恶病质 cachexia
恶病质（cachexia）一词来源于希腊语的“kakos”和“hexis”，字面意思是“恶劣的状况”。它可发生于多种疾病，包括肿瘤、 AIDS、严重创伤、手术后、吸收不良及严重的败血症等，其中以肿瘤伴发的恶病质最为常见，也称为肿瘤恶病质，亦称恶液质。恶液质这个名称来源于体液病理学的概念。体液病理学认为疾病的本质在于体液的异常。原文出自希波克拉底（Hippocrates）和盖伦（Gale-nos）。
The word cachexia is derived from the Greek words "kakos" and "hexis", which literally mean "bad condition". It can occur in a variety of diseases, including tumors, AIDS, severe trauma, post-surgery, malabsorption, and severe sepsis, among which the cachexia associated with tumors is the most common, also known as tumor cachexia, also known as cachexia. The name cachexia is derived from the concept of humoral pathology. Humoral pathology is the belief that the essence of disease lies in the abnormality of bodily fluids. The original text is from Hippocrates and Gale-nos.
临床中通常指的是蛋白质-能量营养不良(Protein energgymalnutrition)极度消瘦状态，是因食物供应不足或者疾病因素引起的营养缺乏病，由于饥饿或疾病造成机体严重消耗，生理功能调节衰竭是临床疾病终末期表现，影响疾病的结局。过去在世界各地特别是不发达国家由于经济文化科学技术落后，尤其是自然灾害与战争时期，食品供应不足，发病率高，近二十年来，随着我国经济的好转，科学技术与医疗水平的提高，恶病质患者已很少见，但在某些特殊情况下，如地震灾害，受困伤员在无食品供应的空间时间过长，处于长期饥饿状态或某些疾病引起机体极度消耗代谢严重失衡胃肠功能紊乱，包括摄入、吸收、转化、利用多个环节失调，如：大面积烧伤、严重感染、脓毒症、癌症和一些难治的，慢性消耗性疾病，注意不到或措施执行不力，仍有发病的危险，一但发展到恶病质状态，治疗难度很大，死亡率很高。因而必须引起重视，加强预防措施，避免发病[1]。
In clinical practice, it usually refers to the extreme emaciation state of protein energgymal nutrition, which is a nutritional deficiency disease caused by insufficient food supply or disease factors, due to severe depletion of the body due to starvation or disease, and physiological function regulation failure is the end-stage manifestation of clinical disease. Affects the outcome of the disease. In the past 20 years, with the improvement of China's economy and the improvement of science and technology and medical level, cachexia patients have been rare, but in some special circumstances, such as earthquake disasters, the trapped and wounded have been in the space without food supply for too long, and they are in a state of long-term hunger or some diseasesCause the body to consume and metabolize serious imbalance gastrointestinal dysfunction, including intake, absorption, transformation, utilization of multiple links of disorders, such as: large-scale burns, serious infection, sepsis, cancer and some refractory, chronic wasting diseases, not paying attention to or poor implementation of measures, there is still a risk of morbidity, once it develops to cachexia, it is very difficult to treat, and the mortality rate is very high. Therefore, it is necessary to pay attention to and strengthen preventive measures to avoid the onset of the disease [1].
发病原因 Causes
恶病质大多发生在肿瘤进展期，但也可见于肿瘤早期。许多研究发现，恶病质与肿瘤负荷、疾病进程、细胞类型之间无恒定关系。恶病质的发生机制很复杂，没有一个单一理论可以满意地解释恶病质状态。事实上，有许多因素可能同时或相继作用，从而引起恶病质。一般认为与肿瘤能量消耗增加、摄入不足、中间代谢紊乱、谷氨酰胺、细胞因子等有关。
Cachexia mostly occurs in the stage of tumor progression, but it can also be seen in the early stages of the tumor. Many studies have found no constant relationship between cachexia and tumor burden, disease progression, and cell type. The mechanisms of cachexia are complex, and there is no single theory that satisfactorily explains cachexia states. In fact, there are many factors that may act simultaneously or sequentially to cause cachexia. It is generally believed to be related to increased tumor energy expenditure, insufficient intake, intermediate metabolic disorders, glutamine, cytokines, etc.
消耗增加 Consumption increases
肿瘤细胞过度增生需要大量的原料和能量。肿瘤细胞又以糖酵解为主要供氧形式而导致乳酸增加，肝脏需将乳酸转化成糖以便肿瘤利用，如此恶性循环，造成大量的能量消耗和糖的低效利用；另外，恶病质的癌症病人代谢异常，脂肪、蛋白质分解增加。
Excessive proliferation of tumor cells requires a lot of raw materials and energy. Tumor cells use glycolysis as the main form of oxygen supply, resulting in an increase in lactate, and the liver needs to convert lactate into sugar for tumor utilization, resulting in a vicious circle, resulting in a large amount of energy consumption and inefficient utilization of sugar; In addition, cancer patients with cachexia have abnormal metabolism and increased decomposition of fat and protein.
摄入不足 Inadequate intake
由于肿瘤性、治疗性厌食的影响，机体对营养摄取不足。因肿瘤本身的局部作用、味觉改变、食欲降低、下丘脑功能不良、饱感调节机制异常及条件反射而引起厌食。许多化疗药物引起恶心、呕吐、粘膜炎症及胃肠功能不良。放疗可产生类似的急性期副作用，还可造成肠道狭窄。手术后可出现肠梗阻、败血症所致的高代谢症候群，还有因住院患者经常被限制进食足够的营养物质(医源性营养不良)。
Due to the effects of neoplastic and therapeutic anorexia, the body does not take enough nutrients. Anorexia is caused by the local effects of the tumor itself, changes in taste, decreased appetite, poor hypothalamic function, abnormal satiety regulation mechanism, and conditioned reflexes. Many chemotherapy drugs cause nausea, vomiting, mucosal inflammation, and poor gastrointestinal function. Radiation therapy can have similar acute-phase side effects and can also cause intestinal strictures. Intestinal obstruction, hypermetabolic syndrome due to sepsis, and frequent restriction of adequate nutrient intake (iatrogenic malnutrition) may occur after surgery.
