Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

How Dangerous Is Droperidol

Continuing from Droperidol – Black Box Warning.

Well, how dangerous is droperidol?

These 271 reports occurred between November 1997 and December 2001. After a review of these records, it appeared that some of these cases represented the same patients reported by different sources. Cases that matched by age, gender, and medication list were eliminated as duplicate and triplicate reports. This left us with what appeared to be 93 unique instances of death reported in association with droperidol use.[1]

93 deaths over a 4 year period.

Out of how many doses?

In an audit in five major hospitals in our metropolitan area, more than 38,000 doses of droperidol are dispensed annually, with 1,200 of those being used in our ED.[1]

Millions of doses.

If the hospitals in Portland, OR use 38,000 doses per year, and Portland is only the 29th largest city in the US,[2] just assuming the same number of doses for all of the larger cities in the US, no matter how many times larger than Portland they may be, would put the number over 1,000,000 doses. The reports of deaths are from all over the world, not just in the US, so millions is not some wild, or exaggerated, guess.

Less than 100 cases of death that might be due to droperidol over a 4 year period.

Millions of doses of droperidol each of those four years. At worst, still much less than 1/100th of 1 percent. A death rate of less than 0.01%.

It could be tens of millions of doses, or even more than 100 million doses. That means that the difference could be a ten times greater safety factor – or it could mean a 100 times greater safety factor than what I conservatively calculated.

How dangerous is excited delirium?

According to an ACEP (American College of Emergency Physicians) task force, the death rate is over 8%. [3]

Over 8% vs. much less than 0.01%.

Excited delirium is much more than 800 times more dangerous than droperidol.

Can we directly compare these numbers?

The first group includes a lot of patients being treated for nausea, vomiting, and pain in addition to some patients being treated for excited delirium.

The second group (excited delirium patients) is probably not even aware of any nausea, vomiting, or pain, but the excited delirium will kill a large number of these patients.

If the best way to prevent the death of these patients is to sedate them and the most appropriate sedative is droperidol, is there any reason to believe that the low death rate blamed on droperidol is even relevant? Is there any reason to believe that the high death rate attributed to excited delirium is due to anything other than a lack of appropriate sedation?

 

Death due to a lack of droperidol during excited delirium is much more than 800 times more likely than death due to droperidol.

 

Is anyone having trouble understanding that math?

Should anyone even hesitate to use droperidol to treat excited delirium?

The most appropriate sedative may be droperidol. I will discuss this in some more posts.

Footnotes:

[1] Droperidol–behind the black box warning.
Horowitz BZ, Bizovi K, Moreno R.
Acad Emerg Med. 2002 Jun;9(6):615-8. No abstract available.
PMID: 12045077 [PubMed – indexed for MEDLINE]

Free Full Text PDF Download from Academic Emergency Medicine

[2] Portland, Oregon
Wikipedia
Article

As of the 2010 Census, it had a population of 583,776,[5] making it the 29th most populous city in the United States.

[3] White Paper Report on Excited Delirium Syndrome
ACEP Excited Delirium Task Force
Vilke GM, Debard ML, Chan TC, Ho JD, Dawes DM, Hall C, Curtis MD, Costello MW, Mash DC, Coffman SR, McMullen MJ, Metzger JC, Roberts JR, Sztajnkrcer MD, Henderson SO, Adler J, Czarnecki F, Heck J, Bozeman WP.
September 10, 2009
Free Full Text PDF

Updated link to PDF 7/23/2018.

.

Comments

  1. Since excited delirium needs to be treated, and this is an area where ALS can improve a patient’s outcome, a better question is what is the best medication for excited delirium?

    My service used to carry Droperidol (before I worked here) but switched to Haldol after the Black Box warning. Haldol and Geodon also have a risk of worsening long QT, is Droperidol worse?

    Dr. Wesley promotes Geodon in a 24/7 EMS video about excited delirium, and Dr. Peter Antevy promotes Ketamine here: http://www.pediatricemergencystandards.com/index.php?option=com_content&view=article&id=59&Itemid=68

    I look forward to reading more about this, and would love to see a trial.

