The Dethroning of 6 ml/kg as the “Go-To” Setting in Acute Respiratory Distress Syndrome

To the Editor:

In the latest of a succession of reanalyses of data from five randomized controlled trials (RCTs) of high versus low Vt in patients with acute respiratory distress syndrome, Goligher and colleagues conclude that clinicians should select Vt on the basis of distending pressure (plateau pressure minus positive end-expiratory pressure [PEEP]) rather than milliliter per kilogram (1). This is the same conclusion I reached when I editorialized on the publication of the ARDSNet RCT in 2000 (2). I recommended that Vt should be set to avoid the plateau pressure that discriminated between life and death (32 cm H₂O).

I pointed out that setting Vt in terms of milliliters per kilogram was misguided because it ignores the physiological variable (plateau pressure) that signals alveolar injury. I proffered the analogy of a patient with hypertension-associated stroke for which antihypertensive therapy is based solely on milligram dosage with disregard to changes in arterial pressure. The passage of time demonstrates that my writing was unpersuasive, and I apologize to patients for having failed them.

After the publication of the ARDSNet report, guidelines promoted the use of 6 ml/kg, although 6 ml/kg has never been shown to be superior to 11 ml/kg (or anything in between). Guidelines now recommend 4 ml/kg (3), which translates to an unnatural Vt of 280 ml for an average person.

In patients who are critically ill with inflamed lungs, sensory receptor stimulation produces heightened respiratory drive and dyspnea. Patients react by attempting deeper inspirations. When a low Vt setting impedes this response, intense dyspnea is guaranteed through corollary discharge from the medulla to the cerebral cortex—amplified by hypercapnia that accompanies hypoventilation (4).

Patients rebel against the racking constraint and buck the ventilator. To combat recalcitrance, pharmacological agents are administered to restrain patients on the Procrustean bed of 6 ml/kg. Sedative agents do not relieve air hunger, and neuromuscular blockade aggravates dyspnea by removing behavioral clues that alert caregivers to patient discomfort (4). For those of us caring for ventilated patients over the past four decades, it is disturbing to observe large doses of sedatives and paralyzing agents being administered nonchalantly—undoing the great strides in the 1980s–1990s to limit their use. It contravenes every physiological principle to employ unnaturally low Vts in patients with plateau pressures in the low 20s.

Cleaving to a physiological framework, Vt should be customized in terms of end-inspiratory alveolar volume. It has been known for decades that airway pressure after an end-inspiratory pause during control mechanical ventilation with a flow square wave provides a reasonable estimate of end-inspiratory alveolar volume (5).

Despite the temptation, it would be foolhardy to undertake an RCT based on one numerical pressure target (whether plateau pressure or plateau minus PEEP). Unlike the exactitude with which arterial oxygen tension can be measured with a Clark electrode, instrumentation for measuring respiratory pressure has lower fidelity (6). Technical limitations combined with biological variation in the elastic properties of the lungs and chest wall exceed the concreteness of one single number.

Several of Dr. Goligher’s coauthors are also authors on the recent guidelines (3). It would be beneficial to patients if they published a codicil advising physicians to no longer base Vt on the nonphysiological target of 6 ml/kg.