骶管注射疗法的药物配伍稳定性及临床运用规范化研究
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摘要
目的：
一、模拟临床用量,研究骶管注射疗法常用药物配伍的稳定性,克服临床实际操作中存在的盲目性和主观性,为临床安全配伍提供理论支持；骶管注射所致并发症多是由于局麻药剂量过大,配伍用药过多,不熟悉局部解剖以及穿刺过深等所致,由此避免此类操作可减少骶管注射疗法并发症的发生率。
二、糖皮质激素是骶管注射疗法中最常用的药物之一,也是最易滥用导致诸多临床意外发生的药物。糖皮质激素具有保钠排钾作用,大剂量应用可致血钾降低,导致低钾血症。如果激素用量太大或药物的刺激性太强,易在椎管内形成高渗透压或刺激,对神经根造成化学性刺激和脱水变性,甚至不可逆损伤,还可引起前列腺增生、过敏性皮炎、肝脏肿大和哮喘等。为此,考察糖皮质激素在骶管注射疗法中常用配伍的稳定性,为规范化的药物配伍供依据。
三、骶管注射疗法是从麻醉学基础上发展起来的,普遍认为骶管注射治疗腰椎间盘突出症的作用机理是通过糖皮质激素注入硬膜外腔直接阻断疼痛的传导通路,阻断化学刺激因子对神经根的刺激及抑制无菌性炎症,消除水肿及抑制粘连而达到治疗目的,以致临床上有人随意加大局麻药或糖皮质激素的用量,以期增加临床疗效。另外,不少学者认为注入大量的等渗药液,对硬膜外腔产生一定的冲击力和压力,有可能达到钝性的无创伤性分离粘连,推移对神经根压迫的突出椎间盘,起到所谓的“液体刀”作用。更有甚者声称中药制剂如丹参注射液、红花注射液等,在骶管注射疗法中的作用好过糖皮质激素,完全可以取代之!通过观测骶管注射疗法对腰椎间盘突出症的临床疗效,以期探究通过增加麻醉药或糖皮质激素用量、注入大量等渗性药液或丹参注射液、红花注射液,其疗效是否优于糖皮质激素。
方法：
一、将骶管注射疗法常用药物配伍按照基本药物组、西药组、中药组和中西医药物组等依次分为13个小组。基本药物组为局麻药(2%利多卡因、2%普鲁卡因)与糖皮质激素(地塞米松注射液)配伍,西药组为基本药物与不同西药(维生素B、碳酸氢钠注射液等)之间的配伍,中药组为基本药物与不同中药注射剂(丹参注射液、红花注射液等)之间的配伍,中西医药物组为基本药物与不同西药和中药注射剂之间的配伍。在室温下,分别配制各组药液后,各自在0min、30min、1.0h、2.0h、4.0h时观察其外观、pH值、紫外吸光度及不溶性微粒变化,详细的检测方法及评判标准见2005版的中华人民共和国药典(二部)附录ⅣA,ⅥH,ⅨC。
二、本课题组在进行预实验时,曾选用醋酸强的松龙悬浊液进行配伍,发现悬浊液本身较容易影响到对溶液微粒数等的观察,且考虑到本研究所涉及的配伍组别多,所以全采用水剂的地塞米松注射液进行配伍稳定性研究,且所配伍的地塞米松注射液的剂量也是固定的。为此,参照上述骶管注射疗法中常用的药物配伍组方,把研究对象按照糖皮质激素的不同剂量、不同剂型及中西医药物配伍分为7个小组进一步进行专项研究。在室温下,分别配制各组药液后,测定在0min、30min、1.0h、2.0h、4.0h时各组的外观、pH值及紫外吸收度变化,并采用高效液相色谱法测定各组配伍液中糖皮质激素的变化。
三、把90例腰椎间盘突出症的患者,随机分为生理盐水组(A组)、地塞米松低剂量组(B组,地塞米松注射液5mg)、地塞米松高剂量组(C组,地塞米松注射液20mmg)、曲安奈德低剂量组(D组,曲安奈德注射液5mg)、曲安奈德高剂量组(E组,曲安奈德注射液20mmg)和丹参注射液组(F组,丹参注射液5ml)；每组各15例,各个组别的性别、年龄、病程、突出部位分布等一般资料比较均无统计学差异(P>0.05),说明各个组别具有较好的均衡性。每组患者均按照各自的组方配制成总液量为20ml的溶液给予骶管注射。治疗前及治疗后即刻、1周和2周均使用改良的日本矫形外科学会(M-JOA)腰痛评分标准和疼痛视觉模拟评分(VAS)进行临床疗效评价。
结果：
一、骶管注射疗法模拟临床时,13个不同配伍组别在4h内,其注射液的外观、pH值、紫外吸收度均无显著性改变；除基本药物组、西药组和中药组的简单配伍组等共5组别的不溶性微粒符合2005年版《中国药典》规定外,其余8组配伍后不溶性微粒均不符合规定。
