帕瑞昔布与静脉镇痛泵对肩关节镜外科术后早期镇痛疗效的病例-对照研究

江小成 鲁谊 姜春岩

通讯作者：姜春岩，Email:chunyanj@hotmail.com

【摘要】目的比较帕瑞昔布及镇痛泵对肩关节镜外科术后早期的镇痛疗效及安全性。方法选取2011年8月到2012年5月肩关节镜外科手术患者178例，根据患者自主选择分为肌注帕瑞昔布(40 mg)组(54例)、自控静脉镇痛泵组(105例)及空白对照组(19例)，采用疼痛视觉模拟评分法评估患者术后3 d静止相及活动相的疼痛情况，并观察用药组患者术后早期的不良反应情况。结果在镇痛效果的研究中，用药组患者术后早期的疼痛评分相比于空白对照组患者显著降低，而帕瑞昔布的镇痛效果显著优于镇痛泵，且帕瑞昔布组的不良反应率显著低于镇痛泵组。结论帕瑞昔布具有高效和安全的镇痛特性，适用于肩外科手术后镇痛。

【关键词】 帕瑞昔布； 镇痛泵； 肩肘外科； 关节镜； 对照研究

【Abstract】BackgroundPostoperative rehabilitation is closely related to the treatment effect of the arthroscopic shoulder operation. Articular contracture or adhesion in shoulder and elbow may result in limited mobility of these large joints. However, early postoperative functional exercise can effectively avoid the limitation of joint motion, and further satisfactory surgical outcomes may be achieved. Such early functional exercise should be based on less postoperative pain or painlessness. Therefore, it is very important to alleviate their early postoperative pain for these patients with the shoulder surgery. At present, a patient-controlled intravenous analgesia (PCIA) pump with opioids is commonly used for the postoperative analgesia in orthopaedics. In recent years, increasing studies have shown that opioids are not the ideal postoperative orthopaedic analgesic for its poorer curative effect of the pain derived from movement, which is not good for patients′ early postoperative functional exercise. Postoperative opioid analgesia can also cause nausea, vomiting, dizziness, respiratory depression, urinary retention, addiction and other adverse reactions. Therefore, selective cox-2 inhibitors-parecoxib has been widely used in surgery.The purpose of this study was to compare the early postoperative analgesia effect of parecoxib with PCIA using opioid for postoperative analgesia of the arthroscopic shoulder-elbow surgery.MethodsThis study selected patients with rotator cuff injury or shoulder instability treated by shoulder arthroscopy from August 2011 to May 2012 in our department. The exclusion criteria include:history of shoulder or elbow surgery, long-term use of analgesics, liver and kidney disfunction, active peptic ulcer patients and other inappropriate patients for the study. A total of 178 cases, including 104 male and 74 female, aged 12 to 78 years old (average 44.45 years), were performed under general anesthesia. According to the patients′ choice, they were divided into the parecoxib group( 54 patients,30.3%), the analgesia pump group (105 patients, 59.0%), and the control group ( 19 patients,10.7%). Degree of pain and results of treatment were estimated using the visual analogue scale (VAS). The specific methods were operated with a scaleplate engraved with 0-10. In this scale 0 signified no pain,10 signified the most painful,1-3 were regarded as mild pain,4-6 was moderate pain, 7-10 was severe pain. After the explanation of the ruler representing their current level of pain, patients selected their corresponding scores, and the researcher registered the scores according to the scaleplate.Medical history collection of all 178 patients was operated by the same research, including their specific diseases, age, gender, height, weight, duration of the disease, living habits, preoperative pain score and so on, and the VAS scores on the day of surgery (>4 hours after operation), the first, sencond and third postoperative days were evaluated, respectively. Generally speaking,VAS scores included the pain scores of resting and those during their early postoperative rehabilitation. In evaluating the pain response, early postoperative adverse reactions should be recorded, including gastrointestinal symptoms such as nausea and vomiting, respiratory depression, oliguria, cardiac abnormalities, metabolic abnormalities, edema, blurred vision, urinary retention, drowsiness, dizziness, thrombocytopenia, allergies, etc. Once the unbearable complications appeared, analgesics should be stopped. Statistical analysis was performed using SPSS version 17.0. All data were presented as the mean±SEM. Differences between groups were analyzed by a two-way analysis of variance, and considered statistically significant, if the p value was less than 0.05.ResultsPreoperative and postoperative data of all the patients presented no statistical differences of age, sex, course, living habits, BMI, diseases and so on, were found in these three groups.The drug administration resulted in lower postoperative pain intensity compared with the control group. Moreover, the parecoxib 40 mg group presented better postoperative pain relief and less adverse effects than the PCIA group during the first 3 days after operation. In order to study their early postoperative pain relief of the three groups, we compared the results that the pain scores of their first three postoperative days minus that on the day of operation, respectively. The results showed that the parecoxib group presented better postoperative pain relief than the PCIA group. Drug adverse reactions were found in 33 out of 105 patients (31.4%) of the analgesia pump group, but only 6 out of 54 patients (11.1%) in the parecoxib group had those adverse reactions. The differences were statistically significant (P<0.05).DiscussionAt present, PCIA has been widely performed in orthopaedic postoperative analgesia for the patients of skeletal and muscle injuries. Fentanyl was one of the most common analgesics among the traditional opioid drugs with the use of the analgesia pump. It acted on the posterior horn of spinal cord, reduced occurance of pain information, and might be a potent narcotic analgesics with characteristics of strong and quick effects, short duration and so on. It can be used in pain of a variety of causes. However, during blocking pain information transmission, fentanyl could produce above-spinal analgesia, accompanied with adverse reactions, such as respiratory depression, reduced gastrointestinal peristalsis, somnolence, nausea and vomiting, calm, skin itching, urinary retention, blurred vision,slow heart rate and drug dependence, and so on. Moreover, these adverse reactions are positively related with dose. Ekman found that opioid analgesics can also activate the damage mechanism of body, which results in the intensified body′s sensitivity to pain and induction of hyperalgesia. The curative effect of opioid is poor for the sport pain, which is not good for their early postoperative exercise and functional recovery. So, with the deepening of the research, more and more scholars believe that opioids are not the ideal analgesics for the shoulder-elbow surgery.Unlike the opioid narcotics, non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit the activity of cyclooxygenase (COX-1 and COX-2) in central nervous system and peripheral nerve system. The cyclooxygenase enzyme is a rate-limiting enzyme of catalyzing arachidonic acid into prostaglandin (PGs), so NSAIDs can reduce prostaglandin around the injuried part and further achieve analgesia. Therefore, NSAIDs can be widely used in postoperative orthopaedic analgesia. The research included 178 patients with an average age of 44. Three groups of patients did not show significant differences in the preoperative general data. Howerver, comparison of their postoperative pain scores in the first three days presented the parecoxib group had better postoperative pain relief than the PCIA group. And no significant difference of the postoperative pain on the operating day was found, which may be related to the long-term analgesic effect. At the same time, in order to reduce the influence of the patients′ difference, we subtracted the pain scores on the operating day from the postoperative pain scores in the first three days. The results are similar, the parecoxib group demonstrated better postoperative pain relief than the PCIA

