Incidence of ARDS in an Adult Population of Northeast Ohio* Alejandro C. Arroliga, MD, FCCP; Ziad W. Ghamra, MD; Alejandro Perez Trepichio, MD; Patricia Perez Trepichio, RRT; John J. Komara Jr., BA, RRT; Andre Smith, MD; and Herbert P. Wiedemann, MD, FCCP Study objectives: To assess the incidence of the ARDS in a well-defined adult population. Design: Kaiser Permanente of northeast Ohio, a health maintenance organization, uses the Cleveland Clinic Foundation as its only tertiary care center. In an ongoing prospective assessment in the Cleveland Clinic ICUs, we identified adult Kaiser Permanente patients with ARDS between 1996 and 1999. ARDS was defined according to the 1994 American-European Consensus Conference criteria. The denominator in the incidence calculation was the adult members of Kaiser Permanente of each year of the study period, and the numerator was the new adult ARDS patients in this particular year. The cause of ARDS, the mortality, and the cause of death were retrospectively identified, as well as other characteristics of the study population. Results: ARDS was diagnosed in 66 patients during the 3-year study period. The incidence per 100,000 population was 11.4 in 1996, 19.8 in 1997, and 14.4 in 1998; the overall incidence was 15.3/100,000/yr. The mean PaO 2 /fraction of inspired oxygen ( SD) was 110.8 37.8, the mean APACHE II was 23.4 6.9, and the mean ICU stay was 12.0 9.5 days. The most common cause of ARDS was direct lung injury (75.8%), and the most common cause of death was septic shock (53.8%). Conclusion: The incidence of ARDS in an adult population in northeast Ohio was 15.3/ 100,000/yr, a number that is slightly higher but comparable to recent estimates reported by other researchers. (CHEST 2002; 121:1972 1976) Key words: ARDS; epidemiology; etiology; ICUs; incidence; mortality Abbreviations: AECC American-European Consensus Conference; Fio 2 fraction of inspired oxygen; HMO health maintenance organization; MICU medical ICU The ARDS is characterized by increased permeability of the pulmonary capillaries and the alveolar epithelium, which results in hypoxemia relatively refractory to oxygenation, decreased lung compliance, and diffuse bilateral alveolar infiltrates on the chest radiograph. Since ARDS was first described 30 years ago, 1 estimates of its incidence have varied considerably, in part because of the absence of a unifying clinical definition and differences in study designs. *From the Department of Pulmonary and Critical Care Medicine (Drs. Arroliga and Wiedemann, Ms. Perez Trepichio, and Mr. Komara), and the Division of Medicine (Dr. Ghamra), The Cleveland Clinic Foundation; Department of Medicine (Dr. Perez Trepichio), Cleveland Clinic Foundation, Weston, FL; and Ohio Permanente Pulmonary Medicine (Dr. Smith), Cleveland, OH. Manuscript received January 30, 2001; revision accepted January 10, 2002. Correspondence to: Alejandro C. Arroliga, MD, FCCP, Head, Section of Critical Care Medicine, 9500 Euclid Ave, G-62, Cleveland, OH, 44195; e-mail: arrolia@ccf.org The initial National Heart and Lung Institute incidence report of 75/100,000 was only an estimate. 2 Subsequent studies had incidence values in the range of 1.5 to 8.5/100,000, 3 6 but most had difficulty defining the study population, with the exception of the Canary Islands report by Villar and Slutsky. 4 A Scandinavian study 7 used the 1994 American-European Consensus Conference (AECC) definition and reported an incidence of 13.5/100,000/yr; preliminary data from the University of Washington in Seattle 8 found a comparable incidence of 12.6/100,000 for the year 1997. Our purpose was to identify all new cases of ARDS diagnosed with the AECC criteria in a well-defined adult population ( 18 years old) of a northeast Ohio health maintenance organization (HMO) over a period of 3 years. We also report the suspected ARDS cause, the mortality, and the causes of death as well as other characteristics of the study population. 1972 Clinical Investigations in Critical Care
