Rationale: Little is known about the long-term outcomes and costs of survivors of acute respiratory distress syndrome (ARDS).
Objectives: To describe functional and quality of life outcomes, health care use, and costs of survivors of ARDS 2 yr after intensive care unit (ICU) discharge.
Methods: We recruited a cohort of ARDS survivors from four academic tertiary care ICUs in Toronto, Canada, and prospectively monitored them from ICU admission to 2 yr after ICU discharge.
Measurements: Clinical and functional outcomes, health care use, and direct medical costs.
Results: Eighty-five percent of patients with ARDS discharged from the ICU survived to 2 yr; overall 2-yr mortality was 49%. At 2 yr, survivors continued to have exercise limitation although 65% had returned to work. There was no statistically significant improvement in health-related quality of life as measured by Short-Form General Health Survey between 1 and 2 yr, although there was a trend toward better physical role at 2 yr (p = 0.0586). Apart from emotional role and mental health, all other domains remained below that of the normal population. From ICU admission to 2 yr after ICU discharge, the largest portion of health care costs for a survivor of ARDS was the initial hospital stay, with ICU costs accounting for 76% of these costs. After the initial hospital stay, health care costs were related to hospital readmissions and inpatient rehabilitation.
Conclusions: Survivors of ARDS continued to have functional impairment and compromised health-related quality of life 2 yr after discharge from the ICU. Health care use and costs after the initial hospitalization were driven by hospital readmissions and inpatient rehabilitation.
Patients with acute respiratory distress syndrome (ARDS) consume significant health care resources in intensive care units (ICUs) because of their severity of illness and long ICU stays (1). The long-term clinical outcomes, health care use, and costs generated by survivors of ARDS have not been studied in detail. The Toronto ARDS Outcomes Group has been conducting a prospective longitudinal cohort study of survivors of ARDS since 1998 with the primary objective of characterizing this long-term trajectory. Our first article examined the clinical, functional, and quality of life outcomes in these survivors 1 yr after discharge from the ICU (2). We showed that our cohort of young, severely ill survivors of ARDS had generalized muscle wasting and weakness, which persisted to 1 yr after ICU discharge, and that the distance they walked in 6 min was 66% of predicted for an age- and sex-matched control population. Scores for the eight domains of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), a health-related quality of life measure, were lower than for the normal population at 1 yr. Pulmonary function measures were within the normal range by 6 mo after ICU discharge but carbon monoxide diffusion capacity remained low at 1-yr follow-up.
The main objectives of this article are to describe the change in functional and quality of life outcomes from 1 to 2 yr after ICU discharge, and the health care use and costs up to 2 yr after ICU discharge. Our secondary objective is to evaluate the relationship between these costs and outcomes. Some preliminary results of this article have been reported previously in abstract form (3–10).
We conducted a prospective longitudinal cohort study of 117 survivors of ARDS, recruited from four academic medical–surgical ICUs in Toronto, Canada between May 1998 and May 2001 (2). Patients were eligible for inclusion if they were at least 16 yr of age, had a PaO2:FiO2 ratio of 200 or less while receiving mechanical ventilation with a positive end-expiratory pressure of at least 5 cm of water, had evidence of airspace changes in all four quadrants on frontal chest radiograph, and an identifiable risk factor for ARDS. Patients were excluded if they were immobile before being admitted to the ICU, had a history of pulmonary resection, or had documented neurologic or psychiatric disease. Consent was obtained for 1-yr follow-up from patients' surrogate decision makers in the ICU and then directly from patients at ICU discharge. At the end of 1 yr, consent was obtained from patients for another 4 yr of follow-up. Two-year follow-up was completed in May 2003. Research ethics board approval was obtained at all participating hospitals.
We collected baseline demographic characteristics and measures of severity of illness in the ICU (2). These measures included the Acute Physiology, Age, and Chronic Health Evaluation (APACHE II; 0 to 71) (11), the Multiple Organ Dysfunction Score (MODS) (0 to 24) (12), and the modified Lung Injury Score (LIS) daily the first week and twice weekly thereafter (0 to 4) (13). Higher scores indicate more severe illness. The rate of change of LIS (LIS slope) is an indicator of the rate of resolution of lung injury; a greater LIS slope indicates slower recovery.