group during the first three postoperative days.The adverse reaction rate of the analgesia pump group was 31.4%, and the rate in parecoxib group was only 11.1%. At the same time, we found that the higher rate of adverse reactions would directly affect the analgesic effects of the patients. The study showed that the parecoxib group had a much lower adverse reaction rate than the opioids group, implying that parecoxib was more effective and safer for patients with orthopaedic surgery. Data of the adverse reaction distribution revealed that the two treatment groups only had mild adverse reactions, gastrointestinal reactions such as nausea and vomiting, but not the severe adverse reactions, including electrolyte disorders, respiratory depression,arhythmia. Obviously，the two analgesic drugs had high security and application in orthopaedic surgery.Also, this study had some shortcomings:(1)The study did not complete long-term follow-up, and the influence of the drugs on the healing process was not further discussed. (2)The groups in this study were determined according to the patient′s choice, not by random, which may impact the results. (3)The level of evidence-based study was low, and higher level studies (level Ⅱ or above) can be performed in the future.ConclusionsFor the early postoperative analgesia of shoulder arthroscopic surgery, parecoxib has proved more effective and safer than the PCIA pump, which can be a better choice of analgesic in early rehabilitation exercise following the shoulder-elbow surgery.

【Keywords】 Parecoxib; Analgesia; Shoulder-elbow surgery; Arthroscopy; Control study

对于肩关节患者而言，术后康复与治疗效果密切相关。由于肩肘关节均为全身活动度较大的关节，一旦出现关节囊挛缩或粘连，必定会影响到肩肘关节各方向的运动，而患者术后早期的功能锻炼可有效避免类似情况的发生，从而达到较满意的手术疗效。这种早期的功能锻炼需建立在患者术后少痛或无痛的基础之上，所以，如何缓解术后早期疼痛对于肩肘外科术后患者显得尤为重要[1-2]。

目前骨科临床中最常用的术后镇痛方式为以阿片类药物为主的自控静脉镇痛泵(PCIA)。近年来，越来越多的研究显示，阿片类药物并非理想的骨科术后镇痛药，其对运动痛的疗效较差，并不利于患者术后早期的功能锻炼，且术后应用阿片类药物可引发恶心、呕吐、眩晕、呼吸抑制、尿潴留、成瘾等不良反应[3-5]，因此，选择性环氧合酶-2(COX-2)抑制剂帕瑞昔布在外科手术后得到广泛的应用[6-8]。

