More than haldol
Clinical Scenario:
You are working in the ED when you see EMS roll in with the all too common "SNF" patient. An 83 yo M with the alphabet soup of co-morbid conditions. HTN, dCHF, OSA, COPD, V-tach s/p AICD, non IDDM, CKD stage III who presents the the ever ubiquitous chief complaint of altered mental status. The patient was reported to be "off" by staff at the nursing facility, he was seen by a psychiatrist who was
concerned about delirium and advised the patient be reevaluated in the ED. Upon arrival the patient is AOx3, conversant,
and pleasant. He gets a delirium workup
that is fairly unremarkable with the exception of a UA showing weak evidence of
UTI. The patient is admitted to the medicine but boards in the busy ER overnight. During his stay he becomes agitated and uncooperative. He is now AOx1 (person) and cannot be
redirected. His thoughts are incoherent
and the patient will not return to his gurney. You make the
decision to administer IV haloperidol.
The patient relaxes, is able to be redirected.
A few hours later several family member approach you about the decision to use Haldol. They are educated, with a large amount of experience in the psychiatric field. They ask if you are aware of the neurotoxic effects of haloperidol and emphasize the use of newer atypical antipsychotics which are neuroprotective. You admittedly aren't that up to date on this topic, but assure them that haloperidol is used frequently at our institution for acute delirium. You perform a brief literature review.
A few hours later several family member approach you about the decision to use Haldol. They are educated, with a large amount of experience in the psychiatric field. They ask if you are aware of the neurotoxic effects of haloperidol and emphasize the use of newer atypical antipsychotics which are neuroprotective. You admittedly aren't that up to date on this topic, but assure them that haloperidol is used frequently at our institution for acute delirium. You perform a brief literature review.
Limited literature review:
You read the reference provided by the family member, which is an editorial from an online psychiatry journal citing that 28 different studies have shown neurotoxic
effects of older antipsychotics based on animal models, cell culture, and
post-mortem human tissue. The author
instead calls for the use of the 9 atypical antipsychotics to be used as they
have reported neuroprotective properties such as neurogenesis. (1) The main difference you note is that the author comes from the perspective of using antipsychotics for long term care, while in the ED we want safe and rapid control for delirium or agitation in the short term.
Haldol structure, wikipedia.org |
In your review you find the American Association of Emergency
Psychiatry released a consensus statement/guidelines on the treatment of acute
agitation in the ED.
Here are some highlights:
1. Prior to giving meds consider verbal redirection and nicotine replacement
Here are some highlights:
1. Prior to giving meds consider verbal redirection and nicotine replacement
2.
1st gen antipsychotics inhibit
dopamine and is structurally similar to GABA
3.
When using haloperidol remember it can prolong
QT (rare), cause extrapyramidal side effects (possibly as high as 20%,why it
is often given with lorazepam which reduces to 6% incidence).
4.
Haloperidol is not FDA approved for IV
administration (PO, IM only), although it is commonly administered this way.
5. Second generation antipsychotics have long been preferred by outpatient psychiatrist for long term management of various psychiatric conditions.
5. Second generation antipsychotics have long been preferred by outpatient psychiatrist for long term management of various psychiatric conditions.
6.
2nd gen antipsychotics include:
a.
Olanzapine (Zyprexa), ziprasidone (Geodon),
aripiprazole (Abilify) – IM and PO
b.
Risperidone (Risperdal), and quetiapine
(Seroquel) – PO only
7.
2nd gen antipsychotics also
antagonize dopamine, but also serotonin as well
8.
There have been very few head to head trials of
2nd generations versus Haldol.
a. However one double blind, placebo study compared both IM olanzapine and IM Haldol for agitation and showed that IM olanzapine reduced agitation significantly more than IM Haldol 15, 30, and 45 minutes following the first injection (2)
a. However one double blind, placebo study compared both IM olanzapine and IM Haldol for agitation and showed that IM olanzapine reduced agitation significantly more than IM Haldol 15, 30, and 45 minutes following the first injection (2)
10.
Two studies have been conducted comparing PO
risperidone and lorazepam versus IM haloperidol and lorazepam. Data showed similar benefits to both
regimens. However, both were conducted
at Psychiatric emergency centers and not typical EDs. (3)
11. Their final recommendation for agitation associated with delirium:
11. Their final recommendation for agitation associated with delirium:
a.
Oral 2nd generation
b.
Oral 1st generation
c.
IM 2nd generation – olanzapine 10 mg
or ziprasidone 10- 20 mg
d.
IM or IV 1st generation
12.
Peak concentration for PO meds is fairly similar
to IM with exception of olanzapine (6h for PO)
13.
IM meds peak concentration is approx. 15-45
minutes for both classes
The consensus statement does not discuss the “neurotoxic”
effects of haloperidol previously mentioned in the editorial citing non-living
human studies.
Take home points:
So which agent do you use? The theoretical neurotoxic effects of haloperidol seems to be more of a potential issue for long term psychiatric disease. ED concerns should focus on causing extrapyramidal side effects or excess sedation. The data for 2nd generation antipsychotics use in the ED is limited, however there is some data to show their efficacy in controlling of acute agitation.
Expert Commentary:
Dr. Holthaus Comments: Nice summary Dr. Miller! The one additional consideration I wanted to
share about carte blanche 5/2 (Haldol/Ativan) for all comers is the potential clinical
“down time” (ranging anywhere from 3-6+ hours depending on comorbidities/age/habitus/co-ingestants)
and its impact on prolonging ED LOS while “waiting” for the patient to recover enough
to allow a formal psychiatric interview and then to make the final disposition
decision (all compounding time in series).
Potential
alternate ways around this in my opinion are to 1) Ask psychiatry to evaluate them
while acutely psychotic (if available/present and safe) then administer the 5/2
and get