郁凱 楊劍 劉敏 楊杰 楊人軍 張殿英,3

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肩峰下間隙藥物注射治療肩關(guān)節(jié)撞擊綜合征療效

郁凱1楊劍1劉敏2楊杰1楊人軍1張殿英1,3

目的 比較曲安奈德、派瑞昔布鈉肩峰下間隙注射治療肩關(guān)節(jié)撞擊綜合征的療效。方法 59例確診為肩關(guān)節(jié)撞擊綜合征患者隨機(jī)分為激素組和非甾體消炎藥(NSAID)組，激素組注射曲安奈德40 mg， NSAID組注射派瑞昔布鈉40 mg，每位患者注射前后分別進(jìn)行疼痛(VAS評分)和肩關(guān)節(jié)功能評價(jià)(HSS評分、外展度)。結(jié)果 37例最終獲得隨訪，3周后隨訪，兩組患者活動(dòng)度與疼痛均明顯改善。肩關(guān)節(jié)HSS評分NSAID組和激素組注射后30 min均明顯優(yōu)于注射前，3周隨訪時(shí)NSAID組優(yōu)于注射前，激素組與注射前比較差異無統(tǒng)計(jì)學(xué)意義。肩關(guān)節(jié)外展，NSAID組和激素組注射后30 min均明顯優(yōu)于注射前，3周隨訪時(shí)NSAID組優(yōu)于激素組，差異有統(tǒng)計(jì)學(xué)意義。結(jié)論 肩峰下注射激素和NSAID藥物均有助于減輕肩關(guān)節(jié)撞擊綜合征患者的疼痛，NSAID組肩關(guān)節(jié)活動(dòng)度和HSS評分優(yōu)于激素組。

肩關(guān)節(jié)撞擊綜合征；保守治療；非甾體消炎藥；激素

肩關(guān)節(jié)撞擊綜合征常見的癥狀是肩部疼痛和活動(dòng)受限，其中疼痛為大多數(shù)患者的主訴[1]。引起疼痛的原因很多，常見的如肩峰下滑囊及肩袖在肩部外展活動(dòng)時(shí)肱骨與肩峰發(fā)生撞擊導(dǎo)致的滑囊炎及肌腱退變。肩袖損傷導(dǎo)致的肱骨頭與肩胛骨活動(dòng)異常也可以導(dǎo)致肩關(guān)節(jié)發(fā)生撞擊而出現(xiàn)癥狀[2]。為了達(dá)到減輕疼痛和增加活動(dòng)度的目的，非手術(shù)治療肩關(guān)節(jié)撞擊綜合征目前常常采用無負(fù)重休息、冷敷、理療、口服非甾體消炎藥(nonsteroidal anti-inflammatory drugs,NSAID)及注射皮質(zhì)激素等方法。國際的多中心研究表明，對采取休息等方法均無效的患者注射皮質(zhì)激素是一種有效手段，但其顯效的機(jī)制尚不明確[3-4]，其中廣為接受的一種解釋就是激素可以減輕無菌性炎癥反應(yīng)。但多次應(yīng)用激素的副作用是明顯的，常見的有岡上肌腱自發(fā)斷裂，注射局部皮膚萎縮及肱骨頭軟骨退變等。

局部注射激素對肩關(guān)節(jié)撞擊綜合征有效的原因是因?yàn)闇p輕了局部的炎癥反應(yīng)，那么局部注射NSAID是否也可以因?yàn)槠淇寡鬃饔毛@得良好療效的同時(shí)還可以避免激素的副作用？本研究的目的就是了解局部注射派瑞昔布鈉對減輕肩關(guān)節(jié)撞擊綜合征與激素的優(yōu)劣。

資 料 與 方 法

一、納入和排除標(biāo)準(zhǔn)

