休克患者使用血管活性药和正性肌力药指南

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Pathophysiology of Shock
休克的病理生理学

Shock can be categorized into 4 main types: distributive, cardiogenic, hypovolemic, and obstructive. While each type of shock has its own unique etiology, the pathophysiology behind each is similar. The categories of shock can be further subcategorized into 3 progressive stages beginning with compensated (nonprogressive) shock, uncompensated (progressive) shock, and ending with irreversible (refractory) shock. In compensated shock, homeostasis is maintained through compensatory mechanisms. Both cardiac output and systemic vascular resistance increase to keep blood pressure within normal limits. This stage of shock is reversible, and clinical presentation reflects the imbalance between tissue oxygen supply and demand. ¹ Blood pressure will decrease due to a decrease in cardiac output (obstructive/cardiogenic/hypovolemic shock) or systemic vascular resistance (distributive shock). However, baroreceptors in the carotid and aortic bodies respond to this drop in blood pressure immediately through activation of the sympathetic nervous system. This activation of the sympathetic nervous system results in vasoconstriction through the release of epinephrine and norepinephrine (potent vasoconstrictors) from the adrenal medulla. Further, as a compensatory measure to prevent vital organ death, blood flow to organs such as the kidneys, skin, lungs, gastrointestinal (GI) tract, and liver is redirected to maintain blood flow to more vital organs such as the heart and brain. This decrease in blood flow to the kidneys activates the renin–angiotensin–aldosterone system (RAAS) resulting in the release of renin. Renin activates angiotensin to produce angiotensin I, which is converted to angiotensin II. Angiotensin II promotes vasoconstriction in the arterial and venous circulation. At this stage of shock, the body can compensate, and the patient will recover with little or no residual effects if treated. If allowed to progress, compensated shock will evolve into uncompensated shock.
休克可分为四大类型：分布性休克、心源性休克、低血容量休克和阻塞性休克。虽然每种休克都有其独特的病因，但其背后的病理生理学原理却大同小异。休克可进一步细分为 3 个进展阶段：代偿性（非进展性）休克、非代偿性（进展性）休克和不可逆转性（难治性）休克。在代偿性休克中，平衡是通过代偿机制来维持的。心输出量和全身血管阻力都会增加，以将血压保持在正常范围内。这一阶段的休克是可逆的，临床表现反映了组织供氧和需氧之间的不平衡。由于心输出量减少（阻塞性/心源性/低血容量性休克）或全身血管阻力减少（分布性休克），血压会下降。然而，颈动脉和主动脉体的气压感受器会通过激活交感神经系统对血压下降立即做出反应。交感神经系统激活后，肾上腺髓质会释放肾上腺素和去甲肾上腺素（强效血管收缩剂），从而导致血管收缩。此外，作为防止重要器官死亡的代偿措施，流向肾脏、皮肤、肺、胃肠道和肝脏等器官的血流会改变方向，以维持流向心脏和大脑等更重要器官的血流。流向肾脏的血流量减少会激活肾素-血管紧张素-醛固酮系统（RAAS），导致肾素释放。肾素激活血管紧张素，产生血管紧张素 I，然后转化为血管紧张素 II。血管紧张素 II 会促进动脉和静脉循环中的血管收缩。 在休克的这一阶段，身体可以进行代偿，如果接受治疗，病人会恢复得很好，几乎不会留下后遗症。如果任其发展，代偿性休克将演变为非代偿性休克。

Uncompensated (progressive) shock occurs when the body is no longer able to compensate for the mismatch in oxygen supply and demand. Aggressive interventions are necessary to prevent the patient from developing multiple organ dysfunction syndrome and continuing into irreversible shock. A distinguishing feature of this type of shock is the continued decrease in cellular perfusion resulting from altered capillary permeability. Altered capillary permeability allows for the leakage of fluid and protein from the vascular space into the interstitial space, decreasing circulating fluid volume and increasing interstitial edema. Fluid loss from the vascular space affects the solid organs, liver, spleen, GI tract, lungs, and peripheral tissues as it further decreases perfusion due to the resultant intravascular hypovolemia.
当机体无法再补偿氧气供需失衡时，就会发生无补偿性（进行性）休克。有必要采取积极的干预措施，以防止患者发展为多器官功能障碍综合征并继续陷入不可逆转的休克。这种休克的一个显著特点是毛细血管通透性改变导致细胞灌注持续减少。毛细血管通透性的改变会使液体和蛋白质从血管间隙渗漏到间质间隙，从而减少循环液量并加重间质水肿。从血管间隙流失的液体会影响到实体器官、肝脏、脾脏、消化道、肺部和外周组织，因为这会导致血管内血容量不足，从而进一步降低灌注量。

The final stage of shock is irreversible (refractory) shock. It is characterized by decreased perfusion from peripheral vasoconstriction and decreased cardiac output exacerbating anaerobic metabolism. Lactic acid accumulates, resulting in an increased capillary permeability and dilation. Increased permeability allows fluid to leave the vasculature and move into the interstitial space. Blood will pool in the capillary beds due to constriction of veins and dilation of arteries. The loss of intravascular volume results in worsening hypotension and tachycardia, decreasing blood flow to the coronary arteries. Reduction in coronary blood flow greatly diminishes cardiac output; as a result, cerebral blood flow cannot be maintained resulting in cerebral ischemia. Irreversible shock, as the name suggests, has progressed past the stage in which therapy is beneficial.
休克的最后阶段是不可逆（难治性）休克。其特点是外周血管收缩导致血流灌注减少，心输出量下降加剧了无氧代谢。乳酸积聚，导致毛细血管通透性增加和扩张。渗透性增加会使液体离开血管进入间质。由于静脉收缩和动脉扩张，血液会在毛细血管床积聚。血管内容量的损失会导致低血压和心动过速恶化，减少冠状动脉的血流量。冠状动脉血流量的减少会大大降低心输出量，从而无法维持脑血流量，导致脑缺血。不可逆休克，顾名思义，已经过了治疗有益的阶段。

Distributive shock, also called vasodilatory shock, is caused by systemic vasodilation that leads to inadequate blood flow to the brain, heart, and kidneys damaging these vital organs. ² This systemic vasodilation results in a decrease in systemic vascular resistance (SVR) and afterload. SVR can be calculated using Poiseuille’s equation (Figure 1A). As the blood vessels dilate, the radius increases, resulting in a net lowering of resistance (blood pressure). ³ Distributive shock may also result in edema fluid loss into the surrounding tissue further lowering blood pressure due to the shift in volume distribution. ² Important etiologies of distributive shock include sepsis, anaphylaxis, and neurogenic causes.
分布性休克又称血管舒张性休克，是由于全身血管扩张导致流向大脑、心脏和肾脏的血流量不足，从而损害了这些重要器官。这种全身性血管扩张会导致全身性血管阻力（SVR）和后负荷下降。SVR 可通过 Poiseuille 方程计算得出（图 1A）。随着血管扩张，半径增加，导致阻力（血压）净降低。 ³ 分布性休克还可能导致水肿液体流失到周围组织，由于容量分布的改变，血压进一步降低。 ² 分布性休克的重要病因包括败血症、过敏性休克和神经源性病因。

Cardiogenic shock is classified broadly as a cardiac disorder characterized by a decrease in ventricular function that results in end-organ hypoperfusion and tissue hypoxia. This decreased cardiac output activates the aforementioned RAAS cascade leading to water and salt retention. ⁴ RAAS cascade activation results in a vicious cycle that ultimately leads to the worsening of coronary ischemia and progressive volume overload with eventual circulatory collapse. ⁵
心源性休克被广泛地归类为一种心脏疾病，其特点是心室功能下降，导致末梢器官灌注不足和组织缺氧。心输出量的减少会激活上述 RAAS 级联反应，导致水和盐潴留。RAAS 级联激活会导致恶性循环，最终导致冠状动脉缺血恶化和进行性容量超载，最终导致循环衰竭。 ⁵

