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2018年02月04日 研究点评, 进展交流 暂无评论

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

Comment

Kathrin Jähne, MD | Jan 25, 2018

Interesting but once again negative septic shock trial

有趣的但结果再次阴性的感染性休克试验

Steroid use in septic shock has multiple targets: Supplement the stress hormone cortisol to overcome TEMPORARY insufficiency. Faster reversal of shock may relate to this. Shock reversal is less likely to influence the primary end-point (90day mortality) and rather a very short term effect at 7-28 days. Assessing baseline cortisol if not the functional response may be useful to determine who should receive cortisol & who not. High cortisol level pt, additional supplementation will have minimal treatment effects. Another physiologically target is the modulation of an overactive immune response. The treatment effect likely is an intermediate in pt who have the cytokine storm/ hyperactive immune response. Pt with normal immune response or subsiding cytokine storm cortisol supplementation may not be useful. The greatest effect of treatment was in the pts who were randomized between 6-12h after shock onset. This highlights Dr Annane’s finding, steroids should be considered early following complete resuscitation. The mortality is different from several septic shock landmark studies during a similar time in similar patients. ARISE had mortalities of 18.7 % versus 28.3% here (Delta 10%).

感染性休克使用激素有多个目标: 补充应激激素皮质醇以克服暂时性的肾上腺皮质功能功能不全。休克的快速逆转可能与此相关。休克逆转很少影响主要终点(90天病死率),而仅仅在7 - 28天显示短期效应。如果无法评估功能反应,那么,评估基线皮质醇水平也可能有助于确定哪些患者应当接受皮质醇治疗。皮质醇水平较高的患者,额外补充激素的疗效非常有限。

另一个生理目标是调节过度的免疫反应。对于有细胞因子风暴或过度免疫反应的患者,激素可能有中等程度的疗效。对于免疫反应正常或细胞因子风暴趋于缓解的患者,补充皮质醇可能无用。休克发生后6 - 12小时间接受随机分组的患者激素疗效最明显。这一结果支持Annane医生的发现,即在复苏完全后应考虑早期使用激素治疗。本研究的病死率与同期类似患者的几项感染性休克研究不同。ARISE研究的病死率为18.7%,而本研究为28.3%(Delta 为10%)。

Lance Gravatt | Jan 22, 2018

Effect of ethnic glucocorticoid receptor polymorphisms

不同种族糖皮质激素受体多态性的影响

Intriguing that the 90 day mortality for Australia (the largest contributor to the study) demonstrated a statistically significant mortality benefit for those receiving steroid therapy. The results for UK and Saudi Arabia were disparate but with wide 95% CI. The impact of human glucocorticoid receptor polymorphisms on steroid response is well documented and known to vary by ethnicity. I am wondering if this may have confounded the results?

有趣之处在于,澳大利亚患者(本研究最大的群体)90天病死率显示,接受激素治疗的患者病死率获益具有统计学显著差异。而英国和沙特阿拉伯的结果与此不同,但95%的置信区间很宽。人类糖皮质激素受体多态性对激素治疗反应的影响已众所周知,且因种族而异。我想知道这是否会影响结果呢?

PANKAJ DUBEY, MD | Jan 22, 2018

Drug interactions with commonly used drugs

与常用药物之间的药物相互作用

The study is very useful in that the protocol can be followed easily, and it replicates the common situation faced by intensivists around the world. It does not particularly add to the cost of treatment and the results seem to ring true from local experience as well. The adverse reactions table is interesting ;there is no additional infection burden, the wound dehiscence shows up in the placebo corner. Electrolyte abnormalities can be explained with free water clearance effect of steroids. It would be interesting to know the drug-drug interactions with commonly used drugs in the ICU and if they were particularly represented in one group or the other. e.g.: erythromycin (enzyme inhibitor) for gut motility or Phenytoin (enzyme inducer) for seizure prophylaxis or for other recorded adverse reactions when used with an aminoglycoside and hypertonic saline.

这项研究非常有用,因为该研究方案很容易遵循,而且反映了全世界ICU医生面对的共同情况。这并未显著增加治疗费用,而且研究结果也符合个人经验。报告不良反应的表格很有意思;激素治疗未增加感染风险,安慰剂组伤口裂开比例稍高。电解质异常可以用激素对自由水清除的影响解释。了解激素与ICU常用药物之间的相互作用,以及这些药物相互作用是否代表一类药物的特点非常有意思:例如,用于促进胃肠动力的红霉素(酶抑制剂),或用于预防癫痫发作的苯妥英钠(酶诱导剂),或氨基糖苷类与高渗盐水一起使用时的其他不良反应。

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