江小成 魯誼 姜春巖

通訊作者：姜春巖，Email:chunyanj@hotmail.com

【摘要】目的比較帕瑞昔布及鎮(zhèn)痛泵對肩關節(jié)鏡外科術后早期的鎮(zhèn)痛療效及安全性。方法選取2011年8月到2012年5月肩關節(jié)鏡外科手術患者178例，根據(jù)患者自主選擇分為肌注帕瑞昔布(40 mg)組(54例)、自控靜脈鎮(zhèn)痛泵組(105例)及空白對照組(19例)，采用疼痛視覺模擬評分法評估患者術后3 d靜止相及活動相的疼痛情況，并觀察用藥組患者術后早期的不良反應情況。結果在鎮(zhèn)痛效果的研究中，用藥組患者術后早期的疼痛評分相比于空白對照組患者顯著降低，而帕瑞昔布的鎮(zhèn)痛效果顯著優(yōu)于鎮(zhèn)痛泵，且帕瑞昔布組的不良反應率顯著低于鎮(zhèn)痛泵組。結論帕瑞昔布具有高效和安全的鎮(zhèn)痛特性，適用于肩外科手術后鎮(zhèn)痛。

【關鍵詞】 帕瑞昔布； 鎮(zhèn)痛泵； 肩肘外科； 關節(jié)鏡； 對照研究

【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

對于肩關節(jié)患者而言，術后康復與治療效果密切相關。由于肩肘關節(jié)均為全身活動度較大的關節(jié)，一旦出現(xiàn)關節(jié)囊攣縮或粘連，必定會影響到肩肘關節(jié)各方向的運動，而患者術后早期的功能鍛煉可有效避免類似情況的發(fā)生，從而達到較滿意的手術療效。這種早期的功能鍛煉需建立在患者術后少痛或無痛的基礎之上，所以，如何緩解術后早期疼痛對于肩肘外科術后患者顯得尤為重要[1-2]。

目前骨科臨床中最常用的術后鎮(zhèn)痛方式為以阿片類藥物為主的自控靜脈鎮(zhèn)痛泵(PCIA)。近年來，越來越多的研究顯示，阿片類藥物并非理想的骨科術后鎮(zhèn)痛藥，其對運動痛的療效較差，并不利于患者術后早期的功能鍛煉，且術后應用阿片類藥物可引發(fā)惡心、嘔吐、眩暈、呼吸抑制、尿潴留、成癮等不良反應[3-5]，因此，選擇性環(huán)氧合酶-2(COX-2)抑制劑帕瑞昔布在外科手術后得到廣泛的應用[6-8]。

本研究的目的是比較帕瑞昔布及阿片類藥物為主的PCIA對肩肘外科關節(jié)鏡下手術術后早期鎮(zhèn)痛療效。

資料與方法

一、研究對象

本研究選取2011年8月至2012年5月間于我科就診患有肩袖損傷、肩關節(jié)不穩(wěn)定或肘關節(jié)粘連，并于肩、肘關節(jié)鏡下行手術修復的患者。排除標準：既往有肩肘關節(jié)病史及手術史患者、就診前有長期服用鎮(zhèn)痛藥史患者、肝腎功能損傷或存在活動性消化道潰瘍等不適宜進行此項研究的患者。共納入研究對象178例，其中男性104例，女性74例；年齡12～78歲，平均44.45歲。手術均于插管全麻下進行，術后根據(jù)患者自主選擇分為帕瑞昔布組(54例，30.3%)、鎮(zhèn)痛泵組(105例，59.0%)和 空白對照組(19例，10.7%)。

二、試劑與方法

鎮(zhèn)痛泵由麻醉醫(yī)師術后給患者配戴，其由100 ml生理鹽水、100 μg舒芬太尼注射液及8 mg歐貝注射液組成,其中舒芬太尼注射液由宜昌人福藥業(yè)有限責任公司生產(chǎn)，每支2 ml(100 μg)，給藥劑量為5 ml/h，可自控給藥，一次2 ml，最短時間間隔為15 min；注射用帕瑞昔布鈉(商品名特耐)每日40 mg肌內(nèi)注射給藥，由美國輝瑞制藥有限公司生產(chǎn)，每支40 mg。

采用疼痛視覺模擬評分法(VAS)評估患者疼痛情況。方法為用一把刻有0～10分的標尺，0分代表不痛，10分為最痛，1～3分為輕度疼痛，4～6分為中度疼痛，7～10分為重度疼痛。解釋完畢后讓患者在直尺上標出能代表自己當前疼痛程度的相應位置，而研究者則根據(jù)患者標出位置評出相應分數(shù)并登記。

所有178例患者在就診時由同一名研究者對其進行詳細病史采集，包括所患疾病、年齡、性別、身高、體質(zhì)量、病程、生活習慣、術前疼痛評分等，然后評估患者術后當天(距離手術結束時間>4 h)、術后第1天、術后第2天、術后第3天的VAS評分，其中VAS評分包括患者靜止時的疼痛評分以及患者術后早期康復活動時的疼痛評分；在評估疼痛反應的同時，記錄患者術后早期的不良反應，主要包括惡心、嘔吐等胃腸道癥狀、呼吸抑制、少尿、心臟異常、代謝異常、水腫、視覺模糊、尿潴留、嗜睡、眩暈、血小板減少、過敏等，一旦出現(xiàn)患者難以耐受的并發(fā)癥，給予停用鎮(zhèn)痛藥處理。