選取我院門診中確診為肩關(guān)節(jié)撞擊綜合征的患者。納入標(biāo)準(zhǔn)：(1)肩外展60°～120°時(shí)存在痛??；(2)Neer′s 癥陽性；(3)Hawkin′s 癥陽性；(4)B超或MRI診斷肩峰下滑囊炎。排除標(biāo)準(zhǔn)：(1)年齡<18歲；(2)病程<1個(gè)月；(3)過去3周有肩關(guān)節(jié)注射史；(4)既往有肩袖撕裂病史；(5)既往有肩關(guān)節(jié)骨性關(guān)節(jié)炎病史；(6)有全身炎癥反應(yīng)性疾?。?7)既往有患肩手術(shù)病史；(8)既往有患肩感染病史；(9)既往有肩關(guān)節(jié)黏連或不穩(wěn)定病史；(10)既往有消化道潰瘍及血液病史。

向每位納入研究的患者說明本研究的目的、方法，需要采集的個(gè)人信息，可能發(fā)生的問題，并簽署知情同意書。本研究經(jīng)天津市第五中心醫(yī)院倫理委員會(huì)批準(zhǔn)實(shí)施。

二、研究設(shè)計(jì)

本研究為隨機(jī)對照試驗(yàn)，為確保雙盲，納入患者由門診醫(yī)師開具局部注射醫(yī)囑后，由一位固定藥師進(jìn)行注射藥物開具及配制，隨機(jī)采用信封法(由患者抽取信封)。配置好的兩種藥物：(1)激素組：40 mg曲安奈德(昆明積大制藥有限公司)加入2%的利多卡因(中國大冢制藥公司)配置到5 ml；(2)NSAID組：派瑞昔布鈉(輝瑞制藥有限公司)加入2%利多卡因配制到5 ml。吸入5 ml注射器并由藥師編號記錄(外加封套無法看到內(nèi)容物)后由開具醫(yī)囑的醫(yī)師完成局部注射。每位患者均采用標(biāo)準(zhǔn)的注射方法，后外側(cè)“軟點(diǎn)”作為進(jìn)針點(diǎn)，肩峰后角向下2 cm，向外1 cm進(jìn)針，指向喙突的方向。注射完成后，肩關(guān)節(jié)外展活動(dòng)時(shí)疼痛減輕作為注射位置正確的標(biāo)志。

三、評價(jià)指標(biāo)

由本文第一作者和第二作者分別對每一位患者注射前、注射后30 min，注射后3周肩關(guān)節(jié)活動(dòng)度(外展)、HSS評分、疼痛(VAS評分)進(jìn)行評估及記錄，完成后每一位患者取兩位醫(yī)師評估和記錄的平均值。

四、統(tǒng)計(jì)學(xué)分析

兩組間結(jié)果的比較采用雙側(cè)t檢驗(yàn)，P<0.05為差異有統(tǒng)計(jì)學(xué)意義。根據(jù)樣本量公式計(jì)算所需的每組患者數(shù)，兩組各需納入14例患者。

結(jié) 果

2012年10月至2014年9月，59例確診為肩關(guān)節(jié)撞擊綜合征患者進(jìn)入研究，經(jīng)納入和排除標(biāo)準(zhǔn)評價(jià)后48例患者入組。隨機(jī)分為激素注射組和NASID注射組，每組24例，4例失訪(激素組2例，NSAID組2例)，2例沒有按時(shí)隨訪(激素組1例，NSAID組1例)，7例注射后2周MRI檢查發(fā)現(xiàn)為肩袖撕裂(激素組2例，NSAID組3例)，最終獲得完全隨訪37例(激素組19例，NSAID組18例)均行MRI或超聲檢查，明確沒有肩袖撕裂。兩組患者一般資料見表1。

表1 納入患者一般資料匯總

兩種藥物注射組均在注射后3周隨訪時(shí)兩種藥物均顯示出明顯的疼痛減輕(NSAID組1.12±2.11，P=0.04；激素組1.48±2.97，P=0.05)，但兩種藥物相比疼痛減輕差異無統(tǒng)計(jì)學(xué)意義(P=0.170)。與注射前相比，3周隨訪時(shí)NSAID注射組肩關(guān)節(jié)HSS評分與注射前相比差異有統(tǒng)計(jì)學(xué)意義(P=0.02)；激素組HSS評分與注射前相比差異無統(tǒng)計(jì)學(xué)意義(P=0.143)(圖1)。NSAID組與激素組外展功能均較術(shù)前有明顯改善，差異均有統(tǒng)計(jì)學(xué)意義(NSAID組P=0.03；激素組P=0.04)，其中3周隨訪時(shí)，NSAID組肩關(guān)節(jié)外展度大于激素組，P=0.03(圖2)。

