Insights in pediatric ventilation: timing of intubation, ventilatory strategies, and weaning

PURPOSE OF REVIEW: Mechanical ventilation is a common intervention provided by pediatric intensivists. This fact notwithstanding, the management of mechanical ventilation in pediatrics is largely guided by a few pediatric trials along with careful interpretation and application of adult data. RECENT FINDINGS: A low tidal volume, pressure limited approach to mechanical ventilation as established by the Acute Respiratory Distress Syndrome Network investigators, has become the prevailing practice in pediatric intensive care. Studies by these investigators suggest that high positive end expiratory pressure and recruitment maneuvers are not uniformly beneficial. High frequency oscillatory ventilation continues to be evaluated in an attempt to provide 'open lung' ventilation. Airway pressure release ventilation is a newer mode of ventilation that may combine the 'open lung' approach with spontaneous breathing. Prone positioning was demonstrated in a recent pediatric trial to have no effect on outcome, while calfactant was found to potentially improve outcomes in pediatric acute respiratory distress syndrome. Ventilator weaning protocols may not be as useful in pediatrics as in adults. Systemic corticosteroids decrease the incidence of post extubation stridor and may reduce reintubation rates. SUMMARY: Mechanical ventilation with pressure limitation and low tidal volumes has become customary in pediatric intensive care units, and this lung protective approach will continue into the foreseeable future. Further investigation is warranted regarding use of high frequency oscillatory ventilation, airway pressure release ventilation, and surfactant to assist pediatric intensivists in application of these therapies.     

Clinical review: high-frequency oscillatory ventilation in adults--a review of the literature and practical applications

It has recently been shown that strategies aimed at preventing ventilator-induced lung injury, such as ventilating with low tidal volumes, can reduce mortality in patients with acute respiratory distress syndrome (ARDS). High-frequency oscillatory ventilation (HFOV) seems ideally suited as a lung-protective strategy for these patients. HFOV provides both active inspiration and expiration at frequencies generally between 3 and 10 Hz in adults. The amount of gas that enters and exits the lung with each oscillation is frequently below the anatomic dead space. Despite this, gas exchange occurs and potential adverse effects of conventional ventilation, such as overdistension and the repetitive opening and closing of collapsed lung units, are arguably mitigated. Although many investigators have studied the merits of HFOV in neonates and in pediatric populations, evidence for its use in adults with ARDS is limited. A recent multicenter, randomized, controlled trial has shown that HFOV, when used early in ARDS, is at least equivalent to conventional ventilation and may have beneficial effects on mortality. The present article reviews the principles and practical aspects of HFOV, and the current evidence for its application in adults with ARDS.     

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

Acute respiratory distress syndrome (ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the “sponge lung” - and the “shape matching” -model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients’ response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort.     

Bench-to-bedside review: High-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

Mechanical ventilation is the cornerstone of therapy for patients with acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation can exacerbate lung damage – a phenomenon known as ventilator-induced lung injury. While new ventilation strategies have reduced the mortality rate in patients with ARDS, this mortality rate still remains high. High-frequency oscillatory ventilation (HFOV) is an unconventional form of ventilation that may improve oxygenation in patients with ARDS, while limiting further lung injury associated with high ventilatory pressures and volumes delivered during conventional ventilation. HFOV has been used for almost two decades in the neonatal population, but there is more limited experience with HFOV in the adult population. In adults, the majority of the published literature is in the form of small observational studies in which HFOV was used as 'rescue' therapy for patients with very severe ARDS who were failing conventional ventilation. Two prospective randomized controlled trials, however, while showing no mortality benefit, have suggested that HFOV, compared with conventional ventilation, is a safe and effective ventilation strategy for adults with ARDS. Several studies suggest that HFOV may improve outcomes if used early in the course of ARDS, or if used in certain populations. This review will summarize the evidence supporting the use of HFOV in adults with ARDS.     

