Strayerisms: Droperidol is Back

Strayerisms: Droperidol is Back

Ruben Strayer, MD

Take-home Points

• Droperidol is a great agent in the agitated but not dangerous patient.
• 5 mg IM is the standard dose but you can go lower or higher depending on the size of the patient.
• Droperidol can be given along with a benzodiazepine if necessary but you need to monitor closely.
• Droperidol has substantial data supporting its use in headache and nausea/vomiting.
• Droperidol can mitigate the side effects of pain dose ketamine and expand its therapeutic window.
• Droperidol is safe and the risk is overblown. 

• In 2001, the FDA issued a black box warning about droperidol indicating that there was a significant risk of cardiac arrhythmias related to QT prolongation. This announcement came as a surprise to many. At the time, droperidol was a hugely popular antiemetic used primarily by anesthesiologists for post-operative nausea and vomiting for thirty years. Despite millions of doses, no one seemed to notice a problem until 71 adverse events were reported to the FDA on the same day.
• This sudden concern over the safety of droperidol coincided with the emergence of a more expensive medication, ondansetron, which coincidentally also treats post-operative nausea and vomiting. Until that time, not a single peer-reviewed case report or prospectively documented ventricular arrhythmia or death had been published.
• After the black box warning, hospitals across the country erected multiple barriers and requirements blocking the use of droperidol. This would make sense if the drug were dangerous. It isn’t. The use of droperidol plummeted and in 2012, the two manufacturers in the US stopped making it. Droperidol disappeared, except at Mayo Clinic, where they compounded their own.
• In 2012, the FDA issued a warning around ondansetron and the risk of QT prolongation and risk of arrhythmias. However, we haven’t seen the same level of panic about the use of ondansetron.
• Much has been written about the suspicious circumstances around the decline of droperidol.Dozens of studies were subsequently published attesting to the safety and efficacy of droperidol, including a cohort study from the Mayo Clinic who described over 6000 administrations of droperidol in their ED over a period of six years. During this time, there was not a single death or arrhythmia attributed to the drug.
  • Gaw, C et al. Effectiveness and safety of droperidol in a United States emergency department. Am J Emerg Med. 2020 Jul;38(7):1310-1314.
• In February of last year, the manufacturer announced that they were bringing droperidol back. Now many of us have access to a drug that seems to have been specifically designed for the needs of an emergency physician.
• Droperidol is a dopamine antagonist that has been classified as a typical or first generation antipsychotic or neuroleptic, although this term has fallen out of favor.The structural class is the butyrophenones along with its close relative haloperidol. It was developed in 1961 and marketed under the tradename Inapsine.
  • In addition to dopamine blockage, it has weaker antagonist affects at the alpha, serotonin, and histamine receptors.
  • Consider it like a faster younger cousin of haloperidol. They have similar effects but droperidol has significantly faster onset, especially when administered intramuscularly. Although there aren’t many head to head studies, droperidol is thought more effective than haloperidol for an array of indications.
• The most important indication is the treatment of emergency agitation. Strayer divides agitation in the ED into three categories; agitated but cooperative, disruptive without danger, and uncontrollably violent.
  • The cooperative patients usually don’t cause too much trouble and can often be managed with non-pharmacologic interventions or an oral medication targeting the underlying problem.
  • The severely agitated, uncontrollably violent patients are rare in most departments. This is the place for dissociative dose ketamine or high dose midazolam in the resuscitation bay.
  • Droperidol shines in the group of moderately agitated patients who are disruptive, not redirectable, require calming medications, but aren’t an immediate threat to themselves/others. There is low suspicion for an immediately dangerous condition. The goal in these patients is to have them sleep for a few hours after which they will wake up refreshed and vibrant and ready to return to society with a new outlook.
• There are multiple options available for the treatment of agitation in these patients.
  • A classic combination is haloperidol and lorazepam at a dose of 5 mg and 2 mg. This is fine and safe. However, haloperidol and lorazepam take a long time to take effect when given IM. Both have erratic absorption. It is not uncommon to need to redose the medications.
  • Midazolam is not a bad choice in this group. It is far superior to lorazepam in speed and reliability when given intramuscularly. The problem with midazolam as a single agent in alcohol related agitation is that it’s not reliably effective at safe doses of 2-4 mg. At reliably effective doses such as 5-7 mg, it is not reliably safe. If you give 5 mg midazolam to enough alcohol intoxicated patients, you will eventually see respiratory depression.
