{"id":22095,"date":"2022-06-25T04:20:00","date_gmt":"2022-06-24T20:20:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=22095"},"modified":"2022-06-25T04:26:38","modified_gmt":"2022-06-24T20:26:38","slug":"nejm%e5%8f%91%e8%a1%a8%e8%bf%b0%e8%af%84%ef%bc%9a%e6%84%9f%e6%9f%93%e6%80%a7%e4%bc%91%e5%85%8b%e7%9a%84%e9%9d%99%e8%84%89%e6%b6%b2%e4%bd%93%e6%b2%bb%e7%96%97%ef%bc%9a%e5%a4%9a%e6%8a%91%e6%88%96","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=22095","title":{"rendered":"[NEJM\u53d1\u8868\u8ff0\u8bc4]\uff1a\u611f\u67d3\u6027\u4f11\u514b\u7684\u9759\u8109\u6db2\u4f53\u6cbb\u7597\uff1a\u591a\u6291\u6216\u5c11\uff1f"},"content":{"rendered":"\n

EDITORIAL<\/a>FREE PREVIEW<\/strong><\/p>\n\n\n\n

Intravenous Fluids in Septic Shock \u2014 More or Less?<\/h1>\n\n\n\n

Lauralyn A. McIntyre, John C. Marshall<\/h3>\n\n\n\n

N Engl J Med June 17, 2022
DOI: 10.1056\/NEJMe2206160<\/h3>\n\n\n\n

\u2026soon the sharpened features, and sunken eye, and fallen jaw, pale and cold, bearing the manifest impress of death\u2019s signet, began to glow with returning animation\u2026.<\/p>\n\n\n\n

\u201c. . .\u00a0\u5f88\u5feb\uff0c\u7626\u524a\u7684\u4e94\u5b98\u3001\u51f9\u9677\u7684\u773c\u775b\u548c\u4e0b\u5782\u7684\u4e0b\u5df4\uff0c\u82cd\u767d\u800c\u51b0\u51b7\u7684\u76ae\u80a4\uff0c\u8fd9\u4e9b\u660e\u663e\u7684\u6b7b\u4ea1\u8ff9\u8c61\u5f00\u59cb\u91cd\u65b0\u7115\u53d1\u6d3b\u529b\u3002\u201d<\/p>\n\n\n\n

\u2014 Dr. Thomas Latta<\/p>\n\n\n\n

During the British cholera epidemic of 1831, William O\u2019Shaughnessy reported that the blood of victims \u201chas lost a large portion of its water\u2026a great proportion of its neutral saline ingredients\u201d and that \u201cof the free alkali contained in healthy serum, not a particle is present in some cholera cases.\u201d1<\/sup>\u00a0He advocated for the restoration of the missing water and salts, an approach that was embraced by the Scottish general practitioner Thomas Latta, who reported the striking resuscitative effects described above.2 Two centuries later, key questions remain: which fluids, how much, and toward what targets?<\/p>\n\n\n\n

1831\u5e74\u82f1\u56fd\u970d\u4e71\u75ab\u60c5\u671f\u95f4\uff0cWilliam O'Shaughnessy\u62a5\u544a\u8bf4\uff0c\u75c5\u4eba\u8840\u6db2\u201c\u5931\u53bb\u4e86\u5f88\u591a\u6c34\u5206\uff0c\u5176\u4e2d\u5927\u90e8\u5206\u662f\u4e2d\u6027\u76d0\u6210\u5206\u201d\uff0c\u800c\u4e14\u201c\u5065\u5eb7\u8840\u6e05\u4e2d\u6240\u542b\u7684\u6e38\u79bb\u78b1\uff0c\u5728\u67d0\u4e9b\u970d\u4e71\u75c5\u4f8b\u4e2d\u5b8c\u5168\u4e0d\u5b58\u5728\u3002\u201d\u4ed6\u63d0\u5021\u8865\u5145\u4e22\u5931\u7684\u6c34\u548c\u76d0\uff0c\u82cf\u683c\u5170\u5168\u79d1\u533b\u751fThomas Latta\u91c7\u7528\u4e86\u8fd9\u4e00\u65b9\u6cd5\uff0c\u5e76\u62a5\u544a\u4e86\u4e0a\u8ff0\u60ca\u4eba\u7684\u590d\u82cf\u6548\u679c\u3002\u4f46\u4e24\u4e2a\u4e16\u7eaa\u540e\uff0c\u5173\u952e\u95ee\u9898\u4ecd\u7136\u6ca1\u6709\u7b54\u6848\uff1a\u4f7f\u7528\u4f55\u79cd\u6db2\u4f53\uff0c\u8f93\u6db2\u91cf\u662f\u591a\u5c11\uff0c\u76ee\u6807\u662f\u4ec0\u4e48\uff1f<\/p>\n\n\n\n

