Prospective Randomized Trial Comparing Pressure-Controlled Ventilation and Volume-Controlled Ventilation in ARDS

doi:10.1378/chest.117.6.1690

Chest

Volume 117, Issue 6, June 2000, Pages 1690-1696

https://doi.org/10.1378/chest.117.6.1690 Get rights and content

Study objectives

To compare in-hospital mortality of patients with ARDS ventilated with either pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV) with a square-wave inspiratory flow.

Design

Multicenter and randomized trial.

Setting

Twelve medical-surgical ICUs located in tertiary-care hospitals.

Patients

Seventy-nine patients having ARDS, as defined by the American-European Consensus Conference.

Interventions

Patients were randomly assigned to be ventilated with either PCV (n = 37) or VCV (n = 42). In both instances, inspiratory plateau pressure was limited to ≤ 35 cm H₂O.

Measurements and results

There were no significant differences among the studied groups at the moment of randomization, although there was a trend toward greater renal failure in patients assigned to VCV. Ventilatory settings and blood gases did not significantly differ over time between the two groups. Patients in the VCV group had both a significantly higher in-hospital mortality rate than those in the PCV group (78% vs 51%, respectively) and a higher number of extrapulmonary organ failures (median, 4 vs 2, respectively). The development of renal failure during the study period was also significantly more frequent among VCV patients (64% vs 32%, respectively). Multivariate analysis showed that factors independently associated with an increased mortality rate were the presence of two or more extrapulmonary organ failures (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.38 to 15.40) and acute renal failure (OR, 3.96; 95% CI, 1.10 to 14.28) but not the ventilatory mode used.

Conclusions

The increased number of extrapulmonary organ failures developed in patients of the VCV group was strongly associated with a higher mortality rate. The development of organ failures was probably not related to the ventilatory mode.

Section snippets

Patients

From February 1995 to January 1996, we enrolled patients at 12 ICUs in 12 tertiary-care hospitals. The study was approved by the institutional review board of each medical center, and informed consent was obtained from each patient or the patient's next of kin. The criteria for enrollment were as follows: (1) one or more underlying disease processes that are known to be associated with ARDS (sepsis, shock, pneumonia, multiple transfusions, pulmonary contusion, multiple fractures, gastric

Results

Seventy-nine patients with ARDS were enrolled in the study, 42 in the VCV group and 37 in the PCV group. There were no significant differences between the studied groups regarding clinical characteristics and risk factors for ARDS at the moment of randomization (Tables 1, 2), although a trend toward a higher rate of acute renal failure was observed in patients of the VCV group (Table 1), and there was also a tendency toward a higher percentage of patients with shock as a risk factor for ARDS in

Discussion

The main finding of this study was that, in patients with ARDS who require mechanical ventilation, the way in which mechanical ventilation is provided to deliberately reduce the inspiratory plateau pressure, by decreasing either Vt on VCV or inspiratory pressure on PCV, does not independently influence mortality. We also have found that the mortality of ARDS patients is strongly associated with the development of multiple organ failure, with especially those patients with acute renal failure

Appendix

Members of the Spanish Lung Failure Collaborative Group are: Juan A. Gomez-Rubí, MD, PhD (Hospital Virgen de la Arrixaca, Murcia); Santiago Macías, MD (Hospital General de Segovia, Segovia); Ana I. Ezpeleta, MD, PhD (Hospital General de Alicante, Alicante); Anselmo Gil, MD (Hospital del S.A.S., Jerez de la Frontera); Alfonso Bonet, MD (Hospital Dr. Josep Trueta, Girona); Demetrio Carriedo, MD (Hospital Virgen Blanca, León); José M. Allegue, MD (Hospital Nuestra Señora del Rosell, Cartagena);

References (28)

AS Slutsky
Mechanical ventilation: American College of Chest Physicians' Consensus Conference
Chest
(1993)
RC Bone et al.
Adult respiratory distress syndrome: sequence and importance of development of multiple organ failure
Chest
(1992)
P Kraft et al.
The acute respiratory distress syndrome: definitions, severity and clinical investigations
Intensive Care Med
(1996)
D Dreyfuss et al.
Ventilator-induced lung injury
JC Parker et al.
Mechanisms of ventilator-induced lung injury
Crit Care Med
(1993)
JJ Marini
Pressure-controlled ventilation
N Al-Sady et al.
Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation
Intensive Care Med
(1985)
RS Tharrat et al.
Pressure controlled inverse ratio ventilation in severe adult respiratory failure
Chest
(1998)
BW Armstrong et al.
Pressure-controlled inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome
Crit Care Med
(1995)
K Davis et al.
Comparison of volume control and pressure control ventilation: is flow waveform the difference?
J Trauma
(1996)

JJ Marini et al.

Re-targeting ventilatory objectives in adult respiratory distress syndrome: new treatment prospects-persistent question

Am Rev Respir Dis

(1992)

MR Lessard et al.

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)

SH Rappaport et al.

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure

Crit Care Med

(1994)

GR Bernard et al.

