Gordon Emma M, Myers Carolyn, Blumer Jeffrey
Division of Pediatric Pharmacology and Critical Care, Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
BMC Pharmacol. 2004 Oct 6;4:21. doi: 10.1186/1471-2210-4-21.
Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro.
The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018microg/ml and 0.45microg/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668microg/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions.
Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo.
静脉注射吗啡与组胺释放增加有关,在一些患者中会导致支气管收缩、水肿和血流动力学不稳定。本研究评估了亚硫酸盐(在许多吗啡制剂中作为防腐剂存在)在体外可能导致组胺释放的可能性。
在细胞培养条件下,将人肥大细胞系HMC-1暴露于不含亚硫酸盐的各种吗啡浓度中。临床达到的吗啡浓度(0.018微克/毫升和0.45微克/毫升)不会导致肥大细胞组胺释放增加。当吗啡浓度增加1184倍(668微克/毫升吗啡)时,组胺释放显著增加。暴露于吗啡和/或亚硫酸盐的肥大细胞释放组胺需要前列腺素H合成酶的存在。使用含亚硫酸盐吗啡溶液的实验中的组胺释放与仅使用吗啡溶液时观察到的情况在统计学上没有差异。
在含亚硫酸盐的吗啡溶液中,临床所见浓度的亚硫酸盐在人肥大细胞系HMC-1的体外实验中不导致组胺释放。但这并不排除亚硫酸盐可能在体内导致组胺水平升高这一事实。