Hypovolemic shock is caused by intravascular volume loss of blood or fluid resulting in circulatory failure. This fluid loss decreases preload, which in turn decreases cardiac output resulting in tissue hypoperfusion and hypoxia. SVR increases in an effort to compensate for declining cardiac output and blood pressure.^3,6
低血容量性休克是由血管内血液或液体容量损失导致循环衰竭引起的。液体流失会降低前负荷，进而降低心输出量，导致组织灌注不足和缺氧。SVR 会增加，以补偿心输出量和血压的下降。 ^3,6

Obstructive shock results in decreased cardiac output usually from extracardiac causes. Obstructive shock may be due to an increase in pulmonary vascular resistance or extrinsic mechanical compression of the superior and inferior vena cava carrying blood to the heart. Increased pulmonary vascular resistance is characterized by right ventricular heart failure due to the inability to overcome the high resistance of the pulmonary vasculature (eg, massive pulmonary embolism), while the latter is due to decreased preload from a reduction in venous return due to compression of the superior and inferior vena cava (eg, tension pneumothorax). Obstructive shock may also be caused by intracardiac obstruction (eg, hypertrophic cardiomyopathy or critical aortic stenosis) or external compression of the heart itself (eg, cardiac tamponade or constrictive pericarditis). ⁷
阻塞性休克通常是由于心外原因导致心输出量减少。阻塞性休克可能是由于肺血管阻力增加或向心脏输送血液的上腔静脉和下腔静脉受到外来机械性压迫。肺血管阻力增加的特征是右心室因无法克服肺血管的高阻力而出现心力衰竭（如大面积肺栓塞），而后者则是由于上腔静脉和下腔静脉受压导致静脉回流减少而导致前负荷降低（如张力性气胸）。阻塞性休克也可能由心脏内部阻塞（如肥厚型心肌病或重度主动脉瓣狭窄）或心脏本身的外部压迫（如心脏填塞或缩窄性心包炎）引起。 ⁷

Distributive Shock   分配冲击

Septic Shock   败血症休克

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. ⁸ The third international consensus definitions for sepsis and septic shock (Sepsis-3) define sepsis as a documented or suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. ⁸ Septic shock (the most common cause of shock) is currently defined as sepsis meeting the above criteria in patients who, despite adequate fluid resuscitation, require vasopressors to maintain a mean arterial pressure (MAP) ≥ 65 mm Hg and have a serum lactate level > 2 mmol/L.^8–12 Hospital mortality for septic shock is often > 40%. ⁸
败血症是由于宿主对感染的反应失调而导致的危及生命的器官功能障碍。 ⁸ 败血症和脓毒性休克的第三次国际共识定义（Sepsis-3）将败血症定义为有记录或疑似感染，且序贯器官衰竭评估（SOFA）评分≥2。 ⁸ 目前，脓毒性休克（休克的最常见原因）被定义为符合上述标准的脓毒症患者，尽管进行了充分的液体复苏，但仍需要使用血管加压药来维持平均动脉压（MAP）≥ 65 mm Hg，且血清乳酸水平> 2 mmol/L。 ^8–12 败血症休克的住院死亡率通常大于 40%。 ⁸

The Surviving Sepsis Campaign (SSC) was created in 2004 to provide international guidelines for the management of sepsis and septic shock, with updates published every 4 years. The most recent version of the SSC (2021) made 6 main recommendation changes from the 2016 iteration: (1) the recommendation of initiating a fluid bolus of 30 mL/kg was downgraded to a weak recommendation based on the low quality of evidence, (2) normal saline is no longer recommended for fluid resuscitation; only balanced crystalloid solutions should be used, (3) for adults in septic shock, prompt initiation of vasopressors is recommended even if this means peripheral administration, (4) the SSC suggests against the use of intravenous (IV) vitamin C, (5) IV corticosteroids are suggested for adults in septic shock with ongoing vasopressor therapy needs, and (6) it is recommended that adult survivors of sepsis or septic shock be assessed for physical, cognitive, and emotional problems after hospital discharge. ¹³ In addition to these changes, the 2021 SSC guidelines no longer recommend the Quick Sequential Organ Failure Assessment (qSOFA) as a single screening tool for suspected sepsis due to a lack of sensitivity and specificity, ¹⁴ which could lead to missed diagnoses. ¹³ These guidelines did not propose new diagnostic criteria for sepsis or septic shock, but did make a weak recommendation for using lactate levels to help screen for sepsis. In patients with suspected sepsis, the presence of an elevated lactate level significantly increases the likelihood of a final diagnosis of sepsis. ¹³
脓毒症生存运动（SSC）创建于 2004 年，旨在为脓毒症和脓毒性休克的治疗提供国际指南，每 4 年发布一次更新。与 2016 年的版本相比，最新版的 SSC（2021 年）对 6 项主要建议进行了修改：(1）由于证据质量较低，开始30毫升/千克液体栓塞的建议被降级为弱建议；（2）不再推荐使用生理盐水进行液体复苏；(3)对于脓毒性休克的成人，建议及时开始使用血管加压药，即使这意味着需要外周给药；(4)SSC 建议不要使用静脉注射维生素 C；(5)建议对需要持续使用血管加压药的脓毒性休克成人使用静脉注射皮质类固醇；(6)建议脓毒症或脓毒性休克的成人幸存者在出院后对身体、认知和情绪问题进行评估。 ¹³ 除了这些变化之外，2021 年 SSC 指南不再推荐将快速器官功能衰竭序列评估（qSOFA）作为疑似败血症的单一筛查工具，因为该方法缺乏敏感性和特异性， ¹⁴ 可能导致漏诊。 ¹³ 这些指南并未提出脓毒症或脓毒性休克的新诊断标准，但对使用乳酸水平帮助筛查脓毒症提出了微弱的建议。在疑似败血症患者中，乳酸水平升高会显著增加最终诊断为败血症的可能性。 ¹³

Pneumonia is responsible for about half of all cases of sepsis. ¹² Other common causes of sepsis include intra-abdominal and urinary tract infections. Hypotension, reduced red-cell deformability, and microvascular thrombosis are potential mechanisms that contribute to reduced oxygen delivery to tissues in septic shock. ¹⁵ In 40% of patients with sepsis, hypotension is the presenting abnormality. ¹⁶
在所有败血症病例中，肺炎约占一半。脓毒症的其他常见病因包括腹腔内感染和尿路感染。低血压、红细胞变形能力降低和微血管血栓形成是导致脓毒性休克时组织供氧减少的潜在机制。 ¹⁵ 在 40% 的败血症患者中，低血压是主要的异常现象。 ¹⁶

Once septic shock is suspected, initial management is important. The initial measures include the use of IV fluid resuscitation (30 mL/kg in the first 3 hours), IV antibiotics within 1 hour, ¹³ oxygen therapy, and mechanical ventilation if clinically indicated.^15,17 These recommendations are concordant with the 2021 SSC guidelines. After the initial fluid bolus of 30 mL/kg, monitoring for dynamic blood pressure response (eg, an increase in cardiac output occurring within 60 seconds of passive leg raising to a 45° incline) helps identify patients who may respond to additional fluids. ¹⁸ It is also advised to use lactate to assess tissue perfusion (lactate clearance) and to maintain a urine output goal of ≥0.5 mL/kg/h. ¹⁴ These measures help to safely guide fluid resuscitation while minimizing fluid overload. Of note, variation in cardiac output after passive leg raising may be more accurate than pulse pressure variation with respiration or using static tests such as central venous pressure in predicting fluid responsiveness in hemodynamically unstable patients. ¹⁸
一旦怀疑发生了脓毒性休克，最初的处理非常重要。初始措施包括静脉输液复苏（头 3 小时内每公斤 30 毫升）、1 小时内静脉注射抗生素、 ¹³ 氧疗，以及在有临床指征时进行机械通气。 ^15,17 这些建议与 2021 年 SSC 指南一致。在首次注射 30 毫升/千克的液体后，监测动态血压反应（例如，在被动抬腿至 45° 倾角的 60 秒内出现心输出量增加）有助于确定哪些患者可能需要额外的液体。 ¹⁸ 还建议使用乳酸来评估组织灌注（乳酸清除率），并将尿量目标保持在≥0.5 mL/kg/h。 ¹⁴ 这些措施有助于安全地指导液体复苏，同时最大限度地减少液体超负荷。值得注意的是，在预测血流动力学不稳定的患者对液体的反应性时，被动抬腿后的心输出量变化可能比脉压随呼吸的变化或使用中心静脉压等静态测试更准确。 ¹⁸

