Droperidol

Brand names  Reversal agents Warnings 
Description  Special circumstances Alternative medications 
Dosing  Side effects and risks Contraindications 
Over sedation
  Common issues   


Brand Names

Inapsine 

Description

Droperidol is a butyrophenone, an antidopaminergic drug with antiemetic and antipsychotic properties. It is used to produce a state of tranquilization and mental detachment. Unlike narcotics, droperidol does not decrease respiratory drive.  Droperidol is also a powerful antiemetic and is used to reduce the incidence of nausea and vomiting in surgical and diagnostic procedures. Droperidol is used in endoscopic sedation as an adjunct to standard sedation for complex procedures or difficult-to-sedate patients such as alcoholics and chronic drug abusers. 

Dosing

 Droperidol Dosing for Endoscopic Sedation

Adult  

  • Initial dose: 1.25-2.5 mg via slow IV
  • Additional doses: Additional 1.25 mg doses may be administered to achieve the desired effect  
  • Onset of action: 3-10 minutes
  • Peak effect: 30 minutes
  • Duration of effect: 120-240 minutes

Dosage should be individualized. Some of the factors to be considered in determining dose are age, body weight, physical status, underlying pathological condition, use of other drugs, the type of anesthesia to be used, and the surgical procedure involved.

Vital signs and EKG should be monitored routinely.

Pediatric*

*Dosing information for droperidol in pediatric populations has not been well studied.

Top of Page

Over sedation

Symptoms
  • Symptoms of droperidol overdose include fast or pounding heartbeats, dizziness, uneven heart rate, or palpitations.

Treatment

  • If hypoventilation or apnea occurs, oxygen should be administered and respiration should be assisted or controlled as indicated. A patent airway must be maintained; an oropharyngeal airway or endotracheal tube might be indicated.
  • The patient should be carefully observed for 24 hours; body warmth and adequate fluid intake should be maintained.
  • If hypotension occurs and is severe or persists, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy.
  • If significant extrapyramidal reactions (e.g. tremor, slurred speech, akathisia, dystonia, anxiety, distress, paranoia, and bradyphrenia) occur in the context of an overdose, an anticholinergic (see atropine) should be administered.

Reversal Agents

  • None

Top of Page

Special Circumstances

  • Carcinogenesis, mutagenesis, impairment of fertility: No carcinogenicity studies have been carried out with droperidol. The micronucleus test in female rats revealed no mutagenic effects in single oral doses as high as 160 mg/kg. An oral study in rats (Segment I) revealed no impairment of fertility in either males or females at 0.63, 2.5 and 10 mg/kg doses (approximately 2, 9 and 36 times maximum recommended human I.V./I.M. dosage).
  • Use in pregnancy: Pregnancy Category C. Droperidol has not been shown to be teratogenic in animals. There are no adequate and well-controlled studies in pregnant women. Droperidol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Use in Labor and Delivery: There are insufficient data to support the use of droperidol in labor and delivery. Therefore, such use is not recommended.
  • Use in Nursing Mothers: It is not known whether droperidol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when droperidol is administered to a nursing mother.
  • Use in pediatric patients: The safety of droperidol in children younger than two years of age has not been established.
  • Use in Elderly and Chronically Ill patients: The initial dose of droperidol should be appropriately reduced in elderly, debilitated and other poor-risk patients. The effect of the initial dose should be considered in determining incremental doses.
  • Impaired Hepatic or Renal Function: Droperidol should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.

Top of Page

Side Effects and Risks

  • Drug interactions
    • CNS depressants: Additive CNS depression may result.
    • Diuretics and drugs known to increase the QT interval (such as cisapride, pimozide): Risk of life-threatening arrhythmias, including torsades de pointes, may be increased.
    • Barbiturates: Physically incompatible with droperidol.
  • Cardiovascular: QT interval prolongation; torsades de pointes; cardiac arrest; ventricular tachycardia; hypotension.
  • CNS: Postoperative drowsiness; extrapyramidal effects; restlessness; hyperactivity; anxiety; dizziness; postoperative hallucinations; mental depression.
  • Respiratory: Respiratory depression; bronchospasm; laryngospasm.
  • Miscellaneous: Muscular rigidity; chills or shivering.
  • Pheochromocytoma: In patients with diagnosed/ suspected pheochromocytoma, severe hypertension and tachycardia have been observed after the administration of droperidol.
  • Neuroleptic malignant syndrome: Rare cases of neuroleptic malignant syndrome (eg, altered consciousness, muscle rigidity, autonomic instability) have been reported.

Common Issues

  • The most common symptoms associated with droperidol use are mild to moderate hypotension and tachycardia, however these usually resolve without treatment. In the case of severe or persistent hypotension, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy.
  • The most frequently seen adverse behavioral effects of droperidol include dysphoria, postoperative drowsiness, restlessness, hyperactivity and anxiety, which can either be the result of an inadequate dosage (lack of adequate treatment effect) or of an adverse drug reaction (part of the symptom complex of akathisia).

