Toronto M.D.'s editorial in current issue of JAMA calls for a new approach to 'physiological-based' research
As more Canadians are diagnosed with H1N1 influenza infection, some will be admitted to hospital. The most severely affected may be treated in the intensive care unit (ICU) and placed on a mechanical ventilator to help them breathe while they recover from the infection.
While mechanical ventilation clearly saves the lives of many people felled by serious illness, in some cases, this supportive measure has been known to damage the lungs, says Dr. Arthur S. Slutsky, a scientist at St. Michael's Hospital in Toronto.
"In clinicians' previous zeal to maintain relatively normal blood gas values, they have ventilated patients using relatively large tidal volumes," Dr. Slutsky explains. "They also tended to ventilate patients in the supine position-that is, while they lay on their backs."
("Tidal volume" refers to the normal volume of air displaced in the lungs between normal inhalation and exhalation when extra effort is not applied. Other studies have found that lowering tidal volumes decreases mortality rates in ventilated patients.)
"Ventilation is what we call a physiological-based treatment," he explains. "We look at the patient's current physiological state, then devise and use treatments aimed at altering this state, hoping the change will translate into recovery."
In the case of severe H1N1 infection of the lungs, patients can develop severe hypoxemia-an abnormally low amount of oxygen in the arterial blood which is the major result of respiratory failure.
In an editorial published this week in the Journal of the American Medical Association (JAMA), Dr. Slutsky comments on new research published by Fabio S. Taccone and colleagues from the University of Milan in Milan, Italy.
The researchers looked at whether patients with Acute Respiratory Distress Syndrome (ARDS) who were mechanically ventilated in the prone position (lying on their stomachs) did better than patients ventilated while they were supine (lying on their backs), as is the standard approach. As in other studies of this physiological-based treatment, blood oxygen levels increased in the prone treatment group. But in the end, the mortality rate among these patients was not statistically different from that of the control group.
In his editorial, Dr. Slutsky asks the following question: "Today, 35 years after prone ventilation was suggested and after hundreds of articles have been published, including more than 150 review articles and more than 10 meta-analyses, why are more definitive conclusions about prone ventilation not available?"
Unfortunately, he says, very few large companies have a commercial interest in this type of intervention-for example, changing a ventilated patient from a supine to a prone position. This explains why funding for such research is hard to obtain and why clear answers about the usefulness of physiological interventions are often lacking.
In this regard, prone ventilation is similar to other physiologically-based interventions for which the effect on important clinical outcomes has not been conclusively proven. In some cases, these physiological "fixes" do not always work as planned-interventions that improve one physiological value may actually worsen another.
In his editorial, Dr. Slutsky says that basing treatments strictly on physiological endpoints-in this case, increasing oxygenation in the blood by mechanically increasing volumes of air in the lungs and changing patients' position during treatment-is "seductive" for several reasons:
- In many ways, the intensive care unit is a physiology laboratory in which patients' vital signs and other functions are monitored and treated around the clock, seven days a week. By explaining why a patient has a physiological abnormality such as a decrease in oxygenation or worsening kidney function, these measurements can suggest therapies to correct the abnormal physiology.
- Many physiological interventions can be quickly instituted and monitored at the bedside. They are usually relatively inexpensive or seen as "free," which makes them attractive and easy to implement.
"But while physiological insights developed at the bedside have led to important, lifesaving therapies, it's been difficult to obtain convincing proof of better clinical outcomes for many such interventions," Dr. Slutsky says.
One solution would be to design large, simple, generalizable trials undertaken by a large global network of investigators. "The time for this may be especially opportune because the world's critical care community is coalescing around an initiative to perform large-scale clinical trials to rapidly address the potential H1N1 pandemic," he says, adding that such trials are necessary to "separate fact from seduction."
Dr. Art Slutsky is a researcher in the Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Professor of Medicine, Surgery and Biomedical Engineering at the University of Toronto. He is also Director of the Interdepartmental Division of Critical Care Medicine, University of Toronto.