二、丹参注射液和红花注射液混合配伍后立即(0min)有大量黄白色沉淀物体生成；丹参注射液组和红花注射液组各自配伍后也即有少量黄白沉淀产生,并且随着放置时间延长沉淀物增加明显。其余各组配伍后液体澄明,未见明显变色及沉淀物生成。
三、除大剂量曲安奈德组出现较多肉眼可见的白色沉淀及中西医药物配伍组出现肉眼可见的大量棕色沉淀物外,其余各组别在4h内,其注射液的外观、pH值、紫外吸收度及高效液相色谱图均无显著性改变
四、用甲醇配置曲安奈德,在13.15处有较大的色谱峰,峰型完美,所以用甲醇配置样品适合于曲安奈德的分析。分别于Omin、30min和1h、2h、4h进样,测得标示量平均值为99.85%,RSD=0.92%(n=5),表明配伍液在4h内基本稳定；但在配伍24h后可见曲安奈德注射液出现少量分解。
五、治疗前各组患者M-JOA腰痛评分和VAS评分差异无统计学意义(P>0.05)；治疗后即刻各组患者的VAS评分与治疗前比较均有降低(P<0.05),但M-JOA评分与治疗前比较无明显差异(P>0.05)；骶管注射治疗后,糖皮质激素各组的M-JOA评分与VAS评分比生理盐水组和丹参注射液组降低明显(P<0.01),但生理盐水组和丹参注射液组、糖皮质激素各剂量组之间的M-JOA评分与VAS评分相比较无明显差异(P>0.05)。
六、骶管注射治疗后1周,曲安奈德组的M-JOA评分与VAS评分降低程度比地塞米松组明显(P<0.05),但治疗后2周,曲安奈德组与地塞米松组的M-JOA评分与VAS评分无明显差异(P>0.05)。依据M-JOA腰椎疾患治疗成绩评分表评定标准,改善率显示：各个组别改善率均达到优良,尤其以糖皮质激素各剂量组改善尤为明显,这表明经过治疗后,绝大多数患者疗效确切,腰椎功能和日常生活能力(ability of daily living, ADL)改善。
结论：
一、骶管注射疗法的药物配伍越简单越稳定,不论是西药还是中药制剂随着配伍药物成分的增加其稳定性降低,中西医药物更是不宜一起配伍使用。
二、骶管注射疗法的药物配伍应该严格遵循最低有效浓度和低剂量给药的原则,不宜盲目通过加大药物剂量来增强临床疗效。
三、在骶管注射疗法的药物配伍中,随糖皮质激素混悬液的剂量增加其药物配伍稳定性下降,不论是水剂的地塞米松注射液,还是醋酸曲安奈德注射混悬液均不宜与中药制剂配伍。中药成分复杂,从众多中药中选出药效肯定、持久、无不良反应且适宜众多药物配伍的药物,还有待去探索研究。
四、在骶管注射疗法的药物配伍中,糖皮质激素混悬液之配伍液在4h内基本稳定,但最好现配现用。
五、腰椎间盘突出症的骶管注射疗法中,从临床疗效观察中药制剂的作用与生理盐水无异,中药制剂在本病的治疗中仍属一种辅助作用。目前临床上用于腰椎间盘突出症的骶管注射所用中药种类较多,用中药取代激素也是一个思路,但从本课题临床观察发现此类配伍还不够成熟。
六、腰椎间盘突出症的骶管注射疗法中,起关键作用的仍是糖皮质激素,且临床临床疗效与糖皮质激素的剂量并不明显相关,考虑到混悬液有误注血管的危险和骶管内结晶可引起的组织粘连等意外,建议临床运用中最好遵循低剂量给药和缓推水剂优先的原则。
1. Objective:
1.1 Through simulating the common dosage clinically and studying the stability of compatibility of medicines used in sacral injection, to overcome the blindness and subjectivity in clinical operation, therefore provide theoretical support for safe compatibility for clinical use; The reason for complication in sacral injection are excessive local anesthetic use, too much drugs being used together, unfamiliarity with anatomy, over depth puncture, and et al, therefore reducing the incidence rate of complication in sacral injection.
