{"id":17850,"date":"2019-10-07T04:55:48","date_gmt":"2019-10-06T20:55:48","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=17850"},"modified":"2019-10-29T22:49:38","modified_gmt":"2019-10-29T14:49:38","slug":"jama%e5%9c%a8%e7%ba%bf%e5%8f%91%e8%a1%a8%ef%bc%9aselepressin%e4%b8%8e%e5%ae%89%e6%85%b0%e5%89%82%e5%af%b9%e6%84%9f%e6%9f%93%e6%80%a7%e4%bc%91%e5%85%8b%e6%82%a3%e8%80%85%e6%97%a0%e6%9c%ba%e6%a2%b0","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=17850","title":{"rendered":"[JAMA\u5728\u7ebf\u53d1\u8868]\uff1aSelepressin\u4e0e\u5b89\u6170\u5242\u5bf9\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\u65e0\u673a\u68b0\u53ca\u65e0\u5347\u538b\u836f\u5929\u6570\u7684\u5f71\u54cd"},"content":{"rendered":"\n

Original Investigation Caring for the Critically Ill PatientOctober 2, 2019<\/p>\n\n\n\n

Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial<\/h1>\n\n\n\n

Pierre-Francois Laterre, Scott M. Berry, Allan Blemings, et al<\/h3>\n\n\n\n

JAMA. <\/em>Published online October 2, 2019. doi:10.1001\/jama.2019.14607<\/h3>\n\n\n\n

Importance<\/strong> \u80cc\u666f<\/h3>\n\n\n\n

Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects.<\/p>\n\n\n\n

\u53bb\u7532\u80be\u4e0a\u817a\u7d20\u662f\u6cbb\u7597\u611f\u67d3\u6027\u4f11\u514b\u7684\u4e00\u7ebf\u5347\u538b\u836f\u7269\uff0c\u4f46\u5e76\u975e\u603b\u662f\u6709\u6548\uff0c\u4e14\u5177\u6709\u513f\u8336\u915a\u80fa\u7c7b\u836f\u7269\u91cd\u8981\u7684\u526f\u4f5c\u7528\u3002Selepressin\u662f\u4e00\u79cd\u9009\u62e9\u6027\u8840\u7ba1\u52a0\u538b\u7d20V1a\u53d7\u4f53\u6fc0\u52a8\u5242\u3002\u4f5c\u4e3a\u4e00\u79cd\u975e\u513f\u8336\u915a\u80fa\u7c7b\u5347\u538b\u836f\u7269\uff0cSelepressin\u80fd\u591f\u7f13\u89e3\u8113\u6bd2\u75c7\u8bf1\u53d1\u7684\u8840\u7ba1\u6269\u5f20\u3001\u8840\u7ba1\u6e17\u6f0f\u53ca\u6c34\u80bf\uff0c\u4e14\u526f\u4f5c\u7528\u66f4\u5c11\u3002<\/p>\n\n\n\n

Objective<\/strong> \u76ee\u7684<\/h3>\n\n\n\n

To test whether selepressin improves outcome in septic shock.<\/p>\n\n\n\n

\u9a8c\u8bc1Selepressin\u80fd\u5426\u6539\u5584\u611f\u67d3\u6027\u4f11\u514b\u7684\u9884\u540e<\/p>\n\n\n\n

Design, Setting, and Participants<\/strong> \u8bd5\u9a8c\u5b9e\u9645\uff0c\u573a\u666f\u53ca\u7814\u7a76\u5bf9\u8c61<\/h3>\n\n\n\n

An adaptive phase 2b\/3 randomized clinical trial comprising 2 parts that included adult patients (n\u2009=\u2009868) with septic shock requiring more than 5 \u03bcg\/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018.<\/p>\n\n\n\n

\u8fd9\u662f\u4e00\u9879\u5305\u62ec\u4e24\u4e2a\u90e8\u5206\u7684\u8c03\u6574\u8bbe\u8ba12b\/3\u671f\u968f\u673a\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u7eb3\u5165\u9700\u8981\u53bb\u7532\u80be\u4e0a\u817a\u7d20\u5242\u91cf\u8d85\u8fc75 \u03bcg\/min\u7684\u6210\u5e74\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005(n\u2009=\u2009868)\u3002\u7b2c\u4e00\u90e8\u5206\u91c7\u7528Bayesian\u7b97\u6cd5\u8c03\u6574\u968f\u673a\u5206\u914d\u81f3\u4e0d\u540cselepressin\u5242\u91cf\u7684\u6982\u7387\uff0c\u5e76\u636e\u6b64\u542f\u52a8\u7b2c\u4e8c\u90e8\u5206\uff0c\u5373\u5c06\u6700\u4f73\u5242\u91cf\u7ec4\u4e0e\u5b89\u6170\u5242\u8fdb\u884c\u6bd4\u8f83\u3002\u8bd5\u9a8c\u4e8e2015\u5e747\u6708\u81f32017\u5e748\u6708\u95f4\u5728\u6bd4\u5229\u65f6\u3001\u4e39\u9ea6\u3001\u6cd5\u56fd\u8377\u5170\u548c\u7f8e\u56fd\u768463\u6240\u533b\u9662\u8fdb\u884c\uff0c\u968f\u8bbf\u4e8e2018\u5e745\u6708\u7ec8\u6b62\u3002<\/p>\n\n\n\n