More than a decade ago, the Fluid Expansion as Supportive Therapy (FEAST) trial showed higher survival with the use of a more fluid-restrictive approach than with a standard approach to intravenous-fluid therapy among children with severe infections.3 A more recent systematic review examined restrictive or active fluid removal approaches with the use of diuretics or renal-replacement therapy in critically ill children and adults.4 In 11 randomized, controlled trials involving a total of 2051 patients, a restrictive-fluids or active-fluid removal approach was associated with more ventilator-free days and shorter intensive care unit (ICU) stays than a liberal fluid approach or standard care, but not lower mortality, which led the authors to conclude that rigorous and adequately powered trials are needed.4<\/p>\n\n\n\n

\u5341\u591a\u5e74\u524d\uff0c\u00a0FEAST\u7814\u7a76\u8868\u660e\uff0c\u5bf9\u4e8e\u91cd\u75c7\u611f\u67d3\u7684\u60a3\u513f\uff0c\u4e0e\u6807\u51c6\u6db2\u4f53\u590d\u82cf\u7597\u6cd5\u76f8\u6bd4\uff0c\u9650\u5236\u6027\u6db2\u4f53\u590d\u82cf\u6cbb\u7597\u7684\u751f\u5b58\u7387\u66f4\u9ad8\u3002\u6700\u8fd1\u7684\u4e00\u9879\u7cfb\u7edf\u7efc\u8ff0\u7814\u7a76\u4e86\u5371\u91cd\u513f\u7ae5\u548c\u6210\u4eba\u60a3\u8005\u4f7f\u7528\u9650\u5236\u6027\u6db2\u4f53\u6cbb\u7597\u548c\u5e94\u7528\u5229\u5c3f\u5242\u6216\u80be\u810f\u66ff\u4ee3\u6cbb\u7597\u4e3b\u52a8\u6e05\u9664\u6db2\u4f53\u7684\u7b56\u7565\u3002\u7cfb\u7edf\u56de\u987e\u5171\u7eb3\u5165\u4e8611\u9879\u968f\u673a\u5bf9\u7167\u8bd5\u9a8c\u4e2d\u76842051\u540d\u60a3\u8005\uff0c\u4e0e\u81ea\u7531\u6db2\u4f53\u6cbb\u7597\u6216\u6807\u51c6\u6cbb\u7597\u76f8\u6bd4\uff0c\u9650\u5236\u6027\u6db2\u4f53\u6cbb\u7597\u6216\u4e3b\u52a8\u6e05\u9664\u6db2\u4f53\u7b56\u7565\u4f34\u968f\u65e0\u673a\u68b0\u901a\u6c14\u5929\u6570\u589e\u52a0\uff0cICU\u4f4f\u9662\u65f6\u95f4\u7f29\u77ed\uff0c\u4f46\u6b7b\u4ea1\u7387\u5e76\u672a\u964d\u4f4e\uff0c\u4f5c\u8005\u7531\u6b64\u5f97\u5230\u7ed3\u8bba\uff0c\u5373\u9700\u8981\u8fdb\u884c\u4e25\u683c\u4e14\u628a\u63e1\u5ea6\u8db3\u591f\u7684\u4e34\u5e8a\u8bd5\u9a8c\u3002<\/p>\n\n\n\n

