Z. Wajima, T. Yoshikawa, A. Ogura
Apr 1, 2002
Citations
1
Influential Citations
14
Citations
Quality indicators
Journal
Critical Care Medicine
Abstract
Objective 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. Design Double-blind, prospective, placebo-controlled randomized study. Setting University teaching hospital. Patients Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). Interventions Intravenous administration of colforsin daropate or placebo (normal saline). Measurements and Main Results Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg·kg−1·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 &mgr;g·kg−1·min−1 (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 &mgr;g/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. Conclusions These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.