We also collected clinical and health-related quality of life data at scheduled study visits 3, 6, 12, 18, and 24 mo after discharge from the ICU. Each visit included an interview, physical examination, measures of pulmonary function, resting oximetry, the 6-min walk test (14–16) with continuous oximetry, and the SF-36 (17). The SF-36 includes eight domains of health-related quality of life: physical functioning, social functioning, physical role, emotional role, mental health, pain, vitality, and general health. Scores for each domain can range from 0 (worst) to 100 (best). We compared their scores with those of an age- and sex-matched control population.
We prospectively collected health care use data from administrative databases, hospital and outpatient clinical records, patients' monthly diaries, and self-reports at scheduled study visits. This approach provided patient-specific and activity-based resource use per day in the ICU, on the wards after discharge from ICU, and after hospital discharge. For health care costs, we took a third-party payer perspective (Ontario Ministry of Health) to estimate direct medical costs (including hospitalization costs, emergency room visit costs, professional fees, outpatient visit costs, drug costs, laboratory and radiologic procedural costs, outpatient and inpatient rehabilitation costs, home care costs, and chronic care hospitalization costs). We excluded indirect medical costs and direct nonmedical costs. Costs were adjusted for inflation rates, using the medical component of the Canadian Consumer Price Index (18), and were expressed in 2002 Canadian dollars. Our methodology for determining health care use and costs is detailed in appendix e1 (see the online supplement).
Details of the statistical analyses can be found in appendix e2. In brief, we summarized descriptive data on clinical outcomes, health care use, and costs. We used t tests to examine the changes in measures of pulmonary function and distance walked in 6 min, and the signed-rank test to assess within-subject changes in SF-36 scores between 1 and 2 yr after discharge from the index hospitalization (19). For missing SF-36 data, we used last observation carried forward for our analyses.
Using backward selection according to the Akaike's information criterion (AIC) (20), we performed multivariable regression analyses to examine how patients' baseline characteristics and time-dependent variables in the ICU influenced health care costs in the ICU, on the wards and from hospital discharge to 2 yr. To test the sensitivity of our model to whether patients were alive or dead, we repeated our analyses including only patients alive at 2 yr. We summarized overall model fits with R2 and used Efron's enhanced bootstrap validation procedure to assess overfitting. For ease of interpretation, the results in Table 4 are the exponentiated parameters, which represent the adjusted ratio of mean costs associated with the corresponding predictor. A ratio greater than 1 indicates that costs associated with the variable are higher.
One hundred and seventeen eligible patients consented to participate in the ICU; of those, 109 consented for 1-yr follow-up at discharge from ICU (Figure 1). The eight survivors of ARDS who did not consent to follow-up after ICU discharge did consent to evaluation of their ICU records and cost data. Our 2-yr follow-up captured 85% of eligible patients for clinical data and 96% for economic data. Among patients for whom follow-up data were available, 86 of 98 (88%) survived to 1 yr and 78 of 92 (85%) survived to 2 yr. Because ICU mortality for our cohort was 40% (2), overall 2-yr mortality from diagnosis to 2 yr after ICU discharge was 49%. Most deaths occurred during the first 6 mo after discharge from the ICU and were related to preexisting medical problems. The median age of patients with ARDS who survived to be discharged from the ICU was 45 yr, and 56% were male (Table 1). They were severely ill (median APACHE II score of 23, median maximal LIS of 3.7, and median MODS of 9 on day of eligibility). Twelve percent of patients (14 of 117) required renal replacement therapy in the ICU; only one continued to undergo dialysis after discharge from the ICU because of preexisting end-stage renal disease. Our cohort spent a median of 25 d in the ICU and 48 d in the acute care hospital.
