PulmCrit - Top ten problems with the new sepsis definitionby Josh Farkas翻譯：北京協(xié)和醫(yī)院 江偉Problem #6: qSOFA is inconsistent with a validated prognostic model (CURB65)問題#6：qSOFA與經(jīng)過驗證的預后模型(CURB65)并不一致Pneumonia is the most common source of septic shock. This naturally leads to a comparison of qSOFA with the CURB65 prognostic score for pneumonia. 肺炎是感染性休克最常見的病因。很自然人們會將qSOFA與肺炎的CURB65預后評分進行比較。 Comparison suggests that qSOFA over-estimates the mortality of a pneumonia patients. For example, consider a 50-year-old patient with pneumonia, respiratory rate of 24 breaths/minute, blood pressure of 95/65, BUN of 15 mg/dL, and normal mental status. According to qSOFA, this patient has sepsis and perhaps should be transferred to the ICU. However, according to the CURB65 score, this patient has a 0.6% mortality and could be sent home with oral antibiotics. 比較提示，qSOFA會高估肺炎患者的病死率。例如，一名50歲肺炎患者呼吸頻率24次/分，血壓95/65，BUN 15 mg/dL，意識狀態(tài)正常。根據(jù)qSOFA，該患者存在全身性感染，可能需要轉(zhuǎn)入ICU。而根據(jù)CURB65評分，該患者病死率為0.6%，可以回家口服抗生素治療。
This is an example of how qSOFA may be less specific in patients with primary pulmonary disease (as discussed above). A respiratory rate >22 is not particularly unusual or alarming in a patient with pneumonia (4). Thus, many pneumonia patients will start out with one qSOFA criteria, only requiring one additional criteria to become qSOFA-positive. 這個例子說明為何qSOFA在原發(fā)肺部疾病患者中特異性偏低（如上所述）。肺炎患者呼吸頻率> 22并不少見，且沒有警示價值(4)。因此，許多肺炎患者據(jù)此就滿足一項qSOFA標準，僅需要額外一項標準就成為qSOFA陽性。
Problem #7: Combining qSOFA and SOFA scores is not evidence-based among patients outside the ICU問題#7：對于非ICU患者聯(lián)合qSOFA和SOFA評分沒有證據(jù)支持A common approach to diagnosis is shown here. When a condition is suspected (e.g. pulmonary embolism), first a screening test is utilized. An ideal screening test has a high sensitivity, but is fast and easy to perform (e.g. D-dimer). Patients who have a positive screening test will need to proceed onward to a definitive test, which is often more expensive or difficult to perform, but has both high sensitivity and specificity (e.g. CT angiogram). 常見的診斷過程如上所述。懷疑某種疾病（如肺栓塞）時，首先采用篩查試驗。理想的篩查試驗應當具有較高的敏感性，而且快速簡便（如D二聚體）。篩查試驗陽性的患者需要進一步接受確證實驗，通常更加昂貴或難以實施，但具有很高的敏感性和特異性（如CT血管造影）。 The sepsis diagnostic algorithm seems to be designed with qSOFA as a screening test and SOFA as a definitive test. On face value this makes sense, because qSOFA is a simple and fast, whereas the full SOFA test is labor intensive. 全身性感染診斷流程中似乎將qSOFA作為篩查試驗，而將SOFA作為確證試驗。從表面看貌似是有道理的，因為qSOFA簡便快速，而完整的SOFA則需要耗費大量人力。 However, the specificity of SOFA is actually lower than the specificity of qSOFA, making this test sequence illogical. Thus, SOFA adds little to qSOFA among patients outside the ICU (5). 但是，SOFA的特異性實際上低于qSOFA，使得這一檢查順序并不符合邏輯。因此，對于非ICU患者，與qSOFA相比，SOFA并無額外意義(5)。
