CHEST
editorials VOLUME 101 / NUMBER 3 / MARCH, 1992
The Changing Medical World Xademically sophisticated scientific assemblies are annual features of European societies of pulrnonology and cardiology. This year their congresses attracted 4,000 pulmonologists and 8,000 cardiovascular specialists, respectively. More than 30 percent of the manuscripts submitted to Chest for publication arrive from European investigators, and similar figures are reported by journals such as the New England Journal of Medicine and other scholarly publications. Superb studies emanate from medical institutions in Japan , Taiwan and other Oriental countries. These observations reflect profound changes in the quality and quantity of teaching, research , and clinical care in countries outside the United States and Canada. In some instances, these changes resulted from a new level of financial security (and in some instances, prosperity) which has made possible the increase in basic and clinical research . So precipitous have these changes been that many American physicians are not yet aware of the altered medical scene. The uninitiated may be startled to find that many ofhislher colleagues now find it necessary to attend congresses overseas as well as meetings held in the United States and Canada. These changes offer both a challenge and an opportunity for American and Canadian physicians. The medical community is challenged to maintain or
improve financial support for basic and clinical research . Unfortunately, the tendency has been the reverse . We should be greatly concerned about the recent lack of support for such investigations. The opportunities reside in the potential for joining with our colleagues overseas in collaborative projects in clinical investigation, as well as in continuing medical education. How has the American College of Chest Physicians responded to the "new medical world "? The changes cited above are indeed reflected by the increasingly large number of excellent studies from Europe and the Orient (as well as selected centers in Mexico and South America) which have been offered to our readership in the pages of Chest . Nearly 2,000 manuscripts were received in these editorial offices in the past 12 months, and this significant increase is indicative of the intellectual medical ferment overseas. We were happy to welcome scientists from all over the world at the recent Annual ACCP Scientific Assembly held in San Francisco. More than 32 countries were represented by officers seated on the dais at our annual Convocation. Regional ACCP congresses will be held in Seoul , South Korea, October 4-7, 1992 and future congresses are to be presented in Mexico and South America. The XVII World Congress on Diseases of the Chest, sponsored by the American College of Chest Physicians (and its overseas affiliate ,
ACCP officials from 32 countries participate in Convocation at 57th Annual ACCP Scientific Assembl y, San Francisco. November 5, 1991. CHEST I 101 I 3 I MARCH. 1992
593
The International Academy of Chest Physicians and Surgeons) will be presented in Amsterdam, June 1318, 1993. Once again, our World Congresses will serve as emphasis that this College considers "the world is our classroom." We believe that the age of "medical educational paternalism" is over. In addition to sharing with our colleagues overseas our recent research and education programs, we are eager to learn from them, via their own projects, programs, and publications. Many American and Canadian ACCP members will plan to go to the international regional congresses and the World Congress cited in this communication. We hope in turn to welcome our overseas friends to the Annual Scientific Assembly to be presented in Chicago in October 25-29, 1992 and to the assemblies in the years that follow: Alfred Soffer, M.D., F.C.C.R
Northbrook, Illinois
Sepsis and Coagulation An Important Link It has been more than 20 years since coagulation abnormalities were first reported in patients with sepsis and its sequelae.P Only now, however, are we beginning to understand how these abnormalities develop-and what can be done to counteract them. In this issue of Chest (see page 816), Fourrier et al extend our knowledge by reporting sequential measurements of antithrombin III, protein C, and protein S in patients with severe septic shock. These authors also assessed the impact of disseminated intravascular coagulation (DIC) on other types of organ dysfunction and on mortality in this population of patients. Fourrier et al examined 60 consecutive patients with severe septic shock, 44 of whom were found to have DIC. Mortality was 77 percent in the patients with DIC, but only 32 percent in the 16 patients without DIC. Patients with DIC had markedly higher blood lactate and transaminase (SCOT and SCPT) levels than did patients without DIC. Not surprisingly, nonsurvivors (with or without DIC) had significantly lower PaO/FIo2 ratios than did survivors." however, these ratios tended to be lower in nonsurvivors without DIC than in nonsurvivors with DIC. All but two patients with DIC had significantly decreased initial antithrombin III and protein C levels. In 16 DIC patients, these levels were assessed daily for 10 days; in survivors, they progressively improved, but they remained depressed in nonsurvivors. An initial antithrombin III level below 50 percent of normal had a 96 percent sensitivity and 76 percent specificity in predicting a fatal outcome. Protein S 594