Baseline Demographics/Clinical Characteristics
|Age, yr [median (IQR)]||45 (36–58)|
|Male sex, no. (%)||66 (56%)|
|Estimated household income, Can$ (median [IQR])*||$43,500 ($35,500–$56,000)|
|Education, yr (median [IQR])||13 (13–16)|
|Ever smoked, no. (%)||49 (42%)|
|Informal caregiver, no. (%)†||89 (82%)|
|Body mass index pre-ARDS ≥ 30, no. (%)‡||28 (32%)|
|Pre-ARDS organ dysfunction, no. (median [IQR])§||1 (0–2)|
|Preexisting pulmonary disease, no. (%)||13 (11%)|
|Risk factor for ARDS, no. (%)|
|APACHE II score, median (IQR)||23 (17–27)|
|Maximal LIS, median (IQR)||3.7 (3.0–4.0)|
|MODS (on day of eligibility), median (IQR)||9 (7–11)|
|Comorbidities acquired in the ICU, no. [median (IQR)]||0 (0–1)|
|Required renal replacement therapy, no. (%)||14 (12%)|
|Neurological event, no. (%)||13 (11%)|
|Gastrointestinal event, no. (%)||26 (22%)|
|Cardiac event, no. (%)||9 (8%)|
|Tracheostomy, no. (%)||60 (51%)|
|Duration of ventilatory support, d (median [IQR])||21 (12–40)|
|Length of stay in ICU, d (median [IQR])||25 (15–45)|
|Length of stay in acute care hospital (ICU plus ward), d (median [IQR])||48 (27–77)|
Exercise capacity of survivors of ARDS, measured by the 6-min walk test, did not significantly improve from 1 to 2 yr after ICU discharge and continued to be lower than normal, based on an age- and sex-matched control population (Table 2). Patients attributed exercise limitation to muscle weakness, although self-reported muscle weakness was less pronounced at 2 yr compared with at 1 yr. Apart from emotional role and mental health domains, all other domains of health-related quality of life as measured by SF-36 remained below those of the normal population. Although the absolute median scores for physical functioning, general health, and social functioning increased from 1 to 2 yr, none reached statistical significance. There was a trend toward better physical role at 2 yr compared with 1 yr (p = 0.0586), but this was not reflected in the distance walked in 6 min, which did not improve over time. There were no significant changes in measures of pulmonary function. Median lung volumes and spirometry remained within the predicted normal range; the median carbon monoxide diffusion capacity in the cohort rose slightly to within the normal range but these changes did not reach statistical significance. Two additional patients had arterial oxygen desaturation below 88% during the 6-min walk test at 2 yr (7 of 62 at 2 yr vs. 5 of 78 at 1 yr), but neither required supplemental oxygen at rest or on exertion. The proportion of patients who returned to their baseline body weight was stable from 1 yr (71%) to 2 yr (70%).
|Clinical Outcome||Median||Percent Predicted||IQR||Median||Percent Predicted||IQR|
|Meters walked in 6 min*||422||66%||277–510||416||68%||285–496|
|FVC, % predicted||85%||—||71–98%||86%||—||71–100%|
|FEV1, % predicted||86%||—||74–100%||87%||—||75–99%|
|Total lung capacity,‡ % predicted||95%||—||81–103%||94%||—||84–108%|
|Residual volume,‡ % predicted||105%||—||90–116%||96%||—||78–118%|
|Carbon monoxide diffusion capacity,‡ % predicted||72%||—||61–86%||78%||—||63–89%|
| Mental health||72||92%||52–88||76||98%||52–84|
Eleven more survivors of ARDS returned to work at 2 yr compared with at 1 yr (65 vs. 49%). Most patients returned to their original job. Those who had not returned to work cited the following reasons: depression, post-traumatic stress disorder, muscle weakness and fatigue, short-term memory loss from closed head injury, and disability secondary to orthopedic injuries. All patients, except one, were ambulatory and lived independently in the community; one patient developed progressive neurologic dysfunction after ICU discharge and was cared for in a retirement home.
Thirty-one of the 109 survivors of ARDS (28%) were transferred to community hospitals: 10 (9%) to another ICU and 21 (19%) to another hospital ward. Once discharged from the acute care hospital, 36 (33%) patients received inpatient rehabilitation, with a median length of stay of 36 d (mean, 52 d). Of those discharged home, 52 (51%) received formal home care support services. During the 2 yr of follow-up, the median number of home care visits for our cohort was 28 (mean, 74 visits), of which 27 (mean, 55 visits) were in the first year; most were for nursing care. Over the 2-yr period, our cohort had a median of 7 (IQR, 2 to 15) visits to their primary care physicians and a median of 7 (IQR, 1 to 15) visits to specialists, with more visits occurring in the first year than in the second year.
