支撑喉镜手术患者术前经鼻滴注右旋美托咪定的随机对照研究

发布时间：2018-04-23 08:23

本文选题：右旋美托咪定 + 经鼻　；参考：《广州医科大学》2014年硕士论文

【摘要】：研究背景术前大部分患者存在不同程度的紧张、焦虑，这使患者的应激反应增强，影响麻醉和手术的正常进行，体内交感系统过度兴奋易致心血管不良事件，影响术后恢复。因此，术前使用一些镇静抗焦虑药物是非常必要的。术前用药是麻醉的重要组成部分，是麻醉的开始，良好的术前用药应具有镇静、抗焦虑、不良反应少等优点。苯巴比妥钠作为传统术前用药，它有镇静不足、抗焦虑弱等缺点。欧美较多国家首选咪达唑仑作为术前用药，它在镇静、催眠、顺行性遗忘等方面均优于苯巴比妥钠。但是，咪达唑仑伴有抑制呼吸、镇静过度、易诱发谵妄、使麻醉恢复期苏醒时间延长等缺点。术前用药在无监测条件下存在一定的安全隐患，并且可能导致苏醒延迟，从而局限了它的应用。右旋美托咪定（Dexmedetomidine，Dex）是一种高选择性的α2肾上腺素能受体激动药，它具有镇静、抗焦虑、抑制交感神经兴奋、镇痛、节省麻醉药物和稳定血流动力学的作用，临床剂量对呼吸抑制轻微。Dex有多种给药方式，如静脉注射、肌肉注射、经鼻滴注等。静脉注射Dex对循环系统的影响较大，且持续输注可能延长麻醉苏醒时间。肌肉注射Dex是有创的，患者的舒适度差，与目前提倡无创术前给药方法相悖，而且肌肉注射的效果比经粘膜吸收差。Dex无色无味，无黏膜刺激作用，经鼻滴注给药方便，患者接受度、舒适度好。经鼻滴注Dex的起效时间为30~45min，半衰期为114min，生物利用度为65%，给予足够的起效时间，其镇静效果与静注、肌注相当。小儿经鼻滴注1μg/kg、2μg/kg Dex分别产生53%、66%的满意镇静。经鼻滴注Dex使药物的血浆浓度逐渐缓慢的增加，有可能减弱其对血压和心率的影响，从而能保证术前用药的安全性。Yuen等研究表明：经鼻滴注1μg/kg、1.5μg/kg Dex后没有出现高血压反应，在滴鼻后45min血压（BP）和心率(HR)有适度的降低，但没有严重的心动过缓或者心电传导阻滞出现。因此，经鼻滴注Dex作为术前用药有一定优势。目前，经鼻滴注Dex作为术前用药的相关研究主要集中于小儿及局麻下行第三磨牙拔除术的患者，对于术前已存在焦虑的成年患者，经鼻滴注Dex作为术前用药的有效性和安全性的研究甚少。支撑喉镜下行声带息肉摘除术用时短，支撑喉镜暴露声门的操作刺激大，此操作直接刺激会厌感受器、舌根、颈部肌群深部感受器，引起体内儿茶酚胺水平升高，导致血流动力学剧烈波动，易致严重的心血管不良反应，尤其对于术前已患有心脑血管疾病的患者术中更易并发心脑血管意外。因此，支撑喉镜手术要求麻醉医生有效的抑制手术操作引起的应激反应，提高围术期血流动力学的稳定性，提供快速安全的苏醒。加深麻醉可以抑制手术操作引起的应激反应，但是易致患者术中出现脑电爆发性抑制、低血压和麻醉苏醒延迟。临床上还将β1受体阻滞剂、钙离子阻滞剂、糖皮质激素等某些非麻醉药物或局部麻醉药应用于支撑喉镜手术的全身麻醉中，从而提高血流动力学的稳定性，并能加快苏醒；但是上述药物本身不具备镇静的作用，却又抑制了HR和BP的变化；因此增加了判断患者麻醉深度的困难，使麻醉医生忽略可能存在麻醉深度不足的问题。 Dex能抑制气管插管、苏醒和拔管诱发的心血管反应，使血流动力学更趋稳定。研究表明，诱导前静注单次剂量的Dex能减少麻醉药用量，提高支撑喉镜手术围术期血流动力学稳定性和苏醒质量。在麻醉恢复期，Dex能减少恶心呕吐、寒颤、术后躁动的发生率，减少患者对镇痛药物的需求，能提高麻醉恢复质量，改善患者对麻醉的满意度。因此，Dex在支撑喉镜手术麻醉中应用有一定优势。但是，持续或大剂量的应用Dex可能会造成苏醒延迟。对于支撑喉镜这种短小手术来说，Dex是否影响麻醉苏醒时间是我们需要考虑的问题之一。经鼻滴注Dex是单次给药，它使药物的血浆浓度逐渐缓慢的增加，它用于支撑喉镜这类应激反应强烈的短小手术，是否影响麻醉苏醒时间以及能否提高血流动力学稳定性有待研究。Dex能节省麻醉药物，它能降低丙泊酚引起患者意识消失半数有效浓度（EC50）。