Meyhoff and colleagues5 now report in the Journal the results of the CLASSIC (Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care) trial, an international, randomized trial to determine whether limiting fluid exposure for patients with septic shock could improve 90-day survival. In this trial, 1554 patients who had had onset of septic shock within 12 hours before screening were randomly assigned to receive either restrictive fluid therapy or standard fluid therapy for the duration of their ICU stay, up to a maximum of 90 days. Randomization was stratified according to trial site and the presence or absence of metastatic or hematologic cancer. Patients received a median of 3 liters of intravenous fluid before they underwent randomization and were enrolled within 3 hours after admission to the ICU. The restrictive-fluid group received intravenous crystalloid fluids in small boluses (250 or 500 ml) that could only be given to treat severe hypoperfusion, as defined by lactate levels, mean arterial pressure, mottling, or urine output; to replace documented fluid losses; or to correct dehydration and electrolyte deficiency if the enteral route was contraindicated. The standard-fluid group had no limits on the volume of fluids that could be administered, but management recommendations were based on the 2016 Surviving Sepsis Campaign guidelines.6<\/p>\n\n\n\n

Meyhoff\u53ca\u5176\u540c\u4e8b\u5728\u65b0\u82f1\u683c\u5170\u533b\u5b66\u6742\u5fd7\u53d1\u8868\u4e86CLASSIC\u7814\u7a76\u7684\u7ed3\u679c\u3002\u8fd9\u662f\u4e00\u9879\u56fd\u9645\u968f\u673a\u5bf9\u7167\u8bd5\u9a8c\uff0c\u65e8\u5728\u786e\u5b9a\u9650\u5236\u8f93\u6db2\u662f\u5426\u53ef\u4ee5\u63d0\u9ad8\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\u768490\u5929\u751f\u5b58\u7387\u3002\u8bd5\u9a8c\u5165\u9009\u4e861554\u540d\u60a3\u8005\uff0c\u5176\u611f\u67d3\u6027\u4f11\u514b\u7684\u53d1\u75c5\u65f6\u95f4\u5728\u5165\u7ec4\u524d12\u5c0f\u65f6\u3002\u8fd9\u4e9b\u60a3\u8005\u63a5\u53d7\u968f\u673a\u5206\u7ec4\uff0c\u5728ICU\u4f4f\u9662\u671f\u95f4\u5206\u522b\u63a5\u53d7\u9650\u5236\u6027\u6db2\u4f53\u6cbb\u7597\u6216\u6807\u51c6\u6db2\u4f53\u6cbb\u7597\uff0c\u7597\u7a0b\u4e0d\u8d85\u8fc790\u5929\u3002\u968f\u673a\u5206\u7ec4\u65f6\u6839\u636e\u8bd5\u9a8c\u5730\u70b9\u4ee5\u53ca\u662f\u5426\u5b58\u5728\u80bf\u7624\u8f6c\u79fb\u6216\u8840\u6db2\u7cfb\u7edf\u80bf\u7624\u8fdb\u884c\u5206\u5c42\u3002\u968f\u673a\u5206\u7ec4\u524d\uff0c\u60a3\u8005\u63a5\u53d7\u9759\u8109\u8f93\u6db2\u7684\u4e2d\u4f4d\u6570\u4e3a3\u5347\uff0c\u4e14\u5728\u6536\u5165ICU\u540e3\u5c0f\u65f6\u5185\u5165\u7ec4\u3002\u9650\u5236\u6027\u6db2\u4f53\u6cbb\u7597\u7ec4\u4ec5\u63a5\u53d7\u5c0f\u5242\u91cf\uff08250\u6216500 ml\uff09\u6676\u4f53\u6db2\u8f93\u6ce8\uff0c\u4e14\u53ea\u80fd\u7528\u4e8e\u6cbb\u7597\u4e25\u91cd\u4f4e\u704c\u6ce8\uff08\u6839\u636e\u4e73\u9178\u6c34\u5e73\u3001\u5e73\u5747\u52a8\u8109\u538b\u3001\u76ae\u80a4\u82b1\u6591\u6216\u5c3f\u91cf\u5b9a\u4e49\uff09\u6216\u8865\u5145\u6db2\u4f53\u4e22\u5931\uff0c\u4ee5\u53ca\u5728\u65e0\u6cd5\u4f7f\u7528\u80a0\u9053\u65f6\u7ea0\u6b63\u8131\u6c34\u548c\u7535\u89e3\u8d28\u7f3a\u4e4f\u3002\u6807\u51c6\u6db2\u4f53\u6cbb\u7597\u7ec4\u5bf9\u8f93\u6db2\u91cf\u6ca1\u6709\u9650\u5236\uff0c\u4f46\u5efa\u8bae\u9075\u5faa2016\u5e74\u62ef\u6551\u8113\u6bd2\u75c7\u8fd0\u52a8\u6307\u5357\u8fdb\u884c\u6cbb\u7597\u3002<\/p>\n\n\n\n

