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Passive leg raising uncovers venous congestion: dynamic fluid intolerance and the Doppler Starling curve
Critical Care ( IF 8.8 ) Pub Date : 2024-11-25 , DOI: 10.1186/s13054-024-05171-z
Jon-Emile S. Kenny

Morosanu and colleagues have recently published a fascinating pilot study in Critical Care [1]. Following elective coronary artery bypass grafting (CABG), patients were enrolled who were mechanically-ventilated within 6 h of admission to the intensive care unit (ICU) and who had acute circulatory failure. In these patients, the authors measured the change in portal vein pulsatility index (PVPI, i.e., as a surrogate of venous filling/congestion) and the left ventricular outflow tract velocity time integral (LVOT VTI, i.e., as a surrogate of stroke volume) at 5 time points: at baseline (T1), one minute (T2) into a passive leg raise (PLR), and two minutes after returning to the semi-recumbent position (T3). Then, if the patient had both low PVPI and an LVOT VTI change of at least 12% during the PLR (i.e., the patient was considered both fluid tolerant and responsive, respectively), the patient received 7 mL/kg of Lactated Ringer’s solution (LR) over 10 min. Two additional measures were then taken: 2 min (T4) and 20 min (T5) following completion of the LR infusion. The authors examined the incidence of venous congestion (VC, i.e., defined as a PVPI ≥ 50%) following the LR and whether the antecedent PLR could predict VC. As well, they reported adverse clinical outcomes (e.g., ICU length of stay and acute kidney injury) and other echocardiographic measures as a pilot investigation.

The authors included 40 patients in their analysis with measures at T1-T5; in nearly one-half of patients, VC (i.e., PVPI of at least 50%) was observed at T4 (i.e., early VC), though this fell to only 5% at T5. Patients with early VC had significantly higher central venous pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. Finally, the PVPI at T2 (i.e., during the PLR) predicted early VC with an area under the curve of 0.998, using a threshold of 44.3%.

When giving IV fluids, 3 basic questions should be answered: 1.) is there an indication for IV fluids? 2.) are IV fluids safe? and 3.) are IV fluids effective [2]? By enrolling only patients with signs of peripheral hypo-perfusion, the answer to the first question for the patients enrolled by Morosanu and colleagues was ‘yes.’ Safety of IV fluid can be considered within the framework of ‘tolerance’ versus ‘intolerance’ [3, 4]. By including only patients with a low PVPI as a sign of low venous pressure, we presume that the post-CABG patients in the investigation of Morosanu et al. are ‘tolerant’; so, the answer to question 2 is also ‘yes’ (barring any other signals of harm such as elevated lung water, etc.). Finally, the ‘efficacy’ of IV fluid hinges upon increased venous return (and, therefore, preload) engaging the Starling mechanism and augmenting stroke volume (SV) (i.e., there is a state of ‘fluid responsiveness’). Yet, to be truly ‘effective,’ the increased SV must also meet an arterial tree with enough vasomotor tone to enhance tissue perfusion, so called ‘circulatory effectiveness [5].’ Because Morosanu and colleagues only investigated patients with a clinically-significant increase in LVOT VTI during PLR, the prerequisite for ‘effective’ fluids was also present in their study.

However, questions 2 and 3 are troublesome because when we think about ‘safety’ and ‘efficacy’ there is conceptual confusion [4]. Can fluids be ‘safe,’ but ‘ineffective’ ? Can fluids be ‘unsafe,’ but ‘effective’? The answer is almost certainly ‘yes’ to both of these questions. A recent investigation by Munoz and colleagues supports the assertion that IV fluid ‘safety’ and ‘efficacy’ might diverge [6, 7]; Morosanu and colleagues reference the Doppler Starling curve – a framework proposed to help explain why [7, 8]. Below is an expansion of their work grounded upon the foundation of the Doppler Starling curve.

First, Morosanu explicitly enrolled only patients with a ‘safe’ and, potentially, ‘effective’ profile as the 40 included had a decongested portal vein and were fluid responsive based upon a PLR. However, in their exclusion flow chart, there were initially 64 patients who had good echocardiographic windows and a low PVPI (i.e., fluid tolerant); of these, 21 were fluid unresponsive. That is to say, 33% of patients who were fluid tolerant were also fluid unresponsive. Within the Doppler Starling framework, we have previously found that 33% of patients in ‘Quadrant 3’ were fluid unresponsive [9] (see Fig. 1A below); this profile has been termed ‘dynamic fluid intolerance [4]’ because VC is expressed only with a dynamic maneuver like a PLR. Morosanu and colleagues did not record the change in PVPI in these patients but, in theory, VC would be likely. The clinical relevance of this finding is that giving fluids based only upon a baseline ‘low preload’ or ‘fluid tolerant’ profile risks giving ineffective IV fluids in a clinically significant proportion of acutely-ill patients; this is the ultrasonographic equivalent of giving fluids for a central venous pressure of less than 8 mmHg [10].