本研究的目的是比较帕瑞昔布及阿片类药物为主的PCIA对肩肘外科关节镜下手术术后早期镇痛疗效。

资料与方法

一、研究对象

本研究选取2011年8月至2012年5月间于我科就诊患有肩袖损伤、肩关节不稳定或肘关节粘连，并于肩、肘关节镜下行手术修复的患者。排除标准：既往有肩肘关节病史及手术史患者、就诊前有长期服用镇痛药史患者、肝肾功能损伤或存在活动性消化道溃疡等不适宜进行此项研究的患者。共纳入研究对象178例，其中男性104例，女性74例；年龄12～78岁，平均44.45岁。手术均于插管全麻下进行，术后根据患者自主选择分为帕瑞昔布组(54例，30.3%)、镇痛泵组(105例，59.0%)和 空白对照组(19例，10.7%)。

二、试剂与方法

镇痛泵由麻醉医师术后给患者配戴，其由100 ml生理盐水、100 μg舒芬太尼注射液及8 mg欧贝注射液组成,其中舒芬太尼注射液由宜昌人福药业有限责任公司生产，每支2 ml(100 μg)，给药剂量为5 ml/h，可自控给药，一次2 ml，最短时间间隔为15 min；注射用帕瑞昔布钠(商品名特耐)每日40 mg肌内注射给药，由美国辉瑞制药有限公司生产，每支40 mg。

采用疼痛视觉模拟评分法(VAS)评估患者疼痛情况。方法为用一把刻有0～10分的标尺，0分代表不痛，10分为最痛，1～3分为轻度疼痛，4～6分为中度疼痛，7～10分为重度疼痛。解释完毕后让患者在直尺上标出能代表自己当前疼痛程度的相应位置，而研究者则根据患者标出位置评出相应分数并登记。

所有178例患者在就诊时由同一名研究者对其进行详细病史采集，包括所患疾病、年龄、性别、身高、体质量、病程、生活习惯、术前疼痛评分等，然后评估患者术后当天(距离手术结束时间>4 h)、术后第1天、术后第2天、术后第3天的VAS评分，其中VAS评分包括患者静止时的疼痛评分以及患者术后早期康复活动时的疼痛评分；在评估疼痛反应的同时，记录患者术后早期的不良反应，主要包括恶心、呕吐等胃肠道症状、呼吸抑制、少尿、心脏异常、代谢异常、水肿、视觉模糊、尿潴留、嗜睡、眩晕、血小板减少、过敏等，一旦出现患者难以耐受的并发症，给予停用镇痛药处理。

表1 3组肩肘疾病患者修复术前临床基本情况对比

表2 3组肩肘疾病患者修复术后不同时间静止相和活动相的疼痛评分

注：与帕瑞昔布组比较，aP<0.05

表3 3组肩肘疾病患者修复术后不同时间静止相和活动相的疼痛缓解程度对比

注：与帕瑞昔布组比较，aP<0.05

三、统计学分析方法

结 果

3组患者术前基本情况对比，显示患者在年龄、性别、病程、生活习惯、体质量指数、病种等方面差异均无统计学意义，详见表1。3组患者术后疼痛评分结果(表2)显示，对于静止相，未使用镇痛药的患者相比于使用镇痛药的患者疼痛评分均显著偏高，而镇痛泵组患者术后早期疼痛评分比帕瑞昔布组患者显著偏高。为了研究这3组患者术后早期疼痛缓解的程度，我们将患者术后前3天的疼痛评分分别与术后当天的疼痛评分相减后再进行组间对比，结果(表3)显示，帕瑞昔布组患者术后早期疼痛缓解程度明显优于镇痛泵组患者；用药组患者不良反应率结果(表4)显示，在镇痛泵组中，共有33例(31.4%)患者出现了不良反应；而在帕瑞昔布组中，只有6例(11.1%)患者出现了不良反应，两组差异有统计学意义(P<0.05)。

表4 两组用药的肩肘疾病患者修复术后不良反应发生情况(例数)