代谢紊乱 Metabolic disorders
肿瘤恶病质常出现葡萄糖、脂肪、蛋白质三大物质的代谢异常。Shaw 和wolfe等证实消化道肿瘤患者肝脏糖异生增加的程度与肿瘤负荷成正相关。因为对胰岛素的敏感性下降，瘤体很大的患者即使是给予葡萄糖输注的同时，其内源性的葡萄糖生成也并不受限制。gundholm等发现，胰岛素B细胞受体对葡萄糖负荷的敏感性下降，表明荷瘤机体处于类似于糖尿病的状态。由于胰岛素对组织的合成代谢非常重要，所以这种改变对组织的消耗起着很大的作用。
Tumor cachexia often has abnormal metabolism of glucose, fat, and protein. Shaw and wolfe et al. demonstrated that the degree of increased hepatic gluconeogenesis in patients with gastrointestinal tumors was positively correlated with tumor burden. Because of reduced sensitivity to insulin, patients with large tumors are not limited in endogenous glucose production, even when they are given glucose infusions. Gundholm et al. found that the sensitivity of insulin B cell receptors to glucose load decreased, suggesting that tumor-bearing organisms are in a state similar to diabetes. Since insulin is very important for the anabolism of tissues, this alteration plays a large role in the consumption of tissues.
谷氨酰胺 glutamine
谷氨酰胺是许多肿瘤赖以生长的主要原料，为肿瘤线粒体极好的氧化底物。因为瘤体必须与宿主竞争氨基酸，而瘤体内血管较少，故它们必须建立高效的机制以摄取营养，特别是在较血浆的营养水平低的环境中(如瘤体内)。研究表明，来源于不同细胞株的实体瘤细胞，无论其组织来源如何，Na 依赖的谷氨酰胺转运几乎均靠一个高效、高亲和力载体来完成，每种类型细胞的谷氨酰胺载体都有一系列动力学参数，但是氨基酸受抑制的机制几乎相同，这与外周系统的ASC载体系列对氨基酸的摄取有关。
Glutamine is the main raw material for the growth of many tumors and is an excellent oxidation substrate for tumor mitochondria. Because tumors must compete with the host for amino acids, and tumors have fewer blood vessels, they must establish efficient mechanisms to take up nutrients, especially in environments with lower nutrient levels than plasma (e.g., in tumors). Studies have shown that solid tumor cells from different cell lines, regardless of their tissue origin, Na-dependent glutamine transport is almost always accomplished by a high-efficiency, high-affinity carrier, and the glutamine carrier of each cell type has a series of kinetic parameters, but the mechanism of amino acid inhibition is almost the same, which is related to the uptake of amino acids by the ASC vector series in the peripheral system.
细胞因子 Cytokines
细胞因子是机体对生长中的肿瘤反应的重要调节因子，是生长着的肿瘤诱发宿主机体细胞产生的多肽信号，它介导着肿瘤宿主体内多种营养和代谢紊乱的过程。包括促恶病质因子如肿瘤坏死因子(TNF)、白细胞介素-1(1L-1)、IL-6、r-干扰素(INF-r)等，抗恶病质因子如可溶性肿瘤坏死因子受体(sTNFR)、II-1受体拮抗物(IL-Ira)、IL-4、Il-lO等，肿瘤恶病质的发生与此两类细胞因子综合作用有关。
Cytokines are important regulators of the body's response to growing tumors, and are the polypeptide signals produced by growing tumors inducing host cells, which mediate a variety of nutritional and metabolic disorders in tumor hosts. Including cachexia factors such as tumor necrosis factor (TNF), interleukin-1 (1L-1), IL-6, r-interferon (INF-r), etc., anti-cachexia factors such as soluble tumor necrosis factor receptor (sTNFR), II-1 receptor antagonist (IL-Ira), IL-4, Il-lO, etc., the occurrence of tumor cachexia is related to the combined effect of these two types of cytokines.
促恶病质因子有刺激基础代谢率、葡萄糖的吸收，动员贮存中的蛋白质和脂肪的利用，减低脂肪细胞脂蛋白脂酶的活性，增加肌肉氨基酸的释放，激发肝脏氨基酸转运活性等作用[2]。
Cachexia factors have the effects of stimulating basal metabolic rate, glucose absorption, mobilizing the utilization of stored proteins and fats, reducing the activity of lipoprotein lipase in fat cells, increasing the release of muscle amino acids, and stimulating liver amino acid transport activity [2].
分型 Typing
临床上个体差异，严重程度和发病的持续时间分为消瘦型（Marasmus）浮肿型（Kwashiorkor）混合型（Marasmus—Kwashiorkor）根据营养缺乏程度分为轻，中、重，三度。
Clinically, individual differences, severity and duration of onset are divided into emaciated type (Marasmus), edema type (Kwashiorkor), mixed type (Marasmus-Kwashiorkor), and mild, moderate, severe, and tertiary according to the degree of nutritional deficiency.
