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新的活体人体血管微量给药技术(微透析)用于去甲肾上腺素经皮给药对烧伤休克复苏的意义。

Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline.

机构信息

Department of Anaesthesia and Intensive Care, County Council of Östergötland, Linköping, Sweden.

出版信息

Burns. 2012 Nov;38(7):975-83. doi: 10.1016/j.burns.2012.05.012. Epub 2012 Jun 27.

DOI:10.1016/j.burns.2012.05.012
PMID:22748196
Abstract

INTRODUCTION

Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support.

METHOD

Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded.

RESULTS

Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine.

CONCLUSION

These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.

摘要

简介

皮肤具有很大的血液流动能力,可以在低灌注状态下(如烧伤休克复苏期间)改变血液流动,因此经常用于招募血液。然而,对于血管活性药物(即去甲肾上腺素)用于循环支持时,真皮中观察到的血流和代谢变化知之甚少。因此,本研究的目的是:开发一种基于皮肤微透析的体内人微剂量模型;并在该模型中,通过微透析系统模拟药物诱导的循环支持,局部应用去甲肾上腺素和硝酸甘油,研究其对血流和代谢的影响。

方法

9 名健康志愿者将微透析导管置于前臂掌侧的真皮内。导管以 3 或 30mmol/L 的去甲肾上腺素灌注,在平衡期后,所有导管均以 2.2mmol/L 的硝酸甘油灌注。尿素清除技术和激光多普勒成像测量真皮血流。同时记录真皮葡萄糖、乳酸和丙酮酸浓度的变化。

结果

通过微透析探针递送至真皮的去甲肾上腺素和硝酸甘油诱导了所有变量的时间和剂量依赖性的大变化。我们特别注意到,组织葡萄糖浓度对低灌注的反应迅速,但仍高于零。此外,去甲肾上腺素给药后仍存在血管收缩,提示血管痉挛和真皮自动调节能力减弱。去甲肾上腺素引起的血管收缩导致的葡萄糖和乳酸变化,直到硝酸甘油主动诱导血管扩张时才会消失。

结论

这些发现,即真皮血流和代谢受损,从烧伤休克复苏的角度来看特别有趣,因为去甲肾上腺素通常用于循环支持。需要进一步探索在健康志愿者体内真皮模型中获得的这些结果的重要性和临床价值,以便在烧伤患者中进行探索。

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