Problem #8: The combined performance of {qSOFA + SOFA} for mortality is not reported問題#8：未報告qSOFA和SOFA聯(lián)合應用對病死率的價值Although evidence is provided regarding the performance of qSOFA and SOFA, there is no evidence provided about the performance of the combination of {qSOFA+SOFA}. Since qSOFA and SOFA scores are not statistically independent, it is difficult to predict how they will function in combination. To explore this, lets imagine two extreme possibilities: qSOFA and SOFA either being maximally concordant or maximally discordant: 雖然文中報告了qSOFA和SOFA預測準確性的相關證據(jù)，但未提供聯(lián)合應用qSOFA和SOFA的數(shù)據(jù)。因為qSOFA和SOFA評分在統(tǒng)計學方面并不完全獨立，所以很難預測其聯(lián)合應用的價值。為此，我們可以假設兩種極端的情況：qSOFA和SOFA完全一致或完全不一致： Discordance improves the specificity of the combined test sequence, because only one test needs to be negative to exclude sepsis. However, discordance impairs the sensitivity, because both tests must be positive to rule in sepsis. The tests are almost certainly more concordant than discordant. Without evidence, the only definitive conclusion is that the combined tests have a sensitivity between 23-55% and a specificity between 84-100% (2). 不一致性會提高聯(lián)合檢測的特異性，因為只要其中一項結果陰性就可以排除全身性感染。但是，不一致性會影響敏感性，因為只有兩項檢測都陽性才能診斷全身性感染。兩項檢查更多情況下趨于一致而非不一致。盡管沒有證據(jù)證實，目前唯一的結論是聯(lián)合檢測的敏感性約23-55%，特異性84-100% (2)。 Problem #9: The overall sensitivity of Sepsis-III for sepsis might be <50% outside="" of="" the="">問題#9：非ICU患者全身性感染-III對全身性感染的總敏感性可能<>As discussed above the sensitivity of {qSOFA+SOFA} for mortality is likely <55%. however,="" the="" most="" important="" patients="" to="" identify="" are="" patients="" who="" receive="" critical="" care="" and="" subsequently="">survive (i.e. truly benefit from their ICU care). These ICU survivors may initially look less ill than the patients who die. Therefore, the sensitivity of {qSOFA+SOFA} for ICU survivors is likely lower than for nonsurvivors (i.e., <> 如上所述，聯(lián)合應用qSOFA和SOFA對病死率的敏感性很可能<><>
Finally, the sensitivity of the 'suspected infection' criteria is unknown (but almost certainly below 100%). Taking all of these factors into account, the sensitivity of Sepsis-III criteria for sepsis could be under 50% (6). 最后，“可疑感染”標準的敏感性尚屬未知（但幾乎肯定低于100%）。鑒于上述各種因素，全身性感染-III標準對全身性感染診斷的敏感性可能不足50% (6)。
Problem #10: Sepsis-III is not a consensus guideline in the United States問題#10：全身性感染-III并非美國的共識指南Sepsis-III has been endorsed by the Society of Critical Care Medicine, the American Thoracic Society, and the American Association of Critical Care Nurses. However, it has not been endorsed by the American College of Chest Physicians, the Infectious Disease Society of America, any of the Emergency Medicine societies, or any of the hospital medicine societies. It is difficult to call this a consensus guideline without support from Emergency Physicians or Hospitalists, who diagnose sepsis most often. 全身性感染-III得到了由美國危重病學會(SCCM)、美國胸科學會(ATS)、美國重癥護理學會(AACCN)的認可。然而，該標準并未得到美國胸科醫(yī)師學院(ACCP)、美國傳染病學會(IDSA)、所有急診醫(yī)學學會或任何醫(yī)院醫(yī)學學會的批準。如果沒有最常診斷全身性感染的急診醫(yī)師或醫(yī)院醫(yī)師(hospitalist)的支持，該標準就很難稱為共識指南。
[Update: since posting this, the American College of Chest Physicians has issued a strong statement opposing Sepsis III] 【更新：本文公開發(fā)表后，美國胸科醫(yī)師學會提出了反對膿毒癥III的強烈聲明】 總結