消瘦型 Emaciated
消瘦型（Marasmus），由于能量严重不足所致。其特点为消瘦，皮下脂肪消失，皮肤干燥松弛及失去弹性和光泽，消瘦严重者呈“皮包骨头”样（skin and bones）。头发枯黄稀疏、容易脱落，双颊凹陷呈猴腮状。患者体弱无力 ，萎靡不振，脉搏细缓，血压、体温偏低，内脏器官萎缩，淋巴结易触及。
Wasting type (Marasmus), caused by severe energy deprivation. It is characterized by emaciation, loss of subcutaneous fat, dry and loose skin, loss of elasticity and luster, and severe weight loss is "skin and bones". The hair is yellow and sparse, easy to fall out, and the cheeks are sunken and gill-like. The patient is weak and weak, malaise, slow pulse, low blood pressure and body temperature, atrophy of internal organs, and easy palpability of lymph nodes.
低蛋白血症型或急性内脏蛋白消耗型 Hypoproteinemic or acute visceral protein-wasting type
低蛋白血症型或急性内脏蛋白消耗型(Kwashiorkor)，该型常见于长期蛋白质摄入不足或创伤和感染等应激状态下。与marasmus型不同，该型伴有明显的生化指标异常，主要为血浆白蛋白值明显下降和淋巴计数下降。病人脂肪储备和肌肉块可在正常范围，因而一些人体测量指标仍正常，但内脏蛋白质迅速下降，毛发易拔脱，水肿及伤口愈合延迟。对此型病人若不采用有效的营养支持，可因免疫力受损，导致格兰氏阴性菌败血症或严重真菌感染。
Hypoproteinemia or acute visceral protein-wasting (Kwashiorkor), which is common in chronic protein inadequacy or stressful conditions such as trauma and infection. In contrast to the Marasmus type, this type is associated with significant biochemical abnormalities, mainly a marked decrease in plasma albumin values and a decrease in lymphatic count. The patient's fat reserves and muscle mass are in the normal range, so some anthropometric measures remain normal, but visceral protein declines rapidly, hair is easily pulled out, edema, and wound healing is delayed. Without effective nutritional support, this type of patient may lead to gram-negative septicemia or severe fungal infections due to impaired immunity.
混合型营养不良 Mixed malnutrition
混合型营养不良(mixed marasmus and viseral malnutrition) ，该型为最严重的一类营养不良，是由于蛋白质和热量的摄入不足和严重消耗性疾病所致。常见于大面积严重烧伤，晚期肿瘤和消化道瘘等病人。这类病人由于能量储备少，在应激状态下，体蛋白急剧消耗，极易发生感染和伤口不愈等并发症，病情危重，死亡率高[1]。
Mixed marasmus and viseral malnutrition, the most severe type of malnutrition, is caused by inadequate protein and calorie intake and severe wasting diseases. It is common in patients with extensive severe burns, advanced tumors and gastrointestinal fistulas. Due to the low energy reserve, such patients are in a state of stress, and their body protein is rapidly depleted, and they are prone to complications such as infection and wound non-healing, and their condition is critical, with a high mortality rate [1].
高危人群 High-risk populations
1、 体重严重丢失：如低于理想体重20％以上，6个月内体重下降超过10％，1个月内体重下降超过5%。
1. Severe weight loss: if it is more than 20% lower than the ideal body weight, the weight loss will be more than 10% within 6 months, and the weight loss will be more than 5% within 1 month.
2、 严重高代谢状态：如高热、大面积烧伤、严重败血症、重度骨折及恶性肿瘤等。
2. Severe hypermetabolic state: such as high fever, large-scale burns, severe sepsis, severe fractures and malignant tumors.
3、 严重营养素丢失增加：如肠瘘、开放性创伤、长期失血、溃疡渗出、严重腹泻及呕吐等。
3. Increased severe nutrient loss: such as intestinal fistula, open trauma, long-term blood loss, ulcer exudation, severe diarrhea and vomiting.
4、 难以控制的慢性消耗性疾病：如糖尿病、心脑血管疾病、慢性肺病、艾滋病、肝病、肾病、风湿病等。
4. Chronic wasting diseases that are difficult to control: such as diabetes, cardiovascular and cerebrovascular diseases, chronic lung diseases, AIDS, liver diseases, kidney diseases, rheumatism, etc.
