Geodon/Zyprexa for agitation management

[Mantis Toboggan]

IV Haldol is generally prohibited because the FDA does not approve its use for intravenous administration. Adverse effects of Haloperidol include: Torsades, elongated QT, tardive dyskinesia, neuroleptic malignant syndrome, et. al. The frequency and/or severity of such complications are increased following IV administration, thus the FDA has deemed the route ‘unsafe’ as a routine therapy. Although Haloperidol is only manufactured as an IM injectable preparation, I have heard of some Docs ordering IV Haldol as an off-label Tx. Often, I’ll see IM Haldol and IV Versed administered concomitantly in the ER; this may be puzzling to some as IV is generally considered to be the preferred and most effective route. I would be very surprised if any state board of physicians allowed paramedics an off-label use Haldol in their protocols.

 

[Summit]

IV Haldol is generally prohibited because the FDA does not approve its use for intravenous administration. Adverse effects of Haloperidol include: Torsades, elongated QT, tardive dyskinesia, neuroleptic malignant syndrome, et. al. The frequency and/or severity of such complications are increased following IV administration, thus the FDA has deemed the route ‘unsafe’ as a routine therapy. Although Haloperidol is only manufactured as an IM injectable preparation, I have heard of some Docs ordering IV Haldol as an off-label Tx. Often, I’ll see IM Haldol and IV Versed administered concomitantly in the ER; this may be puzzling to some as IV is generally considered to be the preferred and most effective route. I would be very surprised if any state board of physicians allowed paramedics an off-label use Haldol in their protocols.

Most of the Haldol I've given has been IVP. I haven't encountered an adverse reaction yet in the over 100 patients I've pushed it and we watch the QTc closely.

That said, first gen antispychotics and later gen are usually regarded with caution in patients where extended QTc is a concern. However, near as I can tell, haloperidol is not nearly as bad as something like Thorazine and the adverse effects are generated by case reports or case controlled studies.

Unfortunately my institution doesn't have access to this journal: The use of low-dose IV haloperidol is not associated with QTc prolongation: post hoc analysis of a randomized, placebo-controlled trial

This 2001 paper was a small case controlled study
This 2004 paper shows about 7.1ms increase in QTc for patients on 15mg/day of haldol
Good Summary

In ICU we are looking for ways to reduce and control delirium. This is a complex problem and could span many threads. One of the adjuncts heavily considered/favored and under research right now is Haloperidol as we do know we want to avoid/minimize benzos on our ICU patients for sedation, agitation, and delirium (note not eliminate because benzos are appropriate at times, even first line). Some of the research is coming out now but there are some big multicenter trials. There is a small study showing it is not a useful prophylaxis.

That shouldn't be a construed as a suggesting that benzos are inappropriate for excited delirium in the prehospital patient.

Prehospital Agitation and Sedation Trial (PhAST): A Randomized Control Trial of Intramuscular Haloperidol versus Intramuscular Midazolam for the Sedation of the Agitated or Violent Patient in the Prehospital Environment.
unfortunately my open athens account is expired...

RESULTS:
Five patients were enrolled in each study group. In the haloperidol group, the mean time to achieve a RASS score of less than +1 was 24.8 minutes (95% CI, 8-49 minutes), and the mean time for the return of a normal mental status was 84 minutes (95% CI, 0-202 minutes). Two patients required additional prehospital doses for adequate sedation. There were no adverse events recorded in the patients administered haloperidol. In the midazolam group, the mean time to achieve a RASS score of less than +1 was 13.5 minutes (95% CI, 8-19 minutes) and the mean time for the return of normal mental status was 105 minutes (95% CI, 0-178 minutes). One patient required additional sedation in the ED. There were no adverse events recorded among the patients administered midazolam.

 

[VentMonkey]

In ICU we are looking for ways to reduce and control delirium. This is a complex problem and could span many threads. One of the adjuncts heavily considered/favored and under research right now is Haloperidol as we do know we want to avoid/minimize benzos on our ICU patients for sedation, agitation, and delirium (note not eliminate because benzos are appropriate at times, even first line). Some of the research is coming out now but there are some big multicenter trials. There is a small study showing it is not a useful prophylaxis.

Like @Summit said, not to deter further from the prehospital angle of this thread, but this did seem to be thing pretty heavily emphasized the last time I was in, and around and ICU setting.

I believe they call(ed) them "sedation vacations":

http://www.aacn.org/wd/nti/nti2012/...n-article-daily-interruptions-of-sedation.pdf

 

[Summit]

Like @Summit said, not to deter further from the prehospital angle of this thread, but this did seem to be thing pretty heavily emphasized the last time I was in, and around and ICU setting.

I believe they call(ed) them "sedation vacations":

http://www.aacn.org/wd/nti/nti2012/docs/pearl/awakening and breathing trial coordination/ccn-article-daily-interruptions-of-sedation.pdf

Sedation vacations serve mulitple purposes ranging from evaluating patient mental status, reducing ICU delirium, and most importantly they are coordinated with SBT (spontaneous breathing trial, aka vent wean)... as dumb as it sounds, for decades patients have failed their ventilator weans because nobody turned down the sedation or coordinated sedation vacation ahead of the SBT. Getting people off the vent sooner gets you lower delirium, fewer VAPs, shorter stays, and better outcomes.

