万古霉素硫酸钙与万古霉素PMMA缓释系统联合治疗慢性创伤性骨髓炎

发布时间：2018-06-05 16:56

本文选题：骨髓炎 + 清创术　；参考：《广西医科大学》2017年博士论文

【摘要】：背景慢性创伤性骨髓炎通常是指由创伤原因(包含开放性骨折、闭合性骨折、火器伤和骨科手术污染等)导致的慢性骨髓炎,主要分为慢性创伤后骨髓炎和慢性术后骨髓炎。慢性创伤后骨髓炎和慢性术后骨髓炎是一种难治性的疾病,一直是创伤骨科的一个重大挑战。慢性创伤后骨髓炎和慢性术后骨髓炎通常需要进行抗生素治疗和清创手术治疗,然而,在治疗后可发生持续感染或者出现感染复发。近年来,尽管在抗生素治疗和手术治疗方面已经取得显著的进展,但是慢性骨髓炎的长期复发率仍然高达20%。万古霉素硫酸钙缓释系统和万古霉素聚甲基丙烯酸甲酯(Polymethylmethacrylate PMMA)缓释系统都被广泛应用于治疗慢性创伤性骨髓炎,并且获得了相当不错的治疗效果。然而,随着它们的广泛应用,两者各自的缺点均已显露出来,但是它们也均具有各自固有的优点。目前,在进行慢性骨髓炎的基础研究以及临床研究时,万古霉素硫酸钙缓释系统或者万古霉素PMMA缓释系统往往被单独使用。有关通过应用万古霉素硫酸钙缓释系统和万古霉素PMMA缓释系统的各自优点,制备万古霉素硫酸钙与万古霉素PMMA联合缓释系统并使用该联合缓释系统治疗慢性创伤性骨髓炎的研究尚未见报道。目的本临床研究的主要目的是通过与万古霉素PMMA缓释系统比较,评价万古霉素硫酸钙与万古霉素PMMA缓释系统联合治疗慢性创伤后骨髓炎及慢性术后骨髓炎的可行性、安全性及有效性。方法本临床研究共纳入77例下肢慢性创伤后或骨折术后骨髓炎的患者。这些患者被分配到万古霉素硫酸钙与万古霉素PMMA缓释系统联合治疗研究组或万古霉素pmma缓释系统治疗对照组。在手术治疗前,两组患者均接受两种抗生素治疗1周以便能更好地控制感染,而不管是否获得细菌培养结果。经过术前抗生素治疗1周后,两组患者均行接受两阶段的手术治疗。在第一阶段的治疗中,骨感染的外科治疗在共同遵循一个标准的方案下进行。该外科手术治疗方案包括多个连续的操作步骤:去除内固定材料,对感染性坏死骨组织及软组织进行清创,使用高速磨钻清除骨感染部位的硬化骨,使用高压脉冲冲洗系统冲洗创口,在清创术后的骨缺损区植入万古霉素pmma缓释系统或者万古霉素硫酸钙与万古霉素pmma联合缓释系统以消灭骨死腔,创口内置入引流管,然后缝合关闭切口。必要时采取稳定骨骼的适当外固定措施。在第一阶段手术治疗后的随访期间,对血液学指标、微生物检查、感染控制率、持续感染率、感染复发率和由于持续感染、复发感染导致的再次手术率进行评价。在第一阶段治疗后6周至8周,对获得感染控制的患者进行第二阶段治疗。在进行第2阶段治疗时,切开皮肤并且逐层分离软组织后,细心地纵形切开masquelet诱导膜,移除pmma骨水泥,在masquelet诱导膜腔里仅仅植入自体松质骨颗粒或者混合植入自体松质骨颗粒和同种异体骨或人工骨替代物以重建骨缺损,植骨后细心缝合masquelet诱导膜,创口内置入引流管,逐层缝合关闭切口。必要时使用接骨板内固定或者外固定支架外固定。第二阶段植骨重建外科手术后的有效性主要通过对植骨区感染复发率、骨缺损区移植骨的愈合及邻近关节功能康复情况进行评估。结果第一阶段手术治疗后的平均随访期为24个月(范围:15个月~48个月)。在万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗研究组中,所有患者在术后平均6周(范围,30天~60天)内影像学检查均表现出完全的硫酸钙吸收;第一阶段手术治疗后的感染控制率为87.18%(34/39)和再次手术率为12.82%(5/39);感染复发的5例患者需要进行了进一步的外科手术治疗,其中3例患者获得感染控制,总的感染控制率达94.87%(37/39)。第一阶段手术治疗后,治疗研究组无持续感染的患者。在万古霉素pmma缓释系统治疗对照组,i期手术治疗后的感染控制率68.42%(26/38),再次手术率为31.58%(12/38);i期手术治疗后,12例发生持续感染或者复发感染的患者需行再次手术治疗,其中4例患者获得感染控制,总的感染控制率为78.95%(30/38)。在第一阶段手术治疗后,万古霉素硫酸钙与万古霉素pmma联合治疗组的感染控制率高于万古霉素pmma缓释系统治疗对照组的感染控制率(万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗研究组,87.18%vs万古霉素pmma缓释系统治疗对照组,68.42%;p0.05)。在经过由于持续感染或者复发感染导致的再次手术治疗后,万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗研究组的总感染控制率仍然高于万古霉素pmma缓释系统治疗对照组的总感染控制率(万古霉素硫酸钙与万古霉素pmma联合缓释系统治疗研究组,94.87%vs万古霉素pmma缓释系统治疗对照组,78.95%;p0.05)。在第一阶段手术治疗后,万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗组的持续感染或者复发感染的总发生率低于万古霉素pmma治疗对照组的持续感染或者复发感染的总发生率(万古霉素硫酸钙与万古霉素pmma联合治疗组,12.82%vs万古霉素pmma缓释系统治疗对照组,31.56%;p0.05)。在再次手术率方面,万古霉素pmma治疗对照组比万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗组更高(万古霉素pmma缓释系统治疗对照组,31.56%vs万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗研究组,12.82%;p0.05)。在i期手术治疗后,万古霉素pmma治疗对照组的总并发症发送率高于万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗组(万古霉素pmma缓释系统治疗对照组,28.95%vs万古霉素硫酸钙与万古霉素pmma联合治疗组,10.26%;p0.05)。通过血液学检查显示,万古霉素硫酸钙与万古霉素pmma缓释系统联合治疗组和万古霉素pmma治疗对照组均无肝毒性及肾毒性。在第二阶段治疗中,获得感染控制的两组患者65例中共有48例患者接受植骨重建手术治疗,采用接骨板内固定30例,使用外固定支架外固定10例,不需要进行内固定或者外固定8例。术后平均随访期间为18个月(范围,12个月~24个月),骨缺损植骨区无感染复发,影像学检查显示骨缺损区植骨愈合平均时间为6个月,末次随访时,患肢均能完全或者部分负重行走和步态基本正常,骨缺损植骨区无疼痛。结论与万古霉素PMMA缓释系统比较,通过万古霉素硫酸钙缓释系统和万古霉素PMMA缓释系统的协同作用,万古霉素硫酸钙与万古霉素PMMA缓释系统联合治疗可更有效治疗慢性创伤性骨髓炎,能有效提高感染控制率、降低持续感染或者复发感染发生率、降低由于持续感染或者复发感染导致的再次手术率及降低并发症症发送率。在慢性创伤性骨髓炎的治疗中,可生物降解性材料和非生物降解性材料的联合应用也许能够实现感染局部的即刻结构稳定和较高浓度的抗生素,从而能更有效治疗慢性创伤性骨髓炎。