注：NSAID為非甾體消炎藥圖1 激素組與NSAID組HSS評分比較

注：NSAID為非甾體消炎藥圖2 激素組與NSAID組肩外展度比較

討 論

我們通過在肩峰下間隙注射NSAID來獲得局部的無菌性炎癥的抑制區(qū)，從而達(dá)到治療肩關(guān)節(jié)撞擊綜合征的目的。國外研究已有局部注射NSAID治療肩關(guān)節(jié)撞擊綜合征的報(bào)道，但均是和安慰劑組相比，缺乏與其他有效治療手段之間的比較。派瑞昔布鈉是近年來推出的NSAID鎮(zhèn)痛效果較好的藥物，其具有選擇性抑制COX-2來抑制前列腺素合成的作用，同時(shí)對心血管及胃腸道安全性以及副作用方面優(yōu)于其他NSAID。人工膝關(guān)節(jié)置換后，局部注射的“雞尾酒”鎮(zhèn)痛劑就包含此藥物。本研究通過隨機(jī)對照實(shí)驗(yàn)的方法，證明了局部注射派瑞昔布鈉和激素具有同樣的鎮(zhèn)痛效果，而3周隨訪時(shí)，肩關(guān)節(jié)活動(dòng)度的改善優(yōu)于注射激素組。

肩關(guān)節(jié)撞擊綜合征的病因很多，常見的為肩峰下肌腱、滑囊炎，肩峰形態(tài)異常，肩峰下骨贅形成，肩鎖關(guān)節(jié)炎等[5]。近年來隨著肩關(guān)節(jié)外科的發(fā)展，肩袖損傷導(dǎo)致的肱骨頭上移，肩胛骨位置異常等原因也逐漸被認(rèn)為是肩關(guān)節(jié)撞擊的病因[6]。上述原因引起的局部組織炎性改變，充血水腫，導(dǎo)致肩關(guān)節(jié)活動(dòng)受限。部分肩峰撞擊征患者通過有效地保守治療可以獲得很好地疼痛減輕和功能恢復(fù)，避免了因病情加重而帶來的手術(shù)治療。保守治療的方法包括局部理療、手法康復(fù)、注射激素、口服NSAID(2～4周)，但療效孰優(yōu)孰劣尚無定論。Cochrane協(xié)作組發(fā)表的系統(tǒng)綜述中也提到，局部注射激素是治療肩關(guān)節(jié)撞擊綜合征的有效方法，但其療效不一定優(yōu)于口服NSAID[4]。

盡管局部注射激素已經(jīng)被證明在治療肩關(guān)節(jié)撞擊綜合征中是有效的，但激素帶來的副作用遠(yuǎn)超過我們的想象。以往認(rèn)為局部應(yīng)用激素是安全的觀點(diǎn)早已被否定，局部注射激素帶來的肱骨頭軟骨退變、岡上肌腱萎縮和自發(fā)斷裂等逐漸引起肩關(guān)節(jié)外科醫(yī)師的重視[7-8]。臨床中局部注射NSAID尚沒有見到影響關(guān)節(jié)軟骨和肌腱組織的報(bào)道，很多動(dòng)物實(shí)驗(yàn)證實(shí)，即使將NSAID注入軟骨內(nèi)，也不會(huì)引起軟骨性狀的改變[9]。一些基礎(chǔ)實(shí)驗(yàn)發(fā)現(xiàn)，NSAID對成纖維細(xì)胞的增殖沒有任何作用，而對于其成熟和塑形具有一定的影響，但影響的程度目前尚不明了[10]。因此局部注射NSAID的安全性明顯優(yōu)于激素。

局部注射激素和NSAID均具有減輕注射區(qū)域炎癥反應(yīng)的效果，雖然其作用機(jī)制不同，但肩關(guān)節(jié)撞擊綜合征導(dǎo)致活動(dòng)受限和疼痛的原因都是局部炎癥反應(yīng)，有效抑制局部炎癥就能獲得較好的治療效果。通過本研究，證明了局部注射派瑞昔布鈉具有與激素相同甚至更好的止痛效果，3周后患者肩關(guān)節(jié)活動(dòng)度的改善優(yōu)于激素組。當(dāng)然肩峰下注射NSAID并非能夠改變肩關(guān)節(jié)撞擊綜合征的病程，但減輕疼痛和水腫后，患者可以配合更好的功能康復(fù)，增加肩袖肌的力量，恢復(fù)正常的肩峰下間隙，從而減少甚至消除撞擊的發(fā)生。

