The Pharmaceutical Composition of Rocuronium Bromide May Promote Catecholamine Release From PC-12 Cells

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 (3x10⁵ 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.