透皮给药系统在镇痛治疗中的临床应用和治疗进展

<正>近年来透皮给药系统以其无需针刺、避免了胃肠道反应、提高了生物利用度等优势被广泛研究。而为了保证镇痛治疗的持续性和有效性,出现了采用透皮给药系统促进止痛药物经皮吸收的新型方法。本文对直流电离子导入技术和超声透皮给药技术促进镇痛药物经皮吸收展开论述,探讨这些技术的安全性和有效性,以及影响药物渗透吸收的因素。传统镇痛常以口服非甾体类抗炎药、局部外用药物或者静脉滴注镇痛药物为主,但分别面临胃肠道反应、镇痛效果有限以及     

局部麻醉缓释药物的制备及镇痛作用

背景：临床常用的局部麻醉药物体内生物半衰期短,且局部组织的高浓度极易造成药物经血管吸收入血产生中枢神经和心血管毒性。因此,国内外学者开始进行局部麻醉缓释给药系统研究。目的：总结近年局部麻醉缓释药物的制备及镇痛效果的研究现状。方法：由作者应用计算机检索维普数据库中与局部麻醉缓释药物的制备及镇痛作用有关的文章,检索时限1998-01/2009-10。检索关键词：局麻药,微球,乳酸羟基乙酸共聚物,药物体外释放,镇痛。选择33篇文献进行分析。结果与结论：采用W1/O/W2双重乳化-溶剂挥发法、乳化溶剂挥发法、乳化-交联法、高压电场法制备的局麻药载体的微球,形态均圆整,流动性好,80%以上的微球粒径在50~100μm之间,可提高载药量和包封率。在对微球的体外释放性能进行考察时均得到了可延长药物的体外释放时间、相对较平稳的血药浓度、明显的缓释作用和良好安全性的结果。     

复方利多卡因乳膏在眼部整形美容手术的应用观察

目的研究和观察在眼部整形美容手术中使用复方利多卡因乳膏的镇痛效果。方法收集行眼部整形美容手术的研究对象共72例,随机分为观察组与对照组,各36例,两组均行常规皮肤消毒,对照组使用利多卡因进行局部注射麻醉,观察组在对照组的基础上于手术前1小时在需要整形的眼部皮肤表面均匀地涂抹复方利多卡因乳膏,将两组研究对象的镇痛效果进行观察和对比。结果观察组的疼痛程度显著低于对照组,观察组的满意度显著高于对照组(P0.05)。结论在眼部整形美容患者的手术过程中,使用复方利多卡因乳膏进行局部麻醉,镇痛效果更好,美容者的满意度更高,值得推广应用。     

药物控释体系用于局部麻醉的研究进展

减少用药次数、延长术后镇痛时间是临床局部麻醉的重要需求。然而,无论是当前临床使用的局麻药,还是生物毒素类潜在新型麻醉药均存在时效较短的问题。利用脂质体、聚合物微球等药物载体装载局麻药进行控释,可实现药物的长效、按需释放,从而满足临床需求。本文简要概述可用于局麻药控释的药物载体,并介绍具有代表性的药物控释体系的设计、功能及其用于局部麻醉的最新研究进展,同时对此研究领域的挑战及未来前景进行讨论。     

连续蛛网膜下腔和硬膜外腔术后镇痛的临床比较

连续蛛网膜下腔阻滞麻醉(continuous spinal anesthesia, CSA)起效快,可小剂量分次给药以达到预期的麻醉平面,镇痛效果好,肌松效果满意,能满足长时间手术的需要,而且避免了全脊髓麻醉、局麻药中毒等风险[1,2].本研究选择ASA Ⅰ～Ⅲ级的下肢骨科手术病人,术后采用病人自控镇痛(PCSA),比较连续蛛网膜下腔PCSA和腰硬联合麻醉术后病人自控镇痛PCEA的镇痛效应以及不良反应.     

局部麻醉缓释药物的制备及镇痛作用

背景:临床常用的局部麻醉药物体内生物半衰期短,局部组织的高浓度极易造成药物经血管吸收入血产生中枢神经和心血管毒性.因此,内外学者开始进行局部麻醉缓释给药系统研究.目的:总结近年局部麻醉缓释药物的制备及镇痛效果的研究现状.方法:由作者应用计算机检索维普数据库中与局部麻醉缓释药物的制备及镇痛作用有关的文章,索时限1998-01/ 2009-10.检索关键词:局麻药,球,酸羟基乙酸共聚物,物体外释放,痛.选择33篇文献进行分析.结果与结论:采用W1/O/W2双重乳化-溶剂挥发法、乳化溶剂挥发法、乳化-交联法、高压电场法制备的局麻药载体的微球,态均圆整,动性好,0%以上的微球粒径在50～100 μm之间,提高载药量和包封率.在对微球的体外释放性能进行考察时均得到了可延长药物的体外释放时间、相对较平稳的血药浓度、明显的缓释作用和良好安全性的结果.     