1.2 Glucocorticoid is (one of) the most commonly used drugs in sacral injection, and also the biggest reason for complication by excessive use. Glucocorticoid have the effects of promotion Na+absorption and elimination of K+,but excessive use can lead to hypokalemia. The excessive use of hormone or intense irritant drugs will probably cause hyperosmolarity or intraspinal irritation, or chemical irritation, dehydration, degeneration and even irreversible damage to nerve root, or prostatic hyperplasia, allergic dermatitis, hepatomegaly, asthma and et al. To study the stability of glucocorticoid in sacral injection is very important in standardization of drug compatibility.
1.3 Sacral injection is developed from anesthesiology, and it is widely accepted that the mechanism of sacral injection in treatment of lumbar disc herniation (LDH) is blocking the conductive pathway of pain directly, blocking the stimulus to nerve roots of chemical factors, eliminating oedema and inhibiting adherence when glucocorticoid being injected into epidural space. Some people arbitrarily increase the dosage of glucocorticoid or local anesthetic in order to increase clinical effect, and some people consider high dose isotonic solution injecting will produce impact force and pressure in epidural space and may noninvasively detach adhesion, remove oppressed nerve root and serves as so-called "liquid knife", even some person allege that Chinese materia medica preparation including Dansen injection, Honghua injection and et al have a better effect than glucocorticoid in sacral injection, and Chinese materia medica preparation can replace glucocorticoid completely. The clinical effect of sacral injection on lumbar disc herniation is being studied in this article to explore the reliable curative effects of each drug injected into sacral.
2. Methods:
2.1 The medicines used in sacral injection is divided into essential medicines group(dexamethasone and 2% lidocaine or 2% procaine), western medicine group(drugs of essential medicines group add B vitamins, sodium bicarbonate injection and et al), Chinese medicine group(drugs of essential medicines group add Dansen injection, Honghua injection and et al), Chinese-Western medicine combined group(drugs of essential medicines group add Western medicine and Chinese materia medica preparation), and is divided into 13 groups further more. Compound medicines of each group were kept at room temperature respectively, and then observation on the changes in appearance, pH value,insoluble particles and UV absorbance at 0min、30min、1.0h、2.0h、4.0h respectively. The detailed detection method and judgment standard can be found in the People's Republic of China pharmacopoeia,2005,(part two), appendixⅣA,ⅥH, IXC.
2.2 Through studying prednisoloneacetate in preliminary experiment, it was found that the suspension can easily affect observation on particulate matter counting. Considering quite a few groups, fixed-dose dexamethason was made to study compatible stability of drugs in Reference to commonly used drugs recipes used in sacral injection, the glucocorticoid used in sacral injection is divided into 7 groups according to the different doses of corticosteroids, different dosage forms and the compatibility of Chinese and Western medicines. Compound medicines of each group was observed on the changes in appearance, pH value and UV absorbance at Omin、30min、1.0h、2.0h、4.0h at the ambient temperature respectively, and then glucocorticoid contents were determined by high performance liquid chromatography(HPLC).
