Gender Influence on Torsadogenic Actions of Droperidol.

Gender Influence on Torsadogenic Actions of Droperidol Used as Postoperative Nausea and Vomiting Prophylaxis.

Postoperative nausea and vomiting (PONV) is a quite common complication affecting patients undergoing general anesthesia. There are a few pharmacological agents of well known effectiveness in reducing the risk of PONV. One of them is droperidol, which is a butyrophenone derivant. It has been widely used for the prevention and treatment of PONV due to its high effectiveness and low cost. Though, droperidol has a relevant side effect, that is a repolarization prolongation. This can lead to life-threatening cardiac arrhythmias: polymorphic ventricular tachycardia (torsades de pointes, TdP) that can degenerate into ventricular fibrillation and cardiac arrest. This was a reason why in 2001 the FDA issued a "black box" warning on droperidol. Ever since papers focused on this problem have described the influence of small doses of droperidol on TdP genesis as weak. This could be explained by the fact, that QT/QTc (corrected QT) interval prolongation, which represents prolonged cardiac repolarization on ECG, is not the sole determinant of a drug's potential to cause arrhythmia. Another electrocardiographical marker of torsadogenic action is increased transmural dispersion of repolarization (TDR). TDR represents differences in the repolarization between myocardial "layers" (like epicardium, endocardium, myocardium cells). It is believed that the induction of QT/QTc lengthening must coexist with TDR increase at the same time to promote torsadogenic changes.

It has been known, on the basis of research, that females have been more potent to torsadogenic actions of pharmacological agents than males. That could be related to estrogen influence on ECG parameters, which had been proven on animal model. It hasn't been investigated, whether gender is an important factor when considering droperidol's torsadogenic potential.

The aim of this study is to answer a hypothesis, that women are more potent to torsadogenic actions of droperidol in comparison with men.

Study Overview

• Status: Completed
• Conditions: Arrhythmia, Droperidol
• Intervention / Treatment: Drug: Droperidol Injectable Solution

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Gdansk, Poland, 80211
    • Medical University of Gdansk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 18 and 45 years old
• ASA (American Society of Anaesthesiologists) physical status 1 and 2

Exclusion Criteria:

• lack of informed consent
• ASA (American Society of Anaesthesiologists) physical status 3 and more
• admittance of repolarisation affecting drugs like: antiarrhythmics (Williams group I-IV), psychotropics, macrolides, antireflux drugs
• ischaemic heart disease
• cardiac failure NYHA (Hew York Heart Association) 1 and more
• congenital or acquired heart defects
• arrhythmias in anamnesis
• hormonal contraception,
• postmenopausal
• neoplasms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Droperidol group; Droperidol (Xomolix, Kyowa Kirin) 1.25 mg i.v. bolus	Drug: Droperidol Injectable Solution; An electrocardiogram analysis in: 5,10,15,20 minutes after injection of 1.25 mg of droperidol used as PONV prophylaxis.; Other Names: electrocardiogram analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QT and corrected QT interval time	measured in milliseconds	Change from baseline QT and corrected QT interval time at 5,10,15 and 20 minutes after administration of 1.25 mg droperidol
Time interval between T wave peak and T wave end	measured in milliseconds	Change from baseline T peak - T end time at 5,10,15 and 20 minutes after administration of 1.25 mg droperidol.

Collaborators and Investigators

• Sponsor: Medical University of Gdansk
• Investigators: Principal Investigator: Radoslaw Owczuk, Professor, Medical University of Gdansk

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 23, 2019
• Primary Completion (ACTUAL): December 31, 2020
• Study Completion (ACTUAL): December 31, 2020

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (ACTUAL): May 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: postoperative nausea and vomiting; torsadogenic action; transmural dispersion of repolarisation; corrected QT interval
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Vomiting; Nausea; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Adjuvants, Anesthesia; Droperidol
• Other Study ID Numbers: KB01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No