芬太尼缓释透皮贴剂用于术后镇痛的疗效观察

目前术后镇痛在临床中的应用日趋广泛,为了寻求新的给药方法,本研究将评价芬太尼缓释透皮贴剂用于中、小手术术后镇痛的疗效.     

吗啡伍用纳洛酮对硬膜外麻醉术后镇痛作用的影响

吗啡既能选择性地阻滞脊髓传导疼痛的阿片受体 ,又能激活内源性镇痛系统 ,临床镇痛效果确切 ,但可引起恶心、呕吐、皮肤瘙痒、尿潴留等不良反应。纳洛酮为纯阿片受体拮抗剂 ,可拮抗阿片类药物的副作用。作者将 2药合用 ,观察其镇痛效果 ,现报告如下。1　资料与方法选择ASAⅠ～Ⅱ级 ,年龄 2 0～ 65岁 ,择期在硬膜外麻醉下行妇科手术的患者 90例。入室后取左侧卧位 ,于L2～ 3间隙行硬膜外穿刺。常规监测ECG ,SpO2 及无创血压。局麻药选择 1 %利多卡因 + 0 2 5 %的卡因 + 1∶2 0万肾上腺素合剂。硬膜外穿刺成功后 ,先给试验量 5ml,麻醉平…     

持续注射局麻药病人的护理

应用局麻药阻滞神经或在手术部位的局部用局麻药浸润可消除术中和术后疼痛。但是当神经阻滞作用消失后，病人常需用其他方法止痛，例如口服长效止痛剂或静脉滴注止痛药。应用局麻药连续局部注射的目的在于连续不间断地缓解疼痛，不但可减少阿片类药物的需要也可避免肌注阿片类药物的副作用（如镇静和呼吸抑制等）。有研究显示局部连续注射局麻药可使患者缩短住院时间，并能及早参与康复活动，如步行和理疗。 局部连续注射局麻药，是术后在皮下组织和临近伤口处的筋膜或肌肉之间插入一根导针（通常为１６号），然后连接导管或通过导针置入导…     

采用丁卡因预防前列地尔治疗性疼痛

前列地尔又名前列腺素E1（PGE1），其冻干粉针剂静脉滴注多有灼样疼痛，部分患者因难以忍受疼痛而放弃治疗。肝病患者因疗程长，静脉炎的发病率更是高达90％以上，为保证疗程临床上多采用静脉内给药，或外用硫酸镁湿敷、冰敷等方法防治静脉炎。由于静脉内给药存在毒副作用，为保证治疗顺利进行，寻求一种简便、安全、无创、无痛的局部表面镇痛方法，我院自2001年1月～2005年8月借鉴皮肤浅表层美容手术麻醉方法，采用1％丁卡因皮透剂外涂，取得了满意效果，现报告如下。     

Effects of Extracorporeal Shock Wave-Mediated Transdermal Local Anesthetic Drug Delivery on Rat Caudal Nerves

Cavitation plays a substantial role in the clinical effects of extracorporeal shock wave therapy (ESWT). It is also generally accepted as a major mechanism in sonophoresis. To identify the enhancing effect of extracorporeal shock wave-mediated transdermal drug delivery, 24 Wistar rats were randomly assigned to four groups: (i) topical application of a eutectic mixture of local anesthetics (EMLA); (ii) 1-MHz ultrasound; (iii) ESWT pre-treatment combined with EMLA application; (iv) ESWT concurrent with EMLA application on rat tails. The degree of anesthesia was assessed using the amplitude and latency of sensory nerve action potentials within 5?min after a 60-min EMLA application. The results indicated that ESWT pre-treatment and concurrent ESWT accelerated the anesthetic effects of the EMLA cream on the tail nerve (p?<?0.05). This finding might indicate that shock wave-mediated transdermal drug delivery is possible during the ESWT period.     

Intrapleural anesthesia following thoracic surgery and in chest trauma

The analgesic effect of intrapleural administration of local anesthetics (lidocaine, trimecaine, azocaine) has been studied in 180 patients after thoracic surgery and with chest trauma. The effect was assessed on the basis of subjective (visual analogue 10-score scale) and objective findings (hemodynamic parameters, spirograms, ECG). In control patients analgesia was performed by intramuscular promedol administration. It has been shown that fractionated intrapleural administration of local anesthetics is an effective and safe analgesic technique after thoracic surgery and in chest trauma.     