Interventions<\/strong> \u5e72\u9884\u63aa\u65bd<\/h3>\n\n\n\n

Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng\/kg\/min; n\u2009=\u2009585) or to placebo (n\u2009=\u2009283), all administered as continuous infusions titrated according to hemodynamic parameters.<\/p>\n\n\n\n

\u968f\u673a\u5206\u81f3selepressin\u4e09\u4e2a\u5242\u91cf\u7ec4(\u8d77\u59cb\u8f93\u6ce8\u5242\u91cf\u5206\u522b\u4e3a1.7, 2.5, \u548c 3.5 ng\/kg\/min; n\u2009=\u2009585) \u6216\u5b89\u6170\u5242 (n\u2009=\u2009283)\uff0c\u6240\u6709\u7814\u7a76\u836f\u7269\u5747\u6301\u7eed\u8f93\u6ce8\uff0c\u6839\u636e\u8840\u6d41\u52a8\u529b\u5b66\u53c2\u6570\u60c5\u51b5\u8c03\u6574\u5242\u91cf\u3002<\/p>\n\n\n\n

Main Outcomes and Measures<\/strong> \u4e3b\u8981\u9884\u540e\u6307\u6807<\/h3>\n\n\n\n

Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy\u2013free days, and ICU-free days.<\/p>\n\n\n\n

\u4e3b\u8981\u9884\u540e\u7ec8\u70b9\u4e3a\u5f00\u59cb\u4f7f\u7528\u7814\u7a76\u836f\u726930\u5929\u5185\u65e0\u673a\u68b0\u901a\u6c14\u4e14\u65e0\u5347\u538b\u836f\u7269\u5929\u6570\uff08\u6b7b\u4ea1\u60a3\u8005\u8fd9\u4e00\u6307\u6807\u4e3a0\u5929\uff09\u3002\u5173\u952e\u7684\u6b21\u8981\u9884\u540e\u7ec8\u70b9\u4e3a90\u5929\u75c5\u6b7b\u7387\uff0c\u65e0\u80be\u810f\u66ff\u4ee3\u6cbb\u7597\u5929\u6570\uff0c\u4ee5\u53ca\u975eICU\u4f4f\u9662\u5929\u6570\u3002<\/p>\n\n\n\n

Results<\/strong> \u7ed3\u679c<\/h3>\n\n\n\n

Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, \u22121.3 to 2.4]; P<\/em>\u2009=\u2009.30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, \u22126.5% to 8.8%]; P<\/em>\u2009=\u2009.77; kidney replacement therapy\u2013free days: 18.5 vs 18.2; difference, 0.3 [95% CI, \u22122.1 to 2.6]; P<\/em>\u2009=\u2009.85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, \u22121.2 to 2.2]; P<\/em>\u2009=\u2009.41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%).<\/p>\n\n\n\n

\u5171\u6709 868 \u540d\u60a3\u8005\u63a5\u53d7\u968f\u673a\u5206\u7ec4\uff0c828 \u540d\u60a3\u8005\u63a5\u53d7\u7814\u7a76\u836f\u7269(\u5e73\u5747\u5e74\u9f84, 66.3 \u5c81; 341 [41.2%] \u540d\u5973\u6027) \u4f5c\u4e3a\u4e3b\u8981\u5206\u6790\u961f\u5217\uff0c\u5176\u4e2d 562 \u540d\u60a3\u8005\u4f7f\u7528selepressin\u4e09\u79cd\u5242\u91cf\u4e2d\u7684\u4e00\u79cd\uff0c266 \u540d\u60a3\u8005\u4f7f\u7528\u5b89\u6170\u5242\uff0c817 \u540d\u60a3\u8005 (98.7%) \u5b8c\u6210\u8bd5\u9a8c\u3002\u5728\u7b2c\u4e00\u90e8\u5206\u7ed3\u675f\u65f6\u8bd5\u9a8c\u56e0\u65e0\u6548\u7ec8\u6b62\u3002\u7814\u7a76\u836f\u7269\u4f7f\u7528\u4e2d\u4f4d\u65f6\u95f4\u4e3a37.8 \u5c0f\u65f6 (IQR, 17.8-72.4)\u3002\u4e3b\u8981\u9884\u540e\u7ec8\u70b9\u65e0\u663e\u8457\u5dee\u5f02 (\u65e0\u673a\u68b0\u901a\u6c14\u4e14\u65e0\u5347\u538b\u836f\u7269\u5929\u6570: selepressin\u7ec415.0 vs \u5b89\u6170\u5242\u7ec414.5; \u5dee\u5f02, 0.6 [95% CI, \u22121.3 to 2.4]; P<\/em>\u2009=\u2009.30)\uff0c\u5173\u952e\u6b21\u8981\u7ec8\u70b9\u4e5f\u6ca1\u6709\u5dee\u5f02 (90\u5929\u75c5\u6b7b\u7387, 40.6% vs 39.4%; \u5dee\u5f02, 1.1% [95% CI, \u22126.5% to 8.8%]; P<\/em>\u2009=\u2009.77; \u65e0\u80be\u810f\u66ff\u4ee3\u6cbb\u7597\u5929\u6570: 18.5 vs 18.2; \u5dee\u5f02, 0.3 [95% CI, \u22122.1 to 2.6]; P<\/em>\u2009=\u2009.85; \u975eICU\u4f4f\u9662\u5929\u6570: 12.6 vs 12.2; \u5dee\u5f02, 0.5 [95% CI, \u22121.2 to 2.2]; P<\/em>\u2009=\u2009.41)\u3002\u4e0d\u826f\u4e8b\u4ef6\u5305\u62ec\u5fc3\u5f8b\u5931\u5e38(27.9% vs 25.2%)\uff0c\u5fc3\u808c\u7f3a\u8840(6.6% vs 5.6%)\uff0c\u80a0\u7cfb\u819c\u7f3a\u8840 (3.2% vs 2.6%)\u53ca\u5916\u5468\u7f3a\u8840(2.3% vs 2.3%)\u3002<\/p>\n\n\n\n

