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A型肉毒毒素注射防治中厚皮片供区瘢痕的效果



A型肉毒毒素注射防治中厚皮片供区瘢痕的效果

褚晶晶1 王和庚1 罗志军1 田举1 齐向东2

本文来源:《中华整形外科杂志》2023年8月 第39卷 第8期

DOI:10. 3760 / cma.j.cn114453-20230504-00094

作者单位:1中山市人民医院烧伤整形美容科, 中山528400;2南方医科大学珠江医院整形美容中心, 广州510220

通信作者:齐向东,Email: create_beauty@hotmail.com

引用本文

褚晶晶,王和庚,罗志军,等. A型肉毒毒素注射防治中厚皮片供区瘢痕的效果[J]. 中华整形外科杂志,2023,39(08):817-822.

DOI:10.3760/cma.j.cn114453-20230504-00094
 


【摘要】 

目的 研究A型肉毒毒素(BTX-A)注射防治中厚皮片供区瘢痕的效果。

方法 采用前瞻性随机对照研究方法,于2021年9月至2022年9月招募中山市人民医院烧伤整形美容科采用大腿中厚皮片移植修复功能部位烧伤及慢性创面的患者。大腿供皮区创面愈合后10 d(约术后4周),采用随机数字表法将患者分为2组:试验组和对照组。试验组术后1、3个月使用等间距注射法于供区注射BTX-A溶液,每点注射0.1 ml(1 U),各点间距1 cm;对照组术后1、3个月在供皮区采用等间距法注射等量生理盐水。观察不良反应发生情况,治疗半年后进行随访,通过医生的温哥华瘢痕量表(VSS)评分(包括色泽、血管分布、柔软度、厚度4个维度)和患者瘢痕痛痒程度的视觉模拟评分法(VAS)评分评估疗效。VSS评分和VAS评分均符合正态分布,以x±s表示,采用独立样本t检验进行分析。

结果 共招募60例受试者,试验组和对照组各30例。试验组男16例,女14例,年龄(32.7±5.4)岁(18~60岁);对照组男13例,女17例,年龄(31.4±4.8)岁(18~55岁)。2组性别构成和年龄的差异均无统计学意义(P均>0.05)。试验组在治疗过程中及治疗后无严重不良反应发生。治疗半年后随访时,试验组VSS总分[(3.57±0.60)分vs. (8.52±0.84)分]以及瘢痕色泽、血管分布、柔软度、厚度4个维度评分[(0.88±0.22)分vs. (2.30±0.52)分;(0.73±0.27)分vs. (2.16±0.40)分;(1.29±0.39)分vs. (2.49±0.39)分;(0.66±0.23)分vs. (1.56±0.34)分]均明显小于对照组,差异均有统计学意义(P均<0.01);试验组的瘢痕痛痒程度VAS评分亦明显小于对照组[(1.06±0.34)分vs. (2.92±0.63)分],差异有统计学意义(P<0.01)。

结论 BTX-A注射防治中厚皮片供区瘢痕安全且有效,同时对缓解瘢痕患者的痛痒症状也具有良好的效果。

【关键词】瘢痕;肉毒毒素类;A型肉毒毒素;中厚皮片供区

基金项目: 中山市医学科研项目(2021J009)
 

The cosmetic effects of botulinum toxin type A in the prevention and treatment of cicatrix on split-thickness skin graft donor site

Chu  Jingjing1, Wang  Hegeng1, Luo  Zhijun1, Tian  Ju1, Qi  Xiangdong2

1Department of Burn & Plastic Surgery, Zhongshan People’s Hospital, Zhongshan 528400, China; 2Plastic Surgery Center, Southern Medical University Zhujiang Hospital, Guangzhou 510220, China

Corresponding author: Qi Xiangdong,  Email: create_beauty@hotmail.com

  【Abstract

Objective To investigate the cosmetic effects of botulinum toxin type A(BTX-A) in the prevention and treatment of cicatrix on split-thickness skin graft donor site.