If the patient remains hypotensive despite fluid resuscitation, vasopressor therapy is indicated.^12,19 However, the notion of starting a vasopressor only after the patient is not fluid-responsive has been challenged. ²⁰ Early administration of vasopressors could reduce fluid overload from excessive fluid use,^21,22 potentially improve tissue oxygenation, and recruit microvessels leading to better microcirculation.^23,24 However, a recent unblinded randomized control trial (The CLOVERS trial) involving 1563 patients with sepsis-induced hypotension refractory to initial treatment with 1 to 3 L of IV fluid, found that a restrictive fluid strategy (with earlier vasopressor use) did not result in significantly lower or higher mortality before discharge by day 90 than a more liberal fluid administration strategy (with later vasopressor use). ²⁵ Thus, it remains unclear if early vasopressor use in septic shock affects outcomes.
如果病人在液体复苏后仍处于低血压状态，则需要使用血管加压疗法。 ^12,19 然而，在患者对液体没有反应后才开始使用血管加压药的观点受到了质疑。 ²⁰ 早期使用血管加压药可减少因过度使用液体而导致的液体超负荷， ^21,22 有可能改善组织氧合，并募集微血管以改善微循环。 ^23,24 然而，最近的一项非盲法随机对照试验（CLOVERS 试验）涉及 1563 名脓毒症诱发的低血压患者，这些患者最初接受 1 至 3 升静脉输液治疗后出现难治性低血压，试验发现，限制性输液策略（较早使用血管加压药）与较宽松的输液策略（较晚使用血管加压药）相比，在第 90 天出院前的死亡率并没有明显降低或升高。 ²⁵ 因此，脓毒性休克患者早期使用血管加压药是否会影响预后仍不清楚。

The first-line vasopressor recommended for septic shock is norepinephrine (Table 1 and Figure 1B).^26–28 Norepinephrine is usually started at a dose between 0.01 and 0.05 µg/kg/min, which may be titrated up at increments of 0.02 to 0.04 µg/kg/min every 5 to 15 minutes until the MAP goal of 65 mm Hg or greater is reached.^29,30 Vasopressin or antidiuretic hormone (ADH) is produced in the supraoptic and paraventricular nuclei in the hypothalamus and then stored in the posterior pituitary gland. The vasoconstrictive property of vasopressin is through the stimulation of V1 receptors in vasculature smooth muscle. ³¹ Low-dose vasopressin (0.03 units/min) may be added as a second-line agent if the MAP goal ≥ 65 mm Hg is not met with high doses of norepinephrine (> 0.2 µg/kg/min).^32–34 Retrospective studies have shown an associated improvement in mortality in patients with septic shock when prehospital norepinephrine was administered, ³⁰ and when vasopressin was added to low-dose norepinephrine (< 0.25 µg/kg/min), but not high-dose norepinephrine (> 0.25 µg/kg/min). ³⁵ However, the high-dose norepinephrine group might have had more severe disease resulting in worse outcomes. It appears that vasopressin has a synergistic effect when combined with norepinephrine, which may allow for a dose reduction of norepinephrine. ³⁶ In addition, vasopressin may still produce vasoconstriction during acidotic states (eg, septic shock) when α₁-agonists (eg, norepinephrine) become less effective. ³⁷
推荐用于脓毒性休克的一线血管抑制剂是去甲肾上腺素（表 1 和图 1B）。0# 去甲肾上腺素的起始剂量通常为 0.01 至 0.05 微克/千克/分钟，之后可每 5 至 15 分钟以 0.02 至 0.04 微克/千克/分钟的剂量递增，直至达到 65 毫米汞柱或更高的血压目标。 ^29,30 加压素或抗利尿激素（ADH）由下丘脑视上核和室旁核产生，然后储存在垂体后叶。血管加压素的收缩血管作用是通过刺激血管平滑肌中的 V1 受体实现的。 ³¹ 如果使用大剂量去甲肾上腺素（> 0.2 µg/kg/min）仍无法达到 MAP ≥ 65 mm Hg 的目标，则可添加小剂量血管加压素（0.03 单位/分钟）作为二线药物。 ^32–34 回顾性研究显示，在院前注射去甲肾上腺素 ³⁰ 和在低剂量去甲肾上腺素（< 0.25 µg/kg/min）中添加血管加压素，而非高剂量去甲肾上腺素（> 0.25 µg/kg/min）时，脓毒性休克患者的死亡率会有所改善。 ³⁵ 不过，大剂量去甲肾上腺素组的病情可能更严重，结果也更糟糕。血管加压素与去甲肾上腺素合用时似乎有协同作用，这可能会减少去甲肾上腺素的剂量。 ³⁶ 此外，在酸中毒状态下（如脓毒性休克），当α ₁ -激动剂（如去甲肾上腺素）的作用减弱时，血管加压素仍可产生血管收缩作用。 ³⁷

Table 1.  表 1. Commonly Used Inotropes and Vasopressors in Shock.

Epinephrine is another second-line vasopressor that may be used, especially if the heart rate or cardiac output is inadequate (as this affect has both inotropic and chronotropic actions). ²⁹ Alternatively, epinephrine may be added as part of a three-drug combination if a prompt response to the second vasopressor is not seen, especially in patients with concomitant myocardial dysfunction.^33,46 It is important to note that epinephrine has a higher risk of inducing tachyarrhythmias when compared to norepinephrine. ³⁶ Further, the 2021 SSC guidelines proposed using hydrocortisone 200 mg/day (either as a bolus of 50 mg every 6 hours or as a continuous infusion) in septic shock patients with ongoing requirements for vasopressors despite adequate fluid resuscitation. ¹³
肾上腺素是另一种可以使用的二线血管抑制剂，尤其是在心率或心输出量不足的情况下（因为肾上腺素同时具有肌力和时动力作用）。 ²⁹ 或者，如果对第二种血管加压剂没有迅速反应，特别是同时伴有心肌功能障碍的患者，可将肾上腺素作为三药联合使用的一部分。 ^33,46 值得注意的是，与去甲肾上腺素相比，肾上腺素诱发快速性心律失常的风险更高。 ³⁶ 此外，2021 年的 SSC 指南建议，尽管进行了充分的液体复苏，但仍需持续使用血管加压剂的脓毒性休克患者，可使用氢化可的松 200 毫克/天（每 6 小时 50 毫克的栓剂或持续输注）。 ¹³

Ideally, vasopressor therapy is given through a central venous catheter (CVC) due to concerns for vasopressor-induced local tissue injury (tissue necrosis) when a peripheral venous catheter (PVC) is used. However, the risk of tissue necrosis with the use of a PVC is limited, especially for short-term use (<6 hours) in a PVC placed proximal to the antecubital fossa.^47–50 Therefore, peripheral administration of vasopressors may be given temporarily until a CVC is placed, ⁴⁹ even in children. ⁵¹
由于担心使用外周静脉导管（PVC）时血管加压引起局部组织损伤（组织坏死），因此最好通过中心静脉导管（CVC）进行血管加压治疗。然而，使用 PVC 造成组织坏死的风险是有限的，尤其是短期使用（<6 小时）置于眶前窝近端的 PVC。 ^47–50 因此，在放置 CVC 之前， ⁴⁹ 即使是儿童，也可暂时在外周使用血管加压药。 ⁵¹

Neurogenic Shock   神经源休克

Neurogenic shock is an important cause of distributive shock when the spinal cord is damaged. The hypoperfusion seen in neurogenic shock is due to loss of sympathetic control of vascular tone that is often seen in upper spinal cord injuries, especially above the T6 level since the sympathetic neurons that innervate the heart reside from T1 to T4.^52,53 Early surgical intervention (< 24 hours) to decompress and stabilize the vertebral column is key.^52,54 It is also important to correct hypotension (systolic blood pressure < 90 mm Hg) to prevent secondary damage of the spinal cord from ischemia resulting in worsening of neurological outcomes. ⁵⁵
神经源性休克是脊髓受损时导致分布性休克的一个重要原因。神经源性休克中出现的低灌注是由于交感神经失去了对血管张力的控制，这在脊髓上部损伤中经常出现，尤其是在 T6 水平以上，因为支配心脏的交感神经元位于 T1 至 T4。 ^52,53 关键是及早进行手术干预（< 24 小时）以减压和稳定椎体。 ^52,54 同样重要的是纠正低血压（收缩压< 90 mm Hg），以防止脊髓因缺血造成二次损伤，导致神经功能恶化。 ⁵⁵