Table I-Agents That May Modulate Coagulation in Patients with Sepsis a-Antitrypsin Pittsburgh Antithrombin III Aprotinin Bradykinin antagonists C l-esterase inhibitor Cyclo-oxygenase inhibitors Hirudin Monoclonal antibodies to contact factors Monoclonal antibodies to phospholipase ~ Plasminogen activators Platelet-activating factor receptor antagonists Prostaglandin 12 Protein C Soybean trypsin inhibitor Thrombomodulin Thromboxane receptor blockers Thromboxane synthetase inhibitors
levels were similar in survivors and nonsurvivors. Other researchers have demonstrated similar results. For example, decreased antithrombin III levels have been found in patients with sepsis," septic shock.v" sepsis-induced ARDS,7 and meningococcal septicemia.v" Depressed protein C levels have been associated with sepsis," sepsis-induced acute lung injury," and meningococcal septicemia." Most of these studies measured only initial values, however. By assaying antithrombin III and protein C levels for ten days, Fourrier et al3 have provided us with a partial look at how the body can fail to reestablish homeostasis in patients with severe septic shock. Although these results are important, they must be interpreted with caution. First, by definition, these authors included patients in their study only if septic shock was sufficiently severe to require treatment with vasoactive drugs for at least 12 h. It would have been interesting to measure antithrombin III and protein C levels at the onset of shock-or even earlier. Second, the incidence of DIC in this study (73 percent) is markedly higher than the incidence found in the other recent studies of patients with sepsis. For example, in the HA-IA trial, the incidence of DIe was approximately 20 percent," in the E5 trial, it was about 16 percent. 12 This discrepancy may result from the fact that Fourrier et al examined patients who were more severely ill than were those in the monoclonal antibody trials, which were designed to identify patients in the early stages of sepsis. One indication of disease severity in this study is that all 60 patients required mechanical ventilation. In a study my colleagues and I did several years ago, 13 we found full-blown DIC in 7 of 30 consecutive patients with adult respiratory distress syndrome, and profound thrombocytopenia in another 12 patients. Thus, a 73 percent incidence of DIC is remarkable in a population with severe sepsis and respiratory failure. Editorials
editorials VOLUME 101 / NUMBER 3 / MARCH, 1992
The Changing Medical World Xademically sophisticated scientific assemblies are annual features of European societies of pulrnonology and cardiology. This year their congresses attracted 4,000 pulmonologists and 8,000 cardiovascular specialists, respectively. More than 30 percent of the manuscripts submitted to Chest for publication arrive from European investigators, and similar figures are reported by journals such as the New England Journal of Medicine and other scholarly publications. Superb studies emanate from medical institutions in Japan , Taiwan and other Oriental countries. These observations reflect profound changes in the quality and quantity of teaching, research , and clinical care in countries outside the United States and Canada. In some instances, these changes resulted from a new level of financial security (and in some instances, prosperity) which has made possible the increase in basic and clinical research . So precipitous have these changes been that many American physicians are not yet aware of the altered medical scene. The uninitiated may be startled to find that many ofhislher colleagues now find it necessary to attend congresses overseas as well as meetings held in the United States and Canada. These changes offer both a challenge and an opportunity for American and Canadian physicians. The medical community is challenged to maintain or
improve financial support for basic and clinical research . Unfortunately, the tendency has been the reverse . We should be greatly concerned about the recent lack of support for such investigations. The opportunities reside in the potential for joining with our colleagues overseas in collaborative projects in clinical investigation, as well as in continuing medical education. How has the American College of Chest Physicians responded to the "new medical world "? The changes cited above are indeed reflected by the increasingly large number of excellent studies from Europe and the Orient (as well as selected centers in Mexico and South America) which have been offered to our readership in the pages of Chest . Nearly 2,000 manuscripts were received in these editorial offices in the past 12 months, and this significant increase is indicative of the intellectual medical ferment overseas. We were happy to welcome scientists from all over the world at the recent Annual ACCP Scientific Assembly held in San Francisco. More than 32 countries were represented by officers seated on the dais at our annual Convocation. Regional ACCP congresses will be held in Seoul , South Korea, October 4-7, 1992 and future congresses are to be presented in Mexico and South America. The XVII World Congress on Diseases of the Chest, sponsored by the American College of Chest Physicians (and its overseas affiliate ,
