, Volume 66, Issue 16, pp 2123-2147
Date: 12 Sep 2012

Intravenous Droperidol

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Summary

Abstract

Droperidol (Dehydrobenzperidol®, Dehidrobenzoperidol®, Dridol®, Droleptan®, Inapsine®) is a dopamine D2 receptor antagonist that has been widely used in adults and children for the prevention and treatment of postoperative nausea and vomiting (PONV) over several decades and, more recently, for the prevention of opioid-induced PONV during patient-controlled analgesia (PCA) in adults. In well controlled clinical trials of patients undergoing surgery, the efficacy of single-dose intravenous (IV) droperidol in preventing PONV was similar to that of ondansetron and dexamethasone. Droperidol significantly reduced opioid-induced PONV in adults during PCA and had a morphine-sparing effect. Droperidol is generally well tolerated and the incidence of adverse effects is similar to that observed with placebo and the serotonin 5-HT3 receptor antagonists (setrons). Guidelines recommend that, in adults, droperidol monotherapy be considered for those at moderate risk of PONV, and droperidol in combination with a setron and/or dexamethasone be considered for patients at moderate or high risk of PONV. In children with moderate or high risk of PONV, droperidol is recommended for first-line use in some countries, and second-line use in others.

Pharmacological Properties

Droperidol is a butyrophenone derivative and dopamine antagonist with high and preferential affinity for D2 receptors and a slightly lower affinity for α1A adrenergic receptors. Droperidol antagonises the effects of apomorphine, and its antiemetic effects in the prevention and treatment of PONV have been demonstrated in patients undergoing anaesthesia for a variety of surgical procedures. No overall respiratory depression has been demonstrated with droperidol, but its coadministration with known respiratory depressants requires monitoring due to individual variation among recipients. The drug has been associated with a dose-dependent prolongation of the frequency-corrected QT interval.

The pharmacokinetics of droperidol are linear for the dose range used to manage PONV and values are similar in anaesthetised patients and healthy volunteers. Droperidol is rapidly distributed into the brain, is extensively metabolised by the liver, and excreted primarily in the urine. The terminal elimination half-life of droperidol is approximately 2 hours. Coadministration of droperidol with halothane or isoflurane does not affect its pharmacokinetics. IV droperidol administered in children results in a lower clearance rate and volume of distribution than in adults, but a similar terminal elimination half-life.

Therapeutic Efficacy

IV droperidol (0.625–2.5mg in adults; 0.02–0.075 mg/kg in children) has demonstrated efficacy in the prevention and treatment of PONV in adults and postoperative vomiting (POV) in children. Overall, in large, well designed clinical trials in the prevention of PONV, the efficacy of single-dose droperidol in adults and children appeared to be similar to that of ondansetron, and similar to or lower than that of granisetron. In adults and children, combination therapy with droperidol plus a setron generally enhanced efficacy compared with monotherapy.

Overall, in the comparative trials of conventional antiemetics reviewed here, droperidol demonstrated similar efficacy in the prevention of PONV to dexamethasone, dimenhydrinate and promethazine, and generally superior efficacy to metoclopramide. A large randomised factorial trial found that droperidol, ondansetron or dexamethasone each reduced the relative risk of PONV by about one-quarter.

In several well controlled trials that investigated the prevention of opioidinduced PONV in patients using PCA after surgery, droperidol was more effective and associated with a lower need for rescue antiemetics than placebo or no prophylaxis. Efficacy against opioid-induced PONV appeared similar with droperidol or ondansetron in two large studies. A morphine-sparing effect was associated with droperidol use in PCA following surgery; morphine use and pain intensity were significantly lower in patients receiving droperidol than in those receiving placebo.

A cost-effectiveness study using a model based on clinical data demonstrated that droperidol 1.25mg was dominant to droperidol 0.625mg, ondansetron 4mg and placebo with regard to gaining one more PONV-free patient. In a further study, the extra cost associated with droperidol plus ondansetron compared with droperidol plus dexamethasone was reasonable given the improved efficacy.

Tolerability

IV droperidol is generally well tolerated in adults and children. In numerous clinical trials of patients undergoing various surgical procedures, the overall incidence of adverse events with single-dose droperidol was similar to that reported with placebo.

The most common adverse event associated with droperidol is sedation, which is dose dependent and more likely to occur in the early postoperative period (i.e. up to 6 hours). In a large well designed trial, the most common adverse events associated with droperidol were sedation, headache and dizziness. Overall, the incidence of adverse effects with droperidol is similar to that seen with setrons, but droperidol is more likely to cause sedation and less likely to cause headaches.

At droperidol dosages used for the prevention of PONV, extrapyramidal symptoms (e.g. dyskinesias) are very unlikely.

Various sections of the manuscript reviewed by: A. Alkaissi, Department of Anesthesiology and Intensive Care, University Hospital in Linkoping, Linkoping, Sweden; G. Bugedo, Department of Intensive Care & Anesthesiology, Pontificial Catholic University of Chile, Santiago, Chile; L. Eberhart, Department of Anaesthesiology & Intensive Care, University Hospital Giessen-Marburg, Marburg, Germany; A.S. Habib, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA; W.S. Jellish, Department of Anesthesiology, Loyola University Medical Center, Maywood, Illinois, USA; P. Pan, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Data Selection

Sources: Medical literature published in any language since 1963 on ‘droperidol’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company marketing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘droperidol’ and ‘postoperative nausea’ or ‘postoperative vomiting’ or ‘PONV’. Searches were last updated 7 November 2006.
Selection: Studies in patients undergoing surgery who received droperidol. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Droperidol, dopamine receptor antagonist, emesis, pharmacodynamics, pharmacokinetics, postoperative nausea and vomiting, prevention, therapeutic use.