讨 论

目前，对于骨骼肌肉损伤患者而言，术后PCIA已经广泛用于骨科术后镇痛，而镇痛泵中多采用传统阿片类药物，如芬太尼。其作用于脊髓后角，可抑制疼痛信息发生，属强效麻醉性镇痛药，具有起效快、镇痛强、持续时间较短的特点，可用于麻醉前、中、后的镇静与镇痛，也用于各种原因引起的疼痛，但芬太尼在阻断疼痛信息传递的同时还可产生脊髓以上镇痛,并容易引起呼吸抑制和较轻的恶心呕吐、嗜睡、皮肤瘙痒、尿潴留、视觉模糊、发痒、心率减慢和药物依赖性等不良反应，且这种不良反应与剂量呈正相关[9]。Ekman等[4]发现，阿片类镇痛药还可激活体内的促伤害机制，导致机体对疼痛的敏感性增强，从而诱发痛觉过敏反应。且单独应用阿片类药物对运动痛的疗效较差，不利于术后早期锻炼和功能恢复。所以，随着研究的深入，越来越多学者认为阿片类药物并非为肩肘外科术后理想镇痛药。

不同于阿片类麻醉剂，非甾体抗炎药可抑制中枢神经及外周神经内COX的活性，而COX-1和COX-2是人体内催化花生四烯酸转化成前列腺素的限速酶，所以非甾体抗炎药可最终通过降低损伤部位周围前列腺素含量，以达到镇痛目的[10-11]。同时前列腺素合成的减少也可降低组织的炎症反应程度，从而使受伤关节较快恢复活动性并可开展康复运动，减少组织愈合期间的肿胀及出血。因此非甾体类抗炎药被广泛用于骨科术后的镇痛。

通过对3组患者术后前3天的疼痛评分对比，发现帕瑞昔布在术后早期的镇痛效果优于PCIA，而术后当天疼痛反应并无显著性差异，这可能与镇痛药物的药物起效时间较长有关；同时，为了降低患者疼痛评分时初始评分的差异性对试验的影响，我们将患者术后前3天的疼痛评分分别与术后当天的疼痛评分相减后，得出疼痛缓解程度评分，再进行3组患者间的组间对比，得出的结果相似，帕瑞昔布在术后前3天的疼痛缓解程度也比镇痛泵效果好。

对于用药组间的不良反应率，镇痛泵组患者不良反应率为31.4%，而帕瑞昔布组患者的不良反应率仅为11.1%，同时我们发现，较高的不良反应率会直接影响患者的镇痛效果。应用帕瑞昔布产生的不良反应率要远低于阿片类药物，表明帕瑞昔布对骨科术后患者具有良好的安全性。两组患者的主要不良反应均为恶心、呕吐等胃肠道反应，属轻度不良反应，重度不良反应如电解质紊乱、呼吸抑制、心率增快等则较少，表明2种镇痛药物在骨科术后均有较高的安全性及应用价值。

本研究也有不足之处：(1)本次研究并没有对患者进行长期随访，并且没有就药物对愈合过程产生的影响进行进一步的研究；(2)本次研究的分组是根据患者的自主选择决定，并未采取随机分组，这可能对结果产生一定影响；(3)本次研究的循证等级较低，可在之后开展更高等级(LEVEL Ⅱ以上)的研究。

参 考 文 献

[1] Urbánek L, Karjagin V.Arthroscopic subacromial decompression- -personal experience and results[J].Acta Chir Orthop Traumatol Cech,2004，71(1):45-49.

[2] 徐建国.疼痛药物治疗学[M].北京：人民卫生出版社，2007：264-266,276.

[3] Skinner HB.Multimodal acute pain management[J].Am J Orthop (Belle Mead NJ),2004，33(5 Suppl):5-9.

[4] Ekman EF, Wahba M, Ancona F.Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery:a double-blind, placebo-controlled study[J].Arthroscopy,2006，22(6):635-642.

[5] Wheeler M, Oderda GM, Ashburn MA, et al.Adverse events associated with postoperative opioid analgesia:a systematic review[J].J Pain,2002,3(3):159-180.

[6] Ott E, Nussmeier NA, Duke PC, et al.Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery[J].J Thorac Cardiovasc Surg,2003,125(6):1481-1492.

[7] Niruthisard S, Werawataganon T, Bunburaphong P, et al.Improving the analgesic efficacy of intrathecal morphine with parecoxib after total abdominal hysterectomy[J].Anesth Analg,2007,105(3):822-824.

[8] Akaraviputh T, Leelouhapong C, Lohsiriwat V, et al.Efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy:a prospective, randomized study[J].World J Gastroenterol,2009,15(16):2005-2008.

[9] 庄心良,曾因明,陈伯銮.现代麻醉学[M].3 版.北京:人民卫生出版社,2003:514-515.

[10] Vane JR.Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs[J].Nat New Biol,1971,231(25):232-235.

[11] Villasís-Keever MA, Rendón-Macías ME, Escamilla-Núez A.Systematic review to assess the effectiveness and safety of parecoxib[J].Acta Ortop Mex,2009,23(6):342-350.