Forty-three patients (39%) were readmitted to hospital in the first 2 yr after ICU discharge. Twenty-two patients (20%) were admitted two or more times for recurring medical problems related to their risk factor for ARDS or complications of their prolonged, complex critical illness. The reasons for readmission were as follows: (1) colostomy reversal, incisional hernia repair, bowel obstruction or anastomotic leak after pancreatitis or complex intraabdominal sepsis (nine patients); (2) treatment for infection, line sepsis, or rejection in oncology or transplant patients (three patients); (3) orthopedic procedures or skin grafting in trauma and/or burn patients (four patients); and (4) inpatient psychiatry for depression and posttraumatic stress disorder (two patients). One patient was admitted for complications directly related to her necrotizing pneumococcal pneumonia, ARDS, and severe organ dysfunction. She was admitted eight times for recurrent lung infections and hemoptysis secondary to bronchiectatic disease resulting from her severe pneumonia and for amputation of bilateral gangrenous toes. One patient had admissions for debridement of heterotopic ossification. One patient, who was initially admitted for mitral valve replacement after endocarditis, sepsis, and ARDS, had a second hospital admission to deliver a term baby. The final patient had admissions for extraction of all his teeth secondary to severe dental caries. The remaining 21 patients (19%) had a single, isolated admission. Five of these patients had admissions similar to those listed above: hernia repair (two patients), reversal of colostomy (two patients), and Hickman line sepsis (one patient); the rest of the patients had admissions unrelated to the episode of ARDS or critical illness. There were a total of 62 readmissions in the first year and 39 in the second year. The mean number of days of subsequent hospitalization was 4.2 ± 15.9 d in the first year and 2.4 ± 8.3 d in the second year.
The mean health care costs for a survivor of ARDS from ICU admission to 2 yr post-ICU discharge are shown in Table 3 and Figure 2. The largest portion of this total cost was the initial hospital stay (mean, Can $128,860; 95% confidence interval, Can $111,970–$151,190), with ICU costs accounting for 76% of these hospital costs. Nursing costs dominated total initial hospital costs, accounting for 75% of total ICU costs and 66% of total ward costs (Figure 2). Other significant cost items in the ICU include physician costs, costs of laboratory examinations and blood processing, imaging costs, and pharmacy costs. On the wards, pharmacy costs were the second most important cost item after nursing costs. The eight survivors of ARDS who did not consent to follow-up after ICU discharge had higher ICU costs than those who did consent (data not shown).
|ICU (n = 117)||Wards (n = 110)||Post-Hospital Discharge to 24 mo (n = 99)|
|Category of Costs||Mean||95% CI||Mean||95% CI||Mean||95% CI|
|Laboratory tests and blood processing||$5,880||$5,060–$7,100||$1,210||$940–$1,630||$520‡||$400–$670‡|
|Allied health services||$1,060||$840–$1,330||$1,420||$1,140–$1,890||—–§||—–§|
The mean costs after discharge from the index hospitalization up to 2 yr were Can $28,350 (95% confidence interval, Can $20,580–$38,350), with subsequent hospitalization costs and inpatient rehabilitation costs predominating. Home care costs, outpatient pharmacy costs, and physician costs were the other significant costs. Nursing was the major component of home care costs. Mean total cost after index hospitalization was Can $16,200 in the first year and Can $12,100 in the second year.
In the ICU, patients with more organ dysfunction acquired during their ICU stay, slower resolution of lung injury, burns, and informal caregivers had higher costs (unadjusted model R2 = 0.50, bootstrap-corrected R2 = 0.44; Table 4). On the wards, those who had more premorbid organ dysfunction, slower resolution of lung injury in the ICU, and who were obese (body mass index ≥ 30) had higher costs (unadjusted model R2 = 0.26, bootstrap-corrected R2 = 0.25). From hospital discharge to 2 yr, patients who were older and had acquired more organ dysfunction during their ICU stay had higher costs (unadjusted model R2 = 0.13, bootstrap-corrected R2 = 0.06) (determinants of health care costs from hospital discharge to 1 yr were the same). When we reanalyzed our data including only those who were alive at 2 yr, we found that the determinants of health care costs were similar (see Table E2 in the online supplement).
