Though there are no drugs to treat ARDS on the immediate horizon, the fact that the medical world has been able to cut the mortality rate roughly in half shows that its lethal nature can be somewhat contained, if not halted.

In the two and a half decades that Barry Fuchs has been practicing medicine, there have been “lots of ideas of potential therapeutic bullets that were going to make a difference in the lives of these patients who have ARDS,” he says. “But in reality all that has really fallen by the wayside. And at present the most remarkable advance in this field during the 20-25 years of my practice is just to change how we ventilate these patients. The new, life-saving ventilator practice is simply to turn down one of the dials to reduce the size of the breath that we give.”

Physicians refer to that as the “tidal volume,” and the gist of it is that less is often more. As much as oxygen is needed, too much of it can cause serious damage when forced into sick lungs. Back in the era when “generous tidal volumes” and often “multiple chest tubes” were used, says Fuchs, the ventilator used to be “associated with a much higher mortality than we see now.”

“I think of the ventilator as a medieval torture instrument,” says Daniel Brodie C’91, assistant professor of clinical medicine and co-director of the Center for Acute Respiratory Failure at New York Presbyterian-Columbia University Medical Center. Not that Brodie is denying the vital role of ventilators in patients with ALI and ARDS. “It’s like what Churchill said about democracy: It’s the worst form of government except all the others. The ventilator is the worst thing we can do to the lungs, except that we have no other choices. If somebody has respiratory failure, it’s life-saving—but it’s also doing all sorts of bad things.” Brodie is a cautious proponent of a device called ECMO, which stands for extracorporeal membrane oxygenator and acts as a kind of external lung (see “The Class of ECMO”). But it can only be used in certain circumstances.

It took roughly a quarter of a century, from the late 1960s to the early ’90s, for the medical world to conclude that putting people on ventilators at maximum tidal volume “was actually perpetuating the injury and sort of accelerating it,” notes Paul Lanken. The introduction of CAT scans made it clear that “what looked like the whiteout in the plain X-ray actually showed heterogeneity of those densities—so that there are some spots that were closed off and some spots that were open.” As a result, “the standard tidal volume didn’t go to a whole lung; it went to a small fraction of the lung, way over-inflated those alveoli, and damaged them. And those damaged alveoli released cytokines, which are biologically active molecules that go in the bloodstream and cause people to go into multi-organ system failure.”

The patient then goes into “what looks like septic shock,” Lanken adds. But unlike sepsis, “most of the time we can’t grow any organisms from their blood or find any source of infection.”

In the late 1990s an NIH-funded study compared the results of high tidal volume versus low tidal volume among 861 patients at sites across the country. The results were “highly significant,” notes Lanken (who was the principal investigator for the Philadelphia part): the mortality rate for low tidal volume was 22 percent lower than in patients receiving high tidal volume. “That was basically the first time in our country that we showed something made a difference.”

Another variation on the theme has been used in recent years: oscillators, which are essentially high-frequency ventilators.

“Imagine a big woofer hooked up to a ventilator, and you’re woofing away,” says Lanken, referring to the bass driver in a stereo speaker. “That’s what it is. Goes from 3.5 to 11 cycles per second. It defies conventional physiology because the woofed movement of the air is less than the dead space. It’s a new way of breathing for people. But it does produce the equivalent of extremely low tidal volumes. So the stretch of those lungs that are still open to air exchange is going to be the least.”

Oscillators have been used in nurseries for some 20 years, and have been approved for use in adults with ARDS for at least 10 years, Lanken notes. But the NIH, with its limited funds, has yet to approve any studies on its efficacy.

“It’s taken the Canadian government and a group of investigators in Canada to actually fund and coordinate this trial,” he says. “The ARDS Network went on to a Phase II trial that I wasn’t part of. But I am part of this oscillate clinical trial, and there’s 400 patients enrolled … So in two years we’ll see whether that is the same, better, or worse.”
 


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