雾化前列环素输送系统的描述与评估

Description and evaluation of a delivery system for aerosolized prostacyclin.

作者信息

Siobal Mark S, Kallet Richard H, Pittet Jean-François, Warnecke Edna L, Kraemer Roger W, Venkayya Rajeev V, Tang Julin F

机构信息

Respiratory Care Services, San Francisco General Hospital, NH:GA-2, 1001 Potrero Avenue, San Francisco CA 94110, USA.

出版信息

Respir Care. 2003 Aug;48(8):742-53.

PMID:12890294

Abstract

INTRODUCTION

Inhaled vasodilators such as nitric oxide and aerosolized prostacyclin (PGI(2)) are used to treat severe hypoxemia in acute respiratory distress syndrome. Preferential distribution of nitric oxide and PGI(2) to ventilated areas of the lung causes selective pulmonary vasodilation, improved ventilation/perfusion matching, and decreased hypoxemia. Because of the technical limitations of previously described methods, we developed a PGI(2) delivery technique that allows the aerosolized drug dose to be easily calculated, set, and adjusted.

METHODS

A 50 mL solution of PGI(2) (3.0x10(4) ng/mL) and a 500 mL normal saline solution were infused by a dual-channel volumetric infusion pump into a MiniHEART jet nebulizer that has a manufacturer-specified output of 8 mL/h at a set flow of 2 L/min. By adjusting the pump infusion rate to achieve a total output of 8 mL/h, the PGI(2) concentration was altered to deliver a calculated aerosolized dose of 10-50 ng/kg/min. The effectiveness of the delivery system was retrospectively evaluated by way of the responses of 11 severely hypoxemic acute respiratory distress syndrome patients who received PGI(2) via the system we describe. The MiniHEART nebulizer output, particle size, and dose delivery were evaluated in a laboratory bench study, using a set flow of 2 L/min.

RESULTS

Aerosolized PGI(2) therapy (mean dose 28 +/- 17 ng/kg/min, range 10-50 ng/kg/min) significantly increased the ratio of P(aO)(2) to fraction of inspired oxygen (P(aO)(2)/F(IO)(2)) (60 +/- 11 mm Hg vs 80 +/- 17 mm Hg, p = 0.003) and arterial oxygen saturation measured via pulse oximetry (86 +/- 8% vs 94 +/- 3%, p = 0.005) (differences evaluated with the Wilcoxon signed rank test). There was no difference in positive end-expiratory pressure, mean airway pressure, or F(IO)(2), before and after aerosolized PGI(2) (p > 0.05). Nebulizer output was 6.8 +/- 0.9 mL/h, range 6.0-7.8 mL/h. The inhaled aerosol particles had a mass median diameter of 3.1 micro m. Emitted dose was 67 +/- 13% (range 57-81%) of the calculated dose.

CONCLUSION

Our system is effective in delivering aerosolized PGI(2) to the alveolar-capillary interface, as indicated by significant oxygenation improvements soon after therapy commenced. The performance of the MiniHEART nebulizer varies from the manufacturer's specifications, which may alter the delivered dose.

摘要

引言

吸入性血管扩张剂如一氧化氮和气雾剂型前列环素（PGI₂）用于治疗急性呼吸窘迫综合征中的严重低氧血症。一氧化氮和PGI₂优先分布于肺的通气区域，从而引起选择性肺血管舒张，改善通气/血流匹配，并减轻低氧血症。由于先前所述方法存在技术局限性，我们开发了一种PGI₂给药技术，该技术能使雾化药物剂量易于计算、设定和调整。

方法

将50 mL的PGI₂溶液（3.0×10⁴ ng/mL）和500 mL生理盐水溶液通过双通道容量输液泵输注到MiniHEART喷射雾化器中，该雾化器在设定流量为2 L/min时制造商规定的输出量为8 mL/h。通过调整泵的输注速率以达到8 mL/h的总输出量，改变PGI₂浓度以输送计算得出的10 - 50 ng/kg/min的雾化剂量。通过11例严重低氧血症急性呼吸窘迫综合征患者接受我们所描述系统给予的PGI₂后的反应，对给药系统的有效性进行回顾性评估。在实验室台架研究中，使用2 L/min的设定流量评估MiniHEART雾化器的输出量、颗粒大小和剂量输送情况。

结果

雾化PGI₂治疗（平均剂量28±17 ng/kg/min，范围10 - 50 ng/kg/min）显著提高了动脉血氧分压与吸入氧分数之比（P(aO)₂/F(IO)₂）（从60±11 mmHg提高到80±17 mmHg，p = 0.003）以及通过脉搏血氧饱和度测定的动脉血氧饱和度（从86±8%提高到94±3%，p = 0.005）（差异采用Wilcoxon符号秩检验评估）。雾化PGI₂前后呼气末正压、平均气道压或F(IO)₂无差异（p>0.05）。雾化器输出量为6.8±0.9 mL/h，范围为6.0 - 7.8 mL/h。吸入的气溶胶颗粒质量中值直径为3.1 µm。喷出剂量为计算剂量的67±13%（范围57 - 81%）。