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非细胞毒性外渗损伤的管理:关于药物、治疗策略以及血管加压药和高渗盐水外周给药的重点更新

Management of noncytotoxic extravasation injuries: A focused update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline.

作者信息

Stefanos Sylvia S, Kiser Tyree H, MacLaren Robert, Mueller Scott W, Reynolds Paul M

机构信息

Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.

Department of Pharmacy, University of Colorado Health, Aurora, Colorado, USA.

出版信息

Pharmacotherapy. 2023 Apr;43(4):321-337. doi: 10.1002/phar.2794. Epub 2023 Apr 1.

Abstract

Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation. Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active agents cause cellular damage as a result of osmotic shifts across cellular membranes in addition to agent-specific toxicities, such as calcium-induced vasoconstriction and calcifications or arginine-induced leakage of potassium causing apoptosis. A new category has been proposed to identify absorption-refractory mechanisms of injury in which agents such as propofol and lipids may persist in the extravasated space and cause necrosis or compartment syndrome. Pharmacological antidotes may be useful in select extravasations but requires prompt recognition and frequently complex administration strategies. Historically, intradermal phentolamine has been the preferred agent for vasopressor extravasations, but frequent supply shortages have led to the emergence of terbutaline, a β -agonist, as an acceptable alternative treatment option. For hyperosmolar and pH-related mechanisms of injuries, hyaluronidase is most commonly used to facilitate absorption and dispersion of injected agents. However, extravasation management is largely supportive and requires a protocolized multidisciplinary approach for early detection, treatment, and timely surgical referral when required to minimize adverse events.

摘要

外渗是指静脉内溶液漏入周围组织,这可能受药物特性、输注技术和患者相关风险因素的影响。尽管外周给予有刺激性的药物可能会增加外渗损伤的风险,但中心静脉导管置入所需的时间和资源可能会延迟对时间敏感型治疗的给药。从越来越多地使用外周血管加压药和高渗钠收集到的最新文献表明,外周启动这些紧急治疗的危害风险较低,这可能会避免延迟并改善患者预后。组织损伤的物理化学原因包括血管收缩、pH介导、渗透压介导和外渗损伤的细胞毒性机制。酸性药物,如异丙嗪、胺碘酮和万古霉素,可能会因细胞脱水导致水肿、脱落和坏死。另外,碱性药物,如苯妥英和阿昔洛韦,由于解离的氢氧根离子对组织的穿透更深,可能更具腐蚀性。除了特定药物的毒性,如钙诱导的血管收缩和钙化或精氨酸诱导的钾泄漏导致细胞凋亡外,具有渗透活性的药物还会因跨细胞膜的渗透变化而导致细胞损伤。有人提出了一个新的类别来识别吸收难治性损伤机制,其中丙泊酚和脂质等药物可能会在外渗空间持续存在并导致坏死或骨筋膜室综合征。药理学解毒剂可能对某些外渗情况有用,但需要迅速识别且给药策略通常较为复杂。从历史上看,皮内注射酚妥拉明一直是治疗血管加压药外渗的首选药物,但频繁的供应短缺导致β受体激动剂特布他林成为一种可接受的替代治疗选择。对于高渗和pH相关的损伤机制,透明质酸酶最常用于促进注射药物的吸收和扩散。然而,外渗管理主要是支持性的,需要一种规范化的多学科方法,以便早期发现、治疗,并在需要时及时进行手术转诊,以尽量减少不良事件。

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