In the Cards was ARDS
(How We Discovered the Acute Respiratory Distress Syndrome)

THOMAS L. PETTY

Division of Pulmonary Science and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado; and Rush-Presbyterian/St. Lukes Medical Center, Chicago, Illinois

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My offer to join the faculty of the University of Colorado was $2,500 to buy blood gas equipment and a 250 square foot "laboratory" with a sink and running water. I have a vivid recollection of that Saturday in August of 1964 when I finally mastered the Clark PO₂ and Severinghaus CO₂ electrodes, which came with my new Radiometer blood gas equipment. Earlier I had learned the Astrup tonometric method for calculation of PCO₂, the pH electrode, and used an American Optical oximeter for oxygen saturation in arterial blood gas analysis. This was less than 2 months after I completed my Chief Residency year, following my pulmonary fellowship. Dave G. Ashbaugh was Chief Surgical Resident at the same time I was Chief Medical Resident. We were both frustrated over our inability to deal with the problems of acute respiratory failure that we occasionally encountered. The inadequate ventilators, including the Drinker tank negative pressure machine and the Bird, and Bennett IPPB machines were all that we had to use in our early attempts at treating acute respiratory failure. We desperately needed blood gas measurements to be able to monitor what we were doing. I finally was convinced that I could do them. As I walked home that day, I was kicking a stone and singing, "I can do blood gasses, tee-hee, tee hee." What a thrill!

My first assignment after I joined the faculty as a young Assistant Professor, was to develop a Respiratory Care Service for the new Colorado General Hospital, which was to open in early 1965. We had no respiratory therapists. Tanks of oxygen for bedside use were delivered by Central Supply by an "Oxygen Orderly." Dave, and two fellows, Bernie E. Levine and D. Boyd Bigelow, joined me as we launched our Respiratory Care Service. On the night that Barry Goldwater accepted the Republican nomination, we received our first call. A patient with emphysema, Earl, was admitted via the Emergency Room to the Medical Intensive Care Unit with advanced COPD and acute respiratory failure. Dave did the tracheostomy while Boyd and Bernie put old Earl on the Bird Mark-VII. I ran the blood gases all night long. Earl recovered, and we were never the same again.

Later that fall, as we tried to mobilize all available resources, Dave found an old 1954 model of the Engstrom anesthesia/ventilator unit in storage. We both read the instructions and still wondered what the "expiratory retard control" on the exhalation manifold meant. One night, Dave was called to the Surgical Intensive Care Unit to take care of a motor vehicle accident victim, who had bilateral symmetrical pulmonary infiltrates, and stiff lungs. The patient could not be adequately ventilated by either the Bird or the Bennett pressure-cycled machines. In desperation, Dave tried the Engstrom. It was a volume-controlled respirator with high inflation pressure capability. As a gesture, Dave set an end-expiratory pressure of 10 cm H₂O when it became impossible to achieve adequate arterial oxygenation. The blood gases that I did that night showed marked improvement in oxygenation with that maneuver. The patient died 48 hours later of progressive hypoxemia. At autopsy, both lungs had the consistency of liver, and each weighed nearly 1,000 grams.

We moved from Colorado General Hospital to a new University Hospital on February 23, 1965. By prior agreement with the Department Chairman, the late Gordon Meiklejohn, I was given a generous laboratory space next door to the 12-bed Medical Intensive Care Unit, and immediately above the Surgical Unit. This is where I moved my Radiometer blood gas equipment and all of our respirators. On this day, we began to make morning rounds at 7:30 in both the Medical and the Surgical Intensive Care Units. Louise M. Nett, R.N., joined the team as the Respiratory Nurse. Susie Tyler was now running blood gases during the daytime, but the fellows did them at night. Dave, the fellows, Louise, Susie, and I, discussed the clinical and physiological features of each patient who was receiving mechanical ventilation at the end of rounds each day in "the lab."

Dave and I had other similar patients that we could not ventilate due to stiff lungs with the pressure-cycled devices that were more available than the Engstrom. Dave liked to use the Engstrom in the postoperative period, following open heart surgery. Thus, the Engstrom was not often available for other use.

Shortly after Michael M. Finigan joined us as a first-year fellow in 1965, he was taking care of a patient with acute hemorrhagic pancreatitis, located next door to the Respiratory Care Laboratory. This patient could not be adequately oxygenated. Mike came and got me. We had just cleaned the Engstrom tubing, and it was available in "the lab." I helped Mike use the Engstrom for the first time in his training. "What does this knob do?" Mike asked. I said, "I think it is probably useful, since Dave could improve oxygenation in a crushed chest patient a few months ago." I then dialed in a positive end-expiratory pressure of 10 cm (at that time, we called this continuous positive pressure breathing, CPPB). It was dramatic to see a blue patient lying in Trendelenburg, gradually flush to a healthy pink color; blood pressure improved. We stood there amazed. "We need another gas to see what's going on." I said to Mike who was astonished over the sudden color change in this desperately ill woman. The PO₂ had increased from 44 to 125 with that simple end-expiratory maneuver. After standing there for about another thirty minutes, we decided to turn the end-expiratory pressure off. Once again, the patient turned blue, and her PO₂ dropped to 45. With reinstitution of end- expiratory pressure, the PO₂ again rose to 135. After three more days, this patient died of refractory hypoxemia and hypercarbia. Autopsy also revealed heavy lungs and alveolar debris and hyaline membrane formation. Bernie Levine, who had learned the method of measuring surface tension of the foamy fluid expressed from the lungs, found markedly elevated surface tension, indicating a deficiency in surfactant. Later, a second specimen showed the same surfactant abnormalities.