Inpatient Cost Ratio (p value)¶
Outpatient Cost Ratio (p value)¶**
|ICU||Wards||Hospital Discharge to 24 mo|
|R2 (bootstrap-corrected R2)||0.50 (0.44)||0.26 (0.25)||0.13 (0.06)|
|Age*||0.99 (0.143)||1.01 (0.154)||1.59 (0.016)|
|Greater number of pre-ARDS organ dysfunctions†||—||1.42 (0.001)||—|
|Greater number of comorbidities acquired during ICU stay‡||1.24 (0.007)||—||1.50 (0.013)|
|Greater LIS slope (slower recovery)§||1.63 (< 0.0001)||1.21 (0.084)||—|
|Burn diagnosis||2.03 (0.042)||—||—|
|Having a caregiver||1.48 (0.012)||—||—|
|More education (in years)||—||—||—|
|Higher neighborhood income (per $10,000)‖||—||1.30 (0.163)||—|
|Pre-ARDS obesity (BMI ≥ 30)||1.21 (0.145)||1.80 (0.010)||—|
In this multisite single-center cohort study, we found that young survivors of ARDS continued to have functional impairment and lower than normal health-related quality of life 2 yr after discharge from the ICU. Despite this, all but one patient were living independently and the majority of ARDS survivors had returned to work. Health care costs up to 2 yr were dominated by initial ICU and ward costs. Health care use and costs after hospital discharge were modest, attributable mainly to hospital readmissions and inpatient rehabilitation. Most of the hospital readmissions were of short duration, but they were related to either the risk factor for ARDS or complications from ARDS and associated critical illness. Those who were older and had acquired more organ dysfunction during their ICU stay had more intense health care use and higher costs in the 2 yr after hospital discharge.
Our 2-yr health-related quality of life data are comparable to those reported by Hopkins and colleagues (21). Neither study showed statistically significant improvement in any of the domains of the SF-36 from 1 to 2 yr after hospital discharge, and our study did not show any improvement in distance walked in 6 min. The differences in health-related quality of life between 1 and 2 yr in our study and the study by Hopkins and colleagues may not have reached statistical significance because of the small numbers of patients and relatively short duration of follow-up. Quality of life measures may continue to improve slowly over many years, but it is also possible that maximum functional and health-related quality of life outcomes are achieved by 1 yr after ICU discharge with the current level of care offered in the community. Targeted interventions have been shown to improve functional performance and to decrease subsequent hospital readmissions and total health care costs, especially in cardiac populations (22–24). At present, there is no organized, systematic follow-up for survivors of ARDS and it is unclear whether an ARDS-specific rehabilitation program could improve both health-related quality of life and functional outcomes.
The mean ICU costs (Can $97,810 in Canadian 2002 dollars) and mean ward costs (Can $31,050) in our study were in the same range as those reported by Valta and colleagues in 1999 for 59 Finnish patients with ARDS (U.S. $73,000 per survivor for ICU costs; or Can $127,900 in Canadian 2002 dollars) (25) and by Hamel and coworkers in 2000 for 963 ARDS or acute respiratory failure patients in the multicenter prospective SUPPORT study (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments in the United States; U.S. $59,100–$70,100 per survivor for initial hospital stay, in 1998 dollars; or Can $94,500–$112,100 in Canadian 2002 dollars) (26). Consistent with previous studies (27–30), we found that those patients with a higher severity of illness and slower recovery of lung injury had longer lengths of stay, more resource use, and higher costs in the ICU, and those who were obese had longer lengths of stay, more resource use, and higher costs on the ward.
Once discharged from the acute care hospital, survivors of ARDS did not consume extensive health care resources. Our mean costs from discharge to 2 yr were Can $28,350, with costs significantly higher in the first year compared with the second year (Can $16,200 vs. $12,100). Posthospitalization costs were related to hospital readmission and need for inpatient rehabilitation. Several patients were readmitted for problems related to prolonged immobilization (heterotopic ossification), intubation, and poor oral hygiene (severe dental caries requiring tooth extraction), and depression and posttraumatic stress disorder. Attention to process of care issues in the ICU and a better understanding of the mechanism of ICU-acquired muscle weakness and dysfunction may help to reduce morbidity and decrease downstream costs.