本研究存在隨訪時(shí)間短，失訪患者數(shù)量多，僅在肩峰下注射1次，未對肩峰形態(tài)進(jìn)行分類等不足。

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(本文編輯：李靜)

郁凱，楊劍，劉敏，等.肩峰下間隙藥物注射治療肩關(guān)節(jié)撞擊綜合征療效[J/CD]. 中華肩肘外科電子雜志,2015,3(3):146-150.

Analysis on the curative effects of subacromial space drug injection therapy on shoulder impingement syndrome

YuKai1,YangJian1,LiuMin2,YangJie1,YangRenjun1,ZhangDianying1,3.

1DepartmentofOrthopedics,TianjinFifthCentralHospital,Tianjin300450,China;2Departmentofpharmacy,TianjinFifthCentralHospital,Tianjin300450,China;3DepartmentofOrthopedicsandTrauma,People′sHospital,PekingUniversity,Beijing100044,China

ZhangDianying,Email:zdy8016@163.com

Background The common symptoms of shoulder impingement syndrome include shoulder pain and shoulder activity limitation, and shoulder pain is the chief complaint of majority of patients. There are many causes for shoulder pain, and the common causes include bursitis and tendon degeneration which are resulted from the impingement between subacromial bursa/rotator cuff and humerus/ acromion in the abduction activity of shoulder. The abnormal activity of humeral head and scapula which is resulted from rotator cuff injury may also cause shoulder impingement and generate symptoms. To alleviate pain and increase joint range of motion, such methods as no-load rest, cold compress, physical therapy, oral administration of nonsteroidalanti-inflammatory drugs (NSAID) and injection of cortical hormone are adopted for non-operational treatment of shoulder impingement. An international multicenter study shows that, injection of cortical hormone is an effective means for the patients for whom the other methods such as rest are ineffective without exception. However, the mechanism of its significant effect has not been made clear, and an widely accepted interpretation to its mechanism is that hormone can relieve sterile inflammatory reaction. However, the adverse effects of application of hormone for many times are obvious, and the common adverse effects include spontaneous rupture of supraspinatus tendon, skin atrophy on local injection site and cartilage degeneration at humeral head etc. The reason why local injection of hormone is effective in treatment of shoulder impingement syndrome is that hormone can relieve local inflammatory reaction. Then, whether local injection of NSAID can also avoid the adverse effects resulted from hormone in the mean time of achieving good curative effects thanks to its anti-inflammatory action? It is the objective of this study to know the effects of local injection of parecoxib sodium in reducing shoulder impingement syndrome as well as the advantages and disadvantages of hormone.Methods Ⅰ. Inclusion and exclusion criteria:The patients with shoulder impingement syndrome confirmed in Outpatient department of our hospital were selected. The inclusion criteria：(1) there exists painful arc when shoulder is abduced by 60°-120°; (2) Neer′s disease positive; (3) Hawkin′s disease positive; (4) subacromial bursitis confirmed through B ultrasound or MRI. Exclusion criteria：(1) Age <18 years; (2) course of disease <1 month; (3) has history of shoulder joint injection in the past 3 weeks; (4) has past history of rotator cuff tear; (5) Has past history of shoulder osteoarthritis; (6) Has systemic inflammatory reaction disease; (7) Has past history of shoulder operation; (8) has past history of shoulder infection; (9) has past history of shoulder joint adhesion or instability; (10) has past history of alimentary tract ulcer and hematopathy. For each patient included in this study, our hospital described the objective and method of this study, the personal information to be acquired, the probable problems and signed informed consent. This study was performed upon approval by the Ethics Committee of Tianjin No.5 Central Hospital. Ⅱ. Study design:This study is a randomized control test. To ensure double blind trial, after the clinic doctor has issued medical advice for local injection, the patients included in study should take medicine from pharmaceutist; one fixed pharmaceutist should issue and prepare the drug for injection, and randomized evelop method is adopted (envelops randomly drawn by patients). Two kinds of drugs are prepared: (1) Hormone group: To 40mg Triamcinolone acetonide(provided by Kunming Jida Pharmacy Co.,Ltd), add 2% lidocaine(China Otsuka Pharmaceutical Co., Ltd), prepare the solution to 5 ml; (2) NSAID group: Add 2% lidocaine to Parecoxib sodium (Pfizer Pharmaceuticals Limited), and prepare the solution to 5ml. The drug is sucked into a 5 ml syringe. After the pharmacist has made numbering and recording (the content cannot be seen since envelope is added), the doctor who issued the medical device should complete local injection. Each patient is injected according to standard injection method. The "soft spot" on posterior-lateral side serves as the needle insertion point, and needle is inserted from posterior angle of acromion and inserted downwards by 2 cm and outwards by 1cm, pointing to the direction of coracoid. After completion of injection, pain relief in the abduction of shoulder joint is used as the mark of correct injection position. Ⅲ. Evaluation indicators:For each patient, the first author and the second author of this article respectively make evaluation and recording for the shoulder joint range of motion(abduction), HSS score and ache (VAS score) at 30 min prior to injection, 30 min after injection and 3 weeks after injection; After completion of evaluation and recording, for each patient, take the mean value evaluated and recorded by two physicians.Ⅳ. Statistical analysis：For the comparison on the results between two groups, two sided t test is performed. IfP<0.05, it is meant that the different has statistical significance. According to the Equation for sample size, calculate the required number of patients in each group. Two groups need to respectively include 14 patients.Results During the period from October 2012 to September 2014, 59 patients with confirmed shoulder impingement syndrome entered the study; After evaluation based on inclusion/exclusion criteria, 48 patients were incorporated into the study groups. Every 24 cases were randomly divided into hormone injection group and NASID injection group, 4 cases lost to follow up (2 cases in hormone group and 2 cases in NSAID group); 2 cases failed to receive follow-up visit on schedule (1 case in hormone group and 1 case in NSAID group). Through MRI at 2 weeks after injection, 7 case were confirmed as rotator cuff tear (2 cases in hormone group and 3 cases in NSAID group). Finally, 37 cases obtained complete follow-up visit (19 cases in hormone group and 18 cases in NSAID) and