Materials and Methods Case Definition and Population at Risk This is a retrospective observational study of a cohort of patients admitted to the medical ICU (MICU), the surgical ICU, and the neurosurgical ICU at the Cleveland Clinic Foundation from April 1996 to March 1999. We reported only patients from the population of Kaiser Permanente, an HMO in northeast Ohio. The population at risk was the adult members of this HMO. The organization administrative office provided population size data for the years 1996, 1997, and 1998. The Cleveland Clinic Foundation is the tertiary care center for the Kaiser Permanente system of northeast Ohio; all critically ill members are admitted or transferred there for ICU care. During the study period, ARDS was diagnosed according to the 1994 AECC criteria: bilateral infiltrates on chest radiograph (as determined by the independent evaluation of a chest radiologist and a critical care physician), Pao 2 /fraction of inspired oxygen (Fio 2 ) 200 mm Hg, and a pulmonary artery wedge pressure of 18 mm Hg or no clinical evidence of elevated left atrial pressure. 9 For the MICU patients, all data were collected prospectively in the first 72 h after hospital admission and entered in a database that is kept by two research coordinators. The prospective screening of all MICU admissions is part of the involvement of our center in the National Institutes of Health ARDS network. 10 Patients admitted to the surgical and neurosurgical ICUs were also identified and their information collected. Only patients 18 years old and meeting strict ARDS criteria were included. Incidence The yearly incidence of ARDS was calculated with the numerator being the new cases of ARDS in adults from April in a specific year to March of the next year and the denominator being the HMO adult population in December of the years 1996, 1997, and 1998. For easier comparison with prior studies, we also calculated the ARDS incidence using the new ARDS cases in adults as a numerator but with the total population enrolled in the HMO as a denominator. Etiology and Outcome We retrospectively reviewed the medical records to identify the major associated clinical condition at the time that ARDS criteria were met. The clinical disorders included direct lung injury (both pneumonia and aspiration) and indirect lung injury (sepsis, multiple transfusions, drug overdose, and multiple trauma). Pneumonia was defined as the clinical, radiologic, and laboratory evidence of a primary lung infection. Aspiration of gastric contents was identified through direct reporting of medical personnel or suction of gastric contents from the trachea of patients. We followed the American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference definition of sepsis. 11 ARDS cases in the setting of known pneumonia were listed under direct lung injury even if systemic sepsis syndrome developed. We also reviewed the causes of death among ARDS patients. Septic shock and multiple organ failure were defined according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria. 11 Failure to maintain oxygenation was defined as a refractory fall in arterial oxygen saturation despite standard ICU interventions. An APACHE (acute physiology and chronic health evaluation) II 12 score was calculated for all patients on the date of ICU Table 1 Incidence of ARDS in a Northeast Ohio Adult Population Periods Cases, No. admission. We also calculated the tidal volume per kilogram of actual and of predicted body weights on days 1, 3, and 7 of the institution of mechanical ventilation. The mean predicted body weight was calculated for male patients as 50 0.91 kg (centimeters of height 152.4); the predicted body weight for female patients was 45.5 0.91 kg (centimeters of height 152.4). 10 ARDS mortality in the ICUs was calculated as the proportion of patients who did not survive the ICU admission. The 28-day mortality was also calculated. Results Population at Risk Incidence/ 100,000 April 1996 March 1997 16 139,541 11.4 April 1997 March 1998 29 146,063 19.8 April 1998 March 1999 21 145,270 14.4 Overall 66 430,874 15.3 There were 66 patients who fulfilled the case definition criteria of ARDS. The populations at risk for the years 1996, 1997, and 1998 were 139,541, 146,063, and 145,270, respectively. The incidence of ARDS over the 3 years varied from a low of 11.4/ 100,000 from April 1996 to March 1997 to a high of 19.8/100,000 from April 1997 to March 1998. The overall incidence of ARDS over the 3-year period for the adult population 18 years old was 15.3/ 100,000/yr (Table 1). The incidence of ARDS using the whole population (including subjects 18 years old) as the denominator was 11.0/100,000/yr. The patients mean age ( SD) was 60.3 14.8 years, and 57.6% were males (n 38). The average ICU stay was 12.0 9.5 days. The mean APACHE II score was 23.4 6.9, and the mean Pao 2 /Fio 2 at diagnosis was 110.8 37.8. In these patients, who were hospitalized prior to the published results of the ARDS network ventilation trial, 10 the mean tidal volume in relation to actual body weight was 8.7 2.4 ml/kg on day 1, 8.6 2.5 ml/kg on day 3, and 8.7 2.4 ml/kg on day 7. The mean tidal volume in relation to predicted body weight was Table 2 Etiology of ARDS in 66 Patients in Northeast Ohio Etiology No. (%) Direct lung injury (pneumonia and aspiration) 50 (75.8) Sepsis (nonpulmonary) 12 (18.2) Transfusion 2 (3.0) Multiple trauma 1 (1.5) Drug overdose 1 (1.5) www.chestjournal.org CHEST / 121 / 6/ JUNE, 2002 1973