5、 胃肠道疾患或手术：如吸收不良、短肠综合征、胃肠道瘘、重症胰腺炎等
5. Gastrointestinal diseases or surgery: such as malabsorption, short bowel syndrome, gastrointestinal fistula, severe pancreatitis, etc
诊断标准
通过疾病史、多种临床表现、指标或综合评价指标均可了解患者的营养耗竭恶病质状态。
1、 3月来渐进性消瘦，体重比原始体重(诊断时)下降≥7.5%；或IBM指标<80% 【注BM=实际体重/理想体重×100%；理想体重(kg)=身高(cm)一105】
2、伴有食欲不振（食欲差，食量比健康时减少1/3）、乏力者。
3、总蛋白<55g/l；白蛋白<35g/ l；前白蛋白<250mg/l。
符合(1) ， (2)两项及(3)中两项标准者诊断为恶病质[2]。
治疗方法
目前尚无有效的方法可以逆转这种进行性的消瘦。正如Barber所说“最好的治疗癌症恶病质的方法就是治愈肿瘤，但在成人晚期实体瘤中几乎不可能。对于绝大多数患者来说，治疗的目的应是改善患者的生活质量以及延长患者的生存期。
针对恶病质的治疗也是多方面的包括药物、手术、营养支持、物理、社会、心理等。
药物治疗
现在对于癌症恶病质治疗较为成熟的药物主要是是与刺激剂和一些控制症状的药物，而许多代谢调节剂也正在研究中或初步应用于临床中。
食欲刺激剂
增加病人食欲以增加病人食量是维持其营养状况的有效方法，同时也能明显提高其生活质量。目前广泛使用并且疗效确切的食欲刺激剂是糖皮质激素和醋酸甲地孕酮大多数临床试验显示糖皮质激素仅在4周内可以明显改善恶病质的各种症状，但很少有体重增加。尽管有许多的不良反应，但糖皮质激素在一些生存期较短的病人中仍被广泛应用。
最早孕前激素被用于治疗激素敏感性的乳腺癌，但后来发现无论肿瘤是否有反应，病人均食欲明显增加，体重上升，先此类要以广泛用于治疗恶病质，多项临床实验显示甲地孕酮能明显增加病人食欲以及进食量，并增加体重，改善营养指标。目前此类药物的机制可能是通过刺激神经肽Y，此外还可能刺激了细胞因子IL-1，IL-6和肿瘤坏死因子（TNF）的活性。现在甲地孕酮已成为恶病质病人的标准治疗用药。
一些控制厌食症状的药物也在临床中广泛应用。甲氧氯普胺用于治疗因胃储留引起的早期饱胀感和厌食症。5-HT3受体拮抗剂如昂丹司琼、格拉斯琼作为在化疗过程中使用的止吐药也可改善食欲，其他在临床上使用的食欲刺激剂药物有屈大麻酚等正在研究的药物有各种神经肽激动剂和拮抗剂，如刺鼠相关蛋白，神经肽Y，黑素皮质受体拮抗剂等。
代谢调节剂
由于认识到癌性恶病质病人中代谢改变是最重要的病因之一，故逆转这些代谢改变的药物是研究的热点，这些药物的主要作用机制包括下调转录因子，阻断细胞因子，促进合成代谢等，目前主要推荐的用药包括鱼油，主要成分是二十二碳五烯酸（EPA）及DHA均为不饱和脂肪酸。非甾体抗炎药：沙利度胺。
EPA是一种重要的ω-3不饱和脂肪酸，在鱼油中种含量丰富。其作用机制是抑制细胞因子的合成和活性，因为它干扰了细胞氧化和脂质氧化代谢径路。同时，ω-3不饱和脂肪酸也能改善机体免疫状态和糖代谢过程。临床和实验研究表明，饮食中增加ω-3不饱和脂肪酸对于治疗和抑制肿瘤的发生和发展是有益的。ω-3不饱和脂肪酸可改善给予IL-1产生厌食大鼠的食欲，体重下降减轻，并改善免疫状态。
在结直肠癌所导致的恶病质病人当中非甾体抗炎药布洛芬可以减少IL-6及皮质醇的水平，稳定全身的蛋白动员。在胰腺癌病人当中同样有效。随即临床对照实验显示，给与晚期肿瘤病人吲哚美辛，可以明显延长生存期，虽然此类要存在一定的不良反应，但仍是一种廉价的抗肿瘤恶病质药物。而新型的环氧化酶-2（COX-2）引起有较高的安全性，可能更适合临床使用。
沙力度胺被认为是TNF-∝的抑制剂，在获得性免疫缺陷综合症（AIDS）相关的恶病质病人中给与沙力度胺可以改善一般状况，增加体重，此外在晚期肿瘤病人中他可以改善睡眠，抑制恶心增加食欲。实验表明它可以抑制血管生成从而具有抗肿瘤的作用。
生长激素可促进体内正氮平衡，增加机体瘦组织群，增加脂肪合成和脂肪酸氧化。恶性肿瘤患者的生长激素代谢作用可能在体重丢失时维持葡萄糖和蛋白质的贮存，这一现象在实验动物中已得到证实.在荷瘤大鼠摄入生长激素可保持体内瘦组织群，减少肿瘤蛋白质合成，在AIDS和癌肿患者中也取得类似效果，但是否刺激肿瘤生长有疑虑。
营养支持治疗
营养支持对分解代谢的改善见效甚微，但可起到预防进一步恶化的作用。
恶病质患者开始营养支持时，首先恢复细胞功能，然后逐步补充机体丢失的组织。营养支持应包括三部分：生理需要量、近期累积营养消耗量，以及疾病恢复与组织合成所需额外的能量、蛋白质与其它营养素。营养支持是综合治疗的一部分，需要与其他治疗措施配合，方能取到预期效果。
营养支持方法
恶病质患者一般病情严重。为提高治愈率，应进行营养补充性治疗，根据患者能够接受的途径，可以分为经口进食补充、肠内营养喂养和肠外营养喂养或三种途径联合喂养。但由于恶病质患者常常伴有低白蛋白血症或免疫功能低下，常常表现为无法经过正常胃肠道给予营养，因此营养支持的启动常常从肠外营养开始，给予基础需要量甚至更低量，旨在输入最基本的营养物质。
1、肠外营养支持
胃肠道功能障碍患者无法经肠道喂养，需肠外营养支持。肠外营养配方既要满足病人需要，又要避免缺乏或过量。呕吐、腹泻、肠瘘等可致额外水盐丢失，需注意补充。水肿患者则应限制补液量。重度营养不良或急性期患者水盐排泄能力减低，长期胃肠道疾病患者可能有微量营养素和矿物质不足。血钾、血磷浓度可能迅速下降。肠外营养用量需达到35kcal/kg/d（蛋白质1.5g/kg/d）。随着胃肠道功能改善，可逐渐恢复肠内喂养，停用肠外营养。
2、肠内营养支持
若病人无法自主进食或吞咽困难，而胃肠道功能良好，可经胃或空肠进行营养支持。肠内营养配方选择需同时考虑肠道耐受性和能量营养素需要量。肠内营养支持开始滴速为20-30ml/小时，一般在3-5天内增至全量。标准肠内营养配方所含电解质、矿物质和微量元素为机体基本需要量。
3、口服营养支持
只要病人能自主进食，应首选口服平衡饮食，由营养师随时调整。另外，需要经静脉补充维生素和钾、磷和镁，并定期监测血电解质浓度。营养支持开始阶段，三大营养素供应量需减半，继而根据病人的耐受性，在3-5天内逐渐增至全量，若经口摄入无法达到全量，需给予肠内或肠外营养支持。
严重耗竭病人需额外补充电解质、矿物质和微量元素。营养支持期间，需定期监测临床体征和生化指标。
调整水电平衡