High-frequency oscillatory ventilation reduces lung inflammation: a large-animal 24-h model of respiratory distress

Objective High-frequency oscillatory ventilation (HFOV) may reduce ventilator-induced lung injury in experimental neonatal respiratory distress. However, these data permit no conclusions for large animals or adult patients with acute respiratory distress syndrome (ARDS), because in neonates higher frequencies and lower amplitudes can be used, resulting in lower tidal volumes (VT) and airway pressures. The aim of this study was to compare gas exchange, lung histopathology and inflammatory cytokine expression during lung-protective pressure-controlled ventilation (PCV) and HFOV in a long-term large-animal model of ARDS. Design Prospective, randomized, controlled pilot study. Setting University animal laboratory. Subjects Sixteen female pigs (55.3 ± 3.9 kg). Interventions After induction of ARDS by repeated lavage, the animals were randomly assigned to PCV (VT = 6 ml/kg) and HFOV (6 Hz). After lung injury, a standardised lung recruitment was performed in both groups, and ventilation was continued for 24 h. Measurements and results: After lung recruitment sustained improvements in the oxygenation index were observed in both groups. The mean airway pressure (mPaw) was significantly lower in the HFOV group during the experiment ( p < 0.01). Histologically, lung inflammation was significantly ameliorated in the HFOV group ( p < 0.05). The messenger RNA expression of IL-1-β in lung tissue was significantly lower in the HFOV-treated animals ( p < 0.01). Conclusions These data suggest that HFOV compared with conventional lung-protective ventilation can reduce lung inflammation in a large-animal 24-h model of ARDS. Furthermore, it was shown that lung recruitment leads to sustained improvements in gas exchange with a significantly lower mPaw when HFOV is used. This article is discussed in the editorial available at: .     

Respiratory controversies in the critical care setting. Does high-frequency ventilation offer benefits over conventional ventilation in adult patients with acute respiratory distress syndrome?

High-frequency ventilation is the application of mechanical ventilation with a respiratory rate > 100 breaths/min. High-frequency oscillatory ventilation (HFOV) is the form of high-frequency ventilation most widely used in adult critical care. The principles of lung-protective ventilation have matured in parallel with the technology for HFOV. The 2 basic principles of lung-protective ventilation are the use of small tidal volume and maintenance of adequate alveolar recruitment. Research in animal models and humans demonstrate that HFOV can support gas exchange with much smaller tidal volume than can be achieved with conventional ventilation. HFOV also provides more effective lung recruitment than conventional mechanical ventilation. However, at present, evidence is lacking that survival in adults with acute respiratory distress syndrome is improved by HFOV. Although HFOV may improve P(aO(2)) in some patients, this improvement is often transitory. Available evidence does not support that pulmonary inflammation is reduced with HFOV in adult acute respiratory distress syndrome. Heavy sedation and often paralysis are necessary. The promise of HFOV as a lung-protective ventilation strategy remains attractive, but additional clinical trials are needed to determine whether this approach is superior to lung-protective ventilation with conventional mechanical ventilation.     

The Use of Dexamethasone in the Prevention of Postextubation Stridor in Pediatric Patients in PICU/NICU Settings: An Analytical Review

ISSUES AND PURPOSE. Dexamethasone has been used to prevent postextubation stridor in children, but its use is controversial. Five randomized, controlled clinical trials were reviewed to analyze the effectiveness of prophylactic dexamethasone on postextubation stridor in pediatric patients.
CONCLUSIONS. Previous studies had inconsistent results. Several factors may contribute to postextubation stridor in pediatric patients. Postextubation stridor and extubation failure do not always result from airway edema.
PRACTICE IMPLICATIONS. In addition to prophylactic dexamethasone, other approaches should be used to prevent postextubation stridor, such as preparing the patient, following established guidelines, and providing appropriate postextubation care.     