A few days later, one cold Saturday morning, I remember walking across the parking lot between the New Colorado General Hospital and the Veterans Administration Hospital, and talking with Dave. We talked about this new patient and his original patient with traumatic injury when he first used the Engstrom respiratory and positive end-expiratory pressure. "Something" is different with these patients, we said. Later over coffee, we concluded that the common denominator was sudden diffuse, and usually symmetrical, pulmonary infiltrates following a variety of seemingly unrelated lung insults, stiff lungs, and marked difficulties with oxygenation.

The first patient with this same clinical picture who survived was a 15-year-old adolescent who suffered hemorrhagic shock following a motor vehicle accident. Like the first two patients, his chest X-ray showed diffuse, bilateral symmetrical pulmonary infiltrates. The ventilator's inflation pressure was high (i.e., 40 to 50 cm H₂O). Arterial PO₂ was dramatically increased with positive end-expiratory pressure. Soon we had 12 similar patients from a total of 272 adult patients who required mechanical ventilation from all causes of acute respiratory failure since the start of our new Respiratory Care Service. These 12 patients all had massive acute lung injury from trauma, shock, presumed viral pneumonia, or hemorrhagic pancreatitis. High inflation pressures were required to ventilate lungs that were densely consolidated in a symmetrical fashion. End-expiratory pressure usually improved the oxygen transfer across the lungs. All of the patients who died had hyaline membrane formation. The five patients who survived made a full or near-full recovery.

On another Saturday morning, Dave and I sat in the lab with the fellows and asked ourselves again what was different about these patients with acute respiratory failure, compared with the other patients who required mechanical ventilation. Because of the marked resemblance of our patients with the infantile respiratory distress syndrome, we wrote up our experience of 12 patients with five survivors and proudly submitted the paper to the New England Journal of Medicine. Since Dave had made the first observation about the value of end-expiratory pressures in improving oxygenation, it was agreed that he should be first author on the manuscript. Our report came back very quickly with the scathing criticism that end-expiratory pressure had been proven to impair cardiac output by causing a reduction in venous return. "What were the idiots in Denver doing, anyway," was implied. We then sent the paper to the Journal of the American Medical Association and got an identical response. It had to be the same reviewers. Dave then got angry and sent the paper to the American Journal of Surgery, being confident that surgeons would appreciate our discovery and the concept of the acute respiratory distress syndrome. It also bounced! Finally, in desperation, we sent the paper to the Lancet, and received word within two weeks that our discovery was of such importance, that it would be published as a lead article, without delay (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE: Acute respiratory distress in adults Lancet 1967;2:319-323). It is impossible to exaggerate the thrill we felt when our first paper on ARDS was accepted.

The timing of this publication was extremely fortunate, because our article was read by military surgeons in Southeast Asia treating casualties in the Vietnam war. Quickly, the surgeons led by Ben Eiseman of our faculty (a Rear Admiral in the Naval Reserve organization) planned a conference in acute lung injury. This was held in Washington D.C. in May, 1968. It was sponsored by the National Science Foundation and the National Research Council on "The Pulmonary Effects of Nonthoracic Trauma." Dave, Henning Pontoppiadan from Boston, and I were among the few civilians at the meeting. Here, I presented our further results in the treatment of a series of 21 patients with ARDS and the anecdotal use of PEEP. Ten of 14 had survived with PEEP, compared with only 2 of 7 who had been treated before we had learned about the effectiveness of PEEP in improving arterial oxygenation in patients with acute lung injury. Alas, this was not a proper clinical trial. We were never willing to treat ARDS patients without PEEP, in view of this experience. To date, no controlled clinical trials have ever been done to learn if PEEP improves survival. I doubt if one will ever be proposed as I once did (Am Rev Respir Dis 1988;138:475-478).

Of course, we were lucky. We were at the right place at the right time. We had modern blood gas technology right next to the patients. We often did arterial blood gases ourselves. We wondered what was different about these patients compared with the usual causes of acute respiratory failure in COPD, pneumonia, in the post-operative period, asthma, and neurological conditions. We were not bound by conventional thinking in those days. We challenged dogma and flew by the seat of our pants. As physicians and surgeons, we worked together, like in the old tuberculosis era. That's why the cards played out ARDS.

	Footnotes

Correspondence and requests for reprints should be addressed to Thomas L. Petty, Clinical Research, 1850 High Street, Denver, CO 80218.