液体反应性与液体复苏六原则(节译)

本文是西佛吉尼亚州著名的Paul E. Marik教授发表于在CCM的专论，重要内容，特做笔记。

Fluid Responsiveness and the Six Guiding Principles of Fluid Resuscitation

Marik, Paul E. MD, FCCM

Passive leg raising Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.

The author has disclosed that he does not have any potential conflicts of interest.

For information regarding this article, E-mail:[email protected]

ICU内应用的高级生命之技术是为了对存在可逆性脏器功能障碍的患者提供一过性的生理支持，使得患者的内稳态机制恢复到病前的功能水平。70年代肺动脉导管的引入使重症医学进入了堪称为“激进”的模式之中：若某种治疗是好的，那么更多的治疗就会更好。根据CVP与肺动脉楔压指导积极的液体复苏已成为复苏治疗的里程碑。这些疗法也开启了固化治疗模式的时代，由此无论血流动力状态如何，重症或创伤患者都会接受大量晶体复苏。但已有证据表明积极地液体复苏会导致严重组织水肿，并影响脏器功能及导致并发症及病死率的增加。近期在46个国家进行的考查液体复苏的全球队列研究显示“当前对重症患者液体管理的评估与实践都过于武断...并非循证且有害...”本文基于6项基本原理提出合理的液体管理方法。根据以下所述的原则，若某人认为应该液体冲击治疗，我更倾向于使用动态而非静态测量对患者进行评价。

The advanced life support technology, which is provided in the ICU, is intended to provide temporary physiologic support for patients with reversible organ dysfunction allowing homeostatic mechanisms to return the patients to their previous level of functioning (1). The introduction of the pulmonary artery catheter in the early 70s ushered in a style of critical care medicine that can best be characterized as “aggressive”; if some care is good, more care is even better. Aggressive fluid resuscitation titrated to the central venous pressure (CVP) or pulmonary artery occlusion pressure became regarded as the cornerstone of resuscitation. This approach ushered in an era of rigid protocolized care, where critically ill and injured patients received large amounts of crystalloids regardless of their hemodynamic status (2–4). However, an emerging body of evidence suggests that aggressive fluid resuscitation leads to severe tissue edema that compromises organ function and leads to increased morbidity and mortality (5, 6). A recent global cohort study that evaluated the approach to fluid resuscitation in 46 countries concluded that the “current practice and evaluation of fluid management in critically ill patients seems to be arbitrary… is not evidence-based and could be harmful.” (7) This article presents a rational, physiological approach to fluid resuscitation, which is based on six fundamental principles. If one is considering giving a fluid bolus, I would recommend using dynamic rather than static measures to assess the patient according to the principles listed below.

1. FLUID RESPONSIVENESS: THE FOUNDATION OF FLUID RESUSCITATION

1. 液体复苏的基本原理：液体反应性

Fundamentally, the only reason to give a patient a fluid challenge is to increase their stroke volume (SV); if this does not happen, fluid administration serves no useful purpose and is likely to be harmful (8). A patient is considered to be fluid responsive if his/her SV increases by at least 10% following a fluid challenge (usually 500 cc of crystalloid) (8). Fluid administration will only increase SV if two conditions are met, namely 1) if the fluid bolus increases the stressed blood volume causing the mean circulating filling pressure to increase greater than the increase in CVP and thereby increasing the gradient for venous return (9, 10) and 2) if both ventricles are functioning on the ascending limb of the Frank-Starling curve (8).

Studies in heterogeneous groups of critically ill and injured patients and those undergoing surgery have reproducibly and consistently demonstrated that only about 50% of hemodynamically unstable patients are fluid responsive (5, 11, 12). This is a fundamental concept that is not widely appreciated (2, 3, 13) and challenges the widely accepted notion that fluid administration is the “cornerstone of resuscitation.” (2, 3) These observations dictate that only patients who are fluid responsive should be resuscitated with fluid boluses. This concept represents a major paradigm shift and places ‘fluid responsiveness” center stage in the management of critically ill and injured patients and those undergoing surgery.

