经食道超声与热稀释法测量心输出量的相关性
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Agreement Between Transesophageal Echocardiography and Thermodilution-Based Cardiac Output
背景与目的
无侵袭性、准确的评估心输出量(CO)仍然是心血管麻醉及重症医学科不可避免的目标。经过近半个世纪的发展，基于肺动脉导管(PAC)的热稀释法仍然是最有效、临床相关的心输出量测量方法。然而，这种技术的侵入性和相关风险导致使用率下降，以期寻求更准确，无创的CO测量方法。忽略左室流出道偏心率的2D经食管超声心动图（TEE）是一种安全普遍的可替代PAC的主要候选方法，并且在3D TEE时代这种忽略被认为是可以纠正的错误。
在 Anesthesia & Analgesia杂志上，Graeser et al比较了2D及3D TEE和热稀释法测量的CO。据推测，如果3D TEE提供比2D TEE更好的LVOT横截面积评估，基于TEE测量的CO与热稀释法所测量的CO相关性更好。
方 法
在 Anesthesia & Analgesia杂志上，Graeser et al比较了2D及3D TEE和热稀释法测量的CO。据推测，如果3D TEE提供比2D TEE更好的LVOT横截面积评估，基于TEE测量的CO与热稀释法所测量的CO相关性更好。
对于热稀释法测量，使用2组连续4次注射10mL冰冷盐水（重复之间的平均偏差为-0.04L / min）。对于TEE测量，LVOT的速度时间积分在6个连续心动周期中取平均值，并且在2D TEE和3D TEE检查中，进行2组10 LVOT直径（2D）和面积（3D）测量。 2D和3D测量的重复之间的平均偏差分别为-0.05和0.07L / min。
结 果
正如作者所提到的，心脏CTA尚未在文献中严格确定，作为确定LVOT横截面积的参考方法，使得3D TEE和CTA都可能是不准确的测量方法。多普勒流动的局限性也被认为是可能的分歧来源，但这些误差同样会影响2D和3D TEE。
但值得考虑的是，热稀释法并不是心输出量的完美测量标准。虽然作者使用冰冷的生理盐水（较高的信号噪音比）和2组4次重复，不考虑呼吸周期的影响进行注射。然而，热稀释法测量的最大精度和准确性需要在通气周期中选择同一时间点，因为右心室输出量变化范围大约30％，最大精度和准确性取决于在通气周期中推注的时间点。所报告的测量的可重复性意味着测量值的任何变化可能都被通气周期有效地平均化了。
此外，虽然肺动脉导管热稀释法是临床标准，也就是临床医生常用的最准确的设备，但它不是金标准。参考标准，如传输时间流量探测器，非常准确，但是侵入性而临床少用。分析热稀释法，TEE和动物与人类真实参考标准之间的3种方式，表明热稀释法和TEE测量差异很小。最重要的是要认识到，相关性研究只能确定两种测量方式的一致性-它们的性质（双向研究），但是无法确定两种测量中哪一种更准确。值得一提的是第三种可能性，作者本身不存在错误，主要是相关性等价局限的 II型统计错误。相关性分析局限的一个关键而未被充分认识的特点就是相关性分析局限周围存在一个相对宽的置信区间。图3的检查揭露了2D 和 3D TEE相对宽的相关性局限置信区间.实际上，基于对这些置信区间的目测检查，2D TEE的真实相关性偏差可能会达到-3.1至1.9 L / min，并且3D TEE真实相关性偏差可能是 小到-1.3到1.9L/min，在这种情况下我们实际上会得出结论，3D TEE表现出与热稀释法更好的一致性（也可以说相反）。Graeser等人的研究还有待回答。
结 论
由于方法学和高重复性，我们可以肯定地说，基于3D TEE的测量可以改善与基于CTA的LVOT区域相关性，但似乎没有改善与基于热稀释法测量心输出量的相关性。 这是否是由于基于热稀释的心输出量的限制，CTA准确性的限制，或由于动力不足而无法确定。 虽然这种“非结论”有点令人不满意，但这是数据得出的结果。 我们希望（和期望）Anesthesia & Analgesia的读者将帮助我们做出这个重要的决心。
原始文献摘要
Millan, Patrick D., MD; Thiele, Robert H., MD Anesthesia & Analgesia: August 2018 - Volume 127 - Issue 2 - p 329 330 doi: 10.1213/ANE.0000000000003322 Editorials: Editorial
Abstract:
Accurate, noninvasive assessment of cardiac output (CO) has remained an elusive goal in the fields of critical care medicine and cardiac anesthesia. Almost a half century after its development,1,2 pulmonary artery catheter-based thermodilution remains the most extensively validated, clinically relevant method of cardiac output measurement.3 However, the invasive nature and associated risks of this technique lead to a decrease in utilization, 4,5 as well as the search for an accurate, noninvasive method of measuring CO. Transesophageal echocardiography (TEE), which is safe6 and increasingly ubiquitous,7 is a leading candidate to replace the PAC. But, is it accurate? Two-dimensional (2D) TEE estimates of cardiac output neglect left ventricular outflow tract (LVOT) eccentricity, and in the 3-dimensional (3D) TEE era are thought to be a correctable source of error.8 In this issue of Anesthesia & Analgesia, Graeser et al9 compared the use of thermodilution to Doppler-derived CO using both 2D and 3D TEE. Presumably, if 3D TEE provides a better estimate of the LVOT cross-sectional area than 2D TEE, Doppler-based estimates of CO would more closely agree with thermodilution.Graeser et al s9 study is notable for its rigorous methodology. For the thermodilution measurements, 2 sets of 4 consecutive injections of 10 mL of ice cold saline were utilized (mean bias between replicates was 0.04 L/min). For the echocardiographic measurements, the velocity time integral of the LVOT was averaged over 6 consecutive cardiac cycles, and in both the 2D and 3D examinations, 2 sets of 10 LVOT diameter (2D) and area (3D) measurements were performed. Mean bias between replicates for the 2D and 3D measurements were 0.05 and 0.07 L/min, respectively. Yet, despite this attention to detail (exhibited by excellent repeatability), when using thermodilution as the reference standard, 3D TEE produced what appeared to be wider limits of agreement when compared to 2D TEE. The authors shed some light