[Abstract]:Background chronic traumatic osteomyelitis usually refers to chronic osteomyelitis caused by the cause of trauma (including open fracture, closed fracture, firearm injury, and Department of orthopedics pollution). It is mainly divided into chronic posttraumatic osteomyelitis and chronic postoperative osteomyelitis. Chronic posttraumatic osteomyelitis and chronic postoperative osteomyelitis are a refractory disease. It is a major challenge in the trauma department of orthopedics. Chronic posttraumatic osteomyelitis and chronic postoperative osteomyelitis are usually treated with antibiotic and debridement. However, persistent infection or recurrence of infection can occur after treatment. In recent years, although significant progress has been made in the treatment and surgical treatment of antibiotics, it is slow but slow The long-term recurrence rate of osteomyelitis is still high up to 20%. vancomycin calcium sulphate slow release system and vancomycin polymethyl methacrylate (Polymethylmethacrylate PMMA) sustained-release system, which are widely used in the treatment of chronic traumatic osteomyelitis, and have obtained considerable therapeutic effect. However, with their extensive application, both of them have been widely used. The shortcomings of the self have been revealed, but they also have their own inherent advantages. At present, in the basic research and clinical study of chronic osteomyelitis, vancomycin sulfate sustained-release system or vancomycin PMMA sustained-release system is often used alone. The study of the combined slow release system of vancomycin sulfate and vancomycin for the treatment of chronic traumatic osteomyelitis has not been reported. The purpose of this clinical study is to evaluate vancomycin calcium sulphate by comparison with the slow release system of vancomycin PMMA and the PMMA release system of vancomycin. The feasibility, safety and effectiveness of the combined treatment of chronic posttraumatic osteomyelitis and chronic postoperative osteomyelitis with vancomycin PMMA system. Methods a total of 77 patients with osteomyelitis after chronic trauma or fracture of the lower extremities were included in this clinical study. These patients were assigned to the combined treatment of vancomycin calcium sulphate and vancomycin PMMA sustained release system. The treatment study group or the vancomycin PMMA sustained-release system treated the control group. Before the operation, the two groups were treated with two antibiotics for 1 weeks in order to better control the infection, regardless of whether the bacterial culture was obtained. After 1 weeks of preoperative antibiotic treatment, the two group received two stages of surgical treatment. In the first stage In treatment, surgical treatment of bone infection is carried out under a common standard program. The surgical treatment includes a number of continuous procedures: removal of internal fixation materials, debridement of necrotic bone tissue and soft tissue, high speed drill to remove the hardened bone in the bone sensing site, and high pressure pulse irrigation system In the bone defect area after debridement, the vancomycin PMMA sustained-release system or vancomycin sulfate and vancomycin PMMA combined with the vancomycin slow-release system is used to eliminate the bone dead cavity, the wound is inserted into the drainage tube, and then the incision is sutured and closed. During the visit, the Hematology Index, microbiological examination, infection control rate, persistent infection rate, infection recurrence rate, recurrent infection and recurrent infection were evaluated. 