The three patients we have presented in detail demonstrate responses of ARDS to a sustained course of ACS. In the first two patients, short ACS trials resulted in temporary, limited responses in clinical condition, oxygenation, and roentgenographic abnormalities which regressed when the dosage was reduced. Subsequently, longer therapeutic trials resulted in a resolution of these abnormalities. Prolonged unimproving cases of ARDS responded to sustained courses of ACS as in cases 1 and 3. Our experience, although limited and uncontrolled, suggests an important role for a sustained course of ACS in the treatment of selected ARDS patients with established disease. These observations enhance our perspective and understanding of ARDS and do not conflict with other published work.
The duration of the therapeutic dosage of ACS we utilized was designed to reverse the established inflammatory process of ARDS and in our patients, ACS worked effectively to achieve that goal. Reports which do not support the use of ACS have uniformly utilized treatment protocols which employ high dosages for short durations. Bernard and associates1 have clearly shown in scientifically exacting studies that the administration of ACS at a dose of 30 mg/kg over 24 hours given early in the course of ARDS has little effect on the outcome of ARDS. Bone and associates administered ACS over 24 hours, Weigelt et al studied ACS over 48 hours, Coffin et al chose to administer one dose, and others gave ACS over three days. In an experience similar to ours, Ashbaugh and Maier were able to demonstrate significant benefit with the use of ACS for periods of greater than three weeks. Dosage and duration of therapy are important variables which must be considered before dismissing any therapeutic drug as ineffective.
Our patient population differs from the population of studies not supporting the use of ACS. All of our patients had survived the primary or causative process, had persistent ARDS, and were free of obvious active infectious processes. If the primary process which produced ARDS cannot be controlled, therapy directed at ARDS, even if highly effective, cannot be expected to be more than a temporizing step in the course of events. Ashbaugh and Maier also successfully treated ARDS with ACS in patients who had established ARDS as their primary clinical problem. However, in reports of studies which did not demonstrate benefit from high dose, short duration therapy, the duration of ARDS before treatment was brief and the state of the process which initiated the ARDS is not mentioned. By treating only patients with established ARDS, we have selected those most likely to respond.
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We believe that our selection of patients with established ARDS for treatment with ACS does not provide a complete explanation for our findings. A study of the natural history of ARDS indicates progression of the primary or causative process occurs in one-fifth of all patients and results in one-third of all deaths within 72 hours. When this 20 percent of patients who died with ARDS within 72 hours is excluded, the remaining patients still have a 59 percent mortality (Table 2). This evidence suggests a substantial mortality for patients we have labeled as having established ARDS which is far in excess of the 20 percent we observed. Ashbaugh and Maier, treating established ARDS with sustained ACS, also observed a mortality rate of 20 percent. This experience and their report, both anecdotal in character, represent the only data available on patients with established ARDS treated with a sustained course of ACS.