严重的营养不良患者常伴有脱水等表现，但典型的脱水征象常由于存在水肿而被掩盖。常有腹泻或呕吐、口渴、尿量少、脉搏弱而快、血压低、四肢冷、神志不清等症状，表现为：①低渗与低血钠；②轻至中度代谢性酸中毒，当电解质得到平衡或给以饮食时则可消失；③对低血钙有耐性，因酸中毒可使钙离子增加，同时低蛋白血症使之与钙离子的结合减少；④总体血钾缺乏，但无低血钾；⑤总体镁缺乏而低血镁可有可无。液体补充应达到儿童每日排尿200ml，成人500ml或每2-3h即排尿一次。液体补充不应含较多的钾和镁与较少的钠。因呕吐而不能口服者用鼻胃管给予。口服液应小量多次给予，12h内约供给70-100ml/kg体重，开始头2h，轻中度脱水的给10ml/(kg·h)，重度脱水的给30ml/(kg·h)。 呕吐停止，脱水好转则改为口服，如2h内能耐受口服，则撤去鼻胃管。当反复呕吐或持续腹胀，及有严重脱水和低血容与休克时，应静脉输液。应用低渗溶液(200-280mmol/L)，钾与钠分别不得超过6mmol/(kg·d)与3mmol/(kg·d)。必须至少供给葡萄糖63-126kJ(15-30kcal)/(kg·d)，如10%葡萄糖溶液与等渗盐水1∶1的混合液。有严重低血蛋白(＜30g/L)、无尿、低血容、循环衰竭的患者应每1h或2h给予10ml血浆/kg，然后每1h或2h给以2份5%葡萄糖溶液与1份等渗盐水的混合液20ml/kg，可使血浆蛋白增加5-10g/L，防止血管内水分移出。有低血钙和手足搐搦症时，可给予钙输液，如葡萄糖酸钙，同时12-24h肌注50%硫酸镁溶液1ml，至低血钙症状不再发作。
多个层面的营养支持
能够帮助增强食欲并逆转体重的下降。在至少15项随机临床研究证实此类药物的作用，可能通过作用于下丘脑系统或者通过细胞因子产生作用刺激食欲。黄体酮只有轻度的毒性反应，能够有效刺激食欲，并可能加强肌肉功能和提高生存质量。
⑵抗心血管药物
他汀类药物独立于降低胆固醇途径具有抗炎症反应作用，能够降低C反应蛋白，并可能由此降低分解代谢，增加合成代谢。ACEI类药物除了降低血压、保护心血管系统外，还可能改善肌肉功能。
⑶肌酸
肌酸磷酸作为合成ATP的必要供体，能够增加肌肉能量，增加健康人的瘦体重。多项研究证实，在肾功能正常的营养不良患者，补充肌酸是安全的。
⑷促合成药物
自二十世纪三十年代一些雄性激素类药物已经用来刺激肌肉的生长，很多研究表明睾酮及其类似物能够促进肌肉生长，但是长期高剂量应用可能产生肝损害或者脂质代谢异常，使用时应注意剂量及使用时间。
⑸氨基酸
在50名非手术肿瘤患者补充口服N-乙酰半胱氨酸能够改善生活质量、增加血中白蛋白的浓度和体细胞质的量，并且与对照组比未发现促进肿瘤增长的现象。在应用包含谷氨酰胺、精氨酸、亮氨酸的代谢产物等的氨基酸混合物在肿瘤患者应用可增加瘦体组织，并且未见明显的副反应，这为恶病质的治疗带来新的方向。
⑹ω-3脂肪酸
EPA与DHA能够抑制蛋白分解作用，富含ω-3PUFA的饮食可阻抑肝脏甘油三酯及载脂蛋白的合成，并使脂质池中的花生酸转换为二十二碳五烯酸（EPA）和二十二碳六烯酸（DHA）。这些脂肪的存在可影响细胞膜流动性和通透性、细胞动力、配体受体结合、酶的分泌、抗原呈递和细胞内信号通路的激活。EPA和DHA释放后可通过血小板、单核细胞及巨噬细胞中的环氧化酶和脂氧化酶抑制ω-6PUFA衍生物（二十碳酸）的合成，从而延迟血小板聚集和动脉粥样硬化的发展。在实验模型中，ω-3PUFA也表现出抑制肿瘤转移及改善恶病质的作用，然而实验发现PUFA中只有EPA可逆转肿瘤转移过程。另一项实验研究发现在大鼠肝静脉中注入结肠癌细胞时，低脂饮食较鱼油或葵花油饮食更能促进癌细胞的肝转移。饮食以鱼类为主的人群冠脉疾病发生率较低，其中ω-3PUFA似乎起着重要作用。临床研究发现富含ω-3PUFA的饮食可降低肾脏和心血管疾病的发生率，可能是由于抑制了血栓形成及依赖细胞因子的炎症发生。胰腺癌病人补充鱼油有助于减少炎症及稳定能量消耗，这可能可以解释给予富含ω-3PUFA饮食时，转移性肿瘤病人生存率延长。
EPA and DHA inhibit proteolysis, and a diet rich in omega-3PUFAs inhibits the synthesis of hepatic triglycerides and apolipoproteins, and converts eicosanic acid in the lipid pool to docosahexaenoic acid (EPA) and docosahexaenoic acid (DHA). The presence of these fats can affect cell membrane fluidity and permeability, cell motility, ligand receptor binding, enzyme secretion, antigen presentation, and activation of intracellular signaling pathways. After the release of EPA and DHA, the synthesis of omega-6 PUFA derivatives (eicosic carbonate) can be inhibited by cyclooxygenase and lipoxidase in platelets, monocytes and macrophages, thereby delaying platelet aggregation and the development of atherosclerosis. In the experimental model, omega-3PUFA also showed the effect of inhibiting tumor metastasis and improving cachexia, but it was found that only EPA in PUFA could reverse the tumor metastasis process. Another experimental study found that when colon cancer cells were injected into the hepatic veins of rats, a low-fat diet was more effective than a fish oil or sunflower oil diet to promote cancer cellsof liver metastases. The incidence of coronary artery disease is lower in people whose diet is predominantly fish, in which omega-3PUFAs appear to play an important role. Clinical studies have found that a diet rich in omega-3PUFA can reduce the incidence of kidney and cardiovascular disease, possibly due to inhibition of thrombosis and cytokine-dependent inflammation. Fish oil supplementation in pancreatic cancer patients helps to reduce inflammation and stabilize energy expenditure, which may explain the prolonged survival of patients with metastatic tumors when given an omega-3PUFA-rich diet.