6 to 8 weeks after the first stage of treatment, second stages of treatment for patients with infection control were treated. The skin was cut during the second stage treatment and the skin was cut. After separating the soft tissue layer by layer, the masquelet induced membrane was carefully cut and the PMMA bone cement was removed. The autologous cancellous bone particles were implanted in the masquelet induced membrane cavity, or the autograft of autogenous cancellous bone particles and the allograft bone or artificial bone substitute were used to reconstruct the bone defect. The masquelet induced membrane was sutured carefully after the bone graft, and the wound was built in. The effectiveness of the second stage bone graft reconstruction is mainly through the recurrence rate of infection in the bone graft region, the healing of the bone graft in the bone defect area and the rehabilitation of the adjacent joint function. Results first stage surgical treatment. The average follow-up period was 24 months (range: 15 months ~48 months). In the combined treatment group of vancomycin calcium sulfate and vancomycin PMMA sustained release system, all patients showed complete calcium sulfate absorption within 6 weeks (range, 30 days ~60 days) after the operation; the infection control rate after the first stage operation was 87.18%. (34/39) and reoperation rate of 12.82% (5/39); 5 patients with recurrent infection needed further surgical treatment, of which 3 patients received infection control, the total infection control rate was 94.87% (37/39). After the first stage of the operation, the study group was treated with no continued infection. In the vancomycin PMMA sustained release system, the control group was treated with the control group The infection control rate after I was 68.42% (26/38) and the reoperation rate was 31.58% (12/38); after the I operation, 12 patients with persistent infection or recurrent infection needed reoperation, of which 4 patients received infection control, the total infection control rate was 78.95% (30/38). After the first stage of operation, vancomycin sulfur The rate of infection control in the combined treatment group of calcium acid and vancomycin PMMA was higher than that of the control group with vancomycin PMMA sustained release system (vancomycin calcium sulfate and vancomycin PMMA sustained-release system combined treatment group, 87.18%vs vancomycin PMMA sustained-release system for control group, 68.42%; P0.05). The total infection control rate of the combined treatment group of vancomycin calcium sulfate and vancomycin PMMA sustained release system was still higher than that of the vancomycin PMMA sustained-release system (vancomycin sulfate and vancomycin PMMA combined slow-release system treatment group, 94.87%vs million) The total incidence of persistent infection or