2.3 To divide 90 lumbar disc protrusion patients into 6 groups at random, they are normal saline injection group(group A)、low dose hexadecadrol injection group(group B, hexadecadrol 5mg、high dose hexadecadrol injection group(group C, hexadecadrol 20mg)、low dose triamcinolone acetonide injection group(group D, triamcinolone 5mg)、high dose triamcinolone acetonide injection group(group E, triamcinolone 20mg) and DanShen injection group(group F, DanShen injection 5mg), each one has 15 patients, and there were no significant (statistic) differences among each groups on gender, age, course of the disease and prolapsed lumbar discs (P<0.05).All the patients received 20ml sacral injection and were accessed by M-JOA and VAS before injection、after injection immediately、1 week and 2 week after injection.
3. Results:
3.1 No significant changes were found for the mixture within 4h in appearance, pH value and UV absorbance; Except the particles of 5 simple compatibility groups in essential medicines group, western medicine group, Chinese medicine group reaching the standard(China Pharmacopoeia.2005 edition), the particles in the 8 other mixtures failed to meet the standard.
3.2 Visible yellow-white precipitates appeared in the groups of Chinese-Western medicine combined group.(Immediately appeared large when hexadecadrol add DanShen injection and Honghua injection; Immediately appeared a little when DanShen injection or Honghua injection add respectively western medicine group, but increased as time followed) The other groups have no color or precipitate.
3.3 No significant changes were found for the mixture within 4h in appearance, pH value, UV absorbance and high performance liquid chromatogram(HPLC), except large dose of triamcinolone group and Chinese-Western medicine combined group with large number of visible white or brown precipitate respectively.
3.4 Being used in confecting triamcinolone and having a bigger perfect chromatographic peak, carbinol is suited to confect triamcinolone. To inject durgs separately after 0min,30min,1h,2h,4h, and the mean is 99.85%, RSD=0.92% (n=5), it shown that the compatibility is stable in 4h, but triamcinolone can be seen after 24h in the compatibility of a small amount of decomposition occurs.
3.5 Their M-JOA and VAS scores are not of statistic significant difference before injection (P>0.05); their VAS scores immediately after injection are significantly lower than before injection (P<0.05), but the M-JOA scores have no significant difference before and immediately after injection (P>0.05); The M-JOA and VAS score of hexadecadrol and triamcinolone acetonide injection groups are significantly lower than normal saline and DanShen groups after injection (P<0.01), the M-JOA and VAS score of groups of different dose glucocorticoid injections, normal saline and DanShen groups have no significant (statistic) difference (P> 0.05).
3.6 The M-JOA and VAS score of triamcinolone acetonide group are significantly lower than hexadecadrol group 1 week after injection(P<0.05), but the M-JOA and VAS score of triamcinolone acetonide group and hexadecadrol group have no significantly difference 2 week after injection (P>0.05).The recovery rate of all groups are excellent especially glucocorticoid groups according to Lumber spine M-JOA standard, and it shown that most of patients have a good curative effect, the function of lumbar vertebra and ADL improved as well.
4. Conclusions:
4.1 For the medicines used in sacral injection, the simpler in compatibility, the more stable; whether western medicine or Chinese medicine, they all decrease in stability with drug increasing, furthermore, both Western medicine and Chinese medicine can not be used together.
4.2 We should strictly follow the principle of the lowest effective concentration and low-dose administration in sacral injection therapy, but should not increase (their) dosage blindly.
4.3 With the dose of glucocorticoid suspension increasing, its compatibility decreases in sacral injection. Both water ague glucocorticoid and triamcinolone acetonide acetate injection can not be mixed with Chinese medicine. Because the composition of Chinese herbs is complicated, it is hard to select one which is of specific, long-lasting effect but without side effect, which deserves our researches
4.4 Glucocorticoid is stable in 4h, and it is better to use the fresh one.
4.5 Traditional Chinese medicine preparation got the same effect as normal saline injection in sacral injection therapy treating lumbar disc protrusion, and Chinese materia medica preparation play an additional role in sacral injection. There are many Chinese materia medica preparations that were used in sacral injection, but we found it immature in our study.
4.6 Glucocorticoid plays an important role in sacral injection, but there have no significant correlation between clinical effect and dosage. Considering the danger of injection into vascular and adhesion caused by crystallization, it must be start from low dose and agent priority.