表1 3組肩肘疾病患者修復術前臨床基本情況對比

表2 3組肩肘疾病患者修復術后不同時間靜止相和活動相的疼痛評分

注：與帕瑞昔布組比較，aP<0.05

表3 3組肩肘疾病患者修復術后不同時間靜止相和活動相的疼痛緩解程度對比

注：與帕瑞昔布組比較，aP<0.05

三、統(tǒng)計學分析方法

結 果

3組患者術前基本情況對比，顯示患者在年齡、性別、病程、生活習慣、體質(zhì)量指數(shù)、病種等方面差異均無統(tǒng)計學意義，詳見表1。3組患者術后疼痛評分結果(表2)顯示，對于靜止相，未使用鎮(zhèn)痛藥的患者相比于使用鎮(zhèn)痛藥的患者疼痛評分均顯著偏高，而鎮(zhèn)痛泵組患者術后早期疼痛評分比帕瑞昔布組患者顯著偏高。為了研究這3組患者術后早期疼痛緩解的程度，我們將患者術后前3天的疼痛評分分別與術后當天的疼痛評分相減后再進行組間對比，結果(表3)顯示，帕瑞昔布組患者術后早期疼痛緩解程度明顯優(yōu)于鎮(zhèn)痛泵組患者；用藥組患者不良反應率結果(表4)顯示，在鎮(zhèn)痛泵組中，共有33例(31.4%)患者出現(xiàn)了不良反應；而在帕瑞昔布組中，只有6例(11.1%)患者出現(xiàn)了不良反應，兩組差異有統(tǒng)計學意義(P<0.05)。

表4 兩組用藥的肩肘疾病患者修復術后不良反應發(fā)生情況(例數(shù))

討 論

目前，對于骨骼肌肉損傷患者而言，術后PCIA已經(jīng)廣泛用于骨科術后鎮(zhèn)痛，而鎮(zhèn)痛泵中多采用傳統(tǒng)阿片類藥物，如芬太尼。其作用于脊髓后角，可抑制疼痛信息發(fā)生，屬強效麻醉性鎮(zhèn)痛藥，具有起效快、鎮(zhèn)痛強、持續(xù)時間較短的特點，可用于麻醉前、中、后的鎮(zhèn)靜與鎮(zhèn)痛，也用于各種原因引起的疼痛，但芬太尼在阻斷疼痛信息傳遞的同時還可產(chǎn)生脊髓以上鎮(zhèn)痛,并容易引起呼吸抑制和較輕的惡心嘔吐、嗜睡、皮膚瘙癢、尿潴留、視覺模糊、發(fā)癢、心率減慢和藥物依賴性等不良反應，且這種不良反應與劑量呈正相關[9]。Ekman等[4]發(fā)現(xiàn)，阿片類鎮(zhèn)痛藥還可激活體內(nèi)的促傷害機制，導致機體對疼痛的敏感性增強，從而誘發(fā)痛覺過敏反應。且單獨應用阿片類藥物對運動痛的療效較差，不利于術后早期鍛煉和功能恢復。所以，隨著研究的深入，越來越多學者認為阿片類藥物并非為肩肘外科術后理想鎮(zhèn)痛藥。

不同于阿片類麻醉劑，非甾體抗炎藥可抑制中樞神經(jīng)及外周神經(jīng)內(nèi)COX的活性，而COX-1和COX-2是人體內(nèi)催化花生四烯酸轉化成前列腺素的限速酶，所以非甾體抗炎藥可最終通過降低損傷部位周圍前列腺素含量，以達到鎮(zhèn)痛目的[10-11]。同時前列腺素合成的減少也可降低組織的炎癥反應程度，從而使受傷關節(jié)較快恢復活動性并可開展康復運動，減少組織愈合期間的腫脹及出血。因此非甾體類抗炎藥被廣泛用于骨科術后的鎮(zhèn)痛。

通過對3組患者術后前3天的疼痛評分對比，發(fā)現(xiàn)帕瑞昔布在術后早期的鎮(zhèn)痛效果優(yōu)于PCIA，而術后當天疼痛反應并無顯著性差異，這可能與鎮(zhèn)痛藥物的藥物起效時間較長有關；同時，為了降低患者疼痛評分時初始評分的差異性對試驗的影響，我們將患者術后前3天的疼痛評分分別與術后當天的疼痛評分相減后，得出疼痛緩解程度評分，再進行3組患者間的組間對比，得出的結果相似，帕瑞昔布在術后前3天的疼痛緩解程度也比鎮(zhèn)痛泵效果好。

對于用藥組間的不良反應率，鎮(zhèn)痛泵組患者不良反應率為31.4%，而帕瑞昔布組患者的不良反應率僅為11.1%，同時我們發(fā)現(xiàn)，較高的不良反應率會直接影響患者的鎮(zhèn)痛效果。應用帕瑞昔布產(chǎn)生的不良反應率要遠低于阿片類藥物，表明帕瑞昔布對骨科術后患者具有良好的安全性。兩組患者的主要不良反應均為惡心、嘔吐等胃腸道反應，屬輕度不良反應，重度不良反應如電解質(zhì)紊亂、呼吸抑制、心率增快等則較少，表明2種鎮(zhèn)痛藥物在骨科術后均有較高的安全性及應用價值。

本研究也有不足之處：(1)本次研究并沒有對患者進行長期隨訪，并且沒有就藥物對愈合過程產(chǎn)生的影響進行進一步的研究；(2)本次研究的分組是根據(jù)患者的自主選擇決定，并未采取隨機分組，這可能對結果產(chǎn)生一定影響；(3)本次研究的循證等級較低，可在之后開展更高等級(LEVEL Ⅱ以上)的研究。

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