The median between-group difference in the volume of intravenous fluids administered was approximately 2 liters. The authors found no significant difference in mortality at 90 days in the total population (the primary outcome), in any of the prespecified secondary outcomes (including renal function) or in the prespecified subgroups, or in the occurrence of ischemic events.<\/p>\n\n\n\n

\u4e24\u7ec4\u95f4\u9759\u8109\u8f93\u6db2\u91cf\u5dee\u5f02\u7684\u4e2d\u4f4d\u6570\u7ea6\u4e3a2\u5347\u3002\u4f5c\u8005\u53d1\u73b0\uff0c\u603b\u4eba\u7fa4\u768490\u5929\u75c5\u6b7b\u7387\uff08\u4e3b\u8981\u7ed3\u5c40\uff09\uff0c\u9884\u5148\u786e\u5b9a\u7684\u6b21\u8981\u7ed3\u5c40\u6307\u6807\uff08\u5305\u62ec\u80be\u529f\u80fd\uff09\u6216\u9884\u5148\u8bbe\u5b9a\u7684\u4e9a\u7ec4\u5206\u6790\uff0c\u6216\u7f3a\u8840\u6027\u4e8b\u4ef6\u53d1\u751f\u7387\u5747\u65e0\u663e\u8457\u5dee\u5f02\u3002<\/p>\n\n\n\n

Can clinicians conclude that clinical outcomes did not differ with a restrictive approach as compared with a more liberal fluid strategy in patients with septic shock? Perhaps, but the CLASSIC trial raises additional questions.<\/p>\n\n\n\n

\u90a3\u4e48\u4e34\u5e8a\u533b\u751f\u80fd\u5426\u5f97\u51fa\u4ee5\u4e0b\u7ed3\u8bba\uff0c\u5373\u5bf9\u4e8e\u611f\u67d3\u6027\u4f11\u514b\u60a3\u8005\uff0c\u9650\u5236\u6027\u8f93\u6db2\u7b56\u7565\u4e0e\u66f4\u81ea\u7531\u7684\u8f93\u6db2\u7b56\u7565\u65f6\u4e34\u5e8a\u7ed3\u5c40\u5e76\u65e0\u5dee\u5f02\uff1f\u7b54\u6848\u6216\u8bb8\u5982\u6b64\uff0c\u4f46CLASSIC\u8bd5\u9a8c\u63d0\u51fa\u4e86\u66f4\u591a\u7684\u95ee\u9898\u3002<\/p>\n\n\n\n

The magnitude of an effect shown in a clinical trial depends not only on the efficacy of the experimental intervention but also on the nature of the control group. If controls are not distinctly different, the absence of a therapeutic signal may suggest that both populations were treated in a broadly similar manner. When the intervention is a drug or device, the use of a placebo or sham allows valid inferences of causality. But when the intervention is a management strategy, the issue becomes more complex. In the CLASSIC trial, the small between-group difference in the median volume of intravenous fluid administered suggests, in the face of a stringent protocol of fluid restriction in the experimental group, that the patients in the standard-care group were also treated according to a conservative fluid strategy, making the detection of a 7-percentage-point difference in 90-day mortality (the difference for which the trial was powered) appear infeasible.<\/p>\n\n\n\n

