BACKGROUND A study was undertaken to investigate possible reductions in mortality and/or changes in outcome predictive factors in patients with the acute respiratory distress syndrome (ARDS) managed in a single centre.
METHODS The study was a prospective observational cohort study of two patient populations with ARDS. Group 1 comprised 41 patients enrolled between May 1990 and April 1993, and group 2 consisted of 78 patients enrolled between June 1993 and March 1997. The end points of the study were mortality and various factors predictive of death.
RESULTS There was a marked reduction in mortality between groups 1 and 2 (66% versus 34%; relative risk 1.77; CI 1.23 to 2.55). There were no significant differences between the groups in terms of age (40.6 (3.3) versus 45.5 (2.2) years), APACHE score (14.5 (0.72) versus 13.6 (0.1)), lung injury score (2.95 (0.07) versus 2.8 (0.1)), incidence of multi-organ failure (29% versus 32%), incidence of sepsis (31% versus 39%), or Pao 2/Fio 2 (kPa) ratio (11.8 (0.67) versus 12.0 (0.6)). There was a significantly lower proportion of men in group 1 (51% versus 74%). The case mix of the two groups was closely matched: following elective surgery 48% versus 48%, trauma 17% versus 16%, primary lung injury 12% versus 24%. Patients in group 1 were supported using several ventilatory and other modes (volume preset, non-inverse ratio ventilation, n = 15; pressure controlled inverse ratio ventilation (PC-IRV), n = 11; ultra high frequency jet ventilation (UHFJV), n = 13; an intravascular oxygenation device (IVOX) and extracorporeal gas exchange (ECGE), n = 2). Within group 1 no significant difference in mortality was observed between the patients on volume controlled ventilation and the remainder. In group 2 all patients received PC-IRV (n = 78) but, in addition, some received other support techniques (UHFJV n = 4, ECGE n = 2). In group 1 only sepsis on admission (21% (survivors) versus 56% (non-survivors)) predicted death. In group 2 age of survivors and non-survivors (41.2 (2.6) versus 52.6 (3.5)), APACHE score (12.2 (0.6) versus 15.8 (0.9)), and Pao 2/Fio 2 (12.8 (0.86) versus 10.5 (0.72)) predicted survival, but not the incidence of sepsis or multi-organ failure.
CONCLUSIONS In recent years a highly significant reduction in mortality associated with ARDS has been observed between two groups of patients well matched for disease severity and case mix. Changes in ICU organisation rather than specific interventions may account for this reduction, although different ventilatory and other management strategies used in the two groups may also be relevant.
- acute respiratory distress syndrome (ARDS)
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The acute respiratory distress syndrome (ARDS) in adults is characterised by refractory hypoxaemia in the presence of radiographic evidence of bilateral pulmonary infiltration. ARDS may be precipitated by a number of direct and indirect pulmonary insults. A survey of the relevant literature suggests that little change occurred in the high associated mortality (40–80%) from 1967 when the syndrome was first formally described1 until approximately 1994.2 Moreover, certain precipitating conditions such as generalised sepsis and primary pulmonary disease are associated with a higher mortality than others such as trauma and fat emboli. Nevertheless, other recent studies suggest that the mortality associated with ARDS has fallen in certain centres3 and that improved modes of ventilatory support may be a major contributing factor to improved outcome.4
Our previously published data5 concerning outcome in ARDS represent the only sizable UK series from a tertiary referral centre and indicated a mortality of 66% from 1990 to April 1993. In view of the suggestion that modern approaches to the clinical management of this condition have made an impact on the mortality associated with ARDS, we have reassessed our outcome data in patients admitted to our unit from June 1993. Direct comparisons were made with our previously published data to assess whether there has been a change in mortality or factors predictive of outcome.
Patients were enrolled prospectively from 1990 to 1997. They were divided into two groups: group 1 (n = 41) enrolled between May 1990 and April 19935 and group 2 (n = 78) enrolled from June 1993 to March 1997. The referral basis of the two groups was identical with 21 of 41 patients (51%) in group 1 and 40 of 78 (51%) in group 2 being referred from other centres.
The enrolment criteria were as follows. Briefly, a clinical condition associated with ARDS was identified in the presence of bilateral pulmonary infiltrates on chest radiography. In group 1 refractory hypoxaemia was defined as a ratio of arterial oxygen tension to fractional inspired oxygen concentration (Pao2 /Fio 2 (kPa)) of <20. Following the publication of the Consensus Guidelines criteria for the definition of ARDS in 19946 a Pao 2/Fio 2 ratio of <26.7 was used for patients in group 2. In both groups the pulmonary artery occlusion pressure (PAOP) was required to be less than 18 mm Hg. In all cases lung injury (LIS, according to the criteria of Murray7 ) and acute physiology and chronic health evaluation (APACHE II) scores were recorded on the day of admission or on the day on which ARDS was diagnosed and were calculated from the worst values obtained within the first 24 hours. Organ system failures were defined according to the criteria of Montgomery et al,8 and sepsis was defined according to the consensus criteria published in 1992.9
All patients were managed with mechanical ventilation (Drager Evita I or II, Drager UK Ltd, Luton, Bedfordshire, UK) using a balloon tipped pulmonary artery catheter of the thermodilution type. The mode of ventilation employed at the time of most severe lung injury was noted. The presence or absence of sepsis (defined according to the criteria of the ACCP/SCCM7 ) and organ dysfunction were noted. Mortality was defined as death in hospital.
