肾脏是调节机体容量平衡的重要器官,当肾脏的结构功能开始发生改变,肾小球过滤率(glomerular filtration rate, GFR)逐渐降低,肾功能持续受损,导致水钠潴留,容量负荷过重。容量超负荷是慢性肾脏病(chronic kidney disease, CKD)常见的并发症,尤其易发生于CKD 5期肾功能替代治疗前后[1-2]。长期的容量超负荷状态可导致患者高血压、肺动脉高压、贫血、蛋白尿、动脉粥样硬化、炎症、左室肥大、心力衰竭等相关并发症的发生或加重[3-8]。目前,容量超负荷是透析患者退出率和死亡率升高的重要原因之一[9],且液体和钠清除不良是透析患者死亡的独立危险因素[10]。相反,如果透析过程中,体液清除过多,则会影响患者的透析依从性及充分性,造成容量负荷过低[11],导致低血压、急性心肌缺血、残存肾功能衰退等不良事件发生,影响患者的生存质量[12-13]。
因此,快速、准确地评估透析患者的容量负荷状态,保持容量负荷平衡,是透析治疗的关键,是透析患者调整治疗方案、判断透析质量的主要指标,对肾脏替代治疗长期稳定、安全有效地进行具有重要意义。本文就透析患者容量负荷评估方法进行综述。
1 透析患者容量负荷评估方法概述目前,普遍接受的评估血液透析患者容量负荷的“金标准”是同位素标记稀释法。其中,氘和氚稀释首选用于测量全身水(total body water, TBW),而氯溴化物和蔗糖稀释用于测量细胞外体积(extracellular volume, ECV)。但由于同位素标记稀释法价格高、操作繁琐,且可对人体造成放射伤害等缺点,目前多用于研究,而在临床上的应用受限,不能作为来评估容量负荷的常规方法[14]。
临床医师对患者容量负荷状态的评估一般基于临床指标,包括血压、中心静脉压(CVP)、体质量、周围水肿状态,以及肺听诊、胸部X线、肺超声特征等[15-16]。下腔静脉内径(inferior vena cava diameter, IVCD)测量、肺超声、血浆标志物测定法、生物电阻抗分析(bioimpedance analysis, BIA)等也有应用。但每种方法都有其局限性,临床应用时应根据患者情况选择合适的方法。
2 临床评估法 2.1 临床症状体征临床上常根据一般症状和体格检查中显性体征初步判断容量负荷状态,当患者出现短期体质量增加,显性水肿,胸闷喘憋,颈静脉怒张,肺部湿啰音增加,肝大或积液(胸腔、腹腔、心包)时,可以判定为容量负荷过重。当患者透析过程中出现体质量骤减、肌肉痉挛、透析后口干、声音嘶哑、耳鸣、皮肤黏膜干燥、皮肤弹性减退时,可以判定为容量负荷不足。但通过症状、体征判断容量负荷状态较为主观,而且初期时症状、体征多不明显,因此敏感性较差。针对透析患者的调查研究[17-18]表明,足周水肿与高血压之间有较强的相关性,但不能准确地反映患者的容量状况。目前尚无确切证据表明,透析患者临床症状、体征与其容量指标有直接关系。
2.2 血压、CVP血压、CVP是临床医师评估患者容量负荷最简单、最直观的指标。血压通常指动脉血压或体循环血压,是重要的生命体征。但除容量负荷外,交感神经功能、肾素-血管紧张素-醛固酮系统状态、心脏收缩力及外周血管弹性、血管舒张因子浓度变化等均会在患者透析过程中影响其血压[19],因此单用血压高低来判断容量负荷并不可靠。CVP指右心房及上、下腔静脉胸腔段的压力,反映心脏对周围回心血量的容纳能力,反映外周血容量及心脏回纳全身血液的功能状况,可用于判断患者血容量、心功能和血管张力[20-21]。但CVP测定方法具有有创侵入性,且容易受到胸腔内压力、心脏功能、导管位置等因素的影响,因此临床应用于判断容量负荷受到限制。
3 影像学评估 3.1 IVCD用超声探头测量IVCD是评价右心房压的方法之一。随着右心房压力增加,压力传导至IVC,导致其塌陷及扩张减少。Rudski等[22]的研究表明,当IVCD<2.1 cm,吸气时减小大于50%时,提示右心房压力为3 mmHg(正常范围为0~5 mmHg,1 mmHg=0.133 kPa)。研究[23-25]表明,IVCD能有效反映患者的容量超负荷状态,尤其在安静状态下,IVCD与心胸比值(r=0.53,P<0.001)和心房钠尿肽(ANP)浓度(r=0.59,P<0.05)相关;相较于BIA,IVCD与细胞内外水比值(r=0.42,P<0.05)、TBW(r=−0.47,P<0.025)相关性更明显。
然而,IVCD在不同个体间存在很大变化,独立预测容量负荷的结果不可靠;三尖瓣关闭不全和右室心力衰竭会导致IVCD增大[26],造成容量超负荷的假象;存在严重的全身感染、肝功能异常或严重营养不良所致的低白蛋白血症时,毛细血管静水压、胶体渗透压及通透性异常改变,也会对IVCD产生影响[27]。
