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局部麻醉药在新生儿中的局部应用。

Topical use of local anesthetics in neonates.

作者信息

Essink-Tjebbes C M, Hekster Y A, Liem K D, van Dongen R T

机构信息

Department of Clinical Pharmacy, University Hospital Nijmegen, The Netherlands.

出版信息

Pharm World Sci. 1999 Aug;21(4):173-6. doi: 10.1023/a:1008623213199.

Abstract

INTRODUCTION

Various local anesthetics as in lidocaine ointment, amethocaine cream and EMLA cream are used topically for minor invasive interventions, such as venipuncture, both in children and adults. Since neonates have a nervous system that, albeit immature, enables them to feel pain, analgesia for these procedures is also indicated. Several studies in neonates have been carried out to establish effectiveness and safety of topically applied local anesthetics. These studies are reviewed in order to assess effectiveness and safety.

METHODS

A Medline search was made in order to review all studies on effectiveness and safety of topical use of local anesthetics in neonates. Effectivity or safety studies using local anesthetics for circumcision were rejected.

RESULTS

Seven studies on effectiveness were found: Three studies examined lidocaine ointment and four examined EMLA cream. Effectiveness of lidocaine ointment was questionable in two studies and negative in one. Effectiveness of EMLA cream was positive in two studies and negative in the other two. Four studies were found on safety of EMLA cream. All studies indicated that use of EMLA cream was safe.

DISCUSSION

The poor effectiveness found in the reviewed studies is possibly due to too long an application time, a lipophilic carrier used and difficulties in assessing pain. The time of application is often based upon studies in children. Since the skin of neonates acts more as a mucosa than as mature skin the local anesthetics are able to cross this barrier more rapidly. Also a high bloodflow in the heel enhances the uptake of the drug. The application time in neonates should therefore be reduced compared to children. The use of a lipophilic carrier should be avoided since a lipophilic carrier impedes the local anesthetic to be absorbed, leading to reduced effect. Various methods of pain assessment were being used. Since not all methods used are validated it is difficult to obtain an objective end point.

CONCLUSION AND RECOMMENDATION

The articles reviewed are non conclusive in their results of effective analgesia. Due to a lipophilic base form and a hydrophilic matrix EMLA cream is most effective. An application time of 30 minutes is recommended. In spite of the present precautions due to fear of methemoglobinemia, use of EMLA cream proved to be safe when used once a day. Since the clinical situation often requires more than one application a day, more research is needed to establish a safe and effective local anesthetic which can be applied topically several times a day in the neonate.

摘要

引言

多种局部麻醉剂,如利多卡因软膏、丁卡因乳膏和复方利多卡因乳膏,可局部用于儿童和成人的轻微侵入性操作,如静脉穿刺。由于新生儿的神经系统虽未发育成熟,但已具备感受疼痛的能力,因此这些操作也需要进行镇痛。已开展多项针对新生儿的研究,以确定局部应用局部麻醉剂的有效性和安全性。现将这些研究进行综述,以评估其有效性和安全性。

方法

进行了一项Medline检索,以回顾所有关于局部应用局部麻醉剂在新生儿中的有效性和安全性的研究。排除使用局部麻醉剂进行包皮环切术的有效性或安全性研究。

结果

共找到七项关于有效性的研究:三项研究检测了利多卡因软膏,四项研究检测了复方利多卡因乳膏。两项研究中利多卡因软膏的有效性存疑,一项研究结果为阴性。复方利多卡因乳膏在两项研究中的有效性为阳性,在另外两项研究中为阴性。找到四项关于复方利多卡因乳膏安全性的研究。所有研究均表明使用复方利多卡因乳膏是安全的。

讨论

综述研究中发现的有效性欠佳可能是由于应用时间过长、使用亲脂性载体以及疼痛评估困难。应用时间通常基于儿童研究。由于新生儿的皮肤更类似于黏膜而非成熟皮肤,局部麻醉剂能够更快地穿过这道屏障。足跟部位的高血流量也会增强药物的吸收。因此,与儿童相比,新生儿的应用时间应缩短。应避免使用亲脂性载体,因为亲脂性载体阻碍局部麻醉剂的吸收,导致效果降低。使用了多种疼痛评估方法。由于并非所有使用的方法都经过验证,因此难以获得客观的终点指标。

结论与建议

所综述的文章在有效镇痛结果方面尚无定论。由于具有亲脂性基质和亲水性基质,复方利多卡因乳膏最为有效。建议应用时间为30分钟。尽管出于对高铁血红蛋白血症的担忧目前采取了预防措施,但复方利多卡因乳膏每天使用一次时被证明是安全的。由于临床情况通常需要一天多次应用,因此需要更多研究来确定一种安全有效的局部麻醉剂,可在新生儿中每天多次局部应用。

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