Benzos are an independent risk factor for ICU Delirium in critically ill patients. Worth a thought in CCT, of course, agitated patients in a CCT rig are far worse. But maybe you've noticed more fent/propofol and precedex hung on your CCT patients instead of fent/midaz?

Good references:
Medication Risk Factors of ICU Delirium
Sedation and Delirium in the ICU
Choice of Sedation
Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

 

[VentMonkey]

Benzos are an independent risk factor for ICU Delirium in critically ill patients. Worth a thought in CCT, of course, agitated patients in a CCT rig are far worse. But maybe you've noticed more fent/propofol and precedex hung on your CCT patients instead of fent/midaz?

Yes, and thanks for the follow up post. There very much is relevance to my post above yours in the prehospital arena.

Particularly, as you've mentioned with weaning trials, etc. I think too often we as prehospital providers forget that treatment doesn't end once these patients are off-loaded.

In my area it typically is the Fentanyl/ Versed combo, or Diprivan alone. Seldom are patients being paralyzed for the trip, unless they're completely unmanageable (e.g., in the helicopter), but even then it isn't as encouraged as it was, say 5-10 years ago.

So, yeah, the relevance is again, definitely there. Also, unfortunately I don't see much Precedex even in the ICU's around here, though, again I did get a taste of it at one recently and the nurses seemed to favor it.

Have you, or any other ICU felt it's a better choice than Versed given it's less likely to result in deleterious effects on their hemodynamic status?

 

[Handsome Robb]

I would be very surprised if any state board of physicians allowed paramedics an off-label use Haldol in their protocols.

Both the systems I have worked in allowed IV haldol on standing orders.


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[VentMonkey]

Both the systems I have worked in allowed IV haldol on standing orders.


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What doesn't your system do??!- said the jealous paramedic from California.

 

[Summit]

Yes, and thanks for the follow up post. There very much is relevance to my post above yours in the prehospital arena.

Particularly, as you've mentioned with weaning trials, etc. I think too often we as prehospital providers forget that treatment doesn't end once these patients are off-loaded.

In my area it typically is the Fentanyl/ Versed combo, or Diprivan alone. Seldom are patients being paralyzed for the trip, unless they're completely unmanageable (e.g., in the helicopter), but even then it isn't as encouraged as it was, say 5-10 years ago.

So, yeah, the relevance is again, definitely there. Also, unfortunately I don't see much Precedex even in the ICU's around here, though, again I did get a taste of it at one recently and the nurses seemed to favor it.

Have you, or any other ICU felt it's a better choice than Versed given it's less likely to result in deleterious effects on their hemodynamic status?

You know I think it depends on the patient, but anyone at risk for delirium or who is appropriate for precedex or propofol I'd rather have that drip than (or in addition to) a midazolam drip unless it is very short term. Precedex (dexmedotamine) has very little respiratory depression (it's an alpha 2 so it isn't hitting the opiiod and GABA receptors that fent and midaz hit), but you can get hypotension/bradycardia on a bolus dose. You can literally wean someone on precedex which is awesome. But it might not have the punch to do the job on its own and you might not want to bolus it so having another agent for changes in agitation is useful.

Propofol (diprivan) is nice. AKA Milk of Amnesia. You can bolus that. but careful it can give you hypotension/bradycardia as well. Run it at high rates for a long time and it can cause lactic acidosis. The thing I like about propofol is it has a short halflife, like fentanyl short.

Even Precedex has a shorter halflife than midazolam (versed). There is a nice comparison in the NEJM link in my previous post.

ETOH w/d delerium / DT patients I love mixing precedex and midazolam (lets me use significantly less midazolam). This is my favorite Precedex article for AWS

 

[VentMonkey]

Getting people off the vent sooner gets you lower delirium, fewer VAPs, shorter stays, and better outcomes.

I just had to go back, and reiterate this to any, and all paramedics, both old and new. I find this to be an extremely enlightening statement from an experienced in-hospital provider that will hopefully help even just some, realize that when we intubate patients in the field, there is waaay more to their care long-term.

This is what drew me to critical care, learning all facets of airway management, from beginning to end, and with that in mind, our end goal even in the prehospital setting should be this right here, exactly. So, thank you, @Summit, you've summed it up quite well.

 

[Rialaigh]

Ketamine, no haldol or geodon here. 3mg/kg IM for aggressive, agitated, violent patients. Usually does the trick....no complaints from me about Ketamine.

As a note about Haldol I have read several very good articles about some possible reasoning behind the black box warning....the only route I have ever seen it given btw is IV and I see it used regularly in the ER. I believe there were less then 10 (possibly less then 5) reported cases of Torsades after hundreds of thousands of uses over the years. From the literature I have read it is in actuality a very safe drug that is used frequently with good effect in many ER's