Physicochemical interaction of local anesthetics with lipid model systems--correlation with in vitro permeation and in vivo efficacy.

In dermal/transdermal drug administration stratum corneum (SC) is often the rate-limiting step. Furthermore, the intercellular lipid domain of SC is nowadays widely accepted as the major contributor to the skin barrier. The current work investigates whether the difference in the level of topical efficacy of local anesthetic compounds correlates with the type of interaction between the drug and the intercellular lipids of SC. Therefore, local anesthetics of varying topical efficacy were evaluated with respect to their effect on the morphology of various model lipid systems using small and wide angle X-ray diffraction (SWAXD) and differential scanning calorimetry (DSC). The model lipids used were glyceryl monooleate, sphingomyelin and lipids isolated from human SC. Furthermore, partitioning into isolated human SC as well as permeation through isolated human SC and human tape-stripped skin were investigated in vitro.The results indicate that local anesthetics may act as their own permeation enhancers by increasing the degree of hydrocarbon chain fluidity of the intercellular lipids. Eventually these interactions may induce non-lamellar reversed types of liquid crystalline structures locally in SC, which further facilitate the drug mobility. The large difference in topical efficacy of the investigated local anesthetics could not be explained simply by looking at their effect on the phase behavior of lipid model systems. Despite the similarities in physicochemical properties of these substances, the in vitro skin permeability differed markedly (AD>EMLA>lidocaine>prilocaine>sameridine). Thus, it was concluded that sufficient drug permeability over SC is essential to obtain local anesthesia by blocking the superficial nociceptors.     

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.     

Anesthesia and analgesia in obstetrics

Anesthesia in obstetrics includes the medical attendance of women in the delivery room as well as giving anesthesia for cesarean sections in the operating room. Over the last years the treatment of labor pain with epidural anesthesia has been modified. Whereas a couple of years ago local anesthetics were used almost exclusively, the recent trend goes toward a combination of local anesthetics with opioids. Using this combination the total amount of local anesthetic can be greatly reduced, whilst maintaining most of the motor function during labor. There is evidence the combination of local anesthetics with opioids can reduce the number of operative vaginal deliveries such as vacuum extraction or forceps. The systemic application of opioids remains unaffected by the local application and its significance is unaltered, even though the effectiveness compared to epidural application in managing labor pain is far inferior. Opioids applied systemically often have an unwanted sedative effect in the mother and have the potential for respiratory depression in the newborn. The question, whether epidural anesthesia increases the frequency of cesarean sections remains to be answered. Studies so far present discrepant results and do not show a causal relationship between the use of epidural anesthesia and increase in cesarean section rate. Regarding cesarean sections, there has been a trend in the operative field over the last years towards the use of regional anesthesia. This is the consequence of the fact that anesthesia related mortality during cesarean sections is still mainly due to hypoxia and aspiration during induction of anesthesia. The advantage of spinal anesthesia over epidural anesthesia is faster onset, more reliable sensitive block and a lower failure rate. Downside of the use of spinal anesthesia is a higher incidence of hypotension in the mother, which, however, is not a serious complication if treated adequately. Regarding the continuous application of local anesthetics via a spinal catheter, no definite statements towards benefits compared to other regional techniques can be made due to the lack of adequate amount of patient studies. Theoretically this method seems advantageous as it allows to adjust the administration of local anesthetics and opioids to the individual needs in a very refined way. Emergency situations, such as emergency cesarean sections, life threatening hemorrhage, eclampsia, and HELLP syndrome, are the main risks of the anesthetic practice in obstetrics. Their beneficial outcome is highly dependent on the coordination of logistic problems, good communication and coordination within an interdisciplinary team of obstetricians and anesthesiologists.     

Principles of office anesthesia: part II. Topical anesthesia

The development of topical anesthetics has provided the family physician with multiple options in anesthetizing open and intact skin. The combination of tetracaine, adrenaline (epinephrine), and cocaine, better known as TAC, was the first topical agent available for analgesia of lacerations to the face and scalp. Cocaine has been replaced with lidocaine in a newer formulation called LET (lidocaine, epinephrine, and tetracaine). For analgesia to nonintact skin, LET gel is generally preferred over TAC because of its superior safety record and cost-effectiveness. EMLA (eutectic mixture of local anesthetics) is perhaps the most well-known topical anesthetic for use on intact skin. EMLA can be used to anesthetize the skin before intramuscular injections, venipuncture, and simple skin procedures such as curettage or biopsy. To be fully effective, EMLA should be applied at least 90 minutes before the procedure. ELA-Max is a new, rapidly acting topical agent for intact skin that works by way of a liposomal delivery system and is available over the counter. Other delivery vehicles for topical anesthesia currently in development, including iontophoresis and anesthetic patches, may one day give patients and physicians even more flexibility.     