Data are presented as mean (SE) throughout. Statistical analysis was performed using Fisher’s exact test or the unpaired ttest with p values equal to or less than 0.05 being considered significant.
There were no significant differences between the two groups in terms of age (40.6 (3.3) versus 45.5 (2.2) years, p = 0.22), APACHE score (14.5 (0.72) versus 13.6 (0.1), p = 0.2), Lung Injury Score (2.95 (0.07) versus 2.8 (0.1), p = 0.22), Pao 2/Fio 2 ratio (11.8 (0.67) versus 12.0 (0.6), p = 0.13), incidence of multi-system organ failure on admission (29% (12/41) versus 32% (25/78), p = 0.5), or incidence of sepsis on admission (31% versus 39%, p = 0.40). There was a significantly lower proportion of men in group 1 (51% versus 74%, p = 0.01; table 1)
The case mix of the two groups was closely matched (postoperative 48% versus 48%, trauma 17% versus 16%, primary lung injury 12% versus 24% for groups 1 and 2, respectively, p = 0.23). Patients in group 1 were ventilated using several different modes (volume preset, non-inverse ratio, n = 15; pressure controlled, PC-IRV, n = 11; ultra high frequency jet ventilation (UHFJV), n = 13; extracorporeal or intracorporeal gas exchange (ECGE), n = 2). All the patients in group 2 received PC-IRV but, in addition, some received other support techniques (UHFJV, n = 4; ECGE, n = 2).
There was a highly significant reduction in mortality between patients in group 1 (66%) and group 2 (34%; p = 0.0037; relative risk, 1.77; CI 1.23 to 2.55).
In group 1 the presence of sepsis on admission, seen in 21% of survivors and 56% of non-survivors, was the sole predictor of death (p = 0.05). No significant difference in mortality was observed between patients receiving volume-controlled ventilation and the remainder. In group 2 age (41.2 (2.6) versus 52.6 (3.5), p = 0.01), APACHE II score (12.2 (0.6) versus 15.8 (0.9), p = 0.001), and Pao 2/Fio 2 (12.8 (0.86) versus 10.5 (0.72), p = 0.04) for survivors and non-survivors, respectively, were significant predictors of survival. Sepsis (survivors 47% versus non-survivors 31%, p = 0.2) and multi-organ failure (survivors 36% versus non-survivors 41%, p = 0.2) at the time of admission were not predictive of survival.
Recent publications3 have suggested that a dramatic reduction in the mortality associated with ARDS may have occurred in recent years and the results of this study seem to confirm this impression. The authors acknowledge that there was a slight loosening of the oxygenation entry criteria in 1994 following publication of the consensus guidelines. However, the two cohorts were not significantly different with regard to lung injury score, APACHE II score, and incidence of multi-organ failure or sepsis on admission, and the case mix was almost identical in terms of precipitating condition which is known to influence outcome in ARDS. In particular, the mean Pao 2/Fio 2 ratio of the two groups was almost identical. Thus, the change in entry Pao 2/Fio 2 ratio cannot explain the reduction in mortality.
Examination of possible predictive factors for mortality was revealing. Age, APACHE II scores, and Pao 2/Fio 2 ratios which predicted survival in group 2 were not significant in group 1. Moreover, the presence of sepsis at admission was a significant predictor of death in group 1, yet was not in group 2. Increased awareness of the dangers of sepsis in recent years has led to advances in the prevention and diagnosis of nosocomial infection10which suggests that strategies to prevent this common complication of critical illness have improved in recent years. However, within group 2 47% of survivors displayed evidence of sepsis at the time of admission compared with 31% of non-survivors (p>0.05), which suggests that better management of sepsis may also have been an important factor in improving outcome.
The predictive power of indices of the severity of illness (APACHE II) and respiratory failure (LIS, Pao 2/Fio 2) was surprising in that neither have had clear prognostic significance in other published series.2 Moreover, the majority of patients with ARDS do not die of respiratory insufficiency but rather of multiple organ failure,11 the incidence of which was not predictive of mortality in this study.
The optimal mode of ventilatory support for patients with ARDS has been the subject of considerable debate in recent years. Specifically, a recently published randomised controlled study has shown improved outcome in patients with ARDS using a low volume, pressure-limited strategy aimed at alveolar recruitment compared with a traditional preset volume-controlled ventilatory approach.4 Our ventilatory strategy has certainly changed in recent years. All patients in group 2 were supported using PC-IRV with only six receiving other support techniques. In contrast, patients in group 1 received a variety of ventilatory and other support techniques. However, within group 1 there were no differences in survival between those who received a traditional volume controlled strategy and those who received other support techniques. Unfortunately, as the various modes of support were not allocated as part of a structured protocol over the eight year period, it is not possible to draw reliable conclusions about the efficacy of any particular mode in this study. Other therapeutic support systems such as inhaled nitric oxide, turning patients prone, and (late) administration of corticosteroids have also been widely used on an individual patient basis. Their potential contribution to the improved overall mortality figures in patients in group 2 cannot therefore be meaningfully assessed.
This study has clearly shown that, within our unit, there has been an improvement in outcome associated with ARDS over an eight year period in patients well matched for disease severity and case mix. Unfortunately no clear answers as to why this should be so have emerged from our data or, indeed, that published by others. We suggest that the improvement is most likely to be multifactorial in origin, attributable both to better general patient management strategies—particularly those of ventilation and sepsis—and to the use of newer therapeutic strategies such as inhaled nitric oxide, prone positioning, and late administration of corticosteroids.
This work was supported in part by the British Lung Foundation.