on this surprising result by randomly selecting 19 patients to undergo cardiac computed tomography angiography (CTA). As expected, they found that 3D measurements of LVOT area agreed with CTA more closely than 2D estimates. How then is it possible that 3D TEE estimates of cross-sectional area agreed more closely with CTA, yet 3D TEE estimates of CO agreed less with thermodilution cardiac output than the 2D estimates? Logic suggests that this conundrum must be the result of errors in either thermodilution or the CTA measurement. As mentioned by the authors, cardiac CTA has not been rigorously established in the literature as a reference method for determining LVOT cross-sectional area, making it possible that both 3D TEE and CTA are inaccurate methods for this measurement. Limitations with Doppler flow were also mentioned as a possible source of disagreement, but these errors would affect 2D and 3D TEE equally. Not mentioned, but worth considering, is that thermodilution is not a perfect measure of cardiac output. While the authors used iced cold saline (higher signal to noise ratio) and 2 sets of 4 repetitions, injections were made irrespective of the ventilator cycle. Yet maximal precision and accuracy of thermodilution requires choosing a consistent time point in the ventilatory cycle, as right ventricular output varies by approximately 30% depending on when in the ventilatory cycle the bolus is initiated.10 The repeatability of the reported measurements implies that any variation due to the influence of ventilator cycling was effectively averaged out. Additionally, while thermodilution is a clinical gold standard, that is, the most accurate device that clinicians use routinely, it is not a reference gold standard. Reference standards, like transit time flow probes, are highly accurate, but invasive and not used clinically. Analysis of 3 way comparisons between thermodilution, Doppler-based techniques, and true reference standards in both animals and human suggests there is minimal difference in accuracy between thermodilution and Doppler-based techniques.3 It is important to recognize that agreement studies only determine how well 2 forms of measurement agree by their nature (2 way study), they are incapable of determining which of 2 measurements is more accurate. This is increasingly important as device studies that lack a validated goal standard have been published.11,12
A third possibility, which deserves mentioning, is that the authors, by no fault of their own, have made the limits of agreement equivalent of a type II statistical error. A key, under-appreciated feature of limits of agreement analysis is that there is a confidence interval around the reported limits of agreement. Examination of Figure 3 reveals relatively wide confidence intervals around the limits of agreement for both 2D and 3D TEE. In fact, based on visual inspection of these confidence intervals, it is possible that the true limits of agreement for 2D TEE could be as large as 3.1 to 1.9 L/min, and that the true limits of agreement for 3D TEE could be as small as 1.3 to 1.9 L/ min, in which case we would actually conclude that 3D TEE exhibited better agreement with thermodilution (the opposite can also be said). Graeser et al s9 study leaves much to be answered. Because of the methodology and high repeatability, we can say with some confidence that 3D TEE-based measures improve agreement with CTA-based LVOT area, but do not appear to improve agreement with thermodilution- based cardiac output. Whether or not this is due to limitations in thermodilution-based cardiac output, to limitations in the accuracy of CTA, or due to an underpowered study cannot be determined. While this nonconclusion is somewhat unsatisfying, it is what the data tell us. It is our hope (and expectation) that the readers of Anesthesia & Analgesia will help us make this important determination.
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