一、模拟临床用量,研究骶管注射疗法常用药物配伍的稳定性,克服临床实际操作中存在的盲目性和主观性,为临床安全配伍提供理论支持；骶管注射所致并发症多是由于局麻药剂量过大,配伍用药过多,不熟悉局部解剖以及穿刺过深等所致,由此避免此类操作可减少骶管注射疗法并发症的发生率。
二、糖皮质激素是骶管注射疗法中最常用的药物之一,也是最易滥用导致诸多临床意外发生的药物。糖皮质激素具有保钠排钾作用,大剂量应用可致血钾降低,导致低钾血症。如果激素用量太大或药物的刺激性太强,易在椎管内形成高渗透压或刺激,对神经根造成化学性刺激和脱水变性,甚至不可逆损伤,还可引起前列腺增生、过敏性皮炎、肝脏肿大和哮喘等。为此,考察糖皮质激素在骶管注射疗法中常用配伍的稳定性,为规范化的药物配伍供依据。
三、骶管注射疗法是从麻醉学基础上发展起来的,普遍认为骶管注射治疗腰椎间盘突出症的作用机理是通过糖皮质激素注入硬膜外腔直接阻断疼痛的传导通路,阻断化学刺激因子对神经根的刺激及抑制无菌性炎症,消除水肿及抑制粘连而达到治疗目的,以致临床上有人随意加大局麻药或糖皮质激素的用量,以期增加临床疗效。另外,不少学者认为注入大量的等渗药液,对硬膜外腔产生一定的冲击力和压力,有可能达到钝性的无创伤性分离粘连,推移对神经根压迫的突出椎间盘,起到所谓的“液体刀”作用。更有甚者声称中药制剂如丹参注射液、红花注射液等,在骶管注射疗法中的作用好过糖皮质激素,完全可以取代之!通过观测骶管注射疗法对腰椎间盘突出症的临床疗效,以期探究通过增加麻醉药或糖皮质激素用量、注入大量等渗性药液或丹参注射液、红花注射液,其疗效是否优于糖皮质激素。
方法：
一、将骶管注射疗法常用药物配伍按照基本药物组、西药组、中药组和中西医药物组等依次分为13个小组。基本药物组为局麻药(2%利多卡因、2%普鲁卡因)与糖皮质激素(地塞米松注射液)配伍,西药组为基本药物与不同西药(维生素B、碳酸氢钠注射液等)之间的配伍,中药组为基本药物与不同中药注射剂(丹参注射液、红花注射液等)之间的配伍,中西医药物组为基本药物与不同西药和中药注射剂之间的配伍。在室温下,分别配制各组药液后,各自在0min、30min、1.0h、2.0h、4.0h时观察其外观、pH值、紫外吸光度及不溶性微粒变化,详细的检测方法及评判标准见2005版的中华人民共和国药典(二部)附录ⅣA,ⅥH,ⅨC。
二、本课题组在进行预实验时,曾选用醋酸强的松龙悬浊液进行配伍,发现悬浊液本身较容易影响到对溶液微粒数等的观察,且考虑到本研究所涉及的配伍组别多,所以全采用水剂的地塞米松注射液进行配伍稳定性研究,且所配伍的地塞米松注射液的剂量也是固定的。为此,参照上述骶管注射疗法中常用的药物配伍组方,把研究对象按照糖皮质激素的不同剂量、不同剂型及中西医药物配伍分为7个小组进一步进行专项研究。在室温下,分别配制各组药液后,测定在0min、30min、1.0h、2.0h、4.0h时各组的外观、pH值及紫外吸收度变化,并采用高效液相色谱法测定各组配伍液中糖皮质激素的变化。
三、把90例腰椎间盘突出症的患者,随机分为生理盐水组(A组)、地塞米松低剂量组(B组,地塞米松注射液5mg)、地塞米松高剂量组(C组,地塞米松注射液20mmg)、曲安奈德低剂量组(D组,曲安奈德注射液5mg)、曲安奈德高剂量组(E组,曲安奈德注射液20mmg)和丹参注射液组(F组,丹参注射液5ml)；每组各15例,各个组别的性别、年龄、病程、突出部位分布等一般资料比较均无统计学差异(P>0.05),说明各个组别具有较好的均衡性。每组患者均按照各自的组方配制成总液量为20ml的溶液给予骶管注射。治疗前及治疗后即刻、1周和2周均使用改良的日本矫形外科学会(M-JOA)腰痛评分标准和疼痛视觉模拟评分(VAS)进行临床疗效评价。
结果：
一、骶管注射疗法模拟临床时,13个不同配伍组别在4h内,其注射液的外观、pH值、紫外吸收度均无显著性改变；除基本药物组、西药组和中药组的简单配伍组等共5组别的不溶性微粒符合2005年版《中国药典》规定外,其余8组配伍后不溶性微粒均不符合规定。
二、丹参注射液和红花注射液混合配伍后立即(0min)有大量黄白色沉淀物体生成；丹参注射液组和红花注射液组各自配伍后也即有少量黄白沉淀产生,并且随着放置时间延长沉淀物增加明显。其余各组配伍后液体澄明,未见明显变色及沉淀物生成。
