Anabolic Steroids The Negative Effects of Anabolic Steroids.
Jeremy Cohen on Steroids
35
‘ROIDS IN SEPSIS Jeremy Cohen, Royal Brisbane Hospital Queensland, Australia Monday, 2 September 13
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Intensivist Jeremy Cohen drills down on the thinking and value of using steroids in sepsis and the current evidence base. He also discusses a large international trial in progress to find some new answers to all the uncertainty. The Audio can be found on Intensive Care Network and iTunes.
Transcript of Jeremy Cohen on Steroids
‘ROIDS IN SEPSIS
Jeremy Cohen, Royal Brisbane Hospital
Queensland, Australia
Monday, 2 September 13
Monday, 2 September 13
The Steroid Controversy
Monday, 2 September 13
Hippocrates
Description of Sepsis
Girolamo Frascatoro
Concept of Contagion
SEPSIS TIMELINE
430 BC 1546
Anthony van Leeuwenhoek
Description of Bacteria
1683
Monday, 2 September 13
Ignaz Semmelweiss
Hand Disinfection
Robert Koch & Louis Pasteur
Germ Theory
1847 1870
SEPSIS TIMELINE
Monday, 2 September 13
Gram negative Sepsis
Multiple Organ Failure
1909
Host Response
1912 1975
SEPSIS TIMELINE
1951
32 Studies on Steroids in Infection
1944
Monday, 2 September 13
Bone et al
NEJM
Annane et al
JAMA
Sprung et al
NEJM
1987 2002 2008
SEPSIS TIMELINE
Monday, 2 September 13
0
15
30
45
60
Poland Germany Belgium Other
Europe
Perc
enta
ge u
se o
f LDS
0
15
30
45
60
Brazil Chile Peru ArgentinaMexico Other
Latin America
Perc
enta
ge u
se o
f LDS
0
15
30
45
60
India Singapore Phillipines Israel Malaysia Other
Asia
Perc
enta
ge u
se o
f LDS
18.0
28.5
39.0
49.5
60.0
N.America Australia Other
Rest of World
Perc
enta
ge u
se o
f LDS
Low Dose Corticosteroid Use By Region
Adapted from Beale at al CC 2010
Monday, 2 September 13
Monday, 2 September 13
Monday, 2 September 13
Patient with Septic Shock
Short Synacthen Test
Overall
Randomised to Steroid or Placebo
Non -Responders
Responders
Monday, 2 September 13
Use of Etomidate
Statistical Analysis
Outcomes reported as time to death rather than mortality
Mortality only significant after using adjusted model
Monday, 2 September 13
Overall
Non Responders
Responders
28 Day Mortality(steroids vs placebo) p value
82 (55%) vs 91(61%)
22 (61%) vs 18(53%)
60 (53%) vs 73 (63%)
0.09
0.96
0.04
0.24
0.63
0.11
Monday, 2 September 13
Patients not as sick
Underpowered
Did not reach recruitment target
Monday, 2 September 13
Severe Stress
Moderate Stress
Mild Stress
Monday, 2 September 13
0
1000
2000
3000
4000
Rothwell Annane Schein Sibbald Bollaert Sam Bouachour Schroeder Beishuizen Aygen Jarek De Jong Dimopoulou Oppert
Cor
tisol
nm
ol/l
Survivors Non Survivors
Cortisol values in Sepsis
Monday, 2 September 13
“There is no greater tragedy in Science than to witness the slaying of a beautiful hypothesis by an ugly fact” Thomas Huxley
Monday, 2 September 13
Annane et al,JAMA 2000
Cortisol < 940, Delta > 250
Cortisol < 940, Delta < 250Cortisol > 940, Delta > 250
Cortisol > 940, Delta < 250
Monday, 2 September 13
Good Outcome
Intermediate Outcome
Bad OutcomeCortisol > 940, Delta < 250
Cortisol < 940, Delta > 250
Cortisol < 940, Delta < 250Cortisol > 940, Delta > 250
Monday, 2 September 13
Monday, 2 September 13
Monday, 2 September 13
250µg 1-24 ACTH
Baseline
IncrementPeak
Time
30 min 60 min0 min
Monday, 2 September 13
Peak vs. Increment
Up to 1/3 healthy controls fail to increase cortisol by 250 n mol/l. Widmer at al JCEM 2005
Increment dependent upon basal concentration May and Carey, Am.J.Med 1985
Increments in repeated tests inversely related to response of the previous challenge
Arvat et al, JCEM 2000Monday, 2 September 13
Correlation vs Causation
Monday, 2 September 13
Baseline:
Peak
Increment
600
900
300
1000
1200
200
Normal InsufficientMonday, 2 September 13
Reproducibility of ACTH tests in Sepsis
Loisa et al 2005
Monday, 2 September 13
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
HPLC RAI AAI RAI RAI AAI AAI RAI AAI AAI
Centaur RAI RAI RAI RAI RAI RAI RAI AAI NORMAL
TDx NORMAL RAI RAI RAI RAI NORMAL RAI AAI NORMAL
Immulite NORMAL RAI RAI RAI RAI NORMAL RAI AAI NORMAL
Adrenal Status by Assay
Monday, 2 September 13
!
Monday, 2 September 13
Monday, 2 September 13
Cohen et al, Shock 2011
Monday, 2 September 13
Cohen et al, Shock 2011
Monday, 2 September 13
Free Cortisol Values in Survivors and Non Survivors
0
50
100
150
Free Cortisol
Co
nce
ntr
atio
n n
mo
l/
Baseline + 30 Minutes + 60 Minutes
Total Cortisol Values in Survivors and Non Survivors
0
200
400
600
800
1000
Co
nce
ntr
atio
n n
mo
l/Baseline + 30 Minutes + 60 Minutes
Total Cortisol
Comparison of Outcomes
**
DiedSurvived
Free Cortisol Total Cortisol
Cohen et al, Shock 2011
Monday, 2 September 13
ADRENALAdjunctive Corticosteroid Treatment in Critically Ill
Patients with Septic Shock
3800 patients200mg hydrocortisone by infusion for 7 days90 day mortality
Monday, 2 September 13
Queensland Princess Alexandra Royal Brisbane & Womens Ipswich Logan Mater Health-‐Public Mater Private HospitalNambour RedcliffeToowoombaWesley
NSWBlacktownCalvary Mater – NewcastleJohn HunterLiverpoolNepeanPrince of WalesRoyal North shoreRoyal Prince AlfredSt GeorgeSt Vincent’s SydneyTamworthWoollongong
Northern TerritoryDarwin
New ZealandAuckland DCCMAuckland CVICUChristchurchMiddlemoreNorth ShoreTaurangaWellington
Western AustraliaFremantleRoyal Perth
TasmaniaHobart
South AustraliaLyell McEwinQueen Elizabeth
VictoriaAusUnBendigoDandenongGeelongMonashNorthernRoyal MelbourneSt Vincent’s MelbourneWestern
ADRENAL
Monday, 2 September 13
United KingdomSt Georges NHS + 7 sites Denmark
Righospitalet
IndiaChris8an Medical College Manipal HospitalColumbia Asia
Saudia ArabiaKing Abdul Aziz Medical City
Republic of IrelandCork University Hospital Norway
ADRENAL
Monday, 2 September 13
