Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.
BACKGROUND
The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients.


METHODS
We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality.


RESULTS
A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment.


CONCLUSIONS
In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo.


BACKGROUND
Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.
Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal. pedrorpovoa@gmail.com.|NOVA Medical School, CEDOC, New University of Lisbon, Lisbon, Portugal. pedrorpovoa@gmail.com.
Pedro
P
Póvoa
D'or Institute for Research and Education, Rio de Janeiro, Brazil. jorgesalluh@gmail.com.|Postgraduation Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. jorgesalluh@gmail.com.
Jorge I F
JI
Salluh
Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain. makilu80@hotmail.com.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. makilu80@hotmail.com.
Maria L
ML
Martinez
Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain. rguillamat@tauli.cat.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. rguillamat@tauli.cat.
Raquel
R
Guillamat-Prats
Duke Clinical Research Institute, Durham, NC, USA. dianne.gallup@duke.edu.
Dianne
D
Gallup
Duke Clinical Research Institute, Durham, NC, USA. hussein.al-khalidi@duke.edu.
Hussein R
HR
Al-Khalidi
Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, USA. TTHOMPSON1@mgh.harvard.edu.
B Taylor
BT
Thompson
Dipartimento di Anestesiologia e Rianimazione, Azienda Ospedaliera Città della Salute e della Scienza e di Torino_Molinette, Università di Torino, Torino, Italy. marco.ranieri@unito.it.
V Marco
VM
Ranieri
Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain. aartigas@tauli.cat.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. aartigas@tauli.cat.
Antonio
A
Artigas
D061605:Administration, Intravenous; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D013256:Steroids / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; D013256:Steroids; C421124:drotrecogin alfa activated