那么，经鼻滴注Dex对丙泊酚引起患者意识消失时EC50的影响如何有待研究。目的1)观察术前经鼻滴注右旋美托咪定作为术前用药的有效性和安全性。2)观察支撑喉镜手术患者术前经鼻滴注右旋美托咪定的麻醉效应。3)研究术前经鼻滴注右旋美托咪定对丙泊酚引起患者意识消失半数有效浓度的影响。第一部分：支撑喉镜手术患者术前经鼻滴注右旋美托咪定的可行性研究目的1)观察术前经鼻滴注右旋美托咪定作为术前用药的有效性和安全性。2)观察支撑喉镜手术患者术前经鼻滴注右旋美托咪定的麻醉效应。方法80例择期行支撑喉镜下声带息肉摘除术的成年患者随机分为两组，，分别为D组和N组。D组在麻醉前45~60min经鼻滴注Dex1μg/kg，N组经鼻滴注0.9%生理盐水。麻醉诱导：患者均行丙泊酚靶控输注（Target-controlled Infusion, TCI），初始血浆靶控输注浓度为2.5μg/mL，调节丙泊酚靶浓度，每次增减0.5μg/mL维持2min直至Narcotrend指数（Narcotrend Index, NI）值维持在“D0”~“E1”水平（NI：64~20）并保持到手术结束；然后行瑞芬太尼TCI，初始效应室浓度设为3.0ng/mL；意识丧失后，静注罗库溴铵0.9mg/kg；60s后气管插管行机械通气。术中通过调节丙泊酚的靶浓度维持NI于“D0”~“E1”水平，调节瑞芬太尼效应室浓度维持SBP升高和降低幅度不超过基础值的25%，HR90bpm。记录滴鼻前后HR、BP、脉搏氧饱和度(SpO2)、改良警觉/镇静评分（OAA/S）和焦虑评分；记录苏醒拔管时间；记录NI达“D0”水平、置入支撑喉镜前、退出支撑喉镜时的丙泊酚效应室浓度，记录置入支撑喉镜前、置入支撑喉镜即刻、退出支撑喉镜时的瑞芬太尼效应室浓度，记录恢复自主呼吸、苏醒时和拔管时的丙泊酚和瑞芬太尼效应室浓度；记录观察期不良事件的发生情况和患者对麻醉的满意度。结果 1、一般情况两组一般情况比较差异无统计学意义（P0.05）。 2、滴鼻前、入室时、诱导前三个时点的镇静和焦虑评分的变化诱导前，D组的OAA/S和焦虑评分分别为4.58±0.12和3.30±0.08，N组的OAA/S和焦虑评分分别为5.60±0.10和2.85±0.10，D组的OAA/S低于N组，D组的焦虑评分高于N组（P0.05）。在D组内，诱导前OAA/S低于滴鼻前，焦虑评分高于滴鼻前（P0.05）。 3、滴鼻前、入室时、诱导前三个时点的HR、BP、SpO2的变化诱导前，D组的HR比N组低8.84%（P0.05）。在D组内，与滴鼻前相比，入室时HR下降6.72%，诱导前HR下降8.53%（P0.05）。三个时点，两组的SBP比较差异无统计学意义（P0.05）。在N组内，入室时和诱导前的SBP、DBP高于滴鼻前（P0.05）。在D组内，入室时和滴鼻前、诱导前和滴鼻前比较差异均无统计学意义（P0.05）。所有患者的SpO2都没有低于95%。 4、丙泊酚和瑞芬太尼效应室浓度在置入支撑喉镜前，D组的丙泊酚效应室浓度比N组低7.3%（P0.05）。在置入支撑喉镜前、置入支撑喉镜即刻、退出支撑喉镜时、恢复自主呼吸时、苏醒时和拔管时，D组的瑞芬太尼效应室浓度均低于N组（P0.05）。 5、滴鼻至入室时间、滴鼻至诱导前时间、麻醉时间、手术时间、恢复自主呼吸时间、苏醒时间和拔管时间两组的滴鼻至入室时间、滴鼻至诱导前时间、麻醉时间、手术时间、恢复自主呼吸时间、苏醒时间和拔管时间比较差异均无统计学意义（P0.05）。 6、观察期心血管不良事件的发生情况麻醉恢复期，N组和D组出现心动过速的患者例数分别为8例和2例，出现高血压的患者例数分别为14例和5例，N组心动过速和高血压的发生率高于D组（P0.05）。 7、观察期其它不良事件的发生情况 N组和D组麻醉恢复期寒战、恶心呕吐、呼吸抑制的发生情况比较差异无统计学意义（P0.05）。 8、患者对麻醉的满意度 D组对麻醉满意的患者比例高于N组（D组为36例，N组为23例）（P0.05）。结论术前经鼻滴注右旋美托咪定1μg/kg应用于支撑喉镜手术能产生有效的镇静抗焦虑作用，对HR、SpO2、BP影响轻微，作为术前用药具有一定的有效性和安全性。