The effect of anesthesia on post-colonoscopy abdominal pain

研究背景: 大腸鏡檢查是一種確診及篩檢大腸癌的有力工具， 但在檢查後常會有腹部不適感。在已有的研究中，有人使用二氧化碳取代空氣作為鏡檢中充氣的主要氣體，因吸收較快，殘餘氣體較少，可減少腹部不適，有人則是在完成鏡檢時再次將大腸鏡深入盲腸將大腸內的氣體逐段抽出，也可減少此項副作用。顯示大腸內的殘餘氣體造成的腸道擴張對鏡檢後腹部不適扮演重要的角色。GABA、opioid、NMDA受器在大腸擴張的動物模型中，已知有參與內臟疼痛的傳遞和臟器痛覺敏感的形成，而且它們都是常用麻醉藥物的作用受器。另一方面，在大腸鏡檢中給予適度的鎮靜或止痛藥物已知可以減少病人在接受鏡檢時的緊張和不適感，但目前還未有相關的研究討論麻醉對大腸鏡檢後腹痛的影響。 研究目的: 在本研究中，我們試圖調查midazolam和alfentanil，各作用在GABA和opioid受器，用於大腸鏡檢麻醉時，是否會減少鏡檢後腹痛的發生率、嚴重度或持續時間。同時我們也研究在動物和人類實驗中皆可有效減少內臟疼痛或臟器痛覺敏感的ketamine，與midazolam和alfentanil合併使用時，是否會進一步影響大腸鏡檢後腹痛的狀況。 研究方法: 本研究的對象是接受全身健康檢查且其中包含大腸鏡檢的民眾。在第一階段的研究中，我們前瞻性地連續收集志願接受麻醉和拒絕麻醉的民眾資料。對志願接受麻醉的民眾我們會給予midazolam和alfentanil，拒絕麻醉的民眾則不會給予任何的止痛或麻醉藥物。結束鏡檢且清醒後，詢問且記錄是否有腹痛、其嚴重度(四等分，無、輕、中、重度)、及持續時間，直到離開醫院為止。同時也記錄是否有麻醉相關的副作用，如噁心、嘔吐、頭暈等。 在第二階段中，志願接受麻醉的民眾被隨機分配為兩組，一組接受和上述相同的麻醉藥物，另一組則另加每公斤體重0.2毫克的ketamine。在此階段中，同樣比較並記錄腹痛和麻醉相關副作用的情形。 研究結果: 在第一階段中，我們收集了494位民眾，其中374位志願接受麻醉，另外的120位則無。兩組間的年齡及身體質量指數大致相同，但接受麻醉的那一組的女性比例明顯較高(43.6% vs. 29.2%，p=0.005)，也有較多的比例有腹部手術的病史(28.3% vs. 16.6%，p=0.029)。所有程度腹痛的發生率在兩組間並無明顯差別，但麻醉的確會減少其中的中、重度腹痛的發生率(9.63% vs. 16.67%, p=0.026)。同時在有腹痛的民眾中，麻醉也會減少腹痛持續的時間(118.7±47.5 vs. 153.3 ±49.9分鐘，p<0.001)。有腹痛的比例在兩組間的差異隨著時間逐漸增加，約在鏡檢後120分鐘相差最大(16.03% vs. 33.33%，p=0.026)。使用多變數廻歸分析針對鏡檢後120分鏡的腹痛發生機會的影響分析，發現性別、腹部手術的病史、大腸鏡檢所花費的時間皆無明顯影響，而麻醉在矯正上述因素的可能干擾後，仍有明顯減生其發生機會的效果(odds ratio 0.43, 95% confidence interval 0.26 ~ 0.73)。 在第二階段的隨機試驗中，總共有151位民眾接受和上述相同的麻醉藥物，另外則有127位在一般藥物之外另加入ketamine。這兩組間，無論是年齡、性別、身高、體重、腹部手術病史的比例及大腸鏡檢所費時間皆無明顯差異。結果ketamine無法明顯減少腹痛的發生機率或持續時間，只會增加副作用，如嘔吐(3.15% vs. 0%, p=0.042)、頭暈(18.11% vs. 9.27%, p=0.031)的發生頻率。 結論: 使用midazolam和alfentanil做大腸鏡檢的麻醉時可以減少鏡檢後腹痛的嚴重度和持續時間。另加入ketamine會增加副作用，但對腹痛無進一步影響。Background: Colonoscopy is a powerful tool to screen and diagnose colon cancer. However, the residual gas used for extending colon usually results in abdominal discomfort after examination. Several methods including using CO2 instead of air for insufflation or total colonic decompression after colonoscopy were tried to decrease post-colonoscopy abdominal discomfort with different degree of success. It appears that the residual gas in the colon plays a major role in the persistence of abdominal pain. GABA, opioid, and NMDA receptors which are the targets of commonly used anesthetics, were found to be involved with the transmission of colon distension pain and the formation of visceral hyperalgesia in animal model. Anesthesia has been known to decrease the patients’ discomfort during colonoscopy but its effect on post-colonoscopy abdominal pain is yet to be clarified. Objective: In this study, we try to find out whether midazolam and alfentanil, as GABA and opioid receptor agonist respectively, used for sedation in colonoscopy, has any role in decreasing severity, incidence, or duration of post-colonoscopy abdominal pain. We also investigate if ketamine, promising in decreasing visceral hyperalgesia in human and animal models, had any impact in pain from colon distension after