The Incidence of QT Prolongation and Torsades des Pointes in Patients Receiving Droperidol in an Urban Emergency Department

Abstract

Introduction: Droperidol carries a boxed warning from the United States Food and Drug Administration for QT prolongation and torsades des pointes (TdP). After a six-year hiatus, droperidol again became widely available in the US in early 2019. With its return, clinicians must again make decisions regarding the boxed warning. Thus, the objective of this study was to report the incidence of QT prolongation or TdP in patients receiving droperidol in the ED. Methods: Patients receiving droperidol at an urban Level I trauma center from 1997-2001 were identified via electronic health record query. All patients were reviewed for cardiac arrest. We reviewed electrocardiogram (ECG) data for both critically-ill and noncritical patients and recorded Bazett's corrected QT intervals (QTc). ECGs from critically-ill patients undergoing resuscitation were further riskstratified using the QT nomogram. Results: Of noncritical patients, 15,374 received 18,020 doses of droperidol; 2,431 had an ECG. In patients with ECGs before and after droperidol, the mean QTc was 424.3 milliseconds (ms) (95% confidence interval [CI], 419.7-428.9) before and 427.6 ms (95% CI, 424.3-430.9), after droperidol (n = 170). Regarding critically-ill patients, 1,172 received droperidol and 396 had an ECG. In the criticallyill group with ECGs before and after droperidol mean QTc was 435.7 ms (95% CI, 426.7-444.7) before and 435.8 ms (95% CI, 427.5-444.1) after droperidol (n = 114). Of 337 ECGs suitable for plotting on the QT nomogram, 13 (3.8%) were above the "at-risk" line; 3/136 (2.2%; 95% CI, 0.05-6.3%) in the before group, and 10/202 (4.9%; 95% CI, 2.4%-8.9%) in the after group. A single case of TdP occurred in a patient with multiple risk factors that did not reoccur after a droperidol rechallenge. Thus, the incidence of TdP was 1/16,546 (0.006%; 95% CI, 0.00015-0.03367%). Conclusion: We found the incidence of QTc prolongation and TdP in ED patients receiving droperidol to be extremely rare. Our data suggest the FDA "black box warning" is overstated, and that close ECG monitoring is useful only in high-risk patients. [West J Emerg Med. 2020;21(4)728-736.] (FDA) for the treatment of postoperative nausea and vomiting (PONV). 1 Over the past 30 years it has also become a cornerstone therapy for nausea and vomiting, 2 headache, 3,4 and agitation 5-7

Response: “The Incidence of QT Prolongation and Torsades des Pointes in Patients Receiving Droperidol in an Urban Emergency Department”

“…We read with interest the recent article discussing QT prolongation and torsade des pointes (TdP) and droperidol. 1 The paucity of readily available antipsychotics and antiemetics that are not associated with QT prolongation makes selection of an appropriate pharmaceutical challenging in ideal situations and decidedly complex when confronted with an agitated, delirious, or intoxicated patient.…”

Randomized Double‐blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department

“…Despite the relatively stern FDA black box warning, the incidence of torsades des pointes is uncommon with droperidol. We recently estimated it to occur in approximately 0.006% of ED patients receiving droperidol 24 . While ziprasidone is described to cause QTc prolongation, the incidence of associated torsades des pointes is less clear.…”

“…From 2004 to 2005 our institution performed a blinded RCT comparing IM droperidol, ziprasidone, and lorazepam for acute agitation in the ED; however, these data were presented as an abstract only 23 . Because droperidol returned to the U.S. market in 2019, 24 we decided that it was important to fully publish these data, which are presented in this article. Because only two previous RCTs studied IM droperidol in the ED, 25 these data have again become relevant as emergency physicians look to make evidence‐based choices in this relatively understudied patient population.…”

Patients treated for acute headache with intranasal droperidol spend less time in the emergency department: A retrospective observational study

“…It acts via blockade of dopamine receptors in the subcortical, midbrain and brainstem reticular formation and produces mild alpha‐adrenergic blockade and peripheral vascular dilatation. Droperidol has been used to produce rapid sedation of psychomotor agitation, as an adjunct to anaesthesia and for the treatment of nausea and vomiting 2–5 . It has high potency, rapid onset and a relatively short duration of action compared to other sedatives.…”