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Article Reviewed:

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

Esteban A, Alia I, Gordo F, et al., for the Lung Failure Collaborative Group

Chest. 2000;117(6):1690-1696. [abstract] [full-text for subscribers]

Reviewed by Andres Pelaez MD , Emory University School of Medicine. Pulmonary and Critical Care Medicine

Review posted January 20, 2003

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I. What is being studied?:

The study objective:

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

The study design:

Multicenter, randomized clinical trial in twelve medical-surgical ICUs located in tertiary-care hospitals.

The patients included:

One or more underlying disease processes that is known to be associated with ARDS, and diagnostic criteria for ARDS as defined by the American-European Consensus Conference (acute onset, bilateral chest radiographic infiltrates, pulmonary artery occlusion pressure < 18 mmHg or no evidence of left atrial hypertension, and PaO2/fraction of inspired oxygen [FiO2] ratio < 200 mmHg).

The patients excluded:

The patients excluded:

1. Age < 18 years old
2. Head injury
3. Coronary disease
4. Immunosuppression
5. Burns
6. Any barotraumas, e.g., pneumothorax, subcutaneous emphysema, etc.
7. Head injury
8. Pregnancy

79 patients were enrolled.

The interventions compared:

A ventilation strategy in which patients were randomly assigned to receive either VCV or PCV. VCV was always delivered with a square-wave inspiratory flow. For both groups, plateau inspiratory pressure was limited to < 35 cm H2O. PEEP and FIO2 were titrated to maintain an oxygen saturation of 89% to 92% with the least FIO2 and a PEEP level never < 5 cm H2O. Tidal volume (VT) was adjusted in the VCV or pressure in the PCV in an attempt to maintain PaCO2 at 35 to 45 mmHg, but hypercarbia was allowed if this target could not be achieved with a plateau pressure < 36 cmH2O. The maximum I/E ratio that was allowed was 3:1.

The outcomes evaluated:

Primary: In-hospital mortality.

Secondary: In-ICU mortality rate, the length of stay in the ICU and in the hospital, the appearance of barotraumas and the number of organ failures.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

A random number table was used, along with sealed envelopes designating the assignment; these were only opened when enrollment was assured. A block design was used based on trial site.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. Seventy-nine patients were included in the study, with 42 in the VCV group and 37 in the PCV group. The authors do not report any patients dropping out or being lost to follow-up.

Were patients analyzed in the groups to which they were randomized?

Yes. There were no crossovers.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

No. The ventilator mode (i.e., VCV vs. PCV) could not be blinded, particularly as adjustments to the ventilator in response to physiological variables such as compliance or gas exchange required specific adjustments in tidal volume (in the VCV group) or inspiratory pressure (in the PCV group).

4. Were the groups similar at the start of the trial?

Although patients were randomly assigned to the two groups in a blinded fashion, the randomization may have failed in this study as there was a higher percentage of patients with acute renal failure enrolled in the VCV group than in the PCV group (28% vs. 13%; p = 0.06) that nearly reached statistical significance. In addition, there was a trend toward a higher percentage of patients in the VCV group who had septic shock as a risk factor for ARDS (52% vs. 38%; p = 0.19). This turns out to be important because the authors ultimately concluded that patients in the VCV treatment group had a higher mortality rate because of a higher incidence of non-pulmonary organ failures such as renal failure (see below).

Therefore the failure of randomization for this critical variable at the start of the study a p value of 0.06 may not technically be significant but in this case one must question the validity of the results, since this may have played a role in the final results as the authors pointed out on their final conclusion.

5. Aside from the experimental intervention, were the groups treated equally?

The authors provide no specific details regarding uniformity of non-ventilator treatment of patients.

III. What were the results?

1. How large was the treatment effect?

The VCV group had significantly higher in-hospital mortality rates than patients in the PCV group (78% vs. 51%), respectively (the authors report the 95% confidence interval [CI] for the absolute difference between the groups as 4.3% to 50.1%, but it is not clear how this was calculated. The appropriate values are in the table below).

Measure of association	Result	95% confidence intervals
ARR	0.27	0.068 to 0.47
RRR	35%	8% to 54%
NNT	4	2 to 15

However, the presence of multiple organ failure (two or more non-pulmonary organ failures; OR 4.6, 95% CI 1.4, 15.4) and/or acute renal failure (OR 4.0, 95% CI 1.1, 14.3) were the only variables found to be independently associated with higher mortality on logistic regression, and, as discussed above, at the onset of the study there was a strong trend toward a higher incidence of renal failure in the VCV group.

2. How precise was the estimate of the treatment effect?

There was a difference in the primary outcome between the VCV and the PCV groups. However, the lower boundary reported for the 95% confidence interval (CI) for the RRR is just 8%, and this is probably not clinically significant, particularly in the setting of an unequal distribution of patients with renal failure and this was then found to be an independent risk factor for higher mortality.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Very unlikely. First, the square wave inspiratory flow used in the VCV group is not standard in the setting of ARDS. Further, one could reasonably argue that there is no significant difference between PCV and VCV with a decelerating inspiratory flow as long as one limits the plateau pressure to < 35 cm H2O. The original 'debate' regarding PCV vs. VCV in patients with ARDS began more than a decade ago when patients were typically ventilated with much higher plateau pressures, and therefore this study does not resolve that debate. At best, one could conclude (with great caution) that this study is at least consistent with the evolving view that the mode of ventilation may not be nearly as important as assiduous attention to preventing overdistension of the acutely injured lung. Supportive of this idea is that the plateau pressures in the two groups were not different and this may avoid overdistension due to an increased transpulmonary pressure.

Finally, the mortality rate in either group in this study is considerably higher than the mortality rate in either the control or treatment group in the ARDS Network study published two years ago (1). Even with these problems it is still not clear what caused the higher incidence of extrapulmonary organ failures, and therefore higher mortality, in those patients treated with VCV in this study.

2. Were all clinically important outcomes considered?

Yes. The primary outcome was in-hospital mortality but common and important morbidities such as barotrauma, other organ dysfunction, and length of stay were also considered.

3. Are the likely treatment benefits worth the potential harms and costs?

This question is not relevant to this study, as one cannot identify either a specific treatment benefit, or a specific treatment-related complication, for the ventilator modes that were studied.

For all of these reasons, with all the usual cautions about a "negative" study, this study failed to show a difference in mortality in PCV vs VCV when plateau pressures were similar.

References:

1. 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;342:1301-1308 [abstract]; PedsCCM EB Journal Club Review

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