Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies

Low-dose steroids have shown contradictory results in trials and three recent meta-analyses. We aimed to assess the efficacy and safety of low-dose steroids for severe sepsis and septic shock by Bayesian methodology. Randomised trials from three published meta-analyses were reviewed and entered in both classic and Bayesian databases to estimate relative risk reduction (RRR) for 28-day mortality, and relative risk increase (RRI) for shock reversal and side effects. Results showed that in septic shock trials only the probability that low-dose steroids decrease mortality by more than 15% was 0.41. For severe sepsis and septic shock trials combined, the results were as follows:(1) for the Annane meta-analysis, the probabilities were 0.57 (RRR > 15%), 0.32 (RRR > 20%), and 0.13 (RRR > 25%); (2) for the Minneci meta-analysis, the probability was 0.57 to achieve mortality RRR > 15%, 0.32 (RRR > 20%), and 0.14 (RRR > 25%). The removal of the Sprung trial from each analysis did not change the overall results. The probability of achieving shock reversal ranged from 65 to 92%. The probability of developing steroid-induced side effects was as follows: for gastrointestinal bleeding, there was a 0.73 probability of steroids causing an RRI > 1%, 0.70 for RRI > 2%, and 0.67 for RRI > 5%; for superinfections, probabilities were 0.81 (RRI > 1%), 0.76 (RRI > 2%), and 0.70 (RRI >5%); and for hyperglycaemia, 0.99 (RRI > 1%), 0.97 (RRI > 2%), and 0.94 (RRI > 5%). Thus, based on clinical meaningful thresholds for mortality reduction in severe sepsis or septic shock, the Bayesian approach to all three meta-analyses consistently showed that low-dose steroids were not associated with survival benefits. The probabilities of developing steroid-induced side effects were high for all analyses.

Authors: Kalil, Andre C.; Sun, Junfeng. ;Full Source: Intensive Care Medicine [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][online computer file] 2011, 37(3), 420-429 (USA). ;