A vasopressor with both α and β activities such as dopamine or norepinephrine is commonly used to manage neurogenic shock when fluid resuscitation is insufficient. A small prospective cross-over interventional study of 11 patients showed that norepinephrine was able to maintain MAP with a lower intrathecal pressure and a higher spinal cord perfusion pressure (∼2 mm Hg) compared to dopamine. ⁵⁶ One review showed that vasopressor complications were greater for dopamine (especially tachyarrhythmias) when compared to phenylephrine in patients with acute spinal cord injuries. ⁵³ A more recent systematic review proposed that in acute traumatic spinal cord injuries, norepinephrine may be the vasopressor of choice. ⁵⁷ Nevertheless, due to lack of high-quality evidence there remains no consensus on the optimal therapy for neurogenic shock. Another commonly used agent, phenylephrine, may induce reflex bradycardia (Table 1) which could be dangerous in patients with spinal injuries above T6, who are already prone to bradycardia due to sympathetic dysfunction. Therefore, it is recommended to use pure vasoconstrictors such as phenylephrine for lower spinal cord injuries (ie, below T6).^58,59 Conversely, norepinephrine or dopamine are used for upper spinal cord injuries (ie, at or above T6). ⁵⁹ However, these agents may cause excessive inotropy in the context of increased peripheral vascular resistance if they are used for lower spinal cord injuries. ⁵³
多巴胺或去甲肾上腺素等同时具有α和β活性的血管抑制剂通常用于在液体复苏不足时控制神经源性休克。一项对 11 名患者进行的小型前瞻性交叉干预研究显示，与多巴胺相比，去甲肾上腺素能够以较低的鞘内压和较高的脊髓灌注压（∼2 mm Hg）维持 MAP。 ⁵⁶ 一篇综述显示，在急性脊髓损伤患者中，多巴胺与苯肾上腺素相比，血管舒张剂并发症（尤其是快速性心律失常）更多。 ⁵³ 最近的一篇系统综述提出，在急性创伤性脊髓损伤中，去甲肾上腺素可能是首选的血管抑制剂。 ⁵⁷ 尽管如此，由于缺乏高质量的证据，关于神经源性休克的最佳疗法仍未达成共识。另一种常用的药物苯肾上腺素可能会诱发反射性心动过缓（表 1），这对于 T6 以上脊柱损伤的患者来说可能很危险，因为交感神经功能障碍已导致患者容易出现心动过缓。因此，建议对脊髓下段损伤（即 T6 以下）患者使用纯血管收缩剂，如苯肾上腺素。 ^58,59 相反，去甲肾上腺素或多巴胺则用于上部脊髓损伤（即 T6 或以上）。 ⁵⁹ 然而，如果这些药物用于下部脊髓损伤，可能会在外周血管阻力增加的情况下导致过度肌力。 ⁵³

The most current guidelines released in 2013 recommend maintaining a MAP within 85-90 mm Hg for 7 days in patients after acute spinal cord injuries. ⁶⁰ However, there is only limited evidence to support this recommendation. Moreover, it is a challenge to maintain such MAP goals in general practice. ⁶¹ A recent retrospective study has shown higher rates of neurologic recovery in patients who maintained a MAP > 85 mm Hg consistently over a shorter period of time of 5 days after spinal cord injury. ⁶² Indeed, another retrospective study showed that higher average MAP values correlated best with improved recovery in the first 2 to 3 days after spinal cord injury, with this correlation becoming weaker in subsequent days. ⁶³ This experience suggests that using vasopressors for less than the recommended 7 days may not negatively affect neurological outcomes. Therefore, maintaining the MAP goal of >85 mm Hg for 5 days after acute spinal injury is reasonable.
2013 年发布的最新指南建议将急性脊髓损伤后患者的血压在 85-90 mm Hg 范围内维持 7 天。 ⁶⁰ 然而，支持这一建议的证据有限。此外，在普通实践中保持这样的血压目标也是一项挑战。 ⁶¹ 最近的一项回顾性研究显示，脊髓损伤后 5 天内持续保持血压 > 85 mm Hg 的患者神经功能恢复率较高。 ⁶² 事实上，另一项回顾性研究显示，在脊髓损伤后的头 2 到 3 天内，较高的平均血压值与恢复改善的相关性最好，而在随后的几天内，这种相关性变得较弱。 ⁶³ 这一经验表明，使用血管加压药的时间少于建议的 7 天可能不会对神经系统的预后产生负面影响。因此，在急性脊髓损伤后 5 天内保持血压 >85 mm Hg 的目标是合理的。

Elderly patients (≥ 65 years of age) might be particularly prone to complications with vasopressor use. Recent studies have shown that elderly patients with spinal cord injuries are particularly susceptible to cardiovascular complications ⁶⁴ from vasopressors, especially with dopamine.^53,65,66 Clinical judgment is needed to determine the risk–benefit balance for vasopressor administration (especially dopamine) in the elderly who are often already burdened by chronic cardiovascular comorbidities. Downward adjustment of MAP goals is advisable, especially if there is no neurological improvement after the first 3 days after spinal cord injury. ⁵² It is important to note that blood pressure augmentation to MAP goals > 85 mm Hg in patients with concurrent hemorrhagic shock, aortic dissection, or intracranial hemorrhage could worsen these conditions, which are not uncommon in trauma. ⁵² More prospective studies are needed not only to determine the optimal vasopressor agent, but also to determine if MAP goals < 85 mm Hg can maintain adequate spinal cord perfusion pressure to minimize the use of vasopressors.
老年患者（≥ 65 岁）使用血管加压药可能特别容易出现并发症。最近的研究表明，脊髓损伤的老年患者特别容易因使用血管加压药（尤其是多巴胺）而引起心血管并发症 ⁶⁴ 。对于已经患有慢性心血管并发症的老年人，使用血管加压药（尤其是多巴胺）的风险与收益之间的平衡需要临床判断。建议下调 MAP 目标，尤其是在脊髓损伤后 3 天内神经功能没有改善的情况下。 ⁵² 需要注意的是，对于同时患有失血性休克、主动脉夹层或颅内出血的患者，将血压升高至 MAP 目标值 > 85 mm Hg 可能会加重这些情况，而这些情况在创伤中并不少见。 ⁵² 需要更多的前瞻性研究，不仅要确定最佳的血管加压药，还要确定 MAP 目标 < 85 mm Hg 是否能够维持足够的脊髓灌注压，以尽量减少血管加压药的使用。

In patients who can tolerate oral medications, Midodrine (an α-1 agonist) may be given as 10 mg orally 3 times daily for prophylaxis or treatment of orthostatic hypotension often seen with spinal cord injuries. ⁶⁷ Interestingly, oral midodrine may reduce IV vasopressor requirements for patients needing prolonged support after cervical spinal cord injury. ⁶⁸ Droxidopa (a synthetic precursor of norepinephrine) is another oral agent that may be used to wean patients off IV vasopressors if patients are intolerant to midodrine. ⁶⁹ Other medications to consider include atropine to treat bradycardia, which most commonly presents as sinus bradycardia. ⁵³
对于可以耐受口服药物的患者，可以口服米多君（一种 α-1 激动剂），每次 10 毫克，每天 3 次，用于预防或治疗脊髓损伤后经常出现的直立性低血压。 ⁶⁷ 有趣的是，对于颈脊髓损伤后需要长期支持的患者，口服米多君可减少静脉血管加压素的需求。 ⁶⁸ Droxidopa（去甲肾上腺素的合成前体）是另一种口服药物，如果患者对米多君不耐受，可用于让患者停用静脉血管加压药。 ⁶⁹ 其他可考虑使用的药物包括治疗心动过缓的阿托品，心动过缓最常见的表现为窦性心动过缓。 ⁵³

Anaphylactic Shock   过敏性休克

Anaphylaxis is a serious allergic reaction that commonly presents with a rash (ie, urticaria), itch, and dyspnea (shortness of breath). ⁷⁰ A diagnostic criteria for anaphylaxis was developed by the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) symposium in 2006 (Table 2). ⁷¹
过敏性休克是一种严重的过敏反应，通常表现为皮疹（即荨麻疹）、瘙痒和呼吸困难（气短）。美国国家过敏和传染病研究所/食品过敏和过敏性休克网络（NIAID/FAAN）研讨会于 2006 年制定了过敏性休克的诊断标准（表 2）。 ⁷¹

Table 2.  表 2. Diagnostic Criteria for Anaphylaxis.