3.2 肺超声肺部超声是临床上用以评估肺部容量负荷最常用的方法,其操作简单、成本低、可在床旁操作,早期评估无症状肺瘀血患者的容量负荷较为灵敏。当肺部存在瘀血时,超声射线回声被增厚的小叶间隔反射,在水肿间隔和覆盖的胸膜之间产生高回声伪影(即“肺彗星”,相当于胸部X线片中的Kerley B线)[28]。Agricola等[29]在心脏术后行肺动脉导管置入及Picco仪监测的患者中发现彗尾征与Picco仪监测的肺血管外间隙含水量正相关,同时与肺动脉导管测量的左室充盈压密切相关。崔琳琳等[30]证实,透析过程中彗尾征的变化与透析超滤量相关,随着超滤增加,彗尾征逐渐减少,彗尾征诊断容量超负荷较为准确。
但慧尾征并不是容量超负荷的特异指标,“肺慧星”的总和与患者的左心室充盈压、左心房容积、肺动脉压、E/é比值和射血分数等均有一定的相关性[31]。间质性肺纤维化、急性呼吸窘迫综合征等其他类型的肺部疾病[32]会引起胸膜壁层或小叶间纤维化,出现胸膜或小叶间隔增厚,造成超声波反射,进而形成彗尾结构[33-34]。
3.3 BIABIA是一种简便、无创、成本低且重复性好的评估手段,通过测量及分析生物组织的电阻特性(包括阻抗特性和容抗特性)来评估透析患者容量负荷状态[35-37]。其基本原理:当低强度交流电(通常是50 kHz)通过身体时,身体组织根据电流频率做出相应反应(称为阻抗),并对此进行分析[38-39]。目前常用的阻抗分析法包括多频生物电阻抗分析(multiple frequency bioelectrical impedance analysis, MFBIA)、生物电阻抗频谱分析(biomipedance electrical spectroscopy, BIS)和生物电阻抗矢量分析(bioelectrical impedance vector analysis, BIVA)。多项研究[40-44]表明,在透析患者治疗过程中,用BIA可以动态监测其容量状态的变化,判断患者预后,是评估透析患者“干体质量”的工具。
但由于目前没有统一的BIA测量仪器,使得测量结果缺乏标准化评估依据。而缺乏准确的数学模型和假设方程,可能使测量结果存在测量误差、回归误差(参照方法的标准误差)、引用方法内在误差、电体积模型误差(如组织各向异性,健康和病变受试者的生物变异)等。另外,BIA主要反映组织内容量负荷状态,适合评估静态容量负荷量,对于血管内容量评估敏感性较差,易受温度、离子浓度、血细胞比容等因素的影响[45]。
4 血浆标志物测定法钠尿肽在患者容量负荷增加或心室肌扩张引起的心室壁张力增加时高表达,包括有生物活性的ANP、脑钠肽(BNP)和无生物活性的代谢产物N端B型脑钠肽前体(NT-proBNP),均为心力衰竭和CKD研究中常用的生物标志物[46-47]。一项针对透析患者进行的横断面研究[48]发现,血浆NT-proBNP浓度升高有助于预测透析患者的容量超负荷状态,从而有利于早期通过适当的容量控制降低心血管相关死亡率。徐敏[49]等发现,无心衰尿毒症患者透析前血NT-proBNP水平与全身水肿程度呈明显正相关。
因此,单纯依靠NT-proBNP升高来诊断透析患者处于容量超负荷状态不可靠。BNP尤其是NT-proBNP的清除主要在肾脏,经过肾小球滤过并在近端小管中降解[50]。除容量超负荷状态外,NT-proBNP浓度随GFR的降低而升高。而晚期CKD患者的NT-proBNP水平受严重结构性心脏病的影响比肾脏清除能力更大。另外,年龄、性别、体质量指数、肾功能等也与NT-proBNP水平有关[51-52]。
5 小结常用的患者容量状态评估方法包括临床评估法、影像学评估法、血浆标志物测定法、同位素测定法等。临床评估法最为常用,患者透析前后体质量变化、超滤量、显性症状体征等的动态评估虽简便易行,但可靠性差,目前没有明确的试验数据支持症状体征与容量负荷失衡之间的关联。同位素稀释法是评估患者负荷状态的金标准,但需要患者摄入同位素,这会对人体产生损伤,且评估方法复杂,可行性差,难以在临床大规模应用。影像学评估法中,超声下IVCD测量与不良超声心动图指标有关,可反映患者容量超负荷状态,但IVCD测量和分析需要有经验的专业人员进行,且成本较高,难以广泛应用。肺超声技术相对较新,能判断肺组织中容量状态,但对全身容量负荷的判断较差。BIA是目前最多用于评估透析患者容量负荷状态的方法。虽然BIA评估得出的容量超负荷与透析技术失败和死亡率升高有关,但其评估容量负荷状态的价值仍无定论,缺乏标准化评价指标是BIA评估容量负荷的主要缺点。NT-proBNP可用于评估患者容量负荷状态,能够特异地反映血管内容量,但其受到心脏基础功能的影响,不能单独用于评估容量负荷状态。
总之,上述方法目前均不能独立、准确地评估患者容量负荷状态。但由于这些技术可以评估身体不同部位的容量负荷状况,因此联合应用可能对患者容量负荷评估更有价值。未来仍须继续寻找无创、简单、精准的容量负荷评估方法。
利益冲突:所有作者声明不存在利益冲突。
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