steroids in ards: past insights, current equipoise, and pathways … · 2019. 9. 27. · steroids...
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Steroids in ARDS: past insights, current equipoise, and pathways to clarity
CCCF 2011
Disclosures
None financial
Academically invested in developing a program of research focused on steroids in ARDS
Steroids in ARDS: past insights
Effects of corticosteroids on mortality in severe pneumonia, ALI and ARDS
Steroids in ARDS: past insights
Lamontagne, JCC 2010
Effects of corticosteroids on mortality in severe pneumonia, ALI and ARDS
Steroids in ARDS: current equipoise
Decreasing uncertainty regarding the effects of steroids in ARDS requires that a significant number of intensivists buy into a research protocol that involves administering either steroids or a placebo
In recent ARDS studies, around half of patients received systemic steroids
Briel, JAMA 2010
Adhikari, CCM 2010
45%
63%
Papazian, NEJM 2011
42% (for septic shock) 19% (for ARDS)
Predictors of steroid use in clinical practice
What determines steroid prescription to patients with ARDS? Observational data taken from an ongoing multinational RCT of high frequency oscillation for ARDS – OSCILLATE trial Of 381 patients enrolled in the trial, 162 (42.5%) received systemic steroids during the study
Unpublished
Self-administered survey of steroid use in critical illness
How frequently do intensivists administer steroids given a series clinical scenarios commonly encountered in ARDS Survey targets intensivists with who 1) care for ARDS patients commonly, 2) have research infrastructure Survey sent to intensivists working in top 13 recruiting ICUs in the OSCILLATE trial
0
10
20
30
40
50
60
70
never usually not sometimes always missing
ALI, ARDS, severe ARDS
ALI
ARDS
Severe ARDS
Self-administered survey of steroid use in critical illness
Preliminary data from 85 respondents (12 of 13 targeted centres)
66
15
4 0
0
10
20
30
40
50
60
70
ALI 57
19
9
0 0
10
20
30
40
50
60
ARDS 44
21 17
2 1
0
5
10
15
20
25
30
35
40
45
50
Severe ARDS
Unpublished
Self-administered survey of steroid use in critical illness
Preliminary data from 85 respondents (12 of 13 targeted centres)
Unpublished
1
10
54
20
0
10
20
30
40
50
60
ARDS of unknown etiology
24
29
24
8
0
5
10
15
20
25
30
35
Vasopressor responsive septic shock
1 3
38 43
0 5
10 15 20 25 30 35 40 45 50
Vasopressor refractory septic shock
12 15
33
24
1
0
5
10
15
20
25
30
35
Previous steroids HD stable
0 0 7
78
0 10 20 30 40 50 60 70 80 90
Previous steroids HD unstable
Steroids in ARDS: current equipoise
In addition to variations between individual intensivists, the perceived need for steroids varies greatly between different clinical scenarios encountered in ARDS
Accordingly, equipoise is also likely to vary, which challenges our capacity to study the effects of steroids in ARDS
Steroids in ARDS: pathways to clarity
The right study? To answer the right question?
Items of consensus
• Short courses of high dose steroids potentially harmful and a future study would likely test the net effects of “small doses”, administered for a prolonged duration
• Steroids should be compared to placebo but other proven therapies should be enforced in both groups
• Certain patient-centred outcomes that have been ignored in previous studies need to be measured in future trials (e.g., PTSD, long-term functional capacity…)
• Choosing the right population balancing what we hope to learn with what is acceptable
Difficult key decisions
Different scenarios for patient selection in a future RCT
Scenario a
A large RCT of patients with ARDS, considered to be identical despite variations in concomitant diagnoses
Scenario b
A RCT of patients who do not have major competing indications, that also allows for a diversity of cases and is designed in a way to test differences in clinical responses to steroids; could incorporate original approaches to treatment allocation for better acceptability
Scenario c
A RCT focused on a very specific population excluding patients with any competing indication
In summary
It is important that we learn what steroids do to patients with ARDS but it is not clear if a RCT of steroids for ARDS is feasible It is not clear what the ideal question / research design is Only a collective decision to resolve uncertainty will make it possible to go beyond sterile debates between current diverging views
Although studying the effect of steroids in ARDS will be difficult, it is more amenable to resolution than other contentious issues
Steroids in ARDS: past insights
Lamontagne, JCC 2010
Predictors of steroid use in clinical practice
Before variables not kept in the model
Predictors of steroid use in clinical practice observed in the ongoing OSCILLATE trial
Observational data taken from an ongoing multinational RCT of high frequency oscillation for ARDS Analysis of patients who spent no more than 2 days in the ICU before enrolment in OSCILLATE
Unpublished
The mortality reducing effect of streptokinase in myocardial infarction is relatively certain
Lau, NEJM 1992
Other important outcomes should be measured in the future
LaSRS NEJM 2006
Other important outcomes should be measured in the future
Schelling CCM 1999
Post-traumatic stress disorder in patients with septic shock may be reduced by corticosteroids
Reasons why it is wise to be prudent with exciting findings
CRASH, Lancet 2004
It may be possible to predict steroid responsiveness
Steroids in ARDS: past insights
The perceived need for a new RCT relies on the premise that clinical trials, despite their imperfections, can inform clinical practice by allowing us to better predict the effects of interventions beforehand in a given patient