Itaya Tomoaki, Takagi Shunichi, Kamiya Takefumi, Nakazawa Keisuke, Katagiri Seidai, Suzuki Takahiro
Anesthesiology, Nihon University School of Medicine, Tokyo, JPN.
Cureus. 2024 Dec 28;16(12):e76537. doi: 10.7759/cureus.76537. eCollection 2024 Dec.
Several cases of pheochromocytoma presenting with hypertensive crises after anesthesia induction, possibly caused by rocuronium injection, have been reported. Rocuronium has two compositions: rocuronium bromide (RB) in sodium acetate hydrate/acetic acid buffer solution (acetic acid vehicle) and RB in glycine/hydrochloric acid buffer solution (hydrochloric acid vehicle). This study assessed the effect of rocuronium composition on the release of catecholamine from PC-12 rat adrenal pheochromocytoma cells.
PC-12 cells (3x10 cells) were cultured for 96 hours, then 1 mL of reagent was added for five minutes. First, the experiment used phosphate-buffered saline (PBS (-)), RB in PBS (-), an acetic acid vehicle, and RB in the acetic acid-based vehicle. Next, the experiment used an acetic acid vehicle and a hydrochloric acid vehicle. Then the experiment used an acetic acid vehicle and a mixed solution of 0.2 mL acetic acid vehicle + 0.8 mL normal saline (NS). Cell supernatants were collected and norepinephrine (NE) and dopamine (DA) concentrations were measured using high-performance liquid chromatography.
Release of NE and DA was caused by acetic acid vehicle, not by RB in PBS (-). Hydrochloric acid vehicles similarly showed a significantly lower release of NE and DA than acetic vehicle acid (NE, P=0.002; DA, P=0.002). In addition, the acetic acid vehicle diluted 5-fold with NS showed a significantly lower release of NE and DA than the acetic acid vehicle alone (NE, P=0.005; DA, P=0.002).
The concentration of acetic acid in the buffer solution, not RB, caused the release of catecholamines from PC-12 cells.
已有报道称，数例嗜铬细胞瘤患者在麻醉诱导后出现高血压危象，可能是由注射罗库溴铵所致。罗库溴铵有两种制剂：在水合醋酸钠/醋酸缓冲溶液（醋酸溶媒）中的溴化罗库溴铵（RB）以及在甘氨酸/盐酸缓冲溶液（盐酸溶媒）中的RB。本研究评估了罗库溴铵制剂对PC-12大鼠肾上腺嗜铬细胞瘤细胞儿茶酚胺释放的影响。
将PC-12细胞（3×10个细胞）培养96小时，然后加入1 mL试剂，作用5分钟。首先，实验使用磷酸盐缓冲盐水（PBS(-)）、PBS(-)中的RB、醋酸溶媒以及醋酸基溶媒中的RB。接下来，实验使用醋酸溶媒和盐酸溶媒。然后，实验使用醋酸溶媒以及0.2 mL醋酸溶媒+0.8 mL生理盐水（NS）的混合溶液。收集细胞上清液，采用高效液相色谱法测量去甲肾上腺素（NE）和多巴胺（DA）的浓度。
NE和DA的释放是由醋酸溶媒引起的，而非PBS(-)中的RB。盐酸溶媒同样显示出NE和DA的释放明显低于醋酸溶媒（NE，P=0.002；DA，P=0.002）。此外，用NS稀释5倍的醋酸溶媒显示出NE和DA的释放明显低于单独的醋酸溶媒（NE，P=0.005；DA，P=0.002）。
缓冲溶液中醋酸的浓度而非RB导致了PC-12细胞释放儿茶酚胺。