它能降低丙泊酚和瑞芬太尼效应室浓度，不影响苏醒、拔管时间，提高麻醉恢复期血流动力学稳定性，提高了麻醉复苏质量。第二部分：术前经鼻滴注右旋美托咪定对丙泊酚引起患者意识消失半数有效浓度的影响目的术前经鼻滴注右旋美托咪定对丙泊酚引起患者意识消失半数有效浓度的影响。方法24例择期行头颈部手术的患者于麻醉前45~60min经鼻滴注Dex1μg/kg。丙泊酚TCI，设其初始血浆靶控输注浓度(Cp)为2.0μg/ml，待Cp与丙泊酚效应室浓度（Ce）达平衡时，观察患者意识是否消失，意识消失的标准为呼之不睁眼，睫毛反射消失。若上一例患者意识消失，则下一例患者Cp下调0.2μg/ml，反之，则上调0.2μg/ml。制作出意识消失分布示意图，待出现6个阴阳拐点后，结束研究。记录每例患者意识消失与否，记录Cp和Ce达平衡的时间。结果经鼻滴注Dex后丙泊酚引起患者意识消失时的EC50为1.38μg/ml，EC50的95％CI为1.373~1.395μg/ml。丙泊酚Cp和Ce达平衡的时间为13.21±0.72min。结论术前经鼻滴注右旋美托咪定1μg/kg后丙泊酚引起患者意识消失时的EC50为1.38μg/ml，EC50的95％CI为1.373~1.395μg/ml。
[Abstract]:In the study background, most patients have different degrees of tension and anxiety. This makes the patient's stress response enhanced, which affects the normal operation of anesthesia and surgery. The hyperexcitability of the sympathetic system in the body causes adverse cardiovascular events and affects the postoperative recovery. Therefore, it is necessary to use some sedative and anti anxiety drugs before operation. An important part of drunken is the beginning of anaesthesia. Good premedication should be composed of sedative, anti anxiety, and less adverse reactions. As a traditional premedication, phenobarbital has shortcomings such as lack of sedative and weak anxiety. Midazolam is the first choice in many countries in Europe and America. It is used in the aspects of sedative, hypnotic, and amnesia. It is superior to phenobarbital sodium. However, midazolam is associated with inhibition of breathing, excessive sedation, delirium easily induced and prolonged awakening in the recovery period. Preoperative medication has a certain safety hazard under no monitoring conditions, and may lead to a delay in revival, thus limiting its application.