Between 30% and 50% of patients with anaphylaxis develop shock.^73,74 Distributive shock from anaphylaxis is due to IgE- and non-IgE mediated release of vasoactive mediators (eg, histamine) from basophils and mast cells resulting in hypotension. ⁷² Vasodilation, bronchoconstriction, and cardiac depression seen in anaphylactic shock are all counteracted by the administration of epinephrine. ⁷⁵ Therefore, epinephrine is the vasopressor of choice in anaphylactic shock. Intramuscular (IM) epinephrine [0.3-0.5 mg, 1:1000 (1 mg/mL)] should be given immediately into the middle anterolateral thigh musculature while intravenous access is being obtained. ⁷² An IV infusion of epinephrine should be started at 1 to 10 µg/min and titrated up by half of the starting dose every 2 to 3 minutes to achieve a MAP > 65 mm Hg. ⁷⁶
30% 至 50% 的过敏性休克患者会出现休克。过敏性休克引起的分布性休克是由于嗜碱性粒细胞和肥大细胞在 IgE 和非 IgE 介导下释放血管活性介质（如组胺），导致低血压。 ⁷² 过敏性休克时出现的血管扩张、支气管收缩和心脏抑制都会被肾上腺素所抵消。 ⁷⁵ 因此，肾上腺素是过敏性休克时首选的血管抑制剂。在获得静脉通道的同时，应立即在大腿中部前外侧肌肉注射（IM）肾上腺素[0.3-0.5 毫克，1:1000（1 毫克/毫升）]。 ⁷² 肾上腺素的静脉输注应从 1 至 10 µg/min 开始，每 2 至 3 分钟增加起始剂量的一半，以达到血压 > 65 mm Hg。 ⁷⁶

Patients on β-blockers may have an inadequate response to epinephrine infusions due to the blunted cardiovascular effect resulting from β-blockade. Glucagon in this scenario might prove useful because it increases inotropy and chronotropy without activating the β-receptors.^76,77 Indeed, glucagon should be given to any patient who is not responding to epinephrine regardless if they are taking a β-blocker or not. ⁷⁸ For adults, glucagon 1 to 5 mg (pediatrics: 20-30 µg/kg) IV should be given over 5 minutes, followed by an infusion of 5 to 15 µg/min. ⁷⁶ A second vasopressor (eg, norepinephrine and vasopressin) may be added as a second-line agent if epinephrine is inadequate. ⁷⁶
使用β-受体阻滞剂的患者可能会因β-受体阻滞导致的心血管效应减弱而对肾上腺素输注反应不足。在这种情况下，胰高血糖素可能会被证明是有用的，因为它可以在不激活β受体的情况下增加心肌收缩力和时速。 ^76,77 事实上，任何对肾上腺素无反应的患者，无论是否服用β-受体阻滞剂，都应给予胰高血糖素。 ⁷⁸ 对于成人，应在 5 分钟内静脉注射胰高血糖素 1 至 5 毫克（儿科：20 至 30 微克/千克），然后每分钟输注 5 至 15 微克。 ⁷⁶ 如果肾上腺素不足，可添加第二种血管加压剂（如去甲肾上腺素和血管加压素）作为二线药物。 ⁷⁶

Cardiogenic Shock   心源性休克

Cardiogenic shock is due to cardiac dysfunction that leads to inadequate tissue perfusion. Acute myocardial infarction is the most common cause of cardiogenic shock. ⁵ Patients are also at risk of developing cardiogenic shock after an out-of-hospital cardiac arrest (OHCA). It is not necessarily the resuscitation that results in cardiac dysfunction (although damage to the heart from resuscitation may contribute) but more likely the coronary malperfusion resulting from the subsequent cardiac arrest. A cardiac ischemic event may result in an OHCA and subsequent cardiogenic shock. Signs of hypoperfusion seen in shock include tachycardia, altered mental status, elevated lactate, and oliguria (<400 mL/day). A low mixed venous oxygen saturation (SvO₂), a high central venous pressure, a reduced cardiac index (≤ 2.2 L/min/m²), and typical echocardiographic features (eg, reduced ejection fraction and enlarged ventricles) are features that help differentiate cardiogenic shock from other etiologies of shock.^5,9
心源性休克是由于心脏功能障碍导致组织灌注不足引起的。急性心肌梗死是导致心源性休克的最常见原因。 ⁵ 患者在院外心脏骤停（OHCA）后也有发生心源性休克的风险。导致心功能不全的不一定是复苏（尽管复苏对心脏造成的损伤可能是原因之一），更可能是随后心脏骤停导致的冠状动脉灌注不良。心脏缺血事件可能导致 OHCA 和随后的心源性休克。休克时出现的低灌注体征包括心动过速、精神状态改变、乳酸升高和少尿（<400 毫升/天）。低混合静脉血氧饱和度（SvO ₂ ）、高中心静脉压、心脏指数降低（≤ 2.2 L/min/m ² ）和典型的超声心动图特征（如射血分数降低和心室扩大）有助于将心源性休克与其他病因引起的休克区分开来。 ^5,9

Though meta-analyses have shown epinephrine to increase survival to hospital admission from OHCA, most of these studies evaluated prehospital epinephrine administration in the context of cardiac arrest and associated return of spontaneous circulation (ROSC), rather than cardiogenic shock specifically.^79–81 Norepinephrine is the recommended first-line vasopressor in cardiogenic shock.^17,39 The duration and severity of hypotension following resuscitation from OHCA have been associated with worse outcomes. ⁸² Observational studies have shown that post-OHCA patients with shock who received norepinephrine were less prone to recurrent cardiac arrest and had lower all-cause mortality when compared to patients who received epinephrine.^83,84 Norepinephrine increases the MAP without a significant effect on heart rate. ²⁶ In cardiogenic shock, the minimal β-adrenergic effect seen with norepinephrine is less likely to lead to arrhythmias or significant myocardial oxygen consumption. ⁸⁵ Unlike norepinephrine, epinephrine efficiently increases the MAP at a higher cost in terms of cardiac energy expenditure leading to more severe side effects (eg, cardiac ischemia). ³⁹ Moreover, norepinephrine does not elevate lactate like epinephrine, allowing lactate to be used as a surrogate marker to monitor for developing organ ischemia. ⁴³ The hyperlactemia and hyperglycemia seen with epinephrine is thought to be due to its strong β₂-stimulation (Figure 1B). Sustained infusions of epinephrine to maintain blood pressure in patients with cardiogenic shock should be avoided,^38,86 especially in patients with acute myocardial infarction. ⁸⁷ Dopamine is not recommended for cardiogenic shock because of its greater chronotropic effects, and norepinephrine has been shown to be superior in the reduction of mortality.^26,88 Phenylephrine should be avoided in most scenarios as it may decrease cardiac output, further worsening cardiogenic shock. ⁴⁵
尽管荟萃分析表明肾上腺素可提高 OHCA 患者入院后的存活率，但这些研究大多是在心脏骤停和相关自发循环恢复（ROSC）的背景下评估院前肾上腺素的使用情况，而不是专门评估心源性休克。 ^79–81 去甲肾上腺素是推荐用于心源性休克的一线血管抑制剂。 ^17,39 OHCA 复苏后低血压的持续时间和严重程度与较差的预后有关。 ⁸² 观察性研究表明，与接受肾上腺素治疗的患者相比，接受去甲肾上腺素治疗的 OHCA 后休克患者不易再次发生心脏骤停，且全因死亡率较低。 ^83,84 去甲肾上腺素可增加血压，但对心率无明显影响。 ²⁶ 在心源性休克中，去甲肾上腺素的β-肾上腺素能效应最小，不太可能导致心律失常或心肌耗氧量显著增加。 ⁸⁵ 与去甲肾上腺素不同，肾上腺素能有效地提高 MAP，但在心脏能量消耗方面代价较高，导致更严重的副作用（如心肌缺血）。 ³⁹ 此外，去甲肾上腺素不会像肾上腺素那样使乳酸升高，因此可将乳酸作为替代标志物来监测器官缺血的发展情况。肾上腺素引起的高乳酸血症和高血糖被认为是由于其强烈的β ₂ -刺激所致（图 1B）。应避免为维持心源性休克患者的血压而持续输注肾上腺素， ^38,86 尤其是急性心肌梗死患者。 ⁸⁷ 多巴胺对心源性休克的作用更大，因此不建议使用，去甲肾上腺素在降低死亡率方面更具优势。 ^26,88 在大多数情况下应避免使用苯肾上腺素，因为它可能会降低心输出量，进一步恶化心源性休克。 ⁴⁵

