 
Putensen C, Zech S, Wrigge H, et al. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001;1641:43-49. [PubMed]
 
Neumann P, Golisch W, Strohmeyer A, Buscher H, Burchardi H, Sydow M. Influence of different release times on spontaneous breathing pattern during airway pressure release ventilation. Intensive Care Med. 2002;2812:1742-1749. [CrossRef] [PubMed]
 
Habashi NM. Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med. 2005;333suppl:S228-S240. [CrossRef] [PubMed]
 
Cane RD, Peruzzi WT, Shapiro BA. Airway pressure release ventilation in severe acute respiratory failure. Chest. 1991;1002:460-463. [CrossRef] [PubMed]
 
Dart BW 4th, Maxwell RA, Richart CM, et al. Preliminary experience with airway pressure release ventilation in a trauma/surgical intensive care unit. J Trauma. 2005;591:71-76. [CrossRef] [PubMed]
 
Schultz TR, Costarino AT Jr, Durning SM, et al. Airway pressure release ventilation in pediatrics. Pediatr Crit Care Med. 2001;23:243-246. [CrossRef] [PubMed]
 
Fessler HE, Hess DR. Respiratory controversies in the critical care setting. Does high-frequency ventilation offer benefits over conventional ventilation in adult patients with acute respiratory distress syndrome? Respir Care. 2007;525:595-605. [PubMed]
 
Hess D, Mason S, Branson R. High-frequency ventilation design and equipment issues. Respir Care Clin N Am. 2001;74:577-598. [CrossRef] [PubMed]
 
Chan KP, Stewart TE, Mehta S. High-frequency oscillatory ventilation for adult patients with ARDS. Chest. 2007;1316:1907-1916. [CrossRef] [PubMed]
 
Fessler HE, Hager DN, Brower RG. Feasibility of very high-frequency ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2008;364:1043-1048. [CrossRef] [PubMed]
 
Ritacca FV, Stewart TE. Clinical review: high-frequency oscillatory ventilation in adults—a review of the literature and practical applications. Crit Care. 2003;75:385-390. [CrossRef] [PubMed]
 
Krishnan JA, Brower RG. High-frequency ventilation for acute lung injury and ARDS. Chest. 2000;1183:795-807. [CrossRef] [PubMed]
 
Hager DN, Fessler HE, Kaczka DW, et al. Tidal volume delivery during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2007;356:1522-1529. [CrossRef] [PubMed]
 
Ferguson ND, Chiche JD, Kacmarek RM, et al. Combining high-frequency oscillatory ventilation and recruitment maneuvers in adults with early acute respiratory distress syndrome: the Treatment with Oscillation and an Open Lung Strategy (TOOLS) Trial pilot study. Crit Care Med. 2005;333:479-486. [CrossRef] [PubMed]
 
Mehta S, MacDonald R, Hallett DC, Lapinsky SE, Aubin M, Stewart TE. Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome. Crit Care Med. 2003;312:383-389. [CrossRef] [PubMed]
 
Demory D, Michelet P, Arnal JM, et al. High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation. Crit Care Med. 2007;351:106-111. [CrossRef] [PubMed]
 
David M, Weiler N, Heinrichs W, et al. High-frequency oscillatory ventilation in adult acute respiratory distress syndrome. Intensive Care Med. 2003;2910:1656-1665. [CrossRef] [PubMed]
 
Mehta S, Granton J, MacDonald RJ, et al. High-frequency oscillatory ventilation in adults: the Toronto experience. Chest. 2004;1262:518-527. [CrossRef] [PubMed]
 
Bollen CW, van Well GT, Sherry T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]. Crit Care. 2005;94:R430-R439. [CrossRef] [PubMed]
 
Sessler CN. Sedation, analgesia, and neuromuscular blockade for high-frequency oscillatory ventilation. Crit Care Med. 2005;333suppl:S209-S216. [CrossRef] [PubMed]
 
Wunsch H, Mapstone J, Takala J. High-frequency ventilation versus conventional ventilation for the treatment of acute lung injury and acute respiratory distress syndrome: a systematic review and cochrane analysis. Anesth Analg. 2005;1006:1765-1772. [CrossRef] [PubMed]
 
Eastman A, Holland D, Higgins J, et al. High-frequency percussive ventilation improves oxygenation in trauma patients with acute respiratory distress syndrome: a retrospective review. Am J Surg. 2006;1922:191-195. [CrossRef] [PubMed]
 
Salim A, Martin M. High-frequency percussive ventilation. Crit Care Med. 2005;3 suppl:S241-S245
 
Paulsen SM, Killyon GW, Barillo DJ. High-frequency percussive ventilation as a salvage modality in adult respiratory distress syndrome: a preliminary study. Am Surg. 2002;6810:852-856 discussion 856.. [PubMed]
 
Salim A, Miller K, Dangleben D, Cipolle M, Pasquale M. High-frequency percussive ventilation: an alternative mode of ventilation for head-injured patients with adult respiratory distress syndrome. J Trauma. 2004;573:542-546. [CrossRef] [PubMed]
 
Gallagher TJ, Boysen PG, Davidson DD, Miller JR, Leven SB. High-frequency percussive ventilation compared with conventional mechanical ventilation. Crit Care Med. 1989;174:364-366. [CrossRef] [PubMed]
 
Lucangelo U, Zin WA, Antonaglia V, et al. High-frequency percussive ventilation during surgical bronchial repair in a patient with one lung. Br J Anaesth. 2006;964:533-536. [CrossRef] [PubMed]
 
Hurst JM, Branson RD, Davis K Jr, Barrette RR, Adams KS. Comparison of conventional mechanical ventilation and high-frequency ventilation. A prospective, randomized trial in patients with respiratory failure. Ann Surg. 1990;2114:486-491. [CrossRef] [PubMed]
 
Lucangelo U, Antonaglia V, Zin WA, et al. High-frequency percussive ventilation improves perioperatively clinical evolution in pulmonary resection. Crit Care Med. 2009;375:1663-1669. [CrossRef] [PubMed]
 
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