MRI or ultrasonic examination, and it was made clear that they did not suffer from rotator cuff tear. Both drug injection groups received follow-up visit at 3 week after injection, when both drugs shown obvious ache relief (NSAID group:1.12±2.11,P=0.04; hormone group:1.48±2.97,P=0.05). However, there was no difference in ache relief when two kinds of drugs were compared (P=0.170). In the 3-week follow-up visit, the difference of shoulder joint HSS score of NSAID injection group in comparison with the value prior to injection has statistical significance (P=0.143). Both NSAID group and hormone group shown obvious improvement in abduction function in comparison with the abduction function prior to operation, with both differences having statistical significance (NSAID group:P=0.03;hormone groupP=0.04). In the 3-week follow-up visit, the shoulder joint abduction range of NSAID group is greater than that of hormone group, withP=0.03.Conclusion Injection of hormone and NSAID drug under acromion can help relieve the pain of patient with shoulder impingement syndrome. The shoulder joint range of motion and HSS score of NSAID injection group are superior to those of hormone group.

Shoulder impingement syndrome;Nonoperative treatment;Nonsteroidal anti-inflammatory drugs;Corticosteroids

10.3877/cma.j.issn.2095-5790.2015.03.004

天津市濱海新區(qū)衛(wèi)生局科技項(xiàng)目(2011BHKY008、2012BWKZ002、2013BWKY009)；衛(wèi)生公益性行業(yè)

300450天津市第五中心醫(yī)院骨科1，藥劑科2；100044北京大學(xué)人民醫(yī)院創(chuàng)傷骨科3

張殿英，Email:zdy8016@163.com

2014-12-16)

科研專項(xiàng)(201002014、201302007)；教育部創(chuàng)新團(tuán)隊(duì)(IRT1201)；北京市科委重大專項(xiàng)基金(Z101107052210001)