  • Droperidol is a magic bullet in these patients. It works quickly and effectively from the IM route. It is more sedating than haloperidol. It is very safe and has a short duration of action.
• The dose of droperidol for sedation is 5 mg IM. For a very agitated patient, you could give 7.5 mg or 10 mg. For a smaller patient who just needs a little pharmacologic encouragement to sleep, 2.5 mg is fine. Droperidol can be used as a single agent whereas haloperidol is often combined with another agent which takes longer to administer and increases the risk of adverse events.
• For patients who are severely agitated, droperidol can be combined with midazolam. 5 mg of droperidol and 2 mg of midazolam is more effective than the classic combination of 5 mg of haloperidol and 2 mg of midazolam. 5 mg droperidol with 5 mg of midazolam will take down just about anyone.
• For the dangerously agitated patient when you don’t want to use ketamine, Strayer has used 10 mg of droperidol with 10 mg of midazolam. However, patients who receive 10 mg of midazolam need to be closely monitored for respiratory depression.
• Another indication for droperidol is headache. Droperidol is very effective for headache and has probably the most literature support of any parenteral abortive therapy for migraine. It is much more sedating than metoclopramide but that might be a good thing in this situation. The dose is about half of that used for agitation (2.5-5 mg IV or IM).
• Droperidol is a terrific antiemetic. The classic dose is 1.25-2.5 mg. It was commonly dosed at 0.625 mg IV by anesthesiologists in the PACU but the ED is more stimulating. Strayer usually gives 2.5 mg IV with a liter of fluid. You can do the same for symptomatic treatment of vertigo.
• Droperidol works for all types of pain, especially if there is an emotional component to the pain. Strayer uses droperidol or haloperidol frequently for abdominal pain that doesn’t to respond to initial medications. He gives 2.5-5 mg of droperidol IV and it works all the time.
• Chronic pain is its own discussion. However, in patients with severe exacerbations of chronic pain where Strayer judges opiates to be more likely to harm than help, he gives 5 mg droperidol IM. If this doesn’t work in 30-60 minutes, he starts an IV and gives another 5 mg IV. The patient usually falls asleep, wakes up, feels better and asks to leave. If the patient is still in pain, you are now set up for analgesic dose ketamine. The problem with low dose ketamine is that there is a narrow therapeutic window between effective analgesia and bothersome psychoperceptual effects. These are usually not a big deal and may manifest as dizziness. However, this can be dysphoric for patients. After receiving 10 mg of droperidol, patients don’t care about the effects of ketamine and it widens the therapeutic index.
• The side effects of droperidol are similar to haloperidol.
  • They may have extrapyramidal symptoms, akasthisia or dystonia. These usually respond to antimuscarinics such as diphenhydramine or benztropine. Dystonic reactions are common and may be subtle and dismissed, especially because they occur in the type of patient you are giving haloperidol/droperidol to. They can be dramatic and mistaken for more serious conditions. Akasthisia is a very uncomfortable feeling of restlessness which is common. It is usually seen after haloperidol or metoclopramide although it can be seen with droperidol as well.
  • Neuroleptic malignant syndrome is rare but dangerous.
  • The one side effect you will probably never see is the one that every freaks out about; torsades. Droperidol, like many medications we use, frequently causes a dose dependent prolongation of the QT interval. There are case reports of torsades and death with droperidol. These usually describe complex circumstances where droperidol was used in a cocktail of other medications or used in extremely high doses, but not always. There are probably some patients who have received a normal dose of droperidol and developed dangerous QT prolongation and torsades. However, these are rare events and case reportable. Droperidol has a decades long record of safety with millions of doses of administered without incident. It is safer than other drugs nobody worries about like midazolam or morphine. You may want to avoid using it in patients with a known long QT, methadone or some cardiac medications.
  • Although some hospital protocols advise it, it is not the standard of care or necessary to routinely get an ECG before or after the administration of droperidol, haloperidol or other QT prolonging medications.
• Ask your pharmacy team if you can get droperidol back on formulary. It is the emergency doctor’s best friend for agitation, headache, vomiting, vertigo, and acute/chronic pain.

Related Material

EM:RAP 2016 February: Paper Chase 1: Is Droperidol Safe?

EMA 2016 February Abstract 23: Training The Mind, And The Food And Drug Administration, On Droperidol