Morphine bioavailability from a topical gel formulation in volunteers

Although available therapies provide relief to many patients with cancer-related pain, swallowing difficulties or intestinal obstruction may preclude oral analgesic delivery in some. Topical morphine might provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. We conducted a randomized, placebo-controlled, double-blind, crossover study of five volunteers after they provided institutionally-approved, written, informed consent. They were admitted to the Northwestern University General Clinical Research Center twice, being randomly assigned to receive either 1mL of morphine compounded at 10mg/mL in pluronic lecithin organogel (PLO) base applied to the wrist and 1mL of normal saline administered subcutaneously, or 1mL of topical drug-free PLO base and 1mL of subcutaneous morphine, 3mg/mL, the first time and the opposite combination the second. Seventeen blood samples were collected from 5minutes to 10hours after dose administration for morphine concentration determination. Plasma samples were prepared by solid-phase extraction and morphine concentrations measured by a mass spectrometric technique with a linear range of 0.5-500ng/mL. Bioavailability of the topical formulation relative to the subcutaneous dose was to be estimated from doses and the plasma morphine concentration versus time relationships. Because morphine was seldom detected in plasma samples after topical administration and was unquantifiable when it was, the low bioavailability of topical morphine was unquantifiable. These results suggest that topical administration of morphine compounded in a PLO base for transdermal drug delivery is unlikely to provide relief of cancer-related pain.     

罗哌卡因局部麻醉用于腹腔镜胆囊切除术后的镇痛效果观察

目的探讨腹腔镜胆囊切除术(LC)中腹腔内予罗哌卡因表面麻醉及术后切口局部浸润对患者术后镇痛的效果。方法选择择期LC手术的患者120例,按随机数字表法分为实验组、对照组各60例,实验组于手术结束前腹腔内喷洒0.25%罗哌卡因30 ml,缝合腹壁切口前向每个切口局部注射0.5%罗哌卡因4 ml。对照组在相应部位喷洒或注射等量注射用水。两组麻醉诱导、维持方法相同,均采用静脉麻醉联合喉罩气道管理。记录术后0、2、6、12、24 h的疼痛视觉模拟(VAS)评分和术后额外镇痛药使用情况及不良反应发生情况。于麻醉诱导前、术后2 h及术后24 h 3个时间点测定血浆皮质醇、白介素(IL)-6和C反应蛋白(CRP)水平。结果实验组术后2、6、12 h镇痛效果优于对照组(P<0.05),术后24 h两组患者疼痛相当;但实验组术后使用额外镇痛药例数及次数明显少于对照组(P<0.05);实验组在抑制胃肠道不良反应方面优于对照组(P<0.05);两组术后血浆皮质醇、IL-6、C反应蛋白水平均高于术前,而实验组水平明显低于对照组(P<0.05)。结论罗哌卡因术中腹腔内表面麻醉及术后切口局部浸润对腹腔镜胆囊切除术患者具有很好的镇痛效果。     

Efficacy of drugs in regional anesthesia: A review

Local anesthetics and opioids are the most commonly used drugs in regional anesthesia. Several other drugs are used as adjuvants in addition to local anesthetics.We will review the drugs currently used in regional anesthesia. In April 2009 we searched the PubMed database and found 143 articles related to the clinical use of drugs in regional anesthesia; we divided them into 3 major chapters: local anesthetics, opioids and adjuvants.Among local anesthetics, ropivacaine and levobupivacaine can be considered the drugs of choice in neuraxial and peripheral techniques because their toxicity is low even in large volume administration; mepivacaine can be considered the drug of choice in peripheral techniques when a shorter blockade is needed.Sufentanil is the opioid of choice in both neuraxial and peripheral techniques because it appears to improve the quality of anesthesia and to prolong sensory blockade in the postoperative period.Among the adjuvants to local anesthetics, clonidine is by far the most used drug in regional anesthesia; its yield in improving and prolonging the effects of local anesthetics is apparent in neuraxial techniques. Other drugs have been studied as adjuvants to local anesthetics but clinical evidence of their benefit is controversial in many cases and further trials are unquestionably warranted.In conclusion, since many different drugs are available for regional anesthesia, we must choose wisely the one that exhibits the best safety-efficacy profile and that suits the chosen technique and type of anesthesia/analgesia best.