Fig. 1
figure 1

The Doppler Starling curve. The 4 hemodynamic phenotypes (1–4) are generated by combinations of normal and low stroke volume on the y-axis and normal or congested venous measures on the x-axis. A.) shows adapted data from Morosanu et.al. Fig. 2 for all patients comparing the passive leg raise (PLR) portion of the study (between T1 and T2) and the change between return to baseline and 2 min following the Lactated Ringer’s (LR) infusion (T3 and T4). T5 is excluded for clarity. The red arrow accounts for the 21 patients who were fluid tolerant but unresponsive. B.) shows the change recorded for PLR and the LR infusion when patients were split into those who did not have early congestion following LR (grey) and those who did have early congestion following LR (blue). This is adapted from Morosanu et al. Fig. 3. Based on mean values, some patients (i.e., early VC) moved from Quadrant 3 to 2 and this progression was predicted by the PLR (i.e., the change from T1 to T2). Advanced echocardiographers might argue that these patients did show signs of fluid intolerance without a PLR given their impaired, baseline right ventricular (RV) function–when the RV is no longer operating as an unstressed chamber [11]

Full size image

Second, Morosanu and colleagues show that patients can begin with a ‘safe’ and potentially ‘effective’ profile but, nevertheless, display another kind of ‘dynamic fluid intolerance’–moving both ‘up’ the Doppler Starling curve (i.e., on the y-axis), but also ‘out’ (i.e., along the x-axis). Based upon averages (see Fig. 1B below), these patients move from quadrant 3 to 2; the evolution of VC was predicted accurately by PLR, before IV fluids. While the slopes of the curves between those who developed early VC (blue curves) and those who did not (grey curves) were found to be statistically the same, this framework implies that with a greater range of measured values, perhaps there were subtle slope differences; this cannot be known given this pilot data. Research on the ‘slope’ of the Doppler Starling curve is underway; more specifically, whether the ratio between the LVOT VTI and VExUS + 1 (to prevent zero in the denominator) can predict patient outcome in the ICU.

In summary, Morosanu and colleagues are to be congratulated for their important pilot investigation. We should continue to anticipate divergence between venous measures and fluid responsiveness, especially with impaired cardiac function. Doppler phenotyping in this manner is an exciting avenue of active investigation.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Health Sciences North Research Institute, 56 Walford Rd, Sudbury, ON, P3E 2H2, Canada

    Jon-Emile S. Kenny

  2. Flosonics Medical, Toronto, ON, Canada

    Jon-Emile S. Kenny

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JESK is the sole author.

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Correspondence to Jon-Emile S. Kenny.

Competing interests

JESK is cofounder and chief medical officer of Flosonics Medical, a start-up working to commercialize a wearable Doppler ultrasound.

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Kenny, JE.S. Passive leg raising uncovers venous congestion: dynamic fluid intolerance and the Doppler Starling curve. Crit Care 28, 388 (2024). https://doi.org/10.1186/s13054-024-05171-z

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中文翻译：

被动抬腿发现静脉充血：动态液体不耐受和多普勒 Starling 曲线


Morosanu 及其同事最近在重症监护 [1] 上发表了一项引人入胜的试点研究。择期冠状动脉旁路移植术 （CABG） 后，入组重症监护病房 （ICU） 后 6 小时内接受机械通气且急性循环衰竭患者。在这些患者中，作者测量了门静脉搏动指数（PVPI，即作为静脉充盈/充血的替代物）和左心室流出道流出道速度时间积分（LVOT VTI，即作为每搏输出量的替代物）的变化在 5 个时间点：基线 （T1），1 分钟 （T2） 进入被动抬腿 （PLR）， 以及回到半卧位后 2 分钟 （T3）。然后，如果患者在 PLR 期间同时具有低 PVPI 和 LVOT VTI 变化至少 12%（即，患者分别被认为对液体有耐受性和反应性），则患者在 10 分钟内接受 7 mL/kg 乳酸林格液 （LR）。然后采取两项额外措施： LR 输注完成后 2 分钟 （T4） 和 20 分钟 （T5）。作者检查了 LR 后静脉充血 （VC，即定义为 PVPI ≥ 50%） 的发生率，以及先前的 PLR 是否可以预测 VC。此外，他们报告了不良临床结局 （例如，ICU 住院时间和急性肾损伤） 和其他超声心动图测量作为试点调查。


作者在他们的分析中纳入了 40 名患者，测量值为 T1-T 5;在近一半的患者中，在 T4 （即早期 VC） 观察到 VC （即 PVPI 至少为 50%），但在 T5 时降至仅 5%。早期 VC 患者的中心静脉压显著升高，基线右心室功能较差，严重 AKI 的发生率较高。最后，T2 处 （即 PLR 期间） 的 PVPI 预测早期 VC，曲线下面积为 0.998，阈值为 44.3%。