Figure 1. Monthly distribution of newly diagnosed cases of ARDS among Kaiser Permanente patients in northeast Ohio. 10.6 2.4 ml/kg on day 1, 10.2 2.2 ml/kg on day 3, and 10.2 2.4 ml/kg on day 7. The most common cause of ARDS was direct lung injury (75.8%), followed by sepsis (nonpulmonary, 18.2%), and by all other causes (6.0%; Table 2). The mortality of patients with ARDS in the ICU was 47.0%, and the 28-day mortality was 48.5%. The leading cause of death in hospital was septic shock (53.8%), followed by multiple organ failure (23.1%), failure to oxygenate (10.3%; n 4), and all other causes (12.8%). The distribution of new cases per month during the 3-year period is shown in Figure 1. There were no statistically significant differences in the monthly frequencies of new ARDS cases ( 2 square test, p 0.11). Discussion The most important finding in this study was that the incidence of ARDS over a 3-year study period in an adult population was 15.3/100,000/yr. All of the patients fulfilled the definition of the AECC published in 1994. 9 This incidence is in general accordance with recent reports from Europe 7,13 and Seattle, 8 which used the same ARDS criteria as ours, and found incidences of ARDS of 13.5/100,000/yr, 14.6/100,000/yr, and 12.6/100,000/yr, respectively (Table 3). However, the incidence found in these studies is higher than previously reported. 3 6 A probable explanation is that the difference is due to variability in ARDS definition among previous investigators (Table 4). Criteria for ARDS used before the 1994 consensus definition had more severe oxygenation cut points and selected only a subset of the ARDS population as currently defined. This also explains the 4.9/100,000 incidence obtained by Valta et al, 15 since all their cases, though prospectively screened using the AECC cut point, had a Pao 2 /Fio 2 150 mm Hg. In addition, some of the earlier studies could not Source Table 3 Incidence of ARDS in Adults Defined by the AECC Criteria Denominator Incidence, Cases/100,000/yr Nolan et al 14 (1997) Half the total population of the Sydney peninsula area, Australia 7.3 9.3 Luhr et al 7 (1999) Population 15 yr old in Sweden, Denmark, and Iceland 13.5 Valta et al 15 (1999) Total population 1 yr old in Kuopio region, Finland 4.9 Hudson and Steinberg 8 (1999) Total King County residents in Seattle, WA 12.6 Antonsen et al 13 (2000) Denmark population 15 yr old 14.6 Arroliga et al (current study) HMO population in Northeast Ohio Age 18 yr 15.3 Total population 11.0 1974 Clinical Investigations in Critical Care
Source Table 4 Non-AECC ARDS Definitions in Incidence Calculation ARDS Definition Incidence, Cases/100,000/yr Webster et al 3 (1988) Pao 2 60 mm Hg with Fio 2 0.5 4.5 Bilateral infiltrates, no heart failure Villar and Slutsky 4 (1989) Pao 2 55 mm Hg 1.5 Pao 2 75 mm Hg 3.5 Fio 2 0.5, bilateral infiltrates, no heart failure Thomsen and Morris 5 (1995) Pao 2 /PAo 2 0.2, bilateral infiltrates, no heart failure 4.8 8.3 static thoracic compliance 50 ml/cm H 2 O Lewandowski et al 6 (1995) Intubated 24 h Lung injury score 2.5 3.0 quantify with accuracy the population base that constitutes the appropriate (adult population) denominator in the incidence calculation. In our study, we were able to accurately define the population at risk 18 years old, and we therefore consider our reported ARDS incidence in the adult population to be more precise. If we used the total population that includes subjects 18 years old, the incidence was 11.0/100,000/yr and was still similar to other reports. 