Methods A prospective randomized controlled study was commenced to recruit patients with functional burns and chronic wounds who were repaired with split-thickness skin graft in the Department of Burn and Plastic Surgery of Zhongshan People’s Hospital from September 2021 to September 2022. Ten days after wound healing in the donor area of the thigh (about 4 weeks after surgery), the patients were randomly divided into two groups: the experimental group and the control group. The experimental group was injected with BTX-A solution at the skin donor site by equal interval injection method 1 and 3 months after surgery, 0.1 ml (1 U) was injected at each point, and the interval of each point was 1 cm. The control group was injected with equal amount of normal saline at the skin donor area by equal spacing method 1 and 3 months after operation. The adverse reactions was observed. Follow-up was performed six months after treatment. Evaluation indicators included the doctor’s Vancouver scar scale (VSS) score (including color, vascular distribution, softness and thickness), the visual analogue scale (VAS) score of the patient’s scar pain and itching degree. Both VSS scores and VAS scores were in line with normal distribution, expressed as Mean±SD, and analyzed by independent sample t-test.

Results A total of 60 subjects were recruited, 30 in the experimental group and 30 in the control group. In the experimental group, there were 16 males and 14 females, aged (32.7±5.4) years (18-60 years). In the control group, there were 13 males and 17 females, aged (31.4±4.8) years (18-55 years). There were no significant differences in gender composition and age between the two groups (all P > 0.05). No serious adverse reactions occurred in the experimental group during and after treatment. At the follow-up six months after treatment, the total score of VSS in the experimental group [(3.57±0.60) points vs. (8.52±0.84) points] and the scores of scar color, vascular distribution, flexibility and thickness[(0.88±0.22) points vs. (2.30±0.52) points; (0.73±0.27) points vs. (2.16±0.40) points; (1.29±0.39) points vs. (2.49±0.39) points; (0.66±0.23) points vs. (1.56±0.34) points] were significantly lower than those in the control group, and the differences were statistically significant (P < 0.01). The VAS score of scar pain and itching degree in the experimental group was also significantly lower than that in the control group [(1.06±0.34) points vs. (2.92±0.63) points], and the difference was statistically significant (P < 0.01).

Conclusion BTX-A injection is safe and effective in preventing and treating cicatrix in the donor area of split-thickness skin graft, and also has a good effect on relieving the pain and itching symptoms of cicatrix patients.

【Key words】Cicatrix; Botulinum toxins; Botulinum toxin type A; Split-thickness skin graft donor site

Fund program: Zhongshan Medical Research Project (2021J009)

Disclosure of Conflicts of Interest: The authors have no financial interest to declare in relation to the content of this article.

Ethical Approval: Ethical approval was given by the Medical Ethics Committee of Zhongshan People’s Hospital(2023-015).

 

    中厚皮片移植是烧伤与整形外科最常用且应用最广泛的皮片移植技术。中厚皮片含有较厚的真皮层纤维组织,具有质地软、弹性佳、耐摩擦、色泽好等优点,尤其适用于修复功能部位的创面。中厚皮片取皮深达真皮层,有研究发现真皮组织缺损厚度与瘢痕的增生程度呈正相关,因此其创面愈合常伴有瘢痕组织增生、疼痛及瘙痒症状,色素沉着明显,影响患者的生活质量。目前国内外已报道多种方法处理供皮区可减少瘢痕增生,如刃厚皮片回植中厚皮片供区、功能性敷料辅助愈合、应用抗瘢痕外用硅凝胶类药物、注射糖皮质激素、激光治疗等。但因供皮区域瘢痕范围大等原因,治疗费用高,且临床中观察到防治瘢痕及治疗疼痛、瘙痒症状等的效果并不很理想。随着对瘢痕的深入研究,目前国内外报道表明A型肉毒毒素(botulinum toxin type A,BTX-A)在防治瘢痕中有一定效果,并可缓解瘢痕患者的瘙痒及疼痛感觉[ 1 , 2 ]。本研究拟探讨BTX-A注射防治中厚皮片供区瘢痕的效果。

 