Notes 備注1. Misunderstanding of qSOFA isn't technically a failure of Sepsis-III, but rather our failure to correctly apply the definition. Nonetheless, qSOFA and SOFA components are emphasized in Sepsis-III (with scant discussion of the 'suspected infection' component). Thus, this may be an easy mistake to make. 對qSOFA的誤解并非全身性感染-III定義在技術上的失敗，而是我們不能準確應用這一定義。無論如何，全身性感染-III定義中對qSOFA和SOFA的各組分進行了強調(diào)（關于“可疑感染”部分的討論較少）。因此，這是個很容易犯的錯誤。
2. All evidence discussed here pertains to patients outside the ICU. The primary clinical utility of sepsis definitions is to determine who is sick and who needs to be admitted to the ICU. Sensitivity and specificity values are obtained from eTable 3 in the supplemental data accompanying Seymour et al. Please note that there appears to be a discrepancy between the text of the article and the table regarding the performance of the SIRS criteria, with data shown here being based on eTable 3 (The text states that for patients outside the ICU, '55% of decedents had 2 or more SIRS criteria, whereas 81% of survivors had less than 2 SIRS criteria' – this is inconsistent with the eTable 3 which shows values of 64% and 65%, respectively). 本文討論的所有證據(jù)都來自非ICU患者。全身性感染定義最主要的臨床用途即發(fā)現(xiàn)病情危重需要收入ICU的患者。敏感性和特異性數(shù)據(jù)來自Seymour等補充數(shù)據(jù)的表3。需要注意的是，正文和表格里關于SIRS標準的診斷準確性的描述似乎并不一致，本文數(shù)據(jù)基于表3（正文中描述非ICU患者，“55%的死亡者具備2條或以上SIRS標準，而81%的存活者具備2條以下的SIRS標準”—這與表3中所述的數(shù)據(jù)不符，分別為64%和65%）。
3. A receiver-operator curve (ROC curve) is a graph of the sensitivity vs. specificity of a test at every possible value of the test. This is a useful method to compare the overall performance of two tests, independent of any specific cutoff. A perfect test would have an area under the ROC curve of 1.0, whereas a completely worthless test would have an area of 0.5. However, once you've selected a cutoff point, the area under the ROC curve is less relevant than the sensitivity and specificity of the cutoff that has been selected. 受試者工作特征曲線（ROC曲線）是用于評價某項檢查在任何可能結果時敏感性和特異性的曲線圖。該曲線可用于比較兩種檢查方法的整體準確性，而與各自的臨界值無關。一項完美的檢查ROC曲線下面積為1.0，而完全無價值的檢查面積為0.5。然而，一旦選定了臨界值，ROC曲線下面積就與選定臨界值所對應的敏感性和特異性不太相關。
4. Respiratory rate clearly has enormous prognostic value in pneumonia, but the cutoff of 22 b/m is too low in this disease process. I usually start getting substantially more worried when the respiratory rate is above 30, consistent with the CURB65 score. 呼吸頻率顯然對肺炎的預后具有重大意義，但臨界值22次/分對于該病而言過低。我通常在呼吸頻率超過30時才會更加擔心，這與CURB65是一致的。
5. SOFA performs better among ICU patients. However, clinically the definition of sepsis is mostly useful outside the ICU (e.g. identifying patients who require ICU transfer). SOFA對ICU患者的價值更高些。然而，臨床上全身性感染的定義在ICU以外更有用（例如發(fā)現(xiàn)需要轉(zhuǎn)入ICU的患者）。 6. The fact that the 'definition' of sepsis may not capture most patients who require ICU care for infection management creates some strange linguistic problems. I suppose that if we accept the Sepsis-III definition then, by definition, it must have a performance of 100%? 全身性感染的“定義”有可能無法篩選出大多數(shù)需要收入ICU接受感染控制的患者，這樣就會帶來一些奇怪的語言問題。我認為如果我們接受全身性感染-III定義，那么，根據(jù)定義，其準確性應當達到100%？ |
|
|
