【摘要】：背景與目的：全身麻醉誘導(dǎo)期間靜脈注射芬太尼誘發(fā)咳嗽(Fentanylinduced cough,FIC)可大大增加誘導(dǎo)期風(fēng)險(xiǎn)。臨床有許多方法和藥物可以抑制FIC，但都不是很理想。臨床常用的鎮(zhèn)咳藥異丙嗪能否抑制FIC，目前未見報(bào)道。本實(shí)驗(yàn)擬觀察靜脈注射小劑量抗組胺藥鹽酸異丙嗪對(duì)FIC的影響，尋找新的抑制FIC的方法，以減少或避免全身麻醉誘導(dǎo)期間FIC。觀察全麻誘導(dǎo)期間注射芬太尼后血漿組胺濃度的變化以及預(yù)注異丙嗪對(duì)芬太尼后血漿組胺濃度的影響，探討組胺在FIC發(fā)生中的作用以及異丙嗪是否通過抑制組胺的釋放而發(fā)揮作用。 方法：第一部分：采用隨機(jī)對(duì)照雙盲實(shí)驗(yàn)，選200例擬行全身麻醉下?lián)衿谑中g(shù)患者，術(shù)前隨機(jī)分為4組：對(duì)照組和實(shí)驗(yàn)1、2、3組。麻醉誘導(dǎo)前各組分別給予0.1ml/kg的4種藥液：0.9%NS，0.5mg/ml異丙嗪，1mg/ml異丙嗪和1.5mg/ml異丙嗪。所有患者麻醉誘導(dǎo)以50μg/s的速度靜脈注射芬太尼3μg/kg，2min后給予丙泊酚1-1.5mg/kg、順式阿曲庫銨0.2mg/kg。吸入1-1.5MAC七氟醚、靜脈泵注瑞芬太尼0.1-0.2μg/kg/min、順式阿曲庫銨0.3mg/kg/h維持麻醉與肌松。注射芬太尼2min內(nèi)記錄患者咳嗽發(fā)生情況，包括咳嗽發(fā)生時(shí)間、次數(shù)、強(qiáng)度，記錄預(yù)注異丙嗪前（T0）、靜注芬太尼前（T1）、氣管插管前（T3）、氣管插管后（T4）血壓和心率值，術(shù)后記錄手術(shù)結(jié)束至拔除氣管導(dǎo)管的時(shí)間，術(shù)后惡心嘔吐的發(fā)生情況。第二部分：根據(jù)第一部分實(shí)驗(yàn)結(jié)果選擇實(shí)驗(yàn)組2所用異丙嗪的劑量繼續(xù)實(shí)驗(yàn)。選30例膽石膽囊炎擬在全麻腹腔鏡下行膽囊切除的患者隨機(jī)分為兩組，芬太尼組（F組）和異丙嗪+芬太尼組（FP組）：分別給予3μg/kg芬太尼和0.1ml/kg異丙嗪（1mg/ml）+3μg/kg芬太尼，麻醉方法同前。給藥前（t0）、給藥后2min（t1）、氣管插管后2min（t2）外周靜脈血2ml，測(cè)定血漿組胺濃度。 結(jié)果：第一部分：（1）4組患者一般資料：年齡、性別、體重、身高、所患疾病及學(xué)科無顯著性差異（p0.05）。 （2）4組患者血壓心率變化：各組收縮壓、舒張壓和心率在T0、T1、T2和T3時(shí)點(diǎn)差異無統(tǒng)計(jì)學(xué)意義（p0.05），T4時(shí)點(diǎn)對(duì)照組、實(shí)驗(yàn)2組、3組的舒張壓升高較實(shí)驗(yàn)1組明顯，差異有統(tǒng)計(jì)學(xué)意義（p0.05），實(shí)驗(yàn)3組心率增快高于對(duì)照組和實(shí)驗(yàn)1、2組，差異有統(tǒng)計(jì)學(xué)意義（p0.05）。組內(nèi)比較：各組T3時(shí)點(diǎn)心率、收縮壓、舒張壓均明顯低于T0、T1、T2和T4，差異有統(tǒng)計(jì)學(xué)意義（p0.05），而各組內(nèi)心率、收縮壓、舒張壓在T0、T1、T2和T4差異無統(tǒng)計(jì)學(xué)意義（p0.05）。 （3）4組患者FIC發(fā)生率：對(duì)照組FIC發(fā)生16例（32%），其中輕、中、重度分別為11、3、2例。實(shí)驗(yàn)1組FIC發(fā)生8例（16%），其中輕、中、重度分別為4、2、2例。實(shí)驗(yàn)2組FIC發(fā)生6例（12%），其中輕、中、重度分別為1、2、3例。實(shí)驗(yàn)3組FIC發(fā)生5例（10%），，其中輕、中、重度分別為2、0、3例。實(shí)驗(yàn)1組、2組、3組總咳嗽發(fā)生率與對(duì)照組相比均明顯下降，差異有統(tǒng)計(jì)學(xué)意義（p0.05）；輕度FIC發(fā)生率實(shí)驗(yàn)1組、2組、3組比對(duì)照組明顯下降，差異有統(tǒng)計(jì)學(xué)意義（p0.05）；FIC中度和重度發(fā)生率各組比較差異無統(tǒng)計(jì)學(xué)意義（p0.05）。組內(nèi)比較：對(duì)照組內(nèi)FIC輕度發(fā)生率明顯高于中度和重度發(fā)生率，差異有統(tǒng)計(jì)學(xué)意義（p0.05），中度和重度沒有顯著性差別（p0.05）。實(shí)驗(yàn)1組、2組、3組內(nèi)輕、中、重度發(fā)生率比較統(tǒng)計(jì)學(xué)無顯著差異（p0.05）。 （4）4組發(fā)生FIC的平均時(shí)間：分別為：12.60s、12.89s、13.36s、12.25s，4組比較無顯著差異（p0.05）。 （5）4組患者蘇醒拔管的時(shí)間：對(duì)照組、實(shí)驗(yàn)1組、2組、3組患者手術(shù)結(jié)束停止所有麻醉藥至蘇醒拔除氣管導(dǎo)管的時(shí)間分別為：7.40±1.80min、7.52±1.81min、7.44±1.89min、7.32±2.11min，四組患者蘇醒拔除氣管導(dǎo)管時(shí)間差異無統(tǒng)計(jì)學(xué)意義（p0.05）。 （6）術(shù)后惡心嘔吐、咳嗽咯痰的發(fā)生情況：對(duì)照組、實(shí)驗(yàn)1組、2組、3組分別為：1、1、1和2例；術(shù)后咳痰的發(fā)生情況：對(duì)照組、實(shí)驗(yàn)1組、2組、3組分別為：7、10、4和4例。4組患者術(shù)后惡心嘔吐、咳嗽咯痰發(fā)生率統(tǒng)計(jì)學(xué)無顯著性差異（p0.05）。第二部分：（1）兩組患者一般資料無統(tǒng)計(jì)學(xué)差異（p0.05）。（2）芬太尼組（F組）t0、t1、t2靜脈血漿組胺濃度分別為：8.53±2.04ng/ml、7.24±2.14ng/ml、7.57±1.83ng/ml；異丙嗪+芬太尼組（FP組）靜脈血漿組胺濃度分別為：8.23±2.58ng/ml、7.33±1.89ng/ml、7.23±2.02ng/ml，兩組組內(nèi)及組間比較均無顯著差異（p0.05）。 結(jié)論：（1）預(yù)注0.05mg/kg、0.1mg/kg、0.15mg/kg鹽酸異丙嗪可降低FIC的發(fā)生率。3種劑量對(duì)麻醉誘導(dǎo)期間血壓有輕度的影響而對(duì)心率、術(shù)后蘇醒拔除氣管導(dǎo)管時(shí)間、術(shù)后并發(fā)癥無明顯影響。 （2）麻醉誘導(dǎo)以50μg/s的速度注射濃度為50μg/ml芬太尼3μg/kg不影響血漿組胺濃度的變化，預(yù)注0.1mg/kg異丙嗪對(duì)注射芬太尼后血漿組胺濃度的變化也無顯著影響。
