Sato Ryota, Nasu Michitaka
Department of Emergency and Critical Care Medicine, Urasoe General Hospital, Okinawa, Japan.
Department of Internal Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, 1356 Lusitana Street, 7th Floor, Honolulu, HI 96813 USA.
J Intensive Care. 2017 Nov 21;5:65. doi: 10.1186/s40560-017-0264-6. eCollection 2017.
Dobutamine is commonly used worldwide and included in the protocol for early goal-directed therapy (EGDT). Since the use of dobutamine in EGDT was reported, it has been considered to be an important component, especially in the treatment of septic patients with myocardial dysfunction. However, it is questionable whether dobutamine improves the mortality of sepsis and septic shock. In three recent randomized controlled trials (ProCESS, ProMISe, and ARISE trials), the frequency of dobutamine use was significantly higher in the EGDT group than in the standard care group, but there were no significant differences in the mortality between the groups. These results suggested that dobutamine use may have been overemphasized despite its insignificant effect on the mortality in septic patients. Further, a propensity score analysis revealed that dobutamine use was associated with higher mortality in patients with septic shock. Although dobutamine leads to an increase in cardiac index, myocardial oxygen demand also increases, thus increasing the risk of myocardial ischemia and tachyarrhythmia. It is well known that the mortality in sepsis complicated with atrial fibrillation (AFib) is worse than that in sepsis without AFib. A propensity score-matched analysis reported that β-blockers were associated with better survival in patients with sepsis complicated with AFib. Further, a randomized controlled trial reported that a short-acting β-blocker improved the survival in patients with septic shock. These studies also indicated the risk of β-stimulation during sepsis. Notably, improvements in surrogate markers, such as CI, do not always indicate improvements in patient-centered outcomes, such as mortality. Conversely, some evidence indicates the worsening of patient-centered outcomes despite improvements in surrogate markers. Thus, available evidence suggests that the benefits of dobutamine in patients with sepsis are unclear, but its use might be harmful rather than beneficial, considering the beneficial effects of β-blockers in sepsis that have been reported in recent clinical studies. From this perspective, we will soon have to rethink regarding dobutamine use in patients with sepsis.
多巴酚丁胺在全球范围内广泛使用,并且被纳入早期目标导向治疗(EGDT)方案。自从EGDT中使用多巴酚丁胺的报道出现以来,它一直被视为一个重要组成部分,尤其是在治疗伴有心肌功能障碍的脓毒症患者时。然而,多巴酚丁胺是否能改善脓毒症和脓毒性休克的死亡率仍存在疑问。在最近的三项随机对照试验(ProCESS、ProMISe和ARISE试验)中,EGDT组多巴酚丁胺的使用频率显著高于标准治疗组,但两组之间的死亡率没有显著差异。这些结果表明,尽管多巴酚丁胺对脓毒症患者的死亡率影响不大,但它的使用可能被过度强调了。此外,倾向评分分析显示,在脓毒性休克患者中,使用多巴酚丁胺与更高的死亡率相关。尽管多巴酚丁胺会导致心脏指数增加,但心肌需氧量也会增加,从而增加心肌缺血和快速心律失常的风险。众所周知,脓毒症合并心房颤动(AFib)的死亡率高于无AFib的脓毒症。一项倾向评分匹配分析报告称,β受体阻滞剂与脓毒症合并AFib患者的更好生存率相关。此外,一项随机对照试验报告称,一种短效β受体阻滞剂可改善脓毒性休克患者生存率。这些研究也表明了脓毒症期间β受体刺激的风险。值得注意的是,诸如心脏指数等替代指标的改善并不总是表明以患者为中心的结局(如死亡率)得到改善。相反,一些证据表明,尽管替代指标有所改善,但以患者为中心的结局却恶化了。因此,现有证据表明,多巴酚丁胺对脓毒症患者的益处尚不清楚,但考虑到最近临床研究报道的β受体阻滞剂在脓毒症中的有益作用,其使用可能有害而非有益。从这个角度来看,我们很快就得重新思考脓毒症患者使用多巴酚丁胺的问题了。