Dexmedetomidine (Dex) is a highly selective alpha 2 adrenergic receptor agonist. It has a sedative, anti anxiety, analgesic, analgesic, analgesic, anaesthetized and hemodynamic role. The clinical dose has a variety of drug delivery methods for breathing inhibition of light.Dex, such as intravenous injection, intramuscular injection. Intravenous injection of Dex has a great influence on the circulation system, and continuous infusion may prolong the time of awakening. The intramuscular injection of Dex is invasive and the patient's comfort is poor, and it is contrary to the current method of advocating noninvasive surgery, and the effect of intramuscular injection is colorless and tasteless than mucous absorption of.Dex. It is convenient to take the medicine, the patient's acceptance and comfort are good. The onset time of Dex is 30~45min, the half-life is 114mIn, the bioavailability is 65%, the effective time is given, the sedative effect and the static injection are equal. The children transnasal infusion 1 mu g/kg, 2 mu g/kg Dex produce 53%, 66% satisfactory sedation respectively. Via nasal drip Dex to make the drug plasma The gradual slow increase in concentration may weaken its effect on blood pressure and heart rate, thus ensuring the safety of preoperatively, such as the safety of.Yuen, and other studies suggest that there is no hypertension response after a nasal drip of 1 g/kg, 1.5 g/kg Dex, and a moderate decrease in 45min blood pressure (BP) and heart rate (HR) after the nose drops, but there is no serious bradycardia or heart. Electrical conduction block appears. Therefore, Dex as a premedication has some advantages. At present, the related research on the use of Dex as a preoperation is mainly focused on the patients with third molar extraction under children and local anesthesia. The efficacy and safety of Dex infusion through nasal drip for preoperatively in adult patients who have been anxious before operation There is little research on sex.
The operation of the laryngoscope is short, and the operation of the laryngoscope exposes the glottis greatly. This operation directly stimulates the epiglottis, the tongue root, the deep receptor of the neck muscle, causes the increase of the level of the catecholamine in the body, causes the severe fluctuation of the hemodynamics, and causes the serious cardiovascular adverse reactions, especially for the preoperation. Patients with cardiovascular and cerebrovascular diseases are more likely to be associated with cardiovascular and cerebrovascular accidents. Therefore, the support laryngoscopy requires the anesthesiologist to effectively inhibit the stress response caused by the operation, improve the stability of the perioperative hemodynamics, and provide a rapid and safe revival. During the operation of the patients, the patients with electroencephalogram, hypotension, and anesthesia are delayed. Some non anesthetic or local anesthetics, such as beta 1 receptor blockers, calcium ion blockers, glucocorticoids, or local anesthetics, are also used in general anesthesia supporting the laryngoscope operation to improve the stability of hemodynamics and accelerate recovery. The drug itself does not have a sedative effect, but it also inhibits the changes in HR and BP, and thus increases the difficulty of judging the depth of the anesthetic, allowing the anesthesiologist to ignore the possibility of a lack of depth of anesthesia.