Our cohort was young (median age, 45 yr), had a significant portion of trauma and burn patients, had little premorbid organ dysfunction, received regular follow-up after hospital discharge, and was recruited from four academic tertiary care ICUs in one metropolitan area in Ontario. As such, our results may not be generalizable to all survivors of ARDS. Rubenfeld and colleagues (31) reported that acute lung injury and ARDS have the highest incidence in elderly individuals with sepsis, predominantly related to pneumonia. Our 2-yr outcome, health care use, and cost data may have limited applicability to an older population of patients; younger patients may have less premorbid organ dysfunction and greater physical and psychological resilience, and may incur less health care cost. On the other hand, our patients received emotional support and facilitation of referrals to specialists as needed as part of their follow-up visits; therefore, we cannot discount the possibility that the research protocol directly contributed to higher costs and better outcomes. Health care use for survivors of ARDS in Ontario may also be quite different from that in other provinces or countries. For example, academic ICUs in Toronto at the time of study enrollment had 1:1 patient-to-nurse ratios; thus, our ICU costs may not be generalizable to units with higher patient-to-nurse ratios. Despite the above limitations on generalizability of our cohort, we had similar health care costs (as noted above) and short-term mortality rate when compared with other ARDS cohorts (Toronto cohort, 40% ICU mortality; King County Lung Injury Project [KCLIP] cohort, 41% hospital mortality; Scandinavian cohort, 41% 90-d mortality; Australian cohort, 34% 28-d mortality) (2, 31).
This longitudinal prospective study demonstrated that survivors of ARDS have persistent functional impairment, exercise limitation, and lower than normal health-related quality of life 2 yr after discharge from the ICU. We showed that long-term health care use and costs are related to age and the degree of organ dysfunction acquired during their ICU stay. Despite their disability, survivors of ARDS gradually adapt and return to work by 2 yr. Future research efforts should be focused on examining whether early intensive ARDS-specific rehabilitation programs will reduce disability and improve long-term outcomes.
The authors thank the survivors of ARDS and their families, who have contributed so much time and effort to this study and have persevered with the long-term follow-up. The authors also thank Dr. Allan Detsky for valuable comments on an earlier draft of this article, and Drs. Murray Krahn and Gary Naglie for methodologic advice.
|1.||Carson SS, Bach PB. The epidemiology and costs of chronic critical illness. Crit Care Clin 2002;18:461–476.|
|2.||Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, et al.; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003;348: 683–693.|
|3.||Herridge MS, Cheung AM, Tansey C, Matte-Martyn A, Cooper A, Guest C, Mazer D, Mehta S, Stewart T, Bohn D, et al.; Canadian Critical Care Trials Group. Survivors of ARDS: clinical and economic sequelae [abstract]. Am J Respir Crit Care Med 2000;161:A382.|
|4.||Cheung AM, Herridge MS, Tansey C, Matte-Martyn A, Cooper A, Guest C, Mazer D, Mehta S, Stewart T, Bohn D, et al.; Canadian Critical Care Trials Group. Health services utilization in survivors of ARDS [abstract]. Am J Respir Crit Care Med 2001;163:A252.|
|5.||Al-Saidi F, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Herridge MS. ICU predictors of functional outcome in ARDS survivors [abstract]. Am J Respir Crit Care Med 2001;163:A252.|
|6.||Diaz-Granados N, Herridge MS, Matte-Martyn A, Tansey CM, Kundhal K, Cheung AM. Use of allied health services in an academic ICU [abstract]. Am J Respir Crit Care Med 2001;163:A689.|
|7.||Cheung AM, Herridge MS, Tansley CM, Diaz-Granados N, Matte-Martyn A, Al-Saidi F, Cooper A, Guest C, Mazer D, Mehta S, et al.; Canadian Critical Care Trials Group. Health care costs in survivors of ARDS [abstract]. Am J Respir Crit Care Med 2002;165:A221.|