⑺抗氧化剂 (7) Antioxidants
机体有一套复杂而且相互作用的氧化防御系统，保护机体不受氧化损伤。这些抗氧化剂存在于体液和各种细胞成分中，包括细胞膜在内。血浆中的一些抗氧化分子是直接从食物衍化来的，如生育酚（维生素E）、抗坏血酸（维生素C）、类胡萝卜素（β-胡萝卜素）、番茄红素和儿茶酸。血浆中还有一些体内合成的蛋白质和肽类如蛙皮素、白蛋白和金属硫蛋白对抗氧化防御反应非常重要。这些物质大部分作为细胞液相成分中的抗氧化剂，而维生素E和维生素C是细胞膜中的主要抗氧化物质。过氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶/还原酶，可将氧化物质转化为无害的副产物。如上所述的抗氧化营养素及其前体都有助于机体的抗氧化防御反应，并能限制炎症过程中释放的、可直接激活NFκB或损害机体组织的氧化剂。
The body has a complex and interacting oxidative defense system that protects the body from oxidative damage. These antioxidants are found in body fluids and various cellular components, including cell membranes. Some antioxidant molecules in plasma are derived directly from food, such as tocopherols (vitamin E), ascorbic acid (vitamin C), carotenoids (β-carotene), lycopene, and catechin. There are also proteins and peptides synthesized in the body such as quercetin, albumin, and metallothionein, which are important in the antioxidant defense response in plasma. Most of these substances act as antioxidants in the cell's liquid-phase components, while vitamin E and vitamin C are the main antioxidants in cell membranes. Peroxide dismutase, catalase, glutathione peroxidase/reductase, which convert oxidizing substances into harmless by-products. Both the antioxidant nutrients mentioned above and their precursors contribute to the body's antioxidant defense response and limit the release of oxidants during the inflammatory process that can directly activate NFκB or damage the body's tissues.
⑻抗癌症恶病质的药物 (8) Anti-cancer cachexia drugs
大多数癌症患者营养衰竭的原因是以代谢改变为主，需要加用促进食欲的药物，如：醋酸甲地孕酮，确有促进食欲和增加体重的作用。经RCT研究证实抗恶病质药物脱氢皮质醇或吲哚美辛（消炎痛）确能改善营养指标，提高生活质量或生存力作用[1]。
The cause of nutritional exhaustion in most cancer patients is mainly metabolic changes, and appetite-promoting drugs, such as megestrol acetate, are needed to promote appetite and increase body weight. RCTs have confirmed that the anticachexia drugs dehydrocortisol or indomethacin (indomethacin) can improve nutritional indicators, quality of life, or viability [1].
中医 Chinese medicine
恶病质 cachexia
恶病质诸多症状表现属中医虚劳范畴。据载，虚劳多由积渐成，大抵病久体羸叫―虚，久虚不复叫―损，损极不复谓―劳。恶病质乃是由于患者久病不愈，气血阴阳不足，脏腑功能衰竭，脾失运化，肌肤失于濡养所致。
Many of the symptoms of cachexia belong to the category of TCM fatigue. It is reported that the lack of labor is mostly gradually formed by accumulation, and most of the people who have been sick for a long time are called - empty, and after a long time of being weak and no longer called - loss, and the loss is extremely no longer called - labor. Cachexia is caused by the patient's long-term illness, lack of qi, blood, yin and yang, failure of visceral function, loss of spleen, and loss of skin nourishment.
《素问•玉机真藏论》有―大骨枯槁，大肉陷下，胸中气满，喘息不便，其气动形，期六月死⋯⋯的记载，就与恶病质的症状极其相似。主症为消瘦、食欲下降、神疲乏力。同时由于发病部位不同，癌症种类不同，患者体质不同，还可出现疼痛、梗阻、出血、发热、腹胀、泄泻、便秘等各异的症状。癌症一旦发展到恶病质，手术、放射、化疗都难以施行。中医认为邪毒鸱张，正气亏损，攻之不得，补之不受[2]。
The "Suwen Yuji Zhenzang Treatise" has a record of large bones withering, large flesh sinking, chest full of qi, inconvenient breathing, and its pneumatic shape, dying in six months, which is very similar to the symptoms of cachexia. The main symptoms are weight loss, decreased appetite, and fatigue. At the same time, due to the different locations of the disease, the different types of cancer, and the different constitutions of patients, there can also be different symptoms such as pain, obstruction, bleeding, fever, abdominal distention, diarrhea, constipation, etc. Once the cancer has progressed to cachexia, surgery, radiation, and chemotherapy are difficult to administer. Traditional Chinese medicine believes that evil poison is abundant, and righteousness is lost, and it cannot be attacked, and it cannot be made up [2].