7,8,13 The possibility exists that we underestimated the true incidence of ARDS because we did not account for the patients who may have developed ARDS and were never admitted to the ICUs. The other interesting finding that may account for some of the discrepancies between the different incidence reports is the variability of ARDS incidence over our 3-year study period from 11.4/100,000 to 19.8/ 100,000 to 14.4/100,000. It is therefore possible that incidence studies conducted over shorter time periods may lead to different results. The most common cause of ARDS in this study was direct lung injury (75.8%), in contrast to previous reports 6,7,16 that found a nearly equal distribution between direct and indirect causes. A likely explanation is that we included the patients with sepsis caused by pneumonia in the direct lung injury group. Patients with ARDS after multiple trauma accounted for a small percentage of our study sample. It is possible that we may have underestimated the number of patients with trauma and ARDS if they were admitted to other hospitals on an emergency basis. The mortality of ARDS in the ICU was 47%, and the 28-day mortality was 48.5%. This is in line with most cohort studies 6,7,14 16 and with the metaanalysis published by Krafft et al. 17 This mortality was higher than the reported 39.8% in the control group (tidal volume of 12 ml/kg) of a study 10 of mechanical ventilation in patients with ARDS. Selection bias almost certainly explains the higher survival of patients with ARDS enrolled in some clinical trials. The ARDS Network reported that only 12.1% of 7,454 patients screened for three trials were included in the studies, and the excluded patients had a mortality of 44%. 18 In our study, the patients received a tidal volume of approximately 8 ml/kg of actual body weight, which corresponds to about 10 ml/kg of predicted body weight, during the first week of mechanical ventilation. The size of the tidal volume is similar to the tidal volumes reported by the Mechanical Ventilation International Study Group, 19 and that were frequently used in clinical practice before the publication of the article by the ARDS Network. 10 The major limitation of this report is the relatively small number of patients, although the study period extends 3 years and the population at risk is very well defined. In conclusion, the incidence of ARDS in an adult population in northeast Ohio was 15.3/ 100,000/yr, a number in line with emerging estimations, but higher than most previous reports. References 1 Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress in adults. Lancet 1967; 2:319 323 2 National Heart, and Lung Institute, National Institutes of Health. Respiratory distress syndromes: task force report on problems, research approaches, needs. Washington, DC: US Government Printing Office, 1972; publication No. 73 432: 165 180 3 Webster NR, Cohen AT, Nunn JF. Adult respiratory distress syndrome: how many cases in the UK? Anaesthesia 1988; 43:923 926 4 Villar J, Slutsky AS. The incidence of the adult respiratory distress syndrome. Am Rev Respir Dis 1989; 140:814 816 5 Thomsen GE, Morris AH. Incidence of the adult respiratory distress syndrome in the state of Utah. Am J Respir Crit Care Med 1995; 152:965 971 6 Lewandowski K, Metz J, Deutschmann C, et al. Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany. Am J Respir Crit Care Med 1995; 151:1121 1125 7 Luhr OR, Antonsen K, Karlsson M, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. Am J Respir Crit Care Med 1999; 159:1849 1861 www.chestjournal.org CHEST / 121 / 6/ JUNE, 2002 1975
8 Hudson LD, Steinberg K. Epidemiology of acute lung injury and ARDS. Chest 1999; 116:74S 82S 9 Bernard GR, Artigas A, Brigham KL, et al. The American- European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818 824 10 The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301 1308 11 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864 874 12 Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13:818 829 13 Antonsen K, Wetterslev J, Blonde J. Incidence, severity, and mortality of acute respiratory failure in Denmark. Ugeskrift Laeger 2000; 162:2876 2881 14 Nolan S, Burgess K, Hopper L, et al. Acute respiratory distress syndrome in a community hospital ICU. Intensive Care Med 1997; 23:530 538 15 Valta P, Uusaro A, Nunes S, et al. Acute respiratory distress syndrome: frequency, clinical course, and costs of care. Crit Care Med 1999; 27:2367 2374 16 Roupie E, Lepage E, Wysocki M, et al. Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients. Intensive Care Med 1999; 25:920 929 17 Krafft P, Fridrich P, Pernerstorfer T, et al. The acute respiratory distress syndrome: definitions, severity, and clinical outcome: an analysis of 101 clinical investigations. Intensive Care Med 1996; 22:519 529 18 Suchyta M, Morris AH, Thompson T. Attributes and outcomes of randomized vs excluded patients in ALI/ARDS clinical trials [abstract]. Am J Respir Crit Care Med 2000; 161:A210 19 Esteban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed in the intensive care unit. Am J Respir Crit Care Med 2000; 161:1450 1458 1976 Clinical Investigations in Critical Care