colonoscopy when used as an adjunct of anesthesia. Methods: The study recruited healthy patients having screen colonoscopy examination as part of their health checkup. In the first phase of study, we prospectively collected data of patients who chose to receive anesthesia or not by themselves. For those having anesthesia, midazolam and alfentanil were given during colonoscopy while those declining anesthesia received no analgesics or anesthetics. Severity (ordinal scale: 1=none, 4=severe) and duration of abdominal pain were recorded after exam and repeatedly measured during their stay in hospital. Side effects of anesthesia (nausea, vomiting, dizziness) colonoscopy were also recorded. In the second phase, the patients willing to have anesthesia were randomized to receive ketamine 0.2mg/kg or not after midazolam and alfentanil. The data about abdominal pain and anesthetic side effects were recorded as in the first phase. Result: The first phase enrolled 494 patients, including 374 with anesthesia and 120 without anesthesia. The anesthesia group had a higher proportion of women and the history of abdominal surgery (43.6% vs. 29.2%; 28.3% vs. 16.6%). While the incidence of abdominal discomfort including all degrees didn’t differ between the two groups, anesthesia did cause reduction in the incidence of moderate to severe pain (9.63% vs. 16.67%, p=0.026). In those did have abdominal discomfort, the duration was shorter with anesthesia (118.7±47.5 vs. 153.3 ±49.9minutes, p<0.001). The difference in the incidence of all abdominal pain became greater as the time progressed and was largest roughly at 120 minutes after exam (16.03% vs. 33.33%, p=0.026). Anesthesia didn’t produce higher incidence of side effect except dizziness (14.7% vs. 3.3%). Analyzing the influence on the risk of abdominal pain 120 minutes after exam by multivariate logistic regression, we found that anesthesia, but not the history of abdominal surgery, gender and the duration of colonoscopy, would decrease the risk (odds ratio 0.43, 95% confidence interval 0.26 ~ 0.73). In the second phase, we recruited 151 patients receiving standard anesthesia and another 127 patients having additional ketamine. The characteristics including age, gender distribution, height, weight, incidence of abdominal surgery and total exam time were not different in these two groups. While producing more frequent vomiting and dizziness (3.15% vs. 0%, p=0.042; 18.11% vs. 9.27%, p=0.031), 0.2mg/kg ketamine didn’t decrease the incidence of abdominal pain or the pain duration (56.69% vs. 54.3%, p=0.69; 121.55 ± 70.07 min vs. 108.93 ± 38.1 min, p= 0.172). Conclusions: Anesthesia with midazolam and alfentanil would reduce the severity and duration of abdominal pain after colonoscopy. The addition of ketamine had no effect on abdominal pain and induced more side effects.一 中文摘要 4 二 英文摘要 6 三 研究背景與目的 8 四 研究方法 14 五 結果 17 六 討論 19 七 臨床意義與未來展望 22 八 論文英文簡述 23 九 參考文獻 24 十 圖表 2