肿瘤恶病质机制 Mechanism of tumor cachexia
肿瘤恶病质应属于中医“虚劳”的范畴，脏腑功能障碍、纳差、消瘦等症状乃是由于患者久病不愈，气血阴阳不足，脏腑功能衰竭，脾失运化，肌肤失于濡养所致。《素问·玉机真藏论》有“大骨枯槁，大肉陷下，胸中气满，喘息不便，其气动形，期六月死……” 的记载，就与晚期肺癌合并恶病质的症状极其相似。“大骨枯搞，大肉陷下，胸中气满，喘息不便，内痛引肩项，期一月死……”，“大骨枯稿，大肉陷下，胸中气满，腹内痛，心中不便肩项身热，破脱肉，目眶陷，真藏见，目不见人，立死”是进一步合并心衰的症状。恶病质不是一个独立的疾病，可发生在许多疾病的过程中，属虚症、赢瘦范围，《内经》的虚弱病证范围很广，凡人体正气不足、五脏精气亏损的病证，概属虚弱病证。如《素问·玉机真藏论》的“五虚死”证；《素问·脏器法时论》的五脏虚症；《素问·宣明五气篇》的“五劳所伤”证；《素问·调经论》的五不足证；《灵枢·决气》的六脱证；《灵枢·海论》的四海不足证；《灵枢·经脉》的十二经别虚症；《灵枢·五禁》的五夺证；《灵枢·淫邪发梦》的十五不足证。此后，《难经》又提出“五损”病证，《金医要略》提出“虚劳病”，《诸病源侯论》还提出“五劳”、“七伤”、“六极”等病证.历代医家对虚症都有大量的研究。
Tumor cachexia should belong to the category of "fatigue" in traditional Chinese medicine, and the symptoms of visceral dysfunction, poor appetite, and weight loss are caused by the patient's long-term illness, lack of qi, blood, yin and yang, visceral failure, spleen loss, and skin loss. "Su Wen Yuji Zhenzang Treatise" has "the big bones are withered, the big flesh is sunken, the chest is full of breath, the wheezing is inconvenient, its pneumatic shape, and the period of death is ...... in June" The symptoms of cachexia are very similar to those of advanced lung cancer. "The big bones are dry, the big flesh is sunken, the chest is full of breath, the wheezing is inconvenient, the internal pain leads to the shoulder, and the ...... dies in January", "the big bones are dry, the big flesh is sunken, the chest is full of qi, the abdominal pain is inconvenient, the shoulder is hot in the heart, the flesh is broken, the eyes are sunken, the eyes are trapped, the eyes are really hidden, the eyes are not visible, and the person is killed" are the symptoms of further heart failure. Cachexia is not an independent disease, it can occur in the process of many diseases, it belongs to the range of deficiency and thinness, and the range of weak symptoms in the "Neijing" is very wide. For example, the "Five False Deaths" certificate of "Suwen Yuji True Tibetan Theory"; the five visceral deficiency diseases of "Su Wen: The Treatise on the Law of Organs"; The certificate of "Five Labor Injuries" of "Su Wen Xuanming Five Qi Chapter"; Five inadequate proofs of "Su Wen and Commentary"; The six certificates of "Lingshu Decisive Qi"; The four seas of "The Soul of the Sea" are not enough evidence; The 12 meridians of "Lingshu Meridians"; the five certificates of "Lingshu Five Forbidden"; The fifteenth is not enough evidence of "The Soul of the Evil Dream". Since then, the "Book of Difficulties" has put forward the "five losses" syndrome, the "Golden Medical Strategy" has proposed "deficiency labor disease", and the "Treatise on the Origin of Diseases" has also put forward "five labor", "seven injuries", "six poles" and other disease syndromes. Generations of physicians have done a great deal of research on deficiency.
癌症恶病质在中医学中并无对应病名，但鉴于其以一系列“虚证”临床表现为特征，应将之归属于“虚劳”范畴。“虚劳”的发病的病理机制为五脏阴阳气血虚损。
Cancer cachexia does not have a corresponding disease name in traditional Chinese medicine, but it should be classified as "deficiency of labor" in view of its characteristics as a series of "false syndrome" clinical manifestations. The pathological mechanism of the pathogenesis of "fatigue" is the deficiency of yin and yang, qi and blood in the five internal organs.
辨证分型 Pattern differentiation
肿瘤恶病质的病机是久病不愈，气血阴阳不足，脏腑功能衰竭，脾失运化，肌肤失于濡养所致。
The pathogenesis of tumor cachexia is caused by long-term illness, lack of qi, blood, yin and yang, failure of visceral organs, loss of spleen, and loss of skin nourishment.
气虚痰湿证 Qi deficiency and phlegm dampness
主症：消瘦，咳嗽痰多 ，胸闷气短。
Main symptoms: weight loss, cough with phlegm, chest tightness and shortness of breath.
次证：神疲乏力，懒言少语 Sub-testimonial: God is tired and tired, and he is lazy to speak
舌脉：舌质淡胖有齿痕，舌苔白腻，脉濡缓或濡滑。
Tongue and vein: the tongue is pale and fat with tooth marks, the tongue coating is white and greasy, and the pulse is slow or slippery.