\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n

Conclusions and Relevance<\/strong> \u7ed3\u8bba\u4e0e\u610f\u4e49<\/h3>\n\n\n\n

Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock.<\/p>\n\n\n\n

\u5bf9\u4e8e\u4f7f\u7528\u53bb\u7532\u80be\u4e0a\u817a\u7d20\u7684\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\uff0c\u4e0e\u5b89\u6170\u5242\u76f8\u6bd4\uff0c\u4f7f\u7528selepressin\u4e0d\u80fd\u6539\u558430\u5929\u5185\u65e0\u5347\u538b\u836f\u7269\u53ca\u65e0\u673a\u68b0\u901a\u6c14\u5929\u6570\u3002\u9700\u8981\u8fdb\u4e00\u6b65\u7814\u7a76\u8bc4\u4ef7selepressin\u5bf9\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\u5176\u4ed6\u9884\u540e\u6307\u6807\u7684\u4f5c\u7528\u3002<\/p>\n\n\n\n

Trial Registration<\/strong> \u8bd5\u9a8c\u6ce8\u518c<\/h3>\n\n\n\n

ClinicalTrials.gov Identifier:\u00a0NCT02508649<\/a><\/p>\n\n\n\n

\u8bc4\u8bba[\u4ec5\u4ee3\u8868\u4e2a\u4eba\u89c2\u70b9]<\/h3>\n\n\n\n
  • \u5305\u62ec\u672c\u9879\u7814\u7a76\u5728\u5185\u7684\u591a\u9879\u968f\u673a\u5bf9\u7167\u8bd5\u9a8c\u8868\u660e\uff0c\u7528\u53e6\u5916\u4e00\u79cd\u5347\u538b\u836f\u7269\u66ff\u4ee3\u73b0\u6709\u7684\u53bb\u7532\u80be\u4e0a\u817a\u7d20\uff0c\u5e76\u4e0d\u80fd\u6539\u5584\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\u7684\u4e34\u5e8a\u7ed3\u5c40<\/li>
  • \u5f53\u7136\uff0c\u8840\u7ba1\u7d27\u5f20\u7d20II\u8fd8\u6ca1\u6709\u505a3\u671f\u4e34\u5e8a\u8bd5\u9a8c\u3002\u4f46\u662f\uff0c\u6839\u636e\u73b0\u6709\u7ed3\u679c\uff0c\u8fd9\u5c06\u4f1a\u662f\u4e00\u4e2a\u6709\u9633\u6027\u7ed3\u679c\u7684\u4e34\u5e8a\u8bd5\u9a8c\u5417\uff1f<\/li>
  • \u591a\u5e74\u524d\uff0cVASST\u7814\u7a76\u53d1\u8868\u540e\uff0cJoseph Parrillo\u8ff0\u8bc4\u4e2d\u7684\u4e00\u6bb5\u8bdd\u4ecd\u7136\u662f\u6b63\u786e\u7684\uff1a\u4e0e\u5176\u8ba8\u8bba\u4f7f\u7528\u54ea\u79cd\u5347\u538b\u836f\u7269\u80fd\u591f\u6539\u5584\u7ed3\u5c40\uff0c\u4e0d\u5982\u8bf4\u4f7f\u7528\u5347\u538b\u836f\u7269\u7684\u65f6\u673a\u66f4\u4e3a\u5173\u952e\u3002<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"

    Original Investigation Caring for the Critically I […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17850"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=17850"}],"version-history":[{"count":3,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17850\/revisions"}],"predecessor-version":[{"id":17859,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17850\/revisions\/17859"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=17850"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=17850"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=17850"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}