    • Bob,

      Since excited delirium needs to be treated, and this is an area where ALS can improve a patient’s outcome, a better question is what is the best medication for excited delirium?

      My service used to carry Droperidol (before I worked here) but switched to Haldol after the Black Box warning. Haldol and Geodon also have a risk of worsening long QT, is Droperidol worse?

      Droperidol is probably not significantly worse.

      Dr. Wesley promotes Geodon in a 24/7 EMS video about excited delirium, and Dr. Peter Antevy promotes Ketamine here: http://www.pediatricemergencystandards.com/index.php?option=com_content&view=article&id=59&Itemid=68

      Ziprasidone (Geodon) is just a newer medication with fewer benefits and with side effects that are less well known. Anything bad that can happen with droperidol, can probably happen with ziprasidone.

      Is there any anti-psychotic/sedative medication that does not lengthen the QT segment, but is effective at sedating excited delirium?

      No.

      Ketamine is interesting, but it is a stimulant, so it may not be a good idea with a patient having extreme sympathetic stimulation to begin with.

      Dr. Antevy works with children, so they are probably more resistant to the increased stimulus with ketamine. It may work well, for adults as well, but we need more research to better understand the complications of using ketamine for excited delirium. As with using a Taser, the extra stimulus probably isn’t helping, but it should be interrupting the extreme sympathetic stimulus. I will watch the video tomorrow.

      I look forward to reading more about this, and would love to see a trial.

      Me, too.

      Excited delirium is a fascinating topic. All of us have the potential for excited delirium.

      It seems that the incidence is much higher among drug/alcohol abusers and the mentally ill and highest among people who combine the two. Similar symptoms are produced by hypoxia and head injuries, but they are usually much more limited by the natural progression of those illnesses. With hypoxia, the lack of oxygen should progress to unconsciousness much more quickly with this amount of sympathetic stimulus. Even a delirious brain needs oxygen. With a head injury, the increased intracranial pressure that might cause this behavior is not going to do well with the dramatically elevated blood pressure that accompanies excited delirium.

      Both are still conditions that would be better interrupted by sedation, so that they can receive appropriate treatment for their underlying conditions.

      Psychiatric problems and drug/alcohol problems are no different.

      PS The link for Dr. Antevy’s page did not work and I could not find it by searching for ketamine on the site.

      .

  2. …and the Rogue asks: “Is anyone having trouble understanding that math?”

    Okay, I’ll bite!

    I actually studied your latest, Rogue because #1) the numbers weren’t adding up to me, #2) I wanted to stretch my aged brain, and #3) I wanted to get a better handle on your logic.

    Besides, just for a moment I wanted to meet YOU in the realm of Scientific Inquiry rather than me urging you to get corrupted by my New Age leanings!

    The conclusion you came to was valid re: the relative safety of droperidol, yet you grossly underestimated just how safe, which led me to question your methodology and from there, further conclusions you drew.

    First of all the study was a three year one month study, not four years; which really has no meaning because the conclusion was drawn from a dose to death ratio.

    When you bring the length of the study up again, however, you’re making it sound like that has relevance to bolster your case. It does not.

    93 deaths out of 38,000 equals a .0024 incidence of deaths from droperidol. Your estimate was .01.

    But if Portland’s study is accurate; here we have a case of “this is this!”

    .0024 is the incidence of death related to the per dose administration of droperidol, whether it be with that 38,000 or with 100,000,000, whether the study is one year or 100 years. So when you say:

    “It could be yens (sic) of millions of doses, or even more than 100 million doses. That means that the difference could be a ten times greater safety factor – or it could mean a 100 times greater safety factor than what I conservatively calculated.”

    You’re right about your calculation being quite conservative; it was off by a factor of 5. But don’t forget, if you increase the numbers of the population treated and extrapolate, the safety factor isn’t going to change one whit. In that respect, you were painting an inaccurate picture.

