Department of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, 68198, USA.
Intensive Care Med. 2011 Mar;37(3):420-9. doi: 10.1007/s00134-010-2121-0. Epub 2011 Jan 18.
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.
Randomized 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.
In septic shock trials only (Marik meta-analysis; N = 965), the probability that low-dose steroids decrease mortality by more than 15% (i.e., RRR > 15%) was 0.41 (0.24 for RRR > 20% and 0.14 for RRR > 25%). For severe sepsis and septic shock trials combined, the results were as follows: (1) for the Annane meta-analysis (N = 1,228), the probabilities were 0.57 (RRR > 15%), 0.32 (RRR > 20%), and 0.13 (RRR > 25%); (2) for the Minneci meta-analysis (N = 1,171), 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 (N = 924), 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 (N = 964), probabilities were 0.81 (RRI > 1%), 0.76 (RRI > 2%), and 0.70 (RRI > 5%); and for hyperglycemia (N = 540), 0.99 (RRI > 1%), 0.97 (RRI > 2%), and 0.94 (RRI > 5%).
Based on clinically meaningful thresholds (RRR > 15-25%) 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 (superinfections, bleeding, and hyperglycemia) were high for all analyses.
低剂量类固醇在试验和三项近期荟萃分析中得出了相互矛盾的结果。我们旨在通过贝叶斯方法评估低剂量类固醇治疗严重脓毒症和脓毒性休克的疗效和安全性。
对三篇已发表荟萃分析中的随机试验进行了回顾，并将其同时纳入经典和贝叶斯数据库，以估计 28 天死亡率的相对风险降低（RRR），以及休克逆转和副作用的相对风险增加（RRI）。
仅在脓毒性休克试验中（Marik 荟萃分析；N=965），低剂量类固醇降低死亡率超过 15%（即 RRR>15%）的概率为 0.41（RRR>20%的概率为 0.24，RRR>25%的概率为 0.14）。对于严重脓毒症和脓毒性休克试验的综合分析，结果如下：（1）对于 Annane 荟萃分析（N=1228），概率分别为 0.57（RRR>15%）、0.32（RRR>20%）和 0.13（RRR>25%）；（2）对于 Minneci 荟萃分析（N=1171），概率为 0.57 实现死亡率 RRR>15%，0.32（RRR>20%）和 0.14（RRR>25%）。从每项分析中剔除 Sprung 试验并未改变整体结果。休克逆转的概率范围为 65%至 92%。类固醇诱导副作用的发生概率如下：胃肠道出血（N=924），类固醇引起 RRI>1%的概率为 0.73，RRI>2%的概率为 0.70，RRI>5%的概率为 0.67；超级感染（N=964），概率分别为 0.81（RRI>1%）、0.76（RRI>2%）和 0.70（RRI>5%）；高血糖（N=540），RRR>1%的概率为 0.99，RRR>2%的概率为 0.97，RRR>5%的概率为 0.94。
基于严重脓毒症或脓毒性休克死亡率降低的临床有意义阈值（RRR>15-25%），所有三项荟萃分析的贝叶斯方法均一致表明，低剂量类固醇与生存获益无关。对于所有分析，类固醇诱导副作用（超级感染、出血和高血糖）的发生概率均较高。