Pediatric acute hypoxemic respiratory failure: management of oxygenation

Acute hypoxemic respiratory failure (AHRF) is one of the hallmarks of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which are caused by an inflammatory process initiated by any of a number of potential systemic and/or pulmonary insults that result in heterogeneous disruption of the capillary-pithelial interface. In these critically sick patients, optimizing the management of oxygenation is crucial. Physicians managing pediatric patients with ALI or ARDS are faced with a complex array of options influencing oxygenation. Certain treatment strategies can influence clinical outcomes, such as a lung protective ventilation strategy that specifies a low tidal volume (6 mL/kg) and a plateau pressure limit (30 cm H(2)O). Other strategies such as different levels of positive end expiratory pressure, altered inspiration to expiration time ratios, recruitment maneuvers, prone positioning, and extraneous gases or drugs may also affect clinical outcomes. This article reviews state-of-the-art strategies on the management of oxygenation in acute hypoxemic respiratory failure in children.     

Update in ARDS management: recent randomized controlled trials that changed our practice

In the last 7 years, 14 randomized controlled trials in patients with acute respiratory distress syndrome (ARDS) have shown that: Mechanical ventilation with a tidal volume of 6 mL/kg of predicted body weight is better than mechanical ventilation with a tidal volume of 12 mL/kg of predicted body weight. Prone positioning improves oxygenation but poses safety concerns. A high level of positive end-expiratory pressure does not improve survival. High-frequency oscillatory ventilation is in theory the ideal "lung-protective" method, but its benefits have not been proven. No drug therapy has been shown to improve survival in patients with ARDS. Exogenous surfactant may improve oxygenation but has no significant effect on the death rate or length of use of mechanical ventilation. Low-dose inhaled nitric oxide has no substantial impact on the duration of ventilatory support or on the death rate. Partial liquid ventilation may be beneficial in young patients with acute lung injury or ARDS, although further study is needed to confirm this.     

Mechanical ventilation in acute lung injury and ARDS. Tidal volume reduction

Traditional mechanical ventilation practices used generous tidal volumes in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). This approach may have caused overdistention of aerated lung units, thus exacerbating lung injury in some patients. Several recent clinical trials of traditional versus lower tidal volume strategies in ALI/ARDS yielded disparate results. In the largest study, the lower tidal volume approach was associated with lower mortality and more ventilator-free days. This article reviews the rationale for tidal volume reduction in ALI/ARDS and the differences between the studies. Several different interpretations of the recent clinical trial results are addressed.     

Prophylactic protective ventilation: lower tidal volumes for all critically ill patients?

High tidal volumes have historically been recommended for mechanically ventilated patients during general anesthesia. High tidal volumes have been shown to increase morbidity and mortality in patients suffering from acute respiratory distress syndrome (ARDS). Barriers exist in implementing a tidal volume reduction strategy related to the inherent difficulty in changing one's practice patterns, to the current need to individualize low tidal volume settings only for a specific subgroup of mechanically ventilated patients (i.e., ARDS patients), the difficulty in determining the predicated body weight (requiring the patient's height and a complex formula). Consequently, a protective ventilation strategy is often under-utilized as a therapeutic option, even in ARDS. Recent data supports the generalization of this strategy prophylactically to almost all mechanically ventilated patients beginning immediately following intubation. Using tools to rapidly and reliably determine the predicted body weight (PBW), as well as the use of automated modes of ventilation are some of the potential solutions to facilitate the practice of protective ventilation and to finally ventilate our patients?? lungs in a more gentle fashion to help prevent ARDS.     

Mechanical ventilation in acute respiratory failure: recruitment and high positive end-expiratory pressure are necessary