[Abstract]:Background and objective: intravenous fentanyl induced cough (Fentanylinduced cough, FIC) during induction of general anesthesia can greatly increase the risk of induction. There are many clinical methods and drugs that can inhibit FIC, but they are not ideal. The clinical antitussive drug, promethazine, can inhibit FIC. This experiment is to observe intravenous injection. The effect of promethazine hydrochloride, a small dose of antihistamine, on FIC, in order to find a new method of inhibiting FIC, in order to reduce or avoid the changes in the plasma histamine concentration after injection of fentanyl during induction of general anesthesia induction during induction of general anesthesia and the effect of preinjection of Promethazine on the concentration of histamine after fentanyl, and to explore the role of histamine in the occurrence of FIC. And whether promethazine can play a role in inhibiting histamine release.
Methods: in the first part, 200 patients undergoing elective surgery under general anesthesia were randomly divided into 4 groups before operation: control group and experimental group 1,2,3. Before anesthesia induction, 4 kinds of 0.1ml/kg solution were given to each group: 0.9%NS, 0.5mg/ml promethazine, 1mg/ml isopromethazine and 1.5mg/ml isopromethazine. All patients were induced by anesthesia induction. At the speed of 50 mu g/s, fentanyl was injected 3 u g/kg, 2min was given 1-1.5mg/kg, CIS atracurium 0.2mg/kg. inhaled 1-1.5MAC sevoflurane, intravenous infusion of remifentanil 0.1-0.2 u g/kg/min, CIS atracurium 0.3mg/kg/h maintenance anesthesia and muscle relaxation. The occurrence of coughing in patients with fentanyl 2min was recorded, including coughing. Interval, times, intensity, recording pre injection of promethazine (T0), intravenous injection of fentanyl (T1), pretracheal intubation (T3), blood pressure and heart rate after endotracheal intubation (T4), the time after operation to remove tracheal catheter and postoperative nausea and vomiting. Second part: select the 2 promethazine agent in the experimental group according to the results of the first part of the experiment. 30 cases of gallstone cholecystitis were randomly divided into two groups, the fentanyl group (group F) and the promethazine + fentanyl group (group FP): 3 mu g/kg fentanyl and 0.1ml/kg isopromethazine (1mg/ml) +3 mu g/kg fentanyl respectively, the anesthesia method was the same before. Before administration (T0), after the administration, the tracheal intubation 2min (T2) 2ml was measured in peripheral venous blood and plasma histamine concentration was measured.
