Clinical application of intra-articular injection drugs in orthopedics: features and value

doi:10.3969/j.issn.2095-4344.2014.31.025

Abstract

Abstract:

BACKGROUND: As a more common method in the orthopedic field, the method of intra-articular injection drugs has distinct curative effects, but there are some complications. In a certain extent, this method caters to the psychological fear of surgery, and can serve as a kind of conservative treatment. But some experts believed that because of the limit of sterile conditions, intra-articular injection of drugs will increase the risk of intra-articular infection and they opposed this method. OBJECTIVE: To review the efficacy and adverse reactions of intra-articular injection drugs in recent years, and explain clinical applications of intra-articular injection drugs in orthopedics.
METHODS: A computer-based search was conducted in PubMed and Wanfang database for articles related to the application of intra-articular injection drugs in orthopedics published between January 2007 and December 2013. The English and Chinese key words were “intra-articular, injection, orthopaedics, tranexamic acid, hyaluronic acid, corticosteroid, drugs”. Data were checked in the first trial, old articles and repetitive studies were excluded. The relevant 43 articles accorded with inclusion criteria were reviewed.
RESULTS AND CONCLUSION: In orthopedics, the method of intra-articular injection drugs is simple, economic and effective, but at the same time, there are some side effects. Tranexamic acid by intra-articular injection can significantly reduce blood loss after total joint replacement, is safety and economic. Intra-articular injection joint lubricant can reduce internal friction of joints and improve the adhesion of joint cavity, can be used as a good conservative treatment for osteoarthritis. Intra-articular injection hormone drugs can treat inflammatory arthritis, and short-term curative effect is obvious, but due to large long-term side effects, the method is not recommended now. Intra-articular injection of analgesic drugs and other drugs have both advantages complications. The efficacy of intra-articular injection drugs in orthopedics is obvious; meanwhile, this method has some complications. Orthopedic surgeons should select related drugs by indications. We still need to further make reasonable regimen with intra-articular injection drugs in future large-scale study.

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

全文链接：

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

全文链接：

Key words: arthroplasty, replacement, osteoarthritis, hormones, tranexamic acid

CLC Number:

R318

Ma Jin-hui, Sun Wei, Gao Fu-qiang, Wang Yun-ting, Li Zi-rong. Clinical application of intra-articular injection drugs in orthopedics: features and value[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(31): 5068-5074.

Figures/Tables 1

2.1 关节腔内注射止血剂——氨甲环酸氨甲环酸是赖氨酸合成的衍生物，作用机制为与纤溶酶原结合，阻止纤溶酶降解纤维蛋白，起到抗纤溶作用，但不增加纤维蛋白的合成[8]。关节内注射氨甲环酸可以减少全膝关节置换后失血量及患者的输血需要，氨甲环酸分子主要在局部伤口的活动性出血点起作用，而并不是在出血的血管内部发挥作用，同时基于关节内的氨甲环酸对纤溶蛋白降解过程存在竞争性与非竞争性抑制作用，继发于非竞争性抑制纤维蛋白溶解作用，其极可能具有促进纤维蛋白凝血块稳定的作用，将有效减少来自于受损伤组织表面所渗出、漏出的血液丢失[9]。此外，关节内注射氨甲环酸与静脉注射比较，能更有效地减少行全膝关节置换患者术后引流管中的血液流失量及术后输血量及输血次数，且不良反应小，尤其适用于患有心血管疾病、肾功能不全等高危患者。同时氨甲环酸能够通过维持患者的血流动力学稳定、减少输血而产生的不良反应、并发症来改善全膝关节置换后患者的一般情况，有助于患者的早期康复及进行早期功能锻炼，减少患者住院时间，降低因住院时间长可能引起的肺部感染等并发症的发生率[10]。研究表明，在接受全膝关节置换的患者中局部(用配有氨甲环酸的盐水冲洗切口)与关节内联合应用氨甲环酸平均减少246 mL的隐性失血，在术后不放置引流的情况下同样可以减少患者术后的失血量与输血需要[11]。Mutsuzaki等[12]指出，在非骨水泥型全膝关节置换手术切口缝合后、松止血带之前，通过患者膝部留置的引流管注射氨甲环酸，并立刻夹闭引流管1 h，可以减少患者置换后48 h内引流管引流量、血液流失与输血需要，与没有注射氨甲环酸和夹闭引流管的患者相比，置换后第7天的血红蛋白水平明显升高，同时由于术后出血的减少，这些患者皮下与关节内血肿的发生率也显著减少。Ishida等[13]同样指出，在全膝关节置换结束时通过引流管向膝关节腔内注射氨甲环酸不仅可以减少置换后失血量，还具有缓解膝关节肿胀的功效，作用机制主要是通过减少膝关节内的隐性失血，这将很有可能降低全膝关节置换后患者的不适感。文献报道，计算机辅助下的全膝关节置换后患者手术切口关闭后，向关节腔内注射低剂量的氨甲环酸溶液(把250 mg的氨甲环酸溶于25 mL生理盐水中，相当于氨甲环酸的浓度为10 g/L)，并立刻夹闭引流管2 h，不但可以维持关节内的氨甲环酸药物浓度，并且由于有足够时间使药物达到抗纤溶作用，还可以阻止血液流动增加而造成的较快速血液流失[14]。关节内注射氨甲环酸联合引流管夹闭可以产生增加局部血栓形成、延长纤维蛋白凝块溶解时间的效应，并且这种效应是暂时的，不会增加远期并发症。由上可知，关节腔内注射氨甲环酸具有以下优点：一是方法简单，易于操作，花费较低；二是关节腔内注射氨甲环酸联合引流管夹闭可以使关节局部达到较高的药物浓度，具促进血栓形成，缩短受损伤血管闭塞时间的作用[7]，避免了静脉用药导致药物全身吸收而带来的全身不良反应；三是关节内注射氨甲环酸不仅可以减少患者术后引流管中的失血量、输血需要与输血率，而且可以减少关节内部的隐性失血，缓解关节肿胀和关节内血肿，令患者术后的满意度提高。因此，关节内注射氨甲环酸较静脉应用是一种更加有效的手段。 2.2 关节腔内注射关节润滑剂——透明质酸、玻璃酸钠透明质酸是一种高分子直链多聚糖[15]，由滑液中的B细胞及单核巨噬细胞所分泌[16]，广泛存在于人体的结缔组织基质中。其化学结构的不规则卷曲状态及溶解状态下的流体动力学特性，使其具有高度的黏弹性、可塑变形性和渗透性。同时透明质酸还具有分子屏障的作用，可以阻止炎症递质在关节腔内扩散，抑制纤维母细胞活动和淋巴细胞游走[17]，降低滑膜下的痛觉器与感觉纤维的兴奋性，从而保护关节的结构，维持关节内环境的稳定[18]。有动物实验报道，对于需要固定8周的膝关节损伤动物模型[19]，对其关节内注射透明质酸可以减少长期固定后的关节黏连，降低滑膜组织中的胶原蛋白含量，增加固定后的关节活动范围。此动物实验提示，对于需要关节固定至少8周的患者，包括接受关节镜下前交叉韧带或后交叉韧带重建的患者、关节内或外骨折的患者、严重创伤后行关节清创的患者等等，关节内应用透明质酸可以预防关节粘连，改善关节活动度。关节内注射透明质酸被公认为是一种可以减轻关节软骨摩擦的有效方法，广泛应用于骨关节炎的治疗与预防，还可以预防膝关节、颞下颌关节、屈肌腱和肩袖手术后的粘连[19]。"

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