ACCP officials from 32 countries participate in Convocation at 57th Annual ACCP Scientific Assembl y, San Francisco. November 5, 1991. CHEST I 101 I 3 I MARCH. 1992
593
The International Academy of Chest Physicians and Surgeons) will be presented in Amsterdam, June 1318, 1993. Once again, our World Congresses will serve as emphasis that this College considers "the world is our classroom." We believe that the age of "medical educational paternalism" is over. In addition to sharing with our colleagues overseas our recent research and education programs, we are eager to learn from them, via their own projects, programs, and publications. Many American and Canadian ACCP members will plan to go to the international regional congresses and the World Congress cited in this communication. We hope in turn to welcome our overseas friends to the Annual Scientific Assembly to be presented in Chicago in October 25-29, 1992 and to the assemblies in the years that follow: Alfred Soffer, M.D., F.C.C.R
Northbrook, Illinois
Sepsis and Coagulation An Important Link It has been more than 20 years since coagulation abnormalities were first reported in patients with sepsis and its sequelae.P Only now, however, are we beginning to understand how these abnormalities develop-and what can be done to counteract them. In this issue of Chest (see page 816), Fourrier et al extend our knowledge by reporting sequential measurements of antithrombin III, protein C, and protein S in patients with severe septic shock. These authors also assessed the impact of disseminated intravascular coagulation (DIC) on other types of organ dysfunction and on mortality in this population of patients. Fourrier et al examined 60 consecutive patients with severe septic shock, 44 of whom were found to have DIC. Mortality was 77 percent in the patients with DIC, but only 32 percent in the 16 patients without DIC. Patients with DIC had markedly higher blood lactate and transaminase (SCOT and SCPT) levels than did patients without DIC. Not surprisingly, nonsurvivors (with or without DIC) had significantly lower PaO/FIo2 ratios than did survivors." however, these ratios tended to be lower in nonsurvivors without DIC than in nonsurvivors with DIC. All but two patients with DIC had significantly decreased initial antithrombin III and protein C levels. In 16 DIC patients, these levels were assessed daily for 10 days; in survivors, they progressively improved, but they remained depressed in nonsurvivors. An initial antithrombin III level below 50 percent of normal had a 96 percent sensitivity and 76 percent specificity in predicting a fatal outcome. Protein S 594
Table I-Agents That May Modulate Coagulation in Patients with Sepsis a-Antitrypsin Pittsburgh Antithrombin III Aprotinin Bradykinin antagonists C l-esterase inhibitor Cyclo-oxygenase inhibitors Hirudin Monoclonal antibodies to contact factors Monoclonal antibodies to phospholipase ~ Plasminogen activators Platelet-activating factor receptor antagonists Prostaglandin 12 Protein C Soybean trypsin inhibitor Thrombomodulin Thromboxane receptor blockers Thromboxane synthetase inhibitors
levels were similar in survivors and nonsurvivors. Other researchers have demonstrated similar results. For example, decreased antithrombin III levels have been found in patients with sepsis," septic shock.v" sepsis-induced ARDS,7 and meningococcal septicemia.v" Depressed protein C levels have been associated with sepsis," sepsis-induced acute lung injury," and meningococcal septicemia." Most of these studies measured only initial values, however. By assaying antithrombin III and protein C levels for ten days, Fourrier et al3 have provided us with a partial look at how the body can fail to reestablish homeostasis in patients with severe septic shock. Although these results are important, they must be interpreted with caution. First, by definition, these authors included patients in their study only if septic shock was sufficiently severe to require treatment with vasoactive drugs for at least 12 h. It would have been interesting to measure antithrombin III and protein C levels at the onset of shock-or even earlier. Second, the incidence of DIC in this study (73 percent) is markedly higher than the incidence found in the other recent studies of patients with sepsis. For example, in the HA-IA trial, the incidence of DIe was approximately 20 percent," in the E5 trial, it was about 16 percent. 12 This discrepancy may result from the fact that Fourrier et al examined patients who were more severely ill than were those in the monoclonal antibody trials, which were designed to identify patients in the early stages of sepsis. One indication of disease severity in this study is that all 60 patients required mechanical ventilation. In a study my colleagues and I did several years ago, 13 we found full-blown DIC in 7 of 30 consecutive patients with adult respiratory distress syndrome, and profound thrombocytopenia in another 12 patients. Thus, a 73 percent incidence of DIC is remarkable in a population with severe sepsis and respiratory failure. Editorials