PURPOSE OF REVIEW: To review as best the critical care clinicians can recruit the acute respiratory distress syndrome (ARDS) lungs and keep the lungs opened, assuring homogeneous ventilation, and to present the experimental and clinical results of these mechanical ventilation strategies, along with possible improvements in patient outcome based on selected published medical literature from 1972 to 2004 (highlighting the period from June 2003 to June 2004 and recent results of the authors' group research). RECENT FINDINGS: In the experimental setting, repeated derecruitments accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate lung injury. In the clinical setting, recruitment maneuvers improve short-term oxygenation in ARDS patients. A recent prospective clinical trial showed that low versus intermediate positive end-expiratory pressure (PEEP) levels (8 vs 13 cm H2O) associated with low tidal ventilation had the same effect on ARDS patient survival. Nevertheless, both conventional and electrical impedance thoracic tomography studies indicate that stepwise PEEP recruitment maneuvers increase lung volume and the recruitment percentage of lung tissue, and higher levels of PEEP (18-26 cm H2O) are necessary to keep the ARDS lungs opened and assure a more homogeneous low tidal ventilation. SUMMARY: Stepwise PEEP recruitment maneuvers can open collapsed ARDS lungs. Higher levels of PEEP are necessary to maintain the lungs open and assure homogenous ventilation in ARDS. In the near future, thoracic CT associated with high-performance monitoring of regional ventilation (electrical impedance tomography) may be used at the bedside to determine the optimal mechanical ventilation of ARDS patients.     

Successful treatment of acute respiratory distress syndrome and severe pulmonary hypertension in a child with Bordetella pertussis infection

Infection with Bordetella pertussis can cause severe illness with neurological and pulmonary complications in children. Pulmonary hypertension is an early sign of potentially fatal disease and can cause failure of conventional respiratory therapy in severe acute respiratory distress syndrome (ARDS). We report a 4 1/2-year-old boy with B. pertussis infection who developed severe ARDS and pulmonary hypertension. Because of severe neurological signs the patient did not qualify for extracorporal membrane oxygenation (ECMO). After conventional ventilation, surfactant and high frequency oscillation ventilation (HFOV) failed, treatment with nitric oxide (NO) improved oxygenation, allowing recovery without the need for ECMO. The patient survived with few sequelae. Thus, this treatment may be an option in high-risk children who meet the criteria for ECMO but are excluded because of poor neurological status, as in our patient.     

Bench-to-bedside review: Recruitment and recruiting maneuvers

In patients with acute respiratory distress syndrome (ARDS), the lung comprises areas of aeration and areas of alveolar collapse, the latter producing intrapulmonary shunt and hypoxemia. The currently suggested strategy of ventilation with low lung volumes can aggravate lung collapse and potentially produce lung injury through shear stress at the interface between aerated and collapsed lung, and as a result of repetitive opening and closing of alveoli. An 'open lung strategy' focused on alveolar patency has therefore been recommended. While positive end-expiratory pressure prevents alveolar collapse, recruitment maneuvers can be used to achieve alveolar recruitment. Various recruitment maneuvers exist, including sustained inflation to high pressures, intermittent sighs, and stepwise increases in positive end-expiratory pressure or peak inspiratory pressure. In animal studies, recruitment maneuvers clearly reverse the derecruitment associated with low tidal volume ventilation, improve gas exchange, and reduce lung injury. Data regarding the use of recruitment maneuvers in patients with ARDS show mixed results, with increased efficacy in those with short duration of ARDS, good compliance of the chest wall, and in extrapulmonary ARDS. In this review we discuss the pathophysiologic basis for the use of recruitment maneuvers and recent evidence, as well as the practical application of the technique.     

Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses

Purpose

Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.

Methods

We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.

Results

We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)—44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.

Conclusions

There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses.     

To ventilate,oscillate, or cannulate?

Ventilatory management of acute respiratory distress syndrome has evolved significantly in the last few decades. The aims have shifted from optimal gas transfer without concern for iatrogenic risks to adequate gas transfer while minimizing lung injury. This change in focus, along with improved ventilator and multiorgan system management, has resulted in a significant improvement in patient outcomes. Despite this, a number of patients develop hypoxemic respiratory failure refractory to lung-protective ventilation (LPV). The intensivist then faces the dilemma of either persisting with LPV using adjuncts (neuromuscular blocking agents, prone positioning, recruitment maneuvers, inhaled nitric oxide, inhaled prostacyclin, steroids, and surfactant) or making a transition to rescue therapies such as high-frequency oscillatory ventilation (HFOV) and/or extracorporeal membrane oxygenation (ECMO) when both these modalities are at their disposal. The lack of quality evidence and potential harm reported in recent studies question the use of HFOV as a routine rescue option. Based on current literature, the role for venovenous (VV) ECMO is probably sequential as a salvage therapy to ensure ultraprotective ventilation in selected young patients with potentially reversible respiratory failure who fail LPV despite neuromuscular paralysis and prone ventilation. Given the risk profile and the economic impact, future research should identify the patients who benefit most from VV ECMO. These choices may be further influenced by the emerging novel extracorporeal carbon dioxide removal devices that can compliment LPV. Given the heterogeneity of acute respiratory distress syndrome, each of these modalities may play a role in an individual patient. Future studies comparing LPV, HFOV, and VV ECMO should not only focus on defining the patients who benefit most from each of these therapies but also consider long-term functional outcomes.     