Top of Page

Warnings

Please note: in December 2001, the United States Food and Drug Administration (FDA) issued a new black box warning due to the potential for serious proarrhythmic effects, and even death, after the administration of droperidol. The FDA noted that cases of QT prolongation and/or torsades de pointes (TdP) were reported, even when doses less than the 2.5 mg labeled dose of droperidol were used. The warning was based on 273 cases reported over a 4-yr period. A possible cardiac event occurred in 74 cases. There were 89 deaths reported, but the dose of droperidol was 2.5 mg or less in only two deaths. The majority of deaths involved droperidol doses that ranged from 25 to 250 mg. Five patients receiving droperidol 2.5 mg or less experienced either ventricular tachycardia or TdP.3 Furthermore, of all the cases reported, cardiac adverse events or death occurred in 10 patients when the recommended 0.625–1.25 mg antiemetic doses of droperidol were used. Careful review of those cases did not reveal evidence of a cause-and-effect relationship.

As a result of this black box warning, many clinicians became reluctant to use droperidol, and many hospitals removed the drug from their formulary. There was a 10-fold decrease in the sales of droperidol in the year after the black box warning. This is despite the fact that, in one survey, 92% of responders did not believe that the black box warning was justified.

QTc is prolonged in a dose-related manner after the administration of droperidol. However, when given at doses <2.5 mg, this prolongation is modest and transient. Although a warning would have been appropriate, the current black box warning is deemed excessive by many clinicians.
Source: Habib AS, Gan TJ. PRO: The Food and Drug Administration black box warning on droperidol is not justified. Anesth Analg 2008;106:1414–7

Another viewpoint is the black box warning is justified. However, the FDA also needs to clarify the existing black box warning. Specifically, the black box warning should be brought into line with the evidence, the regulatory guidelines, and the longstanding safety history of low dose droperidol by adding the following concluding sentence: "Doses of INAPSINE below 2.5 mg are considered off-label. The FDA has no position on the safety or efficacy of doses below 2.5 mg.

BOX WARNING

Cases of QT prolongation and/or torsade de pointes have been reported in patients receiving droperidol at doses at or below recommended doses. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.

Due to its potential for serious proarrhythmic effects and death, droperidol should be reserved for use in the treatment of patients who fail to show an acceptable response to other adequate treatments, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs.

Cases of QT prolongation and serious arrhythmias (e.g., torsade de pointes) have been reported in patients treated with droperidol. Based on these reports, all patients should undergo a 12-lead ECG prior to administration of droperidol to determine if a prolonged QT interval (i.e., QTc greater than 440 msec for males or 450 msec for females) is present. If there is a prolonged QT interval, droperidol should NOT be administered. For patients in whom the potential benefit of droperidol treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2-3 hours after completing treatment to monitor for arrhythmias.

Droperidol is contraindicated in patients with known or suspected QT prolongation, including patients with congenital long QT syndrome.

Droperidol should be administered with extreme caution to patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). Other risk factors may include age over 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anesthetics, and I.V. opiates. Droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect.

  • If hypotension occurs, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy. Repositioning the patient to improve venous return to the heart should be considered when operative conditions permit. It should be noted that in spinal and peridural anesthesia, tilting the patient into a head-down position may result in a higher level of anesthesia than is desirable, as well as impair venous return to the heart. Care should be exercised in the moving and positioning of patients because of a possibility of orthostatic hypotension. If volume expansion with fluids plus these other countermeasures do not correct the hypotension, then the administration of pressor agents other than epinephrine should be considered. Epinephrine may paradoxically decrease the blood pressure in patients treated with droperidol due to the alpha-adrenergic blocking action of droperidol.
  • Since droperidol may decrease pulmonary arterial pressure, this fact should be considered by those who conduct diagnostic or surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient.
  • Vital signs and EKG should be monitored routinely.
  • When the EEG is used for postoperative monitoring, it may be found that the EEG pattern returns to normal slowly.

Top of Page

Alternative Medications

  • Although in a different pharmaceutical class, diphenhydramine is sometimes used for premedication in a similar manner as droperidol.
  • Ondansetron can be used as an alternative antiemetic.
  • Fentanyl, midazolam, or propofol can be used as an alternative for sedation.

Contraindications

  • Droperidol is contraindicated in patients with known or suspected QT prolongation (i.e., QTc interval greater than 440 msec for males or 450 msec for females). This would include patients with congenital long QT syndrome.
  • Droperidol is contraindicated in patients with known hypersensitivity to the drug.
Sources

Cohen LB, DeLegge MH, Aisenberg J, Brill JV, Inadomi JM, et al. AGA institute review of endoscopic sedation. Gastroenterology. 2007;133(2):675-701.

Droperidol. Official FDA Drug Information. Drugs.com. May, 2006.
http://www.drugs.com/pro/droperidol.html

Droperidol. Professional Information: A-Z Drug Facts.
http://www.drugs.com/ppa/droperidol.html

Kost M. Moderate Sedation/Analgesia: Core Competencies for Practice, 2nd Ed. St. Louis, MO: Saunders, St. Louis; 2004:116.

Ludwin DB, Shafer SL. CON: The black box warning on droperidol should not be removed (but should be clarified). Anesth Analg 2008;106:1418–20

Wiener-Kronish J, Grooper. Conscious Sedation. Philadephia, PA: Hanley & Belfus, Inc; 2001:125  

Wilcox CM, Forsmark CE, Cello JP. Utility of droperidol for conscious sedation in gastrointestinal endoscopic procedures. Gastrointest Endosc. 1990;36(2):112-5.    

 

Top of Page

Last Updated December 17, 2008