    To me, when a drug company issues a Black Box Warning for one of its products, — especially with an outrageously miniscule incidence of negative effect as exhibited here — the first thing I wonder is “What are they NOT telling us?”

    One of the things the study cited did not tell us is how many of those patients died directly from the anomaly in cardiac arrythmia it causes, how many were improper dose-related deaths and what proportion of those deaths occurred in the ER which suggests treatment for much more severe conditions than “a lot of patients being treated for nausea, vomiting, and pain.”

    So that led me to really look at how you related that info to Excited Delerium.

    First of all, we don’t know how many doses of the droperidol were administered to Excited Delerium patients. We also don’t know if that population had a higher, lower or average death rate as a result. So when you state:

    “Death due to a lack of droperidol during excited delirium is much more than 800 times more likely than death due to droperidol. “

    You’re saying by NOT administering droperidol you’re 800X more likely to kill the patient.

    You seem to base your premise on this:

    “If the best way to prevent the death of these patients is to sedate them and the most appropriate sedative is droperidol, is there any reason to believe that the low death rate blamed on droperidol is even relevant?”

    The picture I’m getting is you’re advocating administration of droperidol — across the board – to any patient exhibiting signs of Excited Delerium. How more clear could you be than this?

    “Should anyone even hesitate to use droperidol to treat excited delirium?”

    Well, Rogue, if they based it on your logic, YES! they certainly should. And if they’re doing their job right they should at least take the time to evaluate the need to sedate at all.

    The “across the board” thing, I believe, is something we’ll be talking more about shortly when you respond to my latest blog http://emsoutsideagitator.com/2011/11/what-a-trip/.

    • firetender,

      I actually studied your latest, Rogue because #1) the numbers weren’t adding up to me, #2) I wanted to stretch my aged brain, and #3) I wanted to get a better handle on your logic.

      First of all the study was a three year one month study, not four years; which really has no meaning because the conclusion was drawn from a dose to death ratio.

      A. It was not a study, but the time period over which all of these deaths were reported to the FDA.

      Nov. 1997 to Nov. 1998 = 1 year.

      Nov. 1998 to Nov. 1999 = 1 year.

      Nov. 1999 to Nov. 2000 = 1 year.

      Nov. 2000 to Nov. 2001 = 1 year.

      Nov. 2001 to Dec. 2001 = 1 month.

      Total = 4 years, 1 month.

      When you bring the length of the study up again, however, you’re making it sound like that has relevance to bolster your case. It does not.

      93 deaths out of 38,000 equals a .0024 incidence of deaths from droperidol. Your estimate was .01.

      But if Portland’s study is accurate; here we have a case of “this is this!”

      B. The incidence is 93 deaths out of all of the doses given in the world. None of those deaths appear to have happened in Portland. Out of the millions of doses given, 93 deaths is much less than 0.01%.

      The numbers for Portland were used just to calculate the number of doses across the US that might be given in a year. The reporting of deaths comes from all over the world, so the number of doses given in Portland is not relevant to the incidence. That was just a starting point for trying to calculate a minimum number of doses that might be given in a year. That number is in the millions, so the divisor is millions, not 38,000.

      .0024 is the incidence of death related to the per dose administration of droperidol, whether it be with that 38,000 or with 100,000,000, whether the study is one year or 100 years. So when you say:

      But they did not have 93 deaths (possibly due to droperidol) in Portland during any time period. There probably were not any deaths (possibly due to droperidol) in Portland during that 4 year period.

      “It could be yens (sic) of millions of doses, or even more than 100 million doses. That means that the difference could be a ten times greater safety factor – or it could mean a 100 times greater safety factor than what I conservatively calculated.”

      You’re right about your calculation being quite conservative; it was off by a factor of 5. But don’t forget, if you increase the numbers of the population treated and extrapolate, the safety factor isn’t going to change one whit. In that respect, you were painting an inaccurate picture.