Dex can inhibit endotracheal intubation, revive and extubate the cardiovascular response, and make hemodynamics more stable. The study shows that the pre induction of a single dose of Dex can reduce the dosage of anesthetics and improve the hemodynamic stability and revival quality during the perioperative period of laryngoscopy, and Dex can reduce nausea, vomiting, chill, and postoperative chill in the recovery period of drunken laryngoscope. The incidence of agitation, reducing the patient's demand for analgesics, improving the quality of the anesthetic recovery and improving the patient's satisfaction with the anesthetic. Therefore, Dex has a certain advantage in the application of the support for laryngoscopy anesthesia. However, a sustained or large dose of Dex may cause a waking delay. For the short operation of the prop laryngoscope, Dex The effect of the anesthesia recovery time is one of the problems we need to consider. The transnasal infusion of Dex is a single dose, which makes the plasma concentration of the drug slowly increasing. It is used to support the short operation of stress reaction such as laryngoscope. Whether it affects the time of anesthesia recovery and whether to raise the stability of hemodynamics needs to be studied by.Dex. Narcotic drugs, which can reduce the median effective concentration (EC50) of the patient's disappearance of propofol, and how the effect of Dex on EC50 when propofol causes the disappearance of the patient's consciousness remains to be studied.
Objective 1) to observe the efficacy and safety of dexmedetomidine before operation as the efficacy and safety of dexmedetomidine (.2) to observe the effect of dexmedetomidine (dexmedetomidine) by dripping dexmeimidine (dexmedetomidine) before operation for patients with prop laryngoscope surgery (.3).
Part one: feasibility study of preoperative dexmedetomidine instillation via self retaining laryngoscope surgery.
Objective 1) to observe the efficacy and safety of dexmedetomidine (.2) before operation and observe the anesthetic effect of dexmedetomidine on the patients undergoing laryngoscope surgery.
Methods 80 adult patients undergoing elective laryngoscope vocal cord polyps were randomly divided into two groups: group D and group N, group.D, 45~60min via nasal drip Dex1 mu g/kg before anesthesia, and 0.9% physiological saline infusion through nasal drip in group N. The patients were induced by target controlled infusion of propofol (Target-controlled Infusion, TCI), and initial plasma target controlled infusion. The concentration was 2.5 mu g/mL, the target concentration of propofol was adjusted, and the Narcotrend index (Narcotrend Index, NI) was maintained at the level of "D0" ~ "E1" (NI:64~20) and kept to the end of the operation, and the value of Narcotrend Index, NI was maintained at the level of "D0" ~ "E1" (NI:64~20), and the initial effect chamber concentration was set to 3.0ng/mL; after the loss of consciousness, the Narcotrend was injected with rocuronium. After 60s, the endotracheal intubation was ventilated by mechanical ventilation. During the operation, the target concentration of propofol was maintained to maintain NI at "D0" ~ "E1" level, and the concentration of remifentanil effect room was adjusted to maintain the increase and decrease of SBP by 25%. HR90bpm. recorded HR, BP, pulse oxygen saturation (SpO2), improved vigilance / sedation score (OAA/S) and anxiety before and after the nose drops. Score; record the awakening and extubation time; record the level of NI up to "D0", withdraw the propofol effect room concentration before the supporting laryngoscope, record the concentration of the propofol effect room before the supporting laryngoscope, record the remifentanil effect room concentration in the support laryngoscope immediately, withdraw the remifentanil effect room concentration in the support laryngoscope, record the spontaneous breathing, the propofol and the propofol at the time of awakening and extubation. The concentration of remifentanil effect chamber was recorded, and the occurrence of adverse events during observation period and the satisfaction degree of patients to anesthesia were recorded.
Result
1, general situation
There was no significant difference between the two groups in general condition (P0.05).
2, the change of sedation and anxiety scores at the three points before induction.