2. CLINICAL SIGNS, THE CHEST RADIOGRAPH, THE CVP, AND ULTRASONOGRAPHY CANNOT BE USED TO DETERMINE FLUID RESPONSIVENESS

2. 临床体征、胸片、CVP和超声不能用于确定液体反应性

Although clinical signs, such as a hypotension, tachycardia, narrow pulse pressure, poor skin perfusion, and slow capillary refill, may be helpful for identifying inadequate perfusion, these signs are unable to determine volume status or fluid responsiveness (14). The CVP or change in CVP following a fluid challenge is no more accurate in predicting fluid responsiveness than flipping a coin and should be abandoned for this purpose (11). It should also be recognized that the change in the mean arterial pressure (MAP) following a fluid bolus is poorly predictive of fluid responsiveness (12, 15). Although widely recommended (4), ultrasonography of the vena cava and its respiratory variation are no more predictive than the CVP for assessing fluid responsiveness (16). Echocardiography has limited utility for assessing volume status and fluid responsiveness. Transthoracic measurements of left ventricular outflow tract velocities (VTI) for the estimation of SV require considerable expertise and are not easily obtainable or reproducible in ICU patients (17). Furthermore, the VTI is not ideal for detecting rapid changes in SV following a passive leg raising (PLR) maneuver or fluid challenge.

3. THE PLR MANEUVER OR A FLUID CHALLENGE COUPLED WITH REAL-TIME SV MONITORING IS THE ONLY ACCURATE METHOD FOR DETERMINING FLUID RESPONSIVENESS

3.再确定液体反应性方面被动抬腿试验或液体冲击试验结合实时心输出量监测是唯一准确的

Currently, there are only two techniques that are widely available, practical, easy to perform, and physiologically based, which can be used to determine fluid responsiveness with a high degree of accuracy, namely, the PLR maneuver and the fluid challenge (8, 18). These techniques are best coupled with minimally invasive or noninvasive cardiac output monitors, which can track changes in SV dynamically and in real time (8, 19). The PLR is simple to perform taking less than 5 minutes to complete. Beyond its ease of use, this method has the advantage of reversing its effects once the legs are returned to the horizontal position (18). A metaanalysis, which pooled the results of 21 studies, confirmed the excellent diagnostic value of the PLR to predict fluid responsiveness in critically ill patients with a global area under the receiver operating characteristic curve of 0.94 (12). The gold standard to determine fluid responsiveness is the change in SV following a fluid challenge (8). As crystalloids redistribute very rapidly, the fluid bolus should be given as quickly as possible and ideally within a 10–15 minute period. A bolus of between 200 and 500 cc is recommended. Large fluid boluses of 20–30 mL/kg, although still widely recommended (3, 4), are unphysiologic and likely to lead to marked volume overload with severe tissue edema (5, 6).

4. THE HEMODYNAMIC RESPONSE TO A FLUID CHALLENGE IS USUALLY SMALL AND SHORT LIVED

4. 液体冲击时的血流动力学反应常常是微弱而短暂的

Fluid boluses are most frequently administered to patients with hypotension (7). However, it is not widely recognized that the hemodynamic response to a fluid challenge is usually small and short lived. Nunes et al (20) evaluated the duration of the hemodynamic effect of a fluid bolus in patients with circulatory shock. In this study, 65% of patients were fluid responders whose cardiac index increased by 25% at the end of the infusion (30 min). However, the cardiac index had returned to baseline 30 minutes after the end of the infusion. Glassford et al (21) performed a systematic review that examined the hemodynamic response of fluid boluses in patients with sepsis. These authors reported that although the MAP increased by 7.8 ± 3.8 mm Hg immediately following the fluid bolus, the MAP had returned close to baseline at 1 hour with no increase in urine output. In a retrospective analysis of the ARDSnet Fluid and Catheter Treatment Trial, Lammi et el (22) examined the physiological effect of 569 fluid boluses in 127 patients. According to the protocol, fluid challenges were given for hypotension or oliguria. In this study, the MAP increased by 2 mm Hg following the bolus with no increase in urine output. These data indicate that fluid boluses are generally an ineffective treatment strategy for hypotension, circulatory shock, and oliguria.