Inotropic agents need to be considered when cardiac pump impairment is contributing to organ ischemia. Dobutamine acts primarily as a β₁ agonist resulting in increased inotropy with limited effect on blood pressure (Table 1). ⁸⁵ Dobutamine is a commonly used inotrope in cardiogenic shock, especially in combination with norepinephrine in patients requiring both inotropic and vasopressor support. ³⁹ Milrinone is another inotrope that improves cardiac contractility through the inhibition of phosphodiesterase type-3. This mechanism of action of milrinone may allow it to maintain effectiveness during β-blockade (ie, patients on β-blockers). ⁸⁹ Dobutamine has a faster onset of action with a stronger inotropic effect compared with milrinone.^33,90 In a recent trial, 192 patients with cardiogenic shock were randomized to receive either dobutamine or milrinone and showed no difference in outcomes (eg, in-hospital death from any cause, stroke, or cardiovascular or renal events). ⁹¹ However, milrinone should be used with caution in patients with renal dysfunction due to the increased risk of drug accumulation leading to prolonged hypotension. ²⁹ Due to the unpredictable effects of inotropes on blood pressure, MAP should not be used to guide the titration of inotropes. Instead, titration should be guided by achieving adequate end-organ perfusion such as urine output >0.5 mL/kg/h with normalized or decreasing lactate level. ²⁹ Titrating an inotrope to improve SvO₂ or central venous oxygen saturation (ScvO₂) values may also be useful since they reflect the balance between oxygen demand and supply.^9,29
当心脏泵功能受损导致器官缺血时，需要考虑使用肌力药物。多巴酚丁胺主要作为一种 β ₁ 激动剂，可增加肌张力，但对血压的影响有限（表 1）。1# 多巴酚丁胺是心源性休克中常用的肌力药物，尤其是与去甲肾上腺素联合应用于需要肌力和血管加压支持的患者。米力农是另一种肌力药物，它通过抑制 3 型磷酸二酯酶来改善心脏收缩力。米力农的这一作用机制可使其在β受体阻滞期间（即使用β受体阻滞剂的患者）保持有效性。 ⁸⁹ 与米力农相比，多巴酚丁胺起效更快，肌力作用更强。 ^33,90 在最近的一项试验中，192 名心源性休克患者被随机分配接受多巴酚丁胺或米力农治疗，结果显示两者的治疗效果（如任何原因导致的院内死亡、中风、心血管或肾脏事件）并无差异。 ⁹¹ 然而，由于药物蓄积导致长时间低血压的风险增加，肾功能不全患者应慎用米力农。 ²⁹ 由于肌注药物对血压的影响难以预测，因此不应使用血压指数来指导肌注药物的滴定。取而代之的是，应通过实现充足的内脏灌注来指导滴注，如尿量大于 0.5 mL/kg/h，乳酸水平正常或下降。 ²⁹ 滴定肌力药物以改善 SvO ₂ 或中心静脉血氧饱和度（ScvO ₂ ）值也可能有用，因为它们反映了氧需求和氧供应之间的平衡。 ^9,29

Patients with cardiogenic shock from left ventricular dysfunction may still benefit from fluids and appropriate assessment for fluid responsiveness (eg, cardiac output changes after passive leg raise) is advised. ⁹ However, in elderly patients with extensive left ventricular infarction, aggressive fluid resuscitation should be avoided. ³⁸ The SHOCK trial has shown that urgent revascularization is ultimately the definitive therapeutic option in cardiogenic shock following an acute myocardial infarction. ⁹²
左心室功能障碍导致的心源性休克患者仍可从输液中获益，建议对输液反应性（如被动抬腿后的心输出量变化）进行适当评估。 ⁹ 然而，对于左心室广泛梗死的老年患者，应避免积极的液体复苏。 ³⁸ SHOCK 试验表明，对于急性心肌梗死后的心源性休克，紧急血管重建是最终的治疗方案。 ⁹²

Hypovolemic Shock   低血容量休克

Hypovolemic shock leads to inadequate oxygen delivery to tissues due to loss of effective circulating blood volume. Loss of circulating blood volume could be due to nonhemorrhagic (eg, gastrointestinal losses from severe vomiting or diarrhea) or hemorrhagic causes. The most common cause of hemorrhagic hypovolemic shock is traumatic injury. ³
低血容量性休克会因有效循环血容量减少而导致组织供氧不足。循环血容量的丧失可能是由于非出血性原因（如严重呕吐或腹泻造成的胃肠道损失），也可能是由于出血性原因。出血性低血容量休克最常见的原因是外伤。 ³

Volume resuscitation is crucial in patients with nonhemorrhagic hypovolemic shock. Extrapolating from the Sepsis guidelines, a crystalloid bolus solution of 30 mL/kg infused over 3 hours with additional fluid given based on surrogate markers for end-organ ischemia (eg, urine output and lactate clearance) is reasonable for patients presenting with nonhemorrhagic hypovolemic shock.^3,13 More caution is needed with fluid administration in hemorrhagic hypovolemic shock (or hemorrhagic shock) due to the risk of diluting clotting factor concentrations, and exacerbating hypothermia and acidemia.^93,94 Acidemia and hypothermia can further impair the function of clotting factors leading to greater blood loss.^95,96 Studies have shown that patients with penetrating injuries have better outcomes when they receive restrictive ⁹⁷ or delayed ⁹⁸ fluid resuscitation. One caveat is that these findings might only apply to patients with penetrating torso injuries. ⁹⁸ Nevertheless, prehospital care for hemorrhagic shock involves giving limited fluid resuscitation (enough to maintain palpable radial pulse), minimizing further blood loss (eg, applying direct pressure or hemostatic dressings to bleeding sites), avoiding hypothermia, and rapid transport to a medical facility for definite treatment. ⁹⁹ Rapid transport cannot be overemphasized as the median time to death in a cohort of 809 patients in hypovolemic shock was only 2 hours. ¹⁰⁰ It is important to note that significant blood loss may occur with minimal effects on vital signs such as blood pressure, especially in pediatric patients (Table 3). ¹⁰¹
对于非失血性低血容量休克患者来说，血容量复苏至关重要。根据败血症指南推断，对于非出血性低血容量休克患者，在 3 小时内输注 30 毫升/千克晶体液，并根据内脏缺血的替代指标（如尿量和乳酸清除率）给予额外液体是合理的。 ^3,13 出血性低血容量休克（或失血性休克）患者输液需要更加谨慎，因为有可能稀释凝血因子浓度，加剧低体温和酸血症。 ^93,94 酸血症和低体温会进一步损害凝血因子的功能，导致失血量增加。 ^95,96 研究表明，穿透伤患者在接受限制性 ⁹⁷ 或延迟 ⁹⁸ 液体复苏时，预后较好。需要注意的是，这些研究结果可能只适用于躯干穿透伤患者。 ⁹⁸ 尽管如此，失血性休克的院前护理包括给予有限的液体复苏（足以维持可触摸到的桡动脉脉搏）、尽量减少进一步失血（例如，对出血部位直接施压或止血包扎）、避免体温过低，以及快速转运至医疗机构进行明确治疗。 ⁹⁹ 快速转运无论如何强调都不为过，因为在一组 809 名低血容量休克患者中，死亡时间的中位数仅为 2 小时。 ¹⁰⁰ 值得注意的是，大量失血可能对血压等生命体征影响极小，尤其是对儿童患者（表 3）。

Table 3.  表 3. Hemorrhagic Shock Classification.