三、除大剂量曲安奈德组出现较多肉眼可见的白色沉淀及中西医药物配伍组出现肉眼可见的大量棕色沉淀物外,其余各组别在4h内,其注射液的外观、pH值、紫外吸收度及高效液相色谱图均无显著性改变
四、用甲醇配置曲安奈德,在13.15处有较大的色谱峰,峰型完美,所以用甲醇配置样品适合于曲安奈德的分析。分别于Omin、30min和1h、2h、4h进样,测得标示量平均值为99.85%,RSD=0.92%(n=5),表明配伍液在4h内基本稳定；但在配伍24h后可见曲安奈德注射液出现少量分解。
五、治疗前各组患者M-JOA腰痛评分和VAS评分差异无统计学意义(P>0.05)；治疗后即刻各组患者的VAS评分与治疗前比较均有降低(P<0.05),但M-JOA评分与治疗前比较无明显差异(P>0.05)；骶管注射治疗后,糖皮质激素各组的M-JOA评分与VAS评分比生理盐水组和丹参注射液组降低明显(P<0.01),但生理盐水组和丹参注射液组、糖皮质激素各剂量组之间的M-JOA评分与VAS评分相比较无明显差异(P>0.05)。
六、骶管注射治疗后1周,曲安奈德组的M-JOA评分与VAS评分降低程度比地塞米松组明显(P<0.05),但治疗后2周,曲安奈德组与地塞米松组的M-JOA评分与VAS评分无明显差异(P>0.05)。依据M-JOA腰椎疾患治疗成绩评分表评定标准,改善率显示：各个组别改善率均达到优良,尤其以糖皮质激素各剂量组改善尤为明显,这表明经过治疗后,绝大多数患者疗效确切,腰椎功能和日常生活能力(ability of daily living, ADL)改善。
结论：
一、骶管注射疗法的药物配伍越简单越稳定,不论是西药还是中药制剂随着配伍药物成分的增加其稳定性降低,中西医药物更是不宜一起配伍使用。
二、骶管注射疗法的药物配伍应该严格遵循最低有效浓度和低剂量给药的原则,不宜盲目通过加大药物剂量来增强临床疗效。
三、在骶管注射疗法的药物配伍中,随糖皮质激素混悬液的剂量增加其药物配伍稳定性下降,不论是水剂的地塞米松注射液,还是醋酸曲安奈德注射混悬液均不宜与中药制剂配伍。中药成分复杂,从众多中药中选出药效肯定、持久、无不良反应且适宜众多药物配伍的药物,还有待去探索研究。
四、在骶管注射疗法的药物配伍中,糖皮质激素混悬液之配伍液在4h内基本稳定,但最好现配现用。
五、腰椎间盘突出症的骶管注射疗法中,从临床疗效观察中药制剂的作用与生理盐水无异,中药制剂在本病的治疗中仍属一种辅助作用。目前临床上用于腰椎间盘突出症的骶管注射所用中药种类较多,用中药取代激素也是一个思路,但从本课题临床观察发现此类配伍还不够成熟。
六、腰椎间盘突出症的骶管注射疗法中,起关键作用的仍是糖皮质激素,且临床临床疗效与糖皮质激素的剂量并不明显相关,考虑到混悬液有误注血管的危险和骶管内结晶可引起的组织粘连等意外,建议临床运用中最好遵循低剂量给药和缓推水剂优先的原则。
1. Objective:
1.1 Through simulating the common dosage clinically and studying the stability of compatibility of medicines used in sacral injection, to overcome the blindness and subjectivity in clinical operation, therefore provide theoretical support for safe compatibility for clinical use; The reason for complication in sacral injection are excessive local anesthetic use, too much drugs being used together, unfamiliarity with anatomy, over depth puncture, and et al, therefore reducing the incidence rate of complication in sacral injection.