Before induction, the scores of OAA/S and anxiety in group D were 4.58 + 0.12 and 3.30 + 0.08 respectively. The OAA/S and anxiety scores in group N were 5.60 + 0.10 and 2.85 + 0.10 respectively. The OAA/S in D group was lower than that in the N group. The anxiety score in D group was higher than that in the N group (P0.05).
3, the changes of HR, BP and SpO2 at the three points before induction.
Before induction, the HR in the D group was 8.84% lower than that in the N group (P0.05). In the D group, the HR decreased by 6.72% and 8.53% (P0.05) before the induction. The two groups of SBP were not statistically significant (P0.05) at the three time points. In the N group, the admission and pre induction SBP were higher than that before the nose drops. There was no significant difference between the two groups (P0.05). The SpO2 of all patients was not lower than 95%..
4, propofol and remifentanil effect chamber concentration
The propofol effect chamber concentration in group D was 7.3% lower than that of the N group before placing the support laryngoscope. The concentration of remifentanil effect room in group D was lower than that of the N group (P0.05) when the supporting laryngoscope was placed immediately before the prop laryngoscope was placed, and when the support laryngoscope was exited, and the spontaneous breathing was restored. The concentration of remifentanil effect room in group D was lower than that of the N group (P0.05).
5, the time from nose to room, nose to induction time, anesthesia time, operation time, recovery of spontaneous breathing time, recovery time and extubation time.
There was no significant difference between the two groups of intranasal time, the time of intranasal to pre induction, the time of anesthesia, the time of operation, the recovery of the time of spontaneous breathing, the time of awakening and the time of extubation (P0.05).
6, the occurrence of adverse cardiovascular events during the observation period
The number of patients with tachycardia in group N and group D was 8 and 2, respectively. The number of patients with hypertension was 14 and 5 respectively. The incidence of tachycardia and hypertension in group N was higher than that in group D (P0.05).
7, the occurrence of other adverse events during the observation period
There was no significant difference in the incidence of chills, nausea and vomiting and respiratory depression between group N and group D (P0.05).
8, patients' satisfaction with anesthesia
Patients in group D were more satisfied with anesthesia than those in group N (group D was 36 cases and group N was 23 cases) (P0.05).
Conclusion the application of dexmedetomidine 1 g/kg to prop laryngoscopy before operation can produce effective sedative and anti anxiety effect and slight effect on HR, SpO2, BP. It has certain efficacy and safety as preoperatively. It can reduce the concentration of propofol and remifentanil effect room, do not affect recovery, extubation time, and improve the recovery period of anesthesia. The stability of hemodynamics improved the quality of anesthesia recovery.
The second part: the influence of dexmedetomidine on the half effective concentration of propofol induced disconsciousness.
Objective to investigate the effect of dexmedetomidine on the effective half of effective concentration of propofol.
Methods 24 patients undergoing selective head and neck surgery were instilled Dex1 mu g/kg. propofol TCI before anaesthesia. The initial plasma target controlled infusion concentration (Cp) was 2 g/ml, and when the Cp and propofol effect chamber concentration (Ce) reached balance, the consciousness disappeared, the standard of consciousness disappeared and the eyelash reflex disappeared. In one case, the patient's consciousness disappeared, then the next patient Cp was down 0.2 mu g/ml, and on the contrary, the consciousness disappeared distribution map was made up by 0.2 mu g/ml.. After the emergence of 6 Yin and Yang points, the study ended. Record the time for the balance of Cp and Ce to record the disappearance of each patient's consciousness.
Results the EC50 of propofol caused by propofol after Dex was 1.38 mu g/ml, and the 95%CI of EC50 was 13.21 + 0.72min. for 1.373~1.395 g/ml. propofol Cp and Ce.
Conclusion propofol can induce the loss of consciousness in patients with 1.38 EC50 g/ml after intravenous drip of dexmedetomidine 1 micronutre before surgery, and the 95%CI of EC50 is 1.373~1.395 g/ml. g/kg.

【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614.2

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