Droperidol - instructions for use, indications, doses, analogues

Indications for use

Surgery: induction of anesthesia, premedication, potentiation of general and regional anesthesia; neuroleptanalgesia (simultaneously with fentanyl); providing a sedative effect, eliminating vomiting and pain in the postoperative period, vomiting and nausea during surgical and diagnostic procedures;
Therapy: shock and pain in injuries, severe attacks of angina, myocardial infarction, hypertensive crisis, pulmonary edema;
Psychiatric practice: hallucinations, psychomotor agitation.

Contraindications

Coma;
Extrapyramidal disorders;
Increased QT interval on ECG;
Severe depression;
Hypokalemia;
C-section;
Arterial hypotension;
Age up to 2 years;
Hypersensitivity to the components of the drug and morphine derivatives.

The use of Droperidol by pregnant women is possible only in cases where the expected benefit to the health of the mother is higher than the potential risk to the fetus. If it is necessary for women to use the drug during lactation, breastfeeding should be stopped.

Prolonged QT interval, TdP and LQTS

QT prolongation is a significant patient safety concern. The QT interval refers to the time from ventricular depolarization to the end of ventricular repolarization [8]. The QT interval is often corrected to the frequency of the corrected QT interval (QTc interval) through a mathematical formula known as the Bazett formula (QTc = QT/v R interval - R interval). Calculation of the QTc interval takes into account variables such as age, heart rate and gender [9]. According to Moss, “modern research provides an improved definition of QTc prolongation and estimates that the risk of malignant ventricular arrhythmias is exponentially related to the length of the QTc interval” [8]. However, Viskin believes that the actual QT interval is the best prognostic criterion for arrhythmogenic lesions before the QTc interval when significant bradycardia occurs [10]. A prolonged QT interval of more than 0.44 sec is considered pathological and is one of the main components that leads to the development of TdP [9]. A prolonged QTc interval on a standard ECG is often associated with malignant ventricular dysrhythmia, leading to syncope or death. QTc prolongation is only one of many risk factors for TdP, and the prolongation is often not impressively long. A patient with a prolonged interval in combination with metabolic disorders, left ventricular dysfunction and atrial fibrillation has an increased risk of developing malignant ventricular dysrhythmia [11]. The exact mechanism by which TdP develops is unclear. However, there is evidence that the onset of TdP may be related to several mechanisms.

TdP is a life-threatening ventricular tachycardia that is often associated with a prolonged QTc interval, hypokalemia, hypomagnesemia, and drugs known to prolong the QTc interval [12]. Other risk factors include bradycardia, female gender, congestive heart failure, congenital LQTS, and changes in T-wave morphology [10]. TdP occurs if ? 6 consecutive beats of polymorphic ventricular dysrhythmias occur [13], and the frequency ranges from 150 to 250 beats per minute [14]. TdP is often detected by the pause that precedes the dysrhythmia and by the wave of the QRS complex around the axis [10]. Another characteristic feature that often accompanies TdP is a change in the morphology of the T wave and the development of the U wave during strokes only to the point of dysrhythmia [13].

LQTS is a congenital syndrome associated with TdP that is characterized by a long QT interval in patients with a structurally normal heart [15]. LQTS can be classified as acquired and inherited forms, both of which are associated with TdP. TdP often resolves spontaneously, causing mild presyncope symptoms. However, TdP can sometimes worsen to ventricular fibrillation and is therefore potentially fatal. TdP is not always preceded by a prolonged QT interval. In fact, sources such as bradycardia, hypokalemia and hypoxia should be excluded [14]. A longitudinal study including 3343 individuals where one or more family members were found to have LQTS found a significant association with death if QTc, history of heart attack, or heart rate were measured [15].

In LQTS, disruption of the ion channels of the myocyte cell membrane leads to an excess of positive ions, prolonging the QT interval. Risk factors for death in LQTS include symptoms in infancy, deafness, history of cardiac arrest, and lack or absence of β-blocker therapy [10]. β-blocker therapy has traditionally been used as first-line therapy for LQTS.

Treatment of TdP is critical. TdP is known to progress to ventricular fibrillation [14]. Decreased oxygen delivery to the myocardium follows the development of TdP. Ventricular fibrillation can occur as a result of decreased oxygen delivery. Reduced blood flow causes acute ischemic disorders in the myocardium, leading to mechanical, electrical and chemical disintegration of heart cells. Cardiac arrest can occur quickly. If TdP remains untreated, long-term organ damage and death can occur [16].

Treatment of TdP includes defibrillation, intravenous magnesium, and possibly lidocaine infusion [10]. Treatment of metabolic disorders such as hypokalemia and hypomagnesemia is of primary importance. Discontinuation of drugs that have prodysrhythmic properties should be carried out immediately [17]. Ventricular dysrhythmias are associated with sudden death in more than 80% of cases. Early identification and treatment of dysrhythmia is critical for patient survival [16].

Directions for use and dosage

The dose of Droperidol is determined individually, taking into account the nature of the disease, age, general physical condition, body weight, drugs used simultaneously, and the type of anesthesia to be performed.