\u4e34\u5e8a\u8bd5\u9a8c\u6240\u663e\u793a\u7684\u6548\u5e94\u5927\u5c0f\u4e0d\u4ec5\u53d6\u51b3\u4e8e\u5b9e\u9a8c\u6027\u6cbb\u7597\u7684\u7597\u6548\uff0c\u8fd8\u53d6\u51b3\u4e8e\u5bf9\u7167\u7ec4\u7684\u7279\u5f81\u3002\u5982\u679c\u5bf9\u7167\u7ec4\u5e76\u65e0\u663e\u8457\u5dee\u5f02\uff0c\u5219\u7597\u6548\u7684\u7f3a\u4e4f\u53ef\u80fd\u8868\u660e\u8fd9\u4e24\u7ec4\u60a3\u8005\u63a5\u53d7\u4e86\u5927\u81f4\u76f8\u4f3c\u7684\u6cbb\u7597\u3002\u5f53\u5e72\u9884\u63aa\u65bd\u662f\u836f\u7269\u6216\u8bbe\u5907\u65f6\uff0c\u4f7f\u7528\u5b89\u6170\u5242\u6216\u5047\u6cbb\u7597\u7ec4\u53ef\u4ee5\u6709\u6548\u63a8\u65ad\u56e0\u679c\u5173\u7cfb\u3002\u4f46\u5982\u679c\u5e72\u9884\u662f\u4e00\u79cd\u6cbb\u7597\u7b56\u7565\uff0c\u95ee\u9898\u5c31\u4f1a\u53d8\u5f97\u66f4\u52a0\u590d\u6742\u3002\u5728CLASSIC\u8bd5\u9a8c\u4e2d\uff0c\u9759\u8109\u8f93\u6db2\u91cf\u4e2d\u4f4d\u6570\u7684\u7ec4\u95f4\u5dee\u5f02\u5f88\u5c0f\uff0c\u8fd9\u63d0\u793a\uff0c\u9664\u5b9e\u9a8c\u7ec4\u63a5\u53d7\u4e86\u4e25\u683c\u7684\u6db2\u4f53\u9650\u5236\u6cbb\u7597\u5916\uff0c\u6807\u51c6\u6cbb\u7597\u7ec4\u60a3\u8005\u4e5f\u63a5\u53d7\u4e86\u4fdd\u5b88\u7684\u6db2\u4f53\u6cbb\u7597\u7b56\u7565\uff0c\u4ece\u800c\u5bfc\u81f4\u68c0\u9a8c\u4e24\u7ec4\u60a3\u800590\u5929\u75c5\u6b7b\u73877\u4e2a\u767e\u5206\u70b9\u7684\u5dee\u5f02\uff08\u8bd5\u9a8c\u6837\u672c\u91cf\u8db3\u4ee5\u68c0\u9a8c\u8fd9\u4e00\u7a0b\u5ea6\u7684\u5dee\u5f02\uff09\u5e76\u4e0d\u53ef\u884c\u3002<\/p>\n\n\n\n

When investigators seek to show the superiority of a particular approach, a usual-care comparator is generally thought to be better than the creation of a contrasting protocol. But what is usual care, and is it the same everywhere? The amount of intravenous fluid that was received by the patients in the standard-care group in this trial was substantially less than that observed in previous national and international trials of early, goal-directed resuscitation involving patients with septic shock7 and in cohort studies.8,9 The results of work completed previously by the authors that suggested benefit from a more restrictive fluid management strategy might have changed clinical practice in northern Europe sufficiently that this trial was unable to answer the question it set out to address.10<\/p>\n\n\n\n

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Nonetheless, the CLASSIC trial generated rigorous, high-quality evidence related to a complex research question with regard to fluids in patients with septic shock. These findings show that a highly restrictive fluid-management strategy is safe and raise important new questions that challenge conventional wisdom regarding the management of shock \u2014 how much fluid we should give, when we should restrict fluids and with what physiologic thresholds and targets, when we should use fluids and when we should use vasoactive drugs, and finally, whether and when we should begin an active strategy of fluid removal \u2014 all with the ultimate goal of reducing mortality and improving the function and quality of life for our surviving patients.<\/p>\n\n\n\n

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EDITORIALFREE PREVIEW Intravenous Fluids in Septic Shoc […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22095"}],"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=22095"}],"version-history":[{"count":4,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22095\/revisions"}],"predecessor-version":[{"id":22099,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/22095\/revisions\/22099"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22095"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22095"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22095"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}