对象与方法

     一、研究对象

    采用前瞻性双盲随机对照研究方法,于2021年9月至2022年9月招募中山市人民医院烧伤整形美容科采用大腿中厚皮片移植修复功能部位烧伤及慢性创面的患者。纳入标准:(1)年龄>18岁,自愿接受BTX-A治疗,签署知情同意书;(2)大腿取中厚皮片后供区创面基本愈合,无感染、破溃;(3)参与研究前未曾使用其他药物治疗及激光治疗等;(4)能按时随访。排除标准:(1)有BTX-A使用禁忌证;(2)肝肾等重要脏器功能不全;(3)患有免疫缺陷性疾病或自身免疫性疾病;(4)患有糖尿病、高血压等慢性内科疾病;(5)有明确瘢痕疙瘩病史。

    本研究经中山市人民医院医学伦理委员会批准(2023-015),患者均签署知情同意书。

 

     二、方法

     (一)研究分组及样本量估算

    患者中厚皮片移植术中供区均采用肿胀麻醉(肿胀麻醉液为1∶500 000肾上腺素盐水)。用电动取皮机在大腿前外侧切取厚度均匀的完整中厚皮片(厚度约0.4 mm),面积5 cm×5 cm~10 cm×15 cm。供区创面全部愈合后10 d(约术后4周),采用随机数字表法将患者分为2组:试验组和对照组。根据如下随机对照试验样本量计算公式估算所需的样本量:

    设置α为0.05,Zα=1.96,把握度(检验效能)为0.9 ,Zβ=1.28,并根据既往相关文献及预实验分析结果,σ=0.80,δ=0.75,计算得试验组及对照组受试者至少各24例,考虑失访等情况,试验组及对照组各需纳入受试者30例。

     (二)治疗方法

    试验组使用等间距注射法于大腿供区创面愈合区域注射BTX-A。用10 ml 0.9%氯化钠注射液稀释100 U的BTX-A(兰州生物制品研究所有限责任公司,国药准字S10970037),使每0.1 ml溶液中含1 U肉毒毒素。等间距注射时,每点注射0.1 ml BTX-A溶液,各点间距1 cm,注射总量不超过200 U。术后1个月(大腿供区创面全部愈合后约10 d)和3个月各注射治疗1次。对照组术后1、3个月在供区采用等间距法注射生理盐水,注射量和间距与试验组相同。

 

     三、观察指标

    术后观察不良反应发生情况。治疗半年后进行随访,由2名主治及以上职称整形外科医生通过温哥华瘢痕量表(Vancouver scar scale,VSS)从色泽、血管分布、柔软度、厚度4个方面评估患者的瘢痕情况,记录平均分;在医生指导下由患者以视觉模拟评分法(visual analogue scale,VAS)[ 3 ]评估瘢痕的痛痒程度。参与随访评价的医生对患者分组情况均不知情。

     (一)VSS评估瘢痕的色泽、血管分布、柔软度、厚度

    色泽:0分,皮肤颜色与身体其他部分近似;1分,色泽较浅;2分,混合色泽;3分,色泽较深。血管分布:0分,正常肤色,与身体其他部分近似;1分,肤色偏粉红;2分,肤色偏红;3分,肤色呈紫色。柔软度:0分,正常;1分,柔软(在最小阻力下皮肤能变形);2分,柔顺(在压力下能变形);3分,硬(不能变形,移动时呈块状,对压力有阻力);4分,弯曲(组织如绳状,瘢痕伸展时会回缩);5分,挛缩(瘢痕永久性缩短,导致残废与扭曲)。厚度:0分,正常;1分,>0~1 mm;2分,>1~2 mm;3分,>2~4 mm; 4分,>4 mm。量表总分0~15分,分数越高说明瘢痕情况越严重。

     (二)VAS评估瘢痕的痛痒程度

    轻度痛痒:1分;中度痛痒:2~4分;重度痛痒:5~7分;极重度痛痒:8~10分。

     四、统计学处理

    采用SPSS 20.0(美国IBM公司)软件进行统计学分析。正态性检验显示,患者年龄、医生的VSS评分和患者的瘢痕痛痒程度VAS评分均符合正态分布,以x±s表示,采用独立样本t检验进行分析。患者的性别构成采用χ2检验进行分析。P<0.05为差异有统计学意义。

 

结   果

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