recurrent infection in the combined treatment group of vancomycin calcium sulfate and vancomycin PMMA sustained release system was lower than that of vancomycin PMMA treatment group (vancomycin PMMA). The total incidence of vancomycin in the control group (vancomycin) was lower than that of vancomycin PMMA control group. Calcium sulfate and vancomycin PMMA combined treatment group, 12.82%vs vancomycin PMMA sustained release system for the control group, 31.56%; P0.05). In the reoperation rate, vancomycin PMMA treatment control group was higher than vancomycin calcium sulfate and vancomycin PMMA slow release system combined treatment group (vancomycin PMMA sustained-release system treatment control group, 31.56%vs million, 31.56%vs million) The total complication rate of vancomycin PMMA treatment group was higher than that of vancomycin calcium sulfate and vancomycin PMMA sustained-release system (vancomycin PMMA) group (vancomycin PMMA sustained-release system treatment group, 28.95%vs vancomycin, 12.82%; 12.82%; P0.05). After I operation, the total complication rate was higher than that of vancomycin calcium sulfate and vancomycin PMMA slow release system. Calcium sulfate and vancomycin PMMA combined treatment group, 10.26%; P0.05). Through hematological examination, there were no hepatotoxicity and renal toxicity of vancomycin calcium sulfate combined with vancomycin PMMA sustained-release system combined with vancomycin PMMA treatment control group. In the second stage treatment, two groups of patients who received infection control had 48 patients. There were 30 cases of internal fixation with bone grafting and 10 cases with external fixation with external fixation. No internal fixation or external fixation was needed in 8 cases. The average follow-up period was 18 months (range, 12 months ~24 months). No infection recurrence was found in bone defect area. The average time of bone graft healing in bone defect area was revealed by imaging examination. For 6 months, all the limbs were completely or partially weight-bearing walking and gait basically normal at the last follow-up, and there was no pain in the bone defect area. Conclusion compared with vancomycin PMMA sustained-release system, vancomycin sulfate calcium sulfate and vancomycin PMMA sustained-release system were used by the combined use of vancomycin calcium sulfate slow release system and vancomycin PMMA sustained release system. Combined therapy can be more effective in the treatment of chronic traumatic osteomyelitis. It can effectively improve the infection control rate, reduce the incidence of persistent infection or recurrent infection, reduce the reoperation rate due to persistent infection or recurrent infection and reduce the incidence of complications. Biodegradable materials can be used in the treatment of chronic traumatic osteomyelitis. The combined application of non biodegradable materials may be able to achieve immediate structural stability and high concentrations of antibiotics, which can be more effective in the treatment of chronic traumatic osteomyelitis.
【学位授予单位】：广西医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R681.2

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