For premedication, adults are administered 2.5-5 mg of Droperidol intramuscularly 15-45 minutes before the start of surgery; children - at the rate of 100 mcg/kg.

For adults, the drug is prescribed in a dose of 15-20 mg (intravenously) for induction of anesthesia. For children, intravenous (at a dose of 200-400 mcg/kg) or intramuscular (at a dose of 300-600 mcg/kg) administration is possible.

To maintain anesthesia during long-term operations, repeated intravenous administration of Droperidol at a dose of 2.5-5 mg is possible.

In the postoperative period, adults are prescribed 2.5-5 mg intramuscularly every 6 hours.

Side effects

When using Droperidol, it is possible to develop disorders of certain body systems:

Central nervous system: drowsiness, dysphoria in the postoperative period and, conversely, when using high doses - fear, motor excitability, anxiety; rarely – extrapyramidal symptoms; in some cases in the postoperative period – depression, hallucinations;
Cardiovascular system: tachycardia and moderate arterial hypotension (usually no special therapy is required); in very rare cases - arterial hypertension (most likely when combined with fentanyl or other parenterally administered analgesics);
Digestive system: dyspepsia, loss of appetite, nausea; rarely – transient liver dysfunction, jaundice;
Allergic reactions: rarely - dizziness, anaphylactic reactions, trembling, bronchospasm, laryngospasm.

special instructions

Droperidol should only be used in hospital settings.

The drug should be prescribed with caution to patients with functional disorders of the kidneys and liver, depression, epilepsy, as well as in conditions preceding an epileptic seizure.

In case of pheochromocytoma, tachycardia and severe arterial hypertension may develop after administration of Droperidol.

During therapy, the possibility of developing severe arterial hypotension must be anticipated. The drug can also cause a decrease in pressure in the pulmonary artery, which must be taken into account during diagnostic and surgical procedures. Patients receiving Droperidol need careful medical supervision.

The initial dose of the drug should be reduced in elderly, exhausted and physically weakened patients. When increasing the dose, you should be guided by the effect obtained.

Droperidol should be prescribed in a lower dose when used concomitantly with drugs that have a depressant effect on the central nervous system. Accordingly, after Droperidol, the doses of such drugs are also reduced.

The use of Droperidol in high doses (25 mg or more) can lead to sudden death in patients with cardiac arrhythmias due to alcohol withdrawal, hypoxia, or electrolyte imbalance.

In surgical practice, when using the drug, it is necessary to carefully monitor the parameters of the physiological state of the body. When performing epidural or spinal anesthesia, it is possible to develop a blockade of the sympathetic nervous system and intercostal nerves, which, in turn, can lead to difficulty breathing, the development of arterial hypotension and dilation of peripheral vessels.

To avoid the occurrence of orthostatic hypotension, it is recommended to be careful when transporting the patient and to avoid sudden changes in body position.

While Droperidol is in effect and for 24 hours after its use, it is necessary to avoid performing potentially hazardous work that requires rapid psychomotor reactions and high concentration.

Droperidol's Effect on QT Interval

Jason B. Martinez, Daniel D. Moos, Larry L.

On December 4, 2001, the Food and Drug Administration (FDA) issued a letter to healthcare professionals regarding the drug droperidol. The purpose of the alert was to inform healthcare professionals about the possible role of droperidol in the development of torsade de pointes (TdP) in patients. The purpose of this article is to review the role of droperidol in the development of TdP in susceptible patients and to review current recommendations for the use of droperidol as an antiemetic drug.

December 4, 2001

The Food and Drug Administration (FDA) issued a "Dear Healthcare Professionals" letter from Akorn Pharmaceuticals that contained an FDA "black box" warning for the drug
droperidol
[1]. The black box warning alerted healthcare professionals to the possible serious adverse effects of droperidol. Of isolated concern, there have been reports of QT prolongation leading to torsade de pointes (TdP) in patients treated with droperidol at or below recommended dosages. Akorn also issued changes to the indications, use, dosage and prescription of droperidol [1] . This has led some professionals to discontinue the use of droperidol in their practices. Additionally, some institutions have removed droperidol from their formularies [2] . Nurse anesthetists should be aware of FDA recommendations for recording an electrocardiogram (ECG) before prescribing, monitoring patients during prescribing, and contraindications.

Drug interactions

When using Droperidol simultaneously with certain medications, undesirable effects may occur:

Drugs that have a depressant effect on the central nervous system (benzodiazepine derivatives, anesthetics, opioid analgesics, hypnotics): increased depressant effect on the central nervous system;
Antihypertensive drugs: potentiation of their action;
Epinephrine and other adrenergic and sympathomimetic drugs: manifestation of antagonism in their relation;
Dopamine agonists, including bromocriptine, lisuride and levodopa: inhibition of their action.

Droperidol amp. (solution d/i.v. and i.m. injection) 2.5 mg/ml 5 ml No. 10 Dalkhimpharm/Russia