5. FLUID RESPONSIVENESS DOES NOT EQUATE TO THE NEED FOR FLUID BOLUSES

5. 液体反应与液体输注的需要并不等同

Most healthy humans are normally fluid responsive and function on the ascending limb of the Frank-Starling curve; they have preload reserve and do not require fluid “to live” on the flat part of the curve to function optimally. Similarly, critically ill and injured patients and those undergoing surgery do not need to be pushed to the top of their Frank-Starling curve. Patients should only receive a fluid bolus if they are preload responsive and likely to benefit from the fluid bolus, that is, the potential benefits and risk should be evaluated prior to each fluid bolus. Patients should only continue to receive fluid boluses if the hemodynamic benefits are likely to outweigh the risks of an accumulating positive fluid balance. Patients should not receive repeated fluid boluses until they are no longer fluid responsive. As patients “ascend” the Frank-Starling curve, the adverse effects begin to outweigh the benefits as atrial pressures increase with increasing release of natriuretic peptides and increasing hydrostatic edema (Fig. 1). Because of the small and short lived effect of a fluid bolus, it may be preferable to treat the fluid responsive septic patient with norepinephrine (23). Norepinephrine will increase venous return, SV, and MAP, thereby increasing organ perfusion while limiting tissue edema (23).

图1

6. A HIGH CVP IS A MAJOR FACTOR COMPROMISING ORGAN PERFUSION

高CVP是脏器灌注不良的主要因素

MAP与CVP的差值是血流灌注脏器的驱动压，当MAP处于脏器自动调控的范围内时，CVP就成为脏器与微循环灌注的决定因素。

高静脉压增加肾脏被膜下压力降低了肾灌注和GFR，与AKI有明确关系

新的证据表明重症、创伤和外科手术患者的MAP应≥65mmHg，CVP≤8mmHg！这显然与目前的指南冲突！

Organ blood flow is driven by the difference in the pressure between the arterial and venous sides of the circulation. The MAP minus the CVP is the driving force for organ blood flow. However, when the MAP is within an organ autoregulatory range, the CVP becomes the major factor determining organ and microcirculatory (5). The kidney is particularly affected by increased venous pressure, which leads to increased renal subcapsular pressure and lowered renal blood flow and glomerular filtration rate (25). Legrand et al (26) demonstrated a linear relationship between increasing CVP and acute kidney injury (AKI), with a high CVP being the only hemodynamic variable independently associated with AKI. In critically ill patients and those with heart failure, a CVP of greater than 8 mm Hg has been demonstrated to be highly predictive AKI. There are now compelling data that the primary hemodynamic goal in critically ill and injured patients and those undergoing surgery is an MAP of greater than 65 mm Hg and a CVP of less than 8 mm Hg. Remarkably, this CVP target contradicts current guidelines that recommend targeting a CVP of greater than 8 mm Hg (3, 4). Furthermore, fluid loading oliguric patients with a low CVP with the goal of achieving a CVP of greater than 8 mm Hg may paradoxically increase the risk of progression to AKI.

CONCLUSIONS

结论

液体反应性是重症医师、急诊医师、外科医生与麻醉师必备的技巧，现今这些医生老爷们对液体输注的基本原则都了解不多，导致了矛盾的、不一致的和错误的治疗策略。补液应该是在评价液体反应性并结合评估补液的收益与风险进行的。应避免大量输液。

Fluid resuscitation is the defining skill of intensivists, emergency medicine physicians, surgeons, and anesthesiologists, yet many of these clinicians have a poor understanding of the fundamental principles involved in fluid administration resulting in conflicting, inconsistent, and potentially harmful treatment strategies. Fluid administration should be guided by an assessment of fluid responsiveness combined with the determination of the potential benefits and harms of fluid administration. Large fluid boluses should be avoided.

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