A retrospective cohort study showed a significant survival benefit in combat patients who received prehospital blood product transfusions. ¹⁰² Such studies sparked the question if civilians would benefit from such a protocol. One of these studies includes the multicenter PAMPer trial in 2018, which showed that prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality in injured civilians at risk for hemorrhagic shock compared to standard resuscitation. ¹⁰³ Moreover, secondary analysis of this trial showed the greatest mortality benefit was seen in patients who received both prehospital packed red blood cells (PRBCs) and plasma. Patients who received crystalloids had the worst survival. ¹⁰⁴ This is in contrast to the RePHILL trial, which did not show that prehospital PRBC and lyophilized plasma resuscitation were superior to 0.9% sodium chloride for adult patients with traumatic hemorrhagic shock. ¹⁰⁵
一项回顾性队列研究显示，接受院前血液制品输注的战斗患者的存活率显著提高。 ¹⁰² 这些研究引发了平民是否能从这种方案中获益的问题。其中一项研究包括 2018 年进行的多中心 PAMPer 试验，该试验表明，与标准复苏相比，院前输注解冻血浆是安全的，并能降低有失血性休克风险的受伤平民的 30 天死亡率。 ¹⁰³ 此外，该试验的二次分析表明，同时接受院前包装红细胞（PRBC）和血浆的患者死亡率获益最大。接受晶体液的患者存活率最差。 ¹⁰⁴ 这与 RePHILL 试验形成鲜明对比，该试验并未显示院前包装红细胞和冻干血浆复苏对创伤性失血性休克成人患者的疗效优于 0.9% 氯化钠。 ¹⁰⁵

Once the patient with hemorrhagic shock arrives at the hospital, early massive-transfusion-protocol activation allows the mobilization of blood products and hemostatic agents such as tranexamic acid to the patient’s bedside. Tranexamic acid (administered as a loading dose of 1 g IV over 10 minutes, followed by 1 g IV infusion over 8 hours) is recommended as the hemostatic adjunct of choice in hemorrhagic shock. The PROMMTT study showed that higher plasma and platelet ratios used in resuscitation in patients with hemorrhagic shock due to trauma reduced short-term mortality. ¹⁰⁶ These findings were later confirmed in the PROPPR randomized clinical trial, which showed that patients who received plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio resulted in improved hemostasis and fewer deaths due to exsanguination by 24 hours. ¹⁰⁷ The CRASH-2 and MATTERs studies have shown that early administration of tranexamic acid improved survival in bleeding trauma patients.^108,109 A recent international randomized trial (The PATCH-Trauma trial) had a total of 1310 adults with major trauma assessed as being high risk for trauma-induced coagulopathy randomized to receive either tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or placebo in advanced trauma systems. ¹¹⁰ Similar to the CRASH-2 trial, secondary outcomes of this trial showed that tranexamic improved survival at 24 hours and 28 days postinjury when compared to placebo. However, as for the primary outcome, administration of tranexamic acid did not result in more patients surviving with a favorable functional outcome at 6 months versus placebo. This is probably explained by the fact that tranexamic acid saved more critically ill patients with greater disability compared to placebo.
失血性休克患者到达医院后，应尽早启动大量输血方案，以便将血液制品和止血剂（如氨甲环酸）运送到患者床旁。氨甲环酸（10 分钟内静脉注射 1 克负荷剂量，然后在 8 小时内静脉注射 1 克）被推荐为失血性休克的首选止血辅助药物。PROMMTT 研究表明，创伤导致的失血性休克患者在复苏过程中使用较高的血浆和血小板比例可降低短期死亡率。这些研究结果后来在 PROPPR 随机临床试验中得到了证实，该试验表明，与 1:1:2 的比例相比，按 1:1:1 的比例接受血浆、血小板和红细胞的患者的止血效果更好，24 小时内因失血过多死亡的人数更少。 ¹⁰⁷ CRASH-2 和 MATTERs 研究表明，早期使用氨甲环酸可提高出血创伤患者的存活率。 ^108,109 最近的一项国际随机试验（PATCH-Trauma 试验）对 1310 名被评估为创伤诱发凝血病高风险的成人重创患者进行了随机分组，让他们在先进的创伤系统中接受氨甲环酸（入院前静脉注射 1 克，到达医院后 8 小时内输注 1 克）或安慰剂治疗。3#与 CRASH-2 试验类似，该试验的次要结果显示，与安慰剂相比，氨甲环酸可提高伤后 24 小时和 28 天的存活率。然而，就主要结果而言，与安慰剂相比，服用氨甲环酸并没有使更多的患者在 6 个月后获得良好的功能性存活。 这可能是因为与安慰剂相比，氨甲环酸挽救了更多残疾程度更严重的危重病人。

Using whole blood for hemorrhagic shock has the advantage of having all the components of blood in one bag. Using blood component therapy for massive transfusion requires multiple bags to create ratios that mimic whole blood. Moreover, the need to track such product ratios during massive transfusions adds management complexity and increases the risk of error. ¹¹¹ Another randomized trial did show that administering whole blood in patients with hemorrhagic shock reduced transfusion volumes when compared to blood component therapy. ¹¹² More recent prospective observational studies have shown that whole blood transfusions not only decrease blood product use, ¹¹³ but improve mortality^113,114 when compared to component therapy.
使用全血治疗失血性休克的优势在于一袋血液中含有所有成分。而使用血液成分疗法进行大量输血则需要多个血袋，以模拟全血的比例。此外，在大量输血过程中需要跟踪这些产品的比例，这增加了管理的复杂性，也增加了出错的风险。 ¹¹¹ 另一项随机试验显示，与血液成分疗法相比，失血性休克患者使用全血可减少输血量。 ¹¹² 最近的前瞻性观察研究表明，与成分血疗法相比，全血输注不仅减少了血液制品的使用， ¹¹³ 而且提高了死亡率 ^113,114 。

Traditionally, vasopressor use in hypovolemic shock is discouraged due to concerns for worsening tissue perfusion.^109,115 Two recent retrospective studies have shown that early administration of norepinephrine did not adversely affect mortality in trauma patients with hemorrhagic shock.^116,117 Moreover, hemorrhagic shock is often associated with arginine vasopressin deficiency. ¹¹⁸ Supplementing such patients with vasopressin might be helpful. To help answer this question, 2 randomized controlled trials showed that trauma patients with shock who received vasopressin compared to placebo required significantly less total volume of fluid resuscitation ¹¹⁹ and blood products, ¹²⁰ but mortality was similar between study cohorts in both trials. This is in contrast to most previous retrospective cohort studies, which showed that the administration of vasopressors (including vasopressin) ¹²¹ increased mortality in trauma patients with hemorrhagic shock.^122–124 Overall, vasopressors should have a limited role in hypovolemic shock because they do not correct the underlying problem of fluid loss. If patients with life-threatening hypotension do not respond to other measures (eg, fluids, bleeding control, and blood transfusions), vasopressors may be administered with permissive hypotension (MAP goal of 50-60 mm Hg). ¹²⁵ Vasopressin given first as a bolus of 4 units and then as an intravenous infusion of ≤ 0.04 units/min may help achieve such resuscitative goals with less fluid and/or blood product requirements.^119,120 Additional research is needed to determine if early vasopressor (especially vasopressin) administration in patients with hemorrhagic shock improves mortality.
由于担心组织灌注恶化，传统上不鼓励在低血容量休克时使用血管加压素。 ^109,115 最近的两项回顾性研究表明，早期使用去甲肾上腺素不会对失血性休克的创伤患者的死亡率产生不利影响。 ^116,117 此外，失血性休克通常与精氨酸加压素缺乏有关。 ¹¹⁸ 给这类患者补充血管加压素可能会有帮助。为了帮助回答这个问题，两项随机对照试验显示，与安慰剂相比，接受了血管加压素治疗的休克创伤患者所需的液体复苏总量 ¹¹⁹ 和血液制品显著减少， ¹²⁰ 但在这两项试验中，不同研究组别的死亡率相似。这与之前的大多数回顾性队列研究形成了鲜明对比，这些研究显示，使用血管加压药（包括血管加压素） ¹²¹ 会增加失血性休克创伤患者的死亡率。 ^122–124 总的来说，血管加压药在低血容量性休克中的作用有限，因为它们不能纠正液体流失的根本问题。如果危及生命的低血压患者对其他措施（如输液、止血和输血）无反应，可在允许低血压的情况下使用血管加压素（MAP 目标值为 50-60 mm Hg）。 ¹²⁵ 血管加压素先以 4 单位的栓剂给药，然后以≤ 0.04 单位/分钟的速度静脉输注，可能有助于在减少液体和/或血液制品需求的情况下实现上述复苏目标。 ^119,120 还需要进行更多的研究，以确定对失血性休克患者早期使用血管加压素（尤其是血管加压素）是否能改善死亡率。