给予静脉输液时，应回答 3 个基本问题： 1.） 是否有静脉输液的适应症？2.） 静脉输液安全吗？以及 3.）静脉输液有效吗 [2]？通过仅招募有外周低灌注迹象的患者，Morosanu 及其同事招募的患者的第一个问题的答案是“是”。可以在“耐受”与“不耐受”的框架内考虑静脉输液的安全性 [3， 4]。通过仅将低 PVPI 作为低静脉压标志的患者，我们假设 Morosanu 等人调查中的 CABG 后患者是“耐受的”;因此，问题 2 的答案也是“是”（除非任何其他伤害信号，例如肺水位升高等）。最后，静脉输液的“功效”取决于与 Starling 机构接合的静脉回流增加（因此也取决于前负荷）并增加每搏输出量 （SV）（即存在“液体反应”状态）。然而，要真正“有效”，增加的 SV 还必须满足具有足够血管舒缩张力的动脉树，以增强组织灌注，即所谓的“循环有效性”[5]。由于 Morosanu 及其同事仅调查了 PLR 期间 LVOT VTI 临床显着增加的患者，因此他们的研究中也存在“有效”液体的先决条件。


然而，问题 2 和 3 很麻烦，因为当我们考虑“安全性”和“有效性”时，存在概念上的混淆 [4]。液体可以“安全”但“无效”吗？液体可以“不安全”但“有效”吗？几乎可以肯定，这两个问题的答案都是“是”。Munoz 及其同事最近的一项研究支持静脉输液“安全性”和“有效性”可能存在差异的说法 [6， 7];Morosanu 及其同事引用了多普勒史达林曲线——一个为帮助解释原因而提出的框架 [7， 8]。以下是他们基于多普勒 Starling 曲线基础的工作的扩展。


首先，Morosanu 明确仅招募具有“安全”且可能“有效”特征的患者，因为纳入的 40 名患者具有疏通的门静脉充血，并且根据 PLR 对液体有反应。然而，在他们的排除流程图中，最初有 64 名患者具有良好的超声心动图窗口和低 PVPI（即液体耐受性）;其中，21 例液体无反应。也就是说，33% 的液体耐受患者也对液体无反应。在多普勒 Starling 框架中，我们之前发现“象限 3”中 33% 的患者对液体无反应 [9]（见下面的图 1A）;这种特征被称为“动态液体不耐受 [4]”，因为 VC 仅通过动态操作（如 PLR）来表达。Morosanu 及其同事没有记录这些患者 PVPI 的变化，但理论上，VC 是可能的。这一发现的临床相关性是，仅根据基线“低前负荷”或“液体耐受”特征给予液体，在临床上显着比例的急症患者中，静脉输液可能无效;这与超声检查中中心静脉压低于 8 mmHg 时输液等效[10]。

 图 1
figure 1


多普勒 Starling 曲线。4 种血流动力学表型 （1-4） 是由 y 轴上的正常和低每搏输出量以及 x 轴上正常或充血的静脉测量值的组合产生的。A.)显示了来自 Morosanu et.al 的改编数据。图 2 对于比较研究的被动抬腿 （PLR） 部分（T1 和 T2 之间）与乳酸林格氏症 （LR） 输注后 2 分钟恢复到基线和 2 分钟之间的变化（T3 和 T4）的所有患者。为清楚起见，T5 被排除在外。红色箭头表示 21 名液体耐受但无反应的患者。B.)显示了当患者被分为 LR 后没有早期充血的患者（灰色）和 LR 后有早期充血的患者（蓝色）时，PLR 和 LR 输注记录的变化。这改编自 Morosanu 等人，图 3。根据平均值，一些患者 （即早期 VC） 从象限 3 移动到象限 2，并且这种进展由 PLR 预测 （即从 T1 到 T2 的变化）。高级超声心动图医师可能会争辩说，鉴于这些患者基线右心室 （RV） 功能受损，当 RV 不再作为无压力腔室运行时，他们确实表现出无 PLR 的液体不耐受迹象 [11]

 全尺寸图像


其次，Morosanu 及其同事表明，患者可以从“安全”且可能“有效”的特征开始，但仍然表现出另一种“动态液体不耐受”——既“向上”移动多普勒斯塔林曲线（即在 y 轴上），也“向外移动”（即沿 x 轴）。根据平均值（见下面的图 1B），这些患者从象限 3 移动到象限 2;在 IV 液体之前，通过 PLR 准确预测 VC 的演变。虽然发现早期 VC 患者（蓝色曲线）和未发生早期 VC 的患者（灰色曲线）之间的曲线斜率在统计学上相同，但该框架意味着测量值范围越大，可能存在细微的斜率差异;鉴于此试点数据，这无法得知。关于多普勒史达林曲线的“斜率”的研究正在进行中;更具体地说，LVOT VTI 和 VExUS + 1 之间的比率（以防止分母为零）是否可以预测 ICU 中的患者预后。


总之，Morosanu 及其同事们对他们重要的试点调查表示祝贺。我们应该继续预测静脉测量和液体反应性之间的差异，尤其是在心脏功能受损的情况下。以这种方式进行多普勒表型分析是一种令人兴奋的主动研究途径。


在当前研究期间没有生成或分析数据集。


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  1. Health Sciences North Research Institute， 56 Walford Rd， Sudbury， ON， P3E 2H2， 加拿大

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  2. Flosonics Medical，加拿大安大略省多伦多

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JESK 是 Flosonics Medical 的联合创始人兼首席医疗官，这是一家致力于将可穿戴多普勒超声商业化的初创公司。

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