Droperidol causes multifocal ventricular dysrhythmias

We report a case of ventricular chaotic arrhythmia after droperidol administration. A 49-year-old woman with chronic renal failure receiving hemodialysis, was scheduled for total hysterectomy under general anesthesia. General anesthesia was induced with thiopental 200 mg, fentanyl 0.1 mg and vecuronium 5 mg for endotracheal intubation. Anesthesia was maintained with 1% isoflurane and 60% nitrous oxide in oxygen. Droperidol 10 mg was injected for neuroleptanalgesia. After two minutes, ventricular chaotic arrhythmia occurred. Lidocaine 80 mg was injected. General anesthesia was stopped. After two minutes, arrhythmia disappeared. Several reports suggest that patients with preexisting conduction defects or prolonged QTc interval may be at risk to develop ventricular arrhythmias after droperidol administration. Administration of droperidol may have exaggerated prolongation of QTc interval.     

Droperidol Inhibits GABAA and Neuronal Nicotinic Receptor Activation

Background: Droperidol is used in neuroleptanesthesia and as an antiemetic. Although its antiemetic effect is thought to be caused by dopaminergic inhibition, the mechanism of droperidol's anesthetic action is unknown. Because [gamma]-aminobutyric acid type A (GABAA) and neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated as putative targets of other general anesthetic drugs, the authors tested the ability of droperidol to modulate these receptors.

Methods: [gamma]-Aminobutyric acid type A [alpha]1[beta]1[gamma]2 receptor, [alpha]7 and [alpha]4[beta]2 nAChRs were expressed in Xenopus oocytes and studied with two-electrode voltage clamp recording. The authors tested the ability of droperidol at concentrations from 1 nm to 100 [mu]m to modulate activation of these receptors by their native agonists.

Results: Droperidol inhibited the GABA response by a maximum of 24.7 +/- 3.0%. The IC50 for inhibition was 12.6 +/- 0.47 nm droperidol. At high concentrations, droperidol (100 [mu]m) activates the GABAA receptor in the absence of GABA. Inhibition of the GABA response is significantly greater at hyperpolarized membrane potentials. The activation of the [alpha]7 nAChR is also inhibited by droperidol, with an IC50 of 5.8 +/- 0.53 [mu]m. The Hill coefficient is 0.95 +/- 0.1. Inhibition is noncompetitive, and membrane voltage dependence is insignificant.