Obstructive Shock   阻塞性休克

Obstructive shock is considerably less common than other forms of shock. In Denmark, a 12-year cohort population study of circulatory shock had only 0.9% of subjects who presented to the Emergency Department with obstructive shock. ¹²⁶ However, it is important to know when obstructive shock may occur as this may impact treatment. Overall, the main goal of treatment for obstructive shock is to clear the obstruction and restore cardiac output. However, fluid therapy and vasopressors can be used to manage obstructive shock until more definitive treatment can be managed. ¹²⁷
阻塞性休克比其他形式的休克要少见得多。在丹麦，一项为期 12 年的循环休克人群队列研究显示，只有 0.9% 的受试者在急诊科出现阻塞性休克。不过，了解阻塞性休克的发生时间很重要，因为这可能会影响治疗。总体而言，治疗梗阻性休克的主要目标是清除梗阻和恢复心输出量。不过，在进行更明确的治疗之前，可以使用液体疗法和血管加压剂来控制阻塞性休克。 ¹²⁷

The use of IV crystalloids for fluid resuscitation is indicated for obstructive shock if the underlying cause of the obstruction cannot be treated. ¹²⁸ However, if the cause of the obstructive shock is pulmonary embolism there is the caveat that overloading with fluids may worsen the shock as giving IV fluids can cause the right ventricular distension leading to decreasing blood pressure. ¹²⁹ Generally 500 to 1000 mL of normal saline can be given with caution in cases of pulmonary embolism. ¹³⁰
如果无法治疗阻塞性休克的根本原因，则可使用静脉晶体液进行液体复苏。 ¹²⁸ 但是，如果阻塞性休克的病因是肺栓塞，则需要注意液体过量可能会加重休克，因为静脉注射液体会导致右心室扩张，从而导致血压下降。 ¹²⁹ 在肺栓塞的情况下，一般可谨慎给予 500 到 1000 毫升的生理盐水。 ¹³⁰

Vasopressors are indicated if fluid resuscitation for obstructive shock proves to be ineffective. Norepinephrine is considered the first choice for treatment with the option to add vasopressin. ¹²⁹ Another consideration with vasopressor use to support the patient with pulmonary embolism or tension pneumothorax is to prevent increased pulmonary vascular resistance. ¹²⁸ Vasopressin does not increase pulmonary vascular resistance like α₁ agonists (eg, norepinephrine), which makes it useful in patients with predominant right heart failure.^85,131 Another option that may be considered if vasopressin is ineffective is phenylephrine. ¹³⁰
如果对阻塞性休克进行液体复苏无效，则应使用血管加压素。去甲肾上腺素被认为是首选治疗药物，也可选择加用血管加压素。 ¹²⁹ 使用血管加压素为肺栓塞或张力性气胸患者提供支持的另一个考虑因素是防止肺血管阻力增加。 ¹²⁸ 血管加压素不会像α ₁ 激动剂（如去甲肾上腺素）那样增加肺血管阻力，这使得它在右心衰竭为主的患者中很有用。 ^85,131 如果血管加压素无效，还可以考虑使用苯肾上腺素。 ¹³⁰

Depending on the cause of obstructive shock, management may be significantly different. For example, patients with obstructive shock due to left ventricular outflow obstruction (eg, hypertrophic cardiomyopathy) might benefit from pure vasoconstrictors such as phenylephrine or vasopressin since increasing cardiac contractility by giving norepinephrine might further worsen symptoms of outflow obstruction.^39,132 However, the most important treatment in such patients is fluids to support preload leading to increased left ventricular size to reduce outflow obstruction by annular dilation. Unlike cardiogenic shock, inotropes are not as beneficial in managing obstructive shock as the underlying cause is due to blockage, not cardiac dysfunction. Inotropes may be used with IV fluids in the hopes of increasing cardiac output temporarily. ¹²⁸ Dopamine and dobutamine are favorable inotropes in obstructive shock due to pulmonary embolism because they increase pulmonary artery pressure to a lesser extent than cardiac output. ¹³⁰
根据阻塞性休克的病因，治疗方法可能会有很大不同。例如，左心室流出道梗阻（如肥厚型心肌病）导致的梗阻性休克患者可能会从纯血管收缩剂（如苯肾上腺素或血管加压素）中获益，因为通过给予去甲肾上腺素增加心脏收缩力可能会进一步加重流出道梗阻的症状。然而，对这类患者最重要的治疗方法是输液，以支持前负荷，从而增加左心室体积，减少因环扩张而导致的流出道梗阻。与心源性休克不同，肌注对治疗阻塞性休克并无益处，因为其根本原因在于阻塞，而非心功能不全。肌注药物可与静脉输液一起使用，希望能暂时增加心输出量。 ¹²⁸ 多巴胺和多巴酚丁胺是治疗肺栓塞引起的阻塞性休克的良好肌力药物，因为它们增加肺动脉压力的程度低于增加心输出量的程度。 ¹³⁰

Other Newer Vasopressors and Inotropes
其他新型血管加压药和肌注药

Levosimendan   列沃西孟丹

Levosimendan (not currently available in the United States) binds to cardiac troponin C to increase myocyte sensitivity to calcium leading to improved inotropy. ³⁹ Levosimendan also causes vasodilation by opening ATP-dependent potassium channels in the peripheral vascular smooth muscle cells. ⁸⁵ This agent may be useful in reducing cardiac filling pressures in cardiogenic shock, particularly in patients on β-blockers. ¹³³
左西孟旦（目前尚未在美国上市）可与心肌肌钙蛋白 C 结合，提高心肌细胞对钙的敏感性，从而改善肌力。0#左西孟旦还能打开外周血管平滑肌细胞中依赖 ATP 的钾通道，从而导致血管扩张。 ⁸⁵ 这种药物可能有助于降低心源性休克患者的心脏充盈压，尤其是使用β-受体阻滞剂的患者。 ¹³³

Angiotensin II   血管紧张素 II

Angiotensin II or Giapreza is a synthetic human peptide hormone that binds to angiotensin-1 and -2 receptors inducing vasoconstriction, vasopressin release, and aldosterone synthesis. ¹⁷ Like vasopressin, angiotensin II induces vasoconstriction without significant inotropic effects. This agent might be useful in patients with refractory distributive shock and adequate cardiac output.^33,133 Angiotensin II is given initially at 20 ng/kg/min as a continuous IV infusion that may titrated up every 5 minutes to a maximum dose of 80 ng/kg/min in the first 3 hours. Thereafter, the maintenance dose of 1.25 up to 40 ng/kg/min may be used for up to 7 days.^134,135
血管紧张素 II 或 Giapreza 是一种合成的人肽激素，可与血管紧张素-1 和-2 受体结合，诱导血管收缩、血管加压素释放和醛固酮合成。与血管加压素一样，血管紧张素 II 可诱导血管收缩，但无明显的肌力作用。这种药物可能适用于难治性分布性休克和心输出量充足的患者。血管紧张素 II 最初以 20 纳克/千克/分钟的剂量持续静脉输注，每 5 分钟滴注一次，在最初 3 小时内最大剂量为 80 纳克/千克/分钟。此后，可使用 1.25 至 40 纳克/千克/分钟的维持剂量长达 7 天。 ^134,135