|8.||Herridge MS, Cheung AM, Tansley CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper A, Guest C, Maze D, Mehta S, et al.: Canadian Critical Care Trials Group. Long term clinical outcomes in survivors of ARDS [abstract]. Am J Respir Crit Care Med 2002;165: A254.|
|9.||Herridge MS, Tansey CM, Matte-Martyn A, Diaz-Granados N, Cheung AM. Eighteen month functional outcomes in ARDS survivors [abstract]. Am J Respir Crit Care Med 2003;167:A737.|
|10.||Cheung AM, Tansey CM, Tomlinson G, Diaz-Granados N, Matte-Martyn A, Al-Saidi F, Cooper AB, Guest C, Mazer D, Mehta S, et al.; Canadian Critical Care Trials Group. Two-year health care utilization and costs in survivors of the acute respiratory distress syndrome [abstract]. Am J Respir Crit Care Med 2004;169:A780.|
|11.||Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818–829.|
|12.||Marhsall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple Organ Dysfunction Score: a reliable descriptor of a complex clinical outcome. Crit Care Med 1995;23:1638–1652.|
|13.||Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988;138:720–723. [Published erratum appears in Am Rev Respir Dis 1989;139:1065.]|
|14.||American Thoracic Society. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–117.|
|15.||Redelmeier DA, Bayoumi AM, Goldstein RS, Guyatt GH. Interpreting small differences in functional status: the six minute walk test in chronic lung disease patients. Am J Respir Crit Care Med 1997;155:1278–1282.|
|16.||Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med 1998;158:1384–1387.|
|17.||McHorney CA, Ware JE Jr, Lu JFR, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36). III. Tests of data quality, scaling assumptions and reliability across diverse patient groups. Med Care 1994;32:40–66.|
|18.||Statistics Canada. Consumer Price Index. Available from:(accessed July 2006).|
|19.||Conover WJ. Practical nonparametric statistics, 2nd ed. New York: John Wiley & Sons; 1980.|
|20.||Steyerberg EW, Eijkemans MJC, Harrell FE Jr, Dik J, Habbema F. Prognostic modelling with logistic regression analysis: a comparison of selection and estimation methods in small data sets. Stat Med 2000;19:1059–1079.|
|21.||Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan, KJ, Orme JF Jr. Two year cognitive, emotional, and quality of life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med 2005;171:340–347.|
|22.||Verrill DE, Barton C, Beasley W, Lippard M, King CN. Six-minute walk performance and quality of life comparisons in North Carolina cardiac rehabilitation programs: heart and lung. J Acute Crit Care 2003;32: 41–51.|
|23.||Wright DJ, Khan KM, Gossage EM, Saltissi S. Assessment of a low-intensity cardiac rehabilitation programme using the six-minute walk test. Clin Rehabil 2001;15:119–124.|
|24.||Weinberger M, Smith DM, Katz BP, Moore PS. The cost-effectiveness of intensive postdischarge care: a randomized controlled trial. Med Care 1988;26:1092–1102.|
|25.||Valta P, Uusaro A, Nunes S, Ruokonen E, Takala J. Acute respiratory distress syndrome: frequency, clinical course, and costs of care. Crit Care Med 1999;27:2367–2374.|
|26.||Hamel MB, Phillips RS, Davis RB, Teno J, Connors AF, Desbiens N, Lynn J, Dawson NV, Fulkerson W, Tsevat J. Outcomes and cost-effectiveness of ventilator support and aggressive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome. Am J Med 2000;109:614–620.|
|27.||Slatyer MA, James OF, Moore PG, Leeder SR. Costs, severity of illness and outcome in intensive care. Anaesth Intensive Care 1986;14:381–389.|
|28.||Cullen DJ, Ferrara LC, Briggs BA, Walker PF, Gilber J. Survival, hospitalization charges and follow-up results in critically ill patients. N Engl J Med 1976;294:982–987.|
|29.||Dickie H, Vedio A, Dundas R, Treacher DE, Leach RM. Relationship between TISS and ICU cost. Intensive Care Med 1998;24:1009–1017.|
|30.||Tremblay A, Bandi V. Impact of body mass index on outcomes following critical care. Chest 2003;123:1202–1207.|
|31.||Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med 2005;353:1685–1693.|