1.2 Glucocorticoid is (one of) the most commonly used drugs in sacral injection, and also the biggest reason for complication by excessive use. Glucocorticoid have the effects of promotion Na+absorption and elimination of K+,but excessive use can lead to hypokalemia. The excessive use of hormone or intense irritant drugs will probably cause hyperosmolarity or intraspinal irritation, or chemical irritation, dehydration, degeneration and even irreversible damage to nerve root, or prostatic hyperplasia, allergic dermatitis, hepatomegaly, asthma and et al. To study the stability of glucocorticoid in sacral injection is very important in standardization of drug compatibility.
1.3 Sacral injection is developed from anesthesiology, and it is widely accepted that the mechanism of sacral injection in treatment of lumbar disc herniation (LDH) is blocking the conductive pathway of pain directly, blocking the stimulus to nerve roots of chemical factors, eliminating oedema and inhibiting adherence when glucocorticoid being injected into epidural space. Some people arbitrarily increase the dosage of glucocorticoid or local anesthetic in order to increase clinical effect, and some people consider high dose isotonic solution injecting will produce impact force and pressure in epidural space and may noninvasively detach adhesion, remove oppressed nerve root and serves as so-called "liquid knife", even some person allege that Chinese materia medica preparation including Dansen injection, Honghua injection and et al have a better effect than glucocorticoid in sacral injection, and Chinese materia medica preparation can replace glucocorticoid completely. The clinical effect of sacral injection on lumbar disc herniation is being studied in this article to explore the reliable curative effects of each drug injected into sacral.
2. Methods:
2.1 The medicines used in sacral injection is divided into essential medicines group(dexamethasone and 2% lidocaine or 2% procaine), western medicine group(drugs of essential medicines group add B vitamins, sodium bicarbonate injection and et al), Chinese medicine group(drugs of essential medicines group add Dansen injection, Honghua injection and et al), Chinese-Western medicine combined group(drugs of essential medicines group add Western medicine and Chinese materia medica preparation), and is divided into 13 groups further more. Compound medicines of each group were kept at room temperature respectively, and then observation on the changes in appearance, pH value,insoluble particles and UV absorbance at 0min、30min、1.0h、2.0h、4.0h respectively. The detailed detection method and judgment standard can be found in the People's Republic of China pharmacopoeia,2005,(part two), appendixⅣA,ⅥH, IXC.
2.2 Through studying prednisoloneacetate in preliminary experiment, it was found that the suspension can easily affect observation on particulate matter counting. Considering quite a few groups, fixed-dose dexamethason was made to study compatible stability of drugs in Reference to commonly used drugs recipes used in sacral injection, the glucocorticoid used in sacral injection is divided into 7 groups according to the different doses of corticosteroids, different dosage forms and the compatibility of Chinese and Western medicines. Compound medicines of each group was observed on the changes in appearance, pH value and UV absorbance at Omin、30min、1.0h、2.0h、4.0h at the ambient temperature respectively, and then glucocorticoid contents were determined by high performance liquid chromatography(HPLC).