方药： 药用 香砂六君子汤加减
Prescription Medicine: Medicinal Xiangsha Liujunzi Tang plus or minus
阴虚内热证 Yin deficiency and internal heat syndrome
主症：形体消瘦 ，咳嗽无痰，咽干舌燥，五心烦热
Main symptoms: emaciation, cough without phlegm, dry throat and tongue, five heart irritability
次证：五心烦热，或午后低热，心烦失眠
Secondary symptoms: five irritability, or low-grade fever in the afternoon, upset and insomnia
舌脉：舌质红，舌苔花剥，或光绛无苔，脉细数 。
方药：药用 六味地黄丸加减
气阴两虚证
次证：气短懒言，五心烦热
舌脉：舌质或胖大有齿痕，或红，苔或白厚腻，或苔厚而燥，脉细弱。
方药：药用生脉饮
气滞血瘀证
主症： 日渐消瘦 ，胸背疼痛 ，舌质紫暗。
次证：胸胁或肩背疼痛，痛有定处
舌脉：舌质有瘀斑或紫暗，舌苔簿白，脉弦或涩。
辨证施治
汤剂
1.气虚痰湿证
治则：益气健脾化湿
方药： 药用 香砂六君子汤加减
党参12克 白术12克 茯苓12克 炒米仁15克 炒淮山12克 鸡金6克 红枣15克 陈皮6克，半夏12克。神曲9克
2.阴虚内热证
治则：养阴清热
方药：药用 六味地黄丸加减
山药 12克 泽泻15克 茯苓15克 丹皮15克 熟地黄12克 萸肉 15克 神曲9克 鸡金6克
3.气阴两虚证
治则：养阴益气 方药：药用 生麦饮加减
党参 15克 麦冬 15克 五味子15克 南沙参12克 北沙参12克 陈皮9克 神曲9克 鸡金6克
4.气滞血瘀证
治则：疏肝理气 药用：丹栀逍遥散加减
丹皮 9克 栀子 12克 当归 9克 芍药12克 柴胡 9克 茯苓12克 白术15克 甘草9克 生姜 6克 薄荷6克 谷芽12克 麦芽12克
中成药
静脉制剂
1.康莱特注射液 200ml 每日1次 静滴 连用21天
2.爱迪注射液 80-100 ml 每日1次 静滴 连用21天
3.参麦注射液等 30-60 ml 每日1次 静滴 连用14天
治疗
恶液质是癌症晚期大多数病人表现出的机体功能衰退、营养代谢紊乱的一系列症候群，病情复杂，治疗时应掌握辨证与辨病相结合、扶正与祛邪相结合、局部与整体相结合三要点，从复杂的病情中找准不平衡点，在注重调理后天脾胃的基础上，调节阴阳、寒热、虚实。中药治疗象一把钥匙，透过错综复杂的黑糖，拨动晚期癌症病人之枢纽，平衡协调内环境，提高机体的免疫功能，从而控制或杀灭癌细胞。
局部与整体相结合
由于恶病质病人正气虚弱，食欲减退，消瘦乏力，气血、阴阳、脏腑等多方面不平衡，所以即使采用调治，也必须非常谨慎。用温则伤阴，用凉则亡阳，补则碍胃，泻则伤正。对于恶病质的病人，必须从整体调整，创造一个良好的内环境，增强免疫功能，达到延长生命、提高生活质量的目的。
辨证与辨病相结合
中医的辨证与西医的辨病相结合，可以取长补短。西医辨病，可以了解肿瘤生长的部位，细胞良恶程度，癌症的发展及预后，找出产生恶病质的原因，为中医辨证提供一定的依据。中医认为肿块是痰、血瘀、热毒相结合而成。但到恶病质时，由于体质不能耐受，攻痰、化瘀、清热解毒有时难以下手。根据辨证施治的原则，不应急图攻癌，而应调和气血，扶正固本，特别是健运中州，建立一个良好的内环境。
扶正与祛邪相结合
―邪之所凑，其气必虚。患癌后，邪气亢盛，正气虚损。虚损的结果是免疫功能下降，加速癌症扩散，形成恶性循环。恶病质的病人为正不胜邪，故扶正固本，保护机体免疫功能至关重要。在这一点上，无论中医还是西医，都已形成共识。
疗效评价
症状分级
| 症状 | 0度 | Ⅰ度 | Ⅱ度 | Ⅲ度 | Ⅴ度 |
|---|---|---|---|---|---|
| 咳嗽 | 无 | 偶咳 | 间断咳嗽 | 咳嗽频作 | 咳嗽剧烈 |
| 咳血 | 无 | 晨起痰中偶有血丝 | 痰中有血丝 | 痰中带血，量少 | 咳血，量多 |
| 胸痛 | 无 | 偶有胸痛，不须服药 | 胸痛轻微，服用Ⅰ级止痛药 | 胸痛明显，服用Ⅱ级止痛药 | 胸痛剧烈，服用Ⅲ级止痛药 |
| 发热 | 无 | <37.5℃ | <38.5℃ | <39.5℃ | ≥39.5℃ |
| 气短 | 无 | 稍感气短 | 活动后气短 | 动则气促 | 卧床也气促 |
| 乏力 | 正常 | 活动后乏力 | 活动后乏力不易恢复 | 休息时感乏力 | 需卧床 |
| 口干 | 无 | 轻微 | 口干欲饮 | 口干喜饮 | 口干喜饮，饮后难解 |
肺癌症状分级
显效:治疗后比治疗前提高 70%；
有效:治疗后比治疗前提高 30-70%；
无效:治疗后比治疗前提高小于 30%。
注:本研究采用肺癌症状分级法，每个症状的得分合计后乘以 1/8 即折算为百分制得分。
Karnofsky 分级标准
显效:治疗后比治疗前提高 20 分以上(100 分)；
有效:治疗后比治疗前提高 10 分以上(50 分)；
稳定: 治疗后比治疗前提高不足 10 分或没有变化(25 分)；
无效:治疗后比治疗前下降(0 分)[2]。