      I corrected the misspelling of tens. Thank you for pointing that out.

      93 deaths, that might not even be due to droperidol, over a 4 year period, over everywhere droperidol was used in those 4 years, divided by tens of millions or hundreds of millions of doses.

      The doses were tiny, normal, or high, but the blame was put on the droperidol, regardless of what other drugs were used and regardless of what medical conditions were present.

      To me, when a drug company issues a Black Box Warning for one of its products, — especially with an outrageously miniscule incidence of negative effect as exhibited here — the first thing I wonder is “What are they NOT telling us?”

      One of the things the study cited did not tell us is how many of those patients died directly from the anomaly in cardiac arrythmia it causes, how many were improper dose-related deaths and what proportion of those deaths occurred in the ER which suggests treatment for much more severe conditions than “a lot of patients being treated for nausea, vomiting, and pain.”

      Again, it was not a study. This was the total reporting of deaths from all over the world that took place during the 4 years leading up to the black box warning.

      First of all, we don’t know how many doses of the droperidol were administered to Excited Delerium patients. We also don’t know if that population had a higher, lower or average death rate as a result. So when you state:

      “Death due to a lack of droperidol during excited delirium is much more than 800 times more likely than death due to droperidol. “

      You’re saying by NOT administering droperidol you’re 800X more likely to kill the patient.

      Exactly.

      Excited delirium is very much more deadly than the exaggerated danger of droperidol.

      You seem to base your premise on this:

      “If the best way to prevent the death of these patients is to sedate them and the most appropriate sedative is droperidol, is there any reason to believe that the low death rate blamed on droperidol is even relevant?”

      The picture I’m getting is you’re advocating administration of droperidol — across the board – to any patient exhibiting signs of Excited Delerium. How more clear could you be than this?

      “Should anyone even hesitate to use droperidol to treat excited delirium?”

      Well, Rogue, if they based it on your logic, YES! they certainly should. And if they’re doing their job right they should at least take the time to evaluate the need to sedate at all.

      The “across the board” thing, I believe, is something we’ll be talking more about shortly when you respond to my latest blog http://emsoutsideagitator.com/2011/11/what-a-trip/.

      Yes.

      Excited delirium is very deadly.

      Droperidol is very safe.

      My response is at Happy Excited Delirium after 06:30 today.

      Talking a patient down from excited delirium is a nice idea, but it is not as simple as talking someone, who is hyperventilating, into controlling his/her breathing. I have spent over an hour on scene with psych patients talking them down, but not when they have a condition, excited delirium, that is producing a surge of sympathetic stimulation that can kill the patient – stimulation that appears to kill over 8% of these patients.

      That is an unacceptable risk to take with our patients’ lives.

      Everything has a risk, but this is an extremely high risk.

      Don’t sedate the patients and maybe only 8% die.

      Sedate the patients and maybe less than 1% die. I don’t have any research comparing treatments, but the goal is to stop the extreme sympathetic stimulation and talking only does that if the patient is capable of ignoring the irrational impulses. Excited delirium makes that unpredictable.

      .

  3. I am in Melbourne Australia. In 2005 my ex husband, Royston Wilding and lawyer, John Alexander O’Brien wanted me dead and bribed or blacked a monster called Dr Johannes K.L. Khor. I had been on Efexor 150mg for five years due to my ex husbands horrific behaviour. Dr Khor got me falsely sectioned and I calmly read my book in ER. No one before or after has diagnosed me with mania , bipolar etc. He stopped my Efexor cold turkey; put me immediately on risperidone and sodium valporate and had a list of PRN medication with other anti psychotics including droperidol. I was also taking diazapam to sleep. He made fake nursing notes and , God forbid,could have ordered a nurse to inject me with this as well as I just sat there reading. It is going to court.My ex husband was stealing millions and sexually abusing my daughter; proven. I exposed his fraud but was chemically shut up. Love anyone’s opinion on this doctor who should be locked up for a long time.I am sure THIS combination could kill!