2.3 To divide 90 lumbar disc protrusion patients into 6 groups at random, they are normal saline injection group(group A)、low dose hexadecadrol injection group(group B, hexadecadrol 5mg、high dose hexadecadrol injection group(group C, hexadecadrol 20mg)、low dose triamcinolone acetonide injection group(group D, triamcinolone 5mg)、high dose triamcinolone acetonide injection group(group E, triamcinolone 20mg) and DanShen injection group(group F, DanShen injection 5mg), each one has 15 patients, and there were no significant (statistic) differences among each groups on gender, age, course of the disease and prolapsed lumbar discs (P<0.05).All the patients received 20ml sacral injection and were accessed by M-JOA and VAS before injection、after injection immediately、1 week and 2 week after injection.
3. Results:
3.1 No significant changes were found for the mixture within 4h in appearance, pH value and UV absorbance; Except the particles of 5 simple compatibility groups in essential medicines group, western medicine group, Chinese medicine group reaching the standard(China Pharmacopoeia.2005 edition), the particles in the 8 other mixtures failed to meet the standard.
3.2 Visible yellow-white precipitates appeared in the groups of Chinese-Western medicine combined group.(Immediately appeared large when hexadecadrol add DanShen injection and Honghua injection; Immediately appeared a little when DanShen injection or Honghua injection add respectively western medicine group, but increased as time followed) The other groups have no color or precipitate.
3.3 No significant changes were found for the mixture within 4h in appearance, pH value, UV absorbance and high performance liquid chromatogram(HPLC), except large dose of triamcinolone group and Chinese-Western medicine combined group with large number of visible white or brown precipitate respectively.
3.4 Being used in confecting triamcinolone and having a bigger perfect chromatographic peak, carbinol is suited to confect triamcinolone. To inject durgs separately after 0min,30min,1h,2h,4h, and the mean is 99.85%, RSD=0.92% (n=5), it shown that the compatibility is stable in 4h, but triamcinolone can be seen after 24h in the compatibility of a small amount of decomposition occurs.
3.5 Their M-JOA and VAS scores are not of statistic significant difference before injection (P>0.05); their VAS scores immediately after injection are significantly lower than before injection (P<0.05), but the M-JOA scores have no significant difference before and immediately after injection (P>0.05); The M-JOA and VAS score of hexadecadrol and triamcinolone acetonide injection groups are significantly lower than normal saline and DanShen groups after injection (P<0.01), the M-JOA and VAS score of groups of different dose glucocorticoid injections, normal saline and DanShen groups have no significant (statistic) difference (P> 0.05).
3.6 The M-JOA and VAS score of triamcinolone acetonide group are significantly lower than hexadecadrol group 1 week after injection(P<0.05), but the M-JOA and VAS score of triamcinolone acetonide group and hexadecadrol group have no significantly difference 2 week after injection (P>0.05).The recovery rate of all groups are excellent especially glucocorticoid groups according to Lumber spine M-JOA standard, and it shown that most of patients have a good curative effect, the function of lumbar vertebra and ADL improved as well.
4. Conclusions:
4.1 For the medicines used in sacral injection, the simpler in compatibility, the more stable; whether western medicine or Chinese medicine, they all decrease in stability with drug increasing, furthermore, both Western medicine and Chinese medicine can not be used together.
4.2 We should strictly follow the principle of the lowest effective concentration and low-dose administration in sacral injection therapy, but should not increase (their) dosage blindly.
4.3 With the dose of glucocorticoid suspension increasing, its compatibility decreases in sacral injection. Both water ague glucocorticoid and triamcinolone acetonide acetate injection can not be mixed with Chinese medicine. Because the composition of Chinese herbs is complicated, it is hard to select one which is of specific, long-lasting effect but without side effect, which deserves our researches
4.4 Glucocorticoid is stable in 4h, and it is better to use the fresh one.
4.5 Traditional Chinese medicine preparation got the same effect as normal saline injection in sacral injection therapy treating lumbar disc protrusion, and Chinese materia medica preparation play an additional role in sacral injection. There are many Chinese materia medica preparations that were used in sacral injection, but we found it immature in our study.
4.6 Glucocorticoid plays an important role in sacral injection, but there have no significant correlation between clinical effect and dosage. Considering the danger of injection into vascular and adhesion caused by crystallization, it must be start from low dose and agent priority.
引文
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