The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination

Am J Respir Crit Care Med

(1994)

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2022, Critical Care and Resuscitation
Background: Acute respiratory distress syndrome (ARDS) occurs commonly in intensive care units. The reported mortality rates in studies evaluating ARDS are highly variable.
Objective: To investigate mortality rates due to ARDS from before the 2009 H1N1 influenza pandemic began until the start of coronavirus disease 2019 (COVID-19) pandemic.
Design: We performed a systematic search and then ran a proportional meta-analysis for mortality. We ran our analysis in three ways: for randomised controlled trials only, for observational studies only, and for randomised controlled trials and observational studies combined.
Data sources: MEDLINE and Embase, using a highly sensitive criterion and limiting the search to studies published from January 2009 to December 2019.
Review methods: Two of us independently screened titles and abstracts to first identify studies and then complete full text reviews of selected studies. We assessed risk of bias using the Cochrane RoB-2 (a risk-of-bias tool for randomised trials) and the Cochrane ROBINS-1 (a risk-of-bias tool for non-randomised studies of interventions).
Results: We screened 5844 citations, of which 102 fully met our inclusion criteria. These included 34 randomised controlled trials and 68 observational studies, with a total of 24 158 patients. The weighted pooled mortality rate for all 102 studies published from 2009 to 2019 was 39.4% (95% CI, 37.0–41.8%). Mortality was higher in observational studies compared with randomised controlled trials (41.8% [95% CI, 38.9–44.8%] v 34.5% [95% CI, 30.6–38.5%]; P = 0.005).
Conclusions: Over the past decade, mortality rates due to ARDS were high. There is a clear distinction between mortality in observational studies and in randomised controlled trials. Future studies need to report mortality for different ARDS phenotypes and closely adhere to evidence-based medicine.
PROSPERO registration: CRD42020149712 (April 2020).
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We reanalyzed the relationship between CER and ATE by increasing the threshold for accuracy of CER prediction in RCTs with a primary mortality outcome to ± 10% and by extending the Bayesian hierarchical regression model to include all RCTs that reported a mortality outcome (vs only RCTs with mortality as a primary outcome). Primary outcomes were reported in 103 of the 150 ARDS RCTs (68.7%); 98 of these RCTs (95.1%) were superiority RCTs,11-16,32-122 and 5 RCTs (4.9%) had a primary safety outcome.123-127 Eighty-four superiority RCTs reported one or more data elements for sample size estimation or the predicted sample size.
Indeterminate randomized controlled trials (RCTs) in ARDS may arise from sample size misspecification, leading to abandonment of efficacious therapies.
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Only 84 of 150 RCTs (56.0%) reported sample size estimations. In RCTs with mortality as the primary outcome, CER was overestimated in 16 of 28 RCTs (57.1%). To achieve predicted ATE, interventions needed to prevent 40.8% of all deaths, compared with the original prediction of 29.3%. Absolute reduction in mortality ≥ 10% was observed in 5 of 28 RCTs (17.9%) but was predicted in 21 of 28 RCTs (75.0%). For RCTs with mortality as the primary outcome, no association was found between observed CER and observed ATE (pooled OR: β = –0.04; 95% credible interval, –0.18 to 0.09). We identified three interventions that are not currently standard of care with a Bayesian-averaged effect size of > 0.20 and moderate strength of existing evidence: corticosteroids, airway pressure release ventilation, and noninvasive ventilation.
Reporting of sample size estimations was inconsistent in ARDS RCTs, and misspecification of CER and ATE was common. Prognostic enrichment strategies in ARDS RCTs based on all-cause mortality are unlikely to be successful. Bayesian methods can be used to prioritize interventions for future effectiveness RCTs.
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The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021.
The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method.
Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO₂ (PaO₂) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D).
This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.
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Control-arm mortality varies between acute respiratory distress syndrome (ARDS) RCTs.
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^†: A complete list of the members of the Spanish Lung Failure Collaborative Group is located in the Appendix.

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Chest

Clinical Investigations in Critical CareProspective Randomized Trial Comparing Pressure-Controlled Ventilation and Volume-Controlled Ventilation in ARDS

Study objectives

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Section snippets

Patients

Results

Discussion

Appendix

Chest

Chest

The acute respiratory distress syndrome: definitions, severity and clinical investigations

Intensive Care Med

Ventilator-induced lung injury

Mechanisms of ventilator-induced lung injury

Crit Care Med

Pressure-controlled ventilation

Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation

Intensive Care Med

Pressure controlled inverse ratio ventilation in severe adult respiratory failure

Chest

Pressure-controlled inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome

Crit Care Med

Comparison of volume control and pressure control ventilation: is flow waveform the difference?

J Trauma

Re-targeting ventilatory objectives in adult respiratory distress syndrome: new treatment prospects-persistent question

Am Rev Respir Dis

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

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure

Crit Care Med

The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination

Am J Respir Crit Care Med

Clinical Investigations in Critical Care
Prospective Randomized Trial Comparing Pressure-Controlled Ventilation and Volume-Controlled Ventilation in ARDS