Results: the first part: (1) general information of 4 groups of patients: age, sex, weight, height, disease and subjects were not significantly different (P0.05).
(2) the change of blood pressure and heart rate in the 4 groups: there was no significant difference in systolic pressure, diastolic pressure and heart rate in T0, T1, T2 and T3 (P0.05), T4 time point control group, experiment 2 group, and the 3 groups were significantly higher than the experimental group 1, the difference was statistically significant (P0.05), the rate of heart rate in the 3 groups was higher than that of the control group and the experimental 1,2 group, the difference was statistically significant P0.05. In group comparison, the rate of dessert, systolic pressure and diastolic pressure were significantly lower than that of T0, T1, T2 and T4 (P0.05), but there was no significant difference in the heart rate, systolic pressure and diastolic pressure in T0, T1, T2 and T4 (P0.05) in each group (T3).
(3) the incidence of FIC in the 4 groups: 16 cases of FIC in the control group (32%), with light, medium and severe 11,3,2 respectively. 8 cases (16%) occurred in the 1 group of FIC, of which the light, middle and severe cases were 4,2,2 respectively. The 2 groups were 6 (12%) in the experiment, of which the mild, middle and severe cases were respectively 1,2,3 cases. The experimental group of FIC occurred in 5 cases (10%), of which the light, medium, and severe cases were 2,0,3 cases respectively. The 1 groups, 2 groups, 3 groups of total coughing compared with the control group decreased significantly compared with the control group, the difference was statistically significant (P0.05); the mild FIC incidence of experimental 1, 2 groups, 3 groups were significantly lower than the control group, the difference was statistically significant (P0.05); the incidence of moderate and severe incidence of FIC was not statistically significant (P0.05). Group comparison: control group: control group: comparison group: control group: control group The mild incidence of internal FIC was significantly higher than the moderate and severe incidence, the difference was statistically significant (P0.05). There was no significant difference between moderate and severe (P0.05). There was no significant difference between the 1 groups in the experimental group, the 2 groups, and the moderate and severe incidence in the 3 groups (P0.05).
(4) the average time of occurrence of FIC in the 4 groups was 12.60s, 12.89s, 13.36s and 12.25s respectively, and there was no significant difference between the 4 groups (P0.05).
(5) the time of 4 groups of patients awakened and extubation: the control group, the experiment 1 groups, the 2 groups, the 3 groups of patients to stop all the anesthetic to the recovery of the tracheal tube time were 7.40 + 1.80min, 7.52 + 1.81min, 7.44 + 1.89min, 7.32 + 2.11min, four groups of patients to wake up the extraction of tracheal catheter time difference was not statistically significant (P0.05).
(6) postoperative nausea and vomiting, cough and phlegm: control group, experimental 1 groups, 2 groups, 3 groups, 1,1,1 and 2 cases; postoperative expectoration: control group, 1 groups, 2 groups, 3 groups of patients with postoperative nausea and vomiting, cough, cough and sputum incidence of no significant difference (P0.05). Second: Second: Second: (1) The general data of the two groups were not statistically different (P0.05). (2) the concentration of histamine in the venous plasma of the fentanyl group (group F) was 8.53 + 2.04ng/ml, 7.24 + 2.14ng/ml, 7.57 + 1.83ng/ml, and the concentration of histamine in the venous plasma of promethazine + fentanyl group (group FP) was 8.23 + 2.58ng/ml, 7.33 + and 7.23 + 2.02ng/ml, in and between the two groups and groups. There was no significant difference in the comparison (P0.05).
Conclusion: (1) pre injection of 0.05mg/kg, 0.1mg/kg, 0.15mg/kg promethazine hydrochloride can reduce the incidence of FIC,.3 dose has a slight effect on the blood pressure during the induction of anesthesia, and the time of the tracheal catheter removal after the operation, and the postoperative complications have no obvious effect.
(2) the change of plasma histamine concentration was not affected by the velocity injection of 50 mu g/s at the concentration of 50 mu g/ml fentanyl 3 u g/kg, and there was no significant effect on the change of plasma histamine concentration after injection of promethazine after injection of fentanyl.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R614

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