High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]

Introduction

To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted.

Methods

Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up.

Results

The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22–2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43–3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI.

Conclusion

No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.     

Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome

OBJECTIVE: Both prone position and high-frequency oscillatory ventilation (HFOV) have the potential to facilitate lung recruitment, and their combined use could thus be synergetic on gas exchange. Keeping the lung open could also potentially be lung protective. The aim of this study was to compare physiologic and proinflammatory effects of HFOV, prone positioning, or their combination in severe acute respiratory distress syndrome (ARDS). DESIGN:: Prospective, comparative randomized study. SETTING: A medical intensive care unit. PATIENTS: Thirty-nine ARDS patients with a Pao2/Fio2 ratio <150 mm Hg at positive end-expiratory pressure > or =5 cm H2O. INTERVENTIONS: After 12 hrs on conventional lung-protective mechanical ventilation (tidal volume 6 mL/kg of ideal body weight, plateau pressure not exceeding the upper inflection point, and a maximum of 35 cm H2O; supine-CV), 39 patients were randomized to receive one of the following 12-hr periods: conventional lung-protective mechanical ventilation in prone position (prone-CV), HFOV in supine position (supine-HFOV), or HFOV in prone position (prone-HFOV). MEASUREMENTS AND MAIN RESULTS: Prone-CV (from 138 +/- 58 mm Hg to 217 +/- 110 mm Hg, p < .0001) and prone-HFOV (from 126 +/- 40 mm Hg to 227 +/- 64 mm Hg, p < 0.0001) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio (from 134 +/- 57 mm Hg to 138 +/- 48 mm Hg). The oxygenation index ({mean airway pressure x Fio2 x 100}/Pao2) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group. Interleukin-8 increased significantly in the bronchoalveolar lavage fluid (BALF) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV. Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group. CONCLUSIONS: Although HFOV in the supine position does not improve oxygenation or lung inflammation, the prone position increases oxygenation and reduces lung inflammation in ARDS patients. Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation. In contrast, supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation.     

Surfactant use based on the oxygenation response to lung recruitment during HFOV in VLBW infants

Purpose  

Early lung recruitment (ELR) during high-frequency oscillatory ventilation (HFOV) in combination with prophylactic surfactant use has been reported to reduce mortality, improve respiratory outcomes, and reduce the need for repeated surfactant dosing, suggesting that surfactant might be used more selectively in very low birth weight (VLBW) infants on HFOV than generally recommended. We report our first experience from such a selective early rescue use of surfactant in VLBW infants on HFOV.     

High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation

OBJECTIVE: The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High-frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position. DESIGN: Prospective, comparative randomized study. SETTING: A medical intensive care unit. PATIENTS: Forty-three ARDS patients with a Pao2/Fio2 ratio <150 at positive end-expiratory pressure > or =5 cm H2O. INTERVENTIONS: After an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (CV(prone)-CV(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CV(supine)-HFOV(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CV(prone)-HFOV(supine) group). MEASUREMENTS AND MAIN RESULTS: Pao2/Fio2 ratio was higher at the end of the study period in the CV(prone)-HFOV(supine) group than in the CV(prone)-CV(supine) group (p < .02). Venous admixture at the end of the study period was lower in the CV(prone)-HFOV(supine) group than in the two other groups. CONCLUSIONS: HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.