Wajima Zen'ichiro, Yoshikawa Tatsusuke, Ogura Akira, Imanaga Kazuyuki, Shiga Toshiya, Inoue Tetsuo, Ogawa Ryo
Department of Anesthesia, Chiba Hokusoh Hospital, Chiba, Japan.
Crit Care Med. 2002 Apr;30(4):820-6. doi: 10.1097/00003246-200204000-00017.
Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction.
Double-blind, prospective, placebo-controlled randomized study.
University teaching hospital.
Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18).
Intravenous administration of colforsin daropate or placebo (normal saline).
Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60.
These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.
福斯高林是一种腺苷酸环化酶的直接激活剂，与其他增加细胞内环磷酸腺苷的药物类似，它能舒张气道平滑肌。然而，福斯高林的水溶性较差，限制了其在治疗支气管痉挛方面的潜在用途。可乐必妥福斯高林是一种新型强效水溶性福斯高林衍生物。关于该药物的支气管舒张作用尚无临床数据发表。本研究的目的是调查静脉注射可乐必妥福斯高林是否能预防硫喷妥钠 - 芬太尼引起的支气管收缩。
双盲、前瞻性、安慰剂对照随机研究。
大学教学医院。
36例患者被随机分为两组：对照组（n = 18）和可乐必妥福斯高林组（n = 18）。
静脉注射可乐必妥福斯高林或安慰剂（生理盐水）。
用5mg/kg硫喷妥钠和0.3mg/kg维库溴铵诱导麻醉。麻醉诱导后，以15mg·kg⁻¹·hr⁻¹持续输注硫喷妥钠。维持控制通气，输送含50%氧化亚氮的氧气。麻醉诱导20分钟后，对照组患者开始接受7.5mL/hr持续输注生理盐水，可乐必妥福斯高林组患者开始接受0.75μg·kg⁻¹·min⁻¹（7.5mL/hr）持续输注可乐必妥福斯高林，持续60分钟。之后，两组均接受5μg/kg芬太尼。在基线、即将给予芬太尼前（T30）、芬太尼注射后连续三个6分钟间隔（T36、T42和T48）以及芬太尼注射后30分钟（T60）测量收缩压和舒张压、心率、平均气道阻力（Rawm）、呼气气道阻力（Rawe）和动态肺顺应性（Cdyn）。在基线时，两组的Rawm、Rawe和Cdyn值相当。在对照组中，与基线相比，T36 - 60时Rawm显著增加，T36 - 48时Rawe显著增加，T36 - 60时Cdyn显著降低。在可乐必妥福斯高林组中，T36 - 60时Rawm、Rawe或Cdyn无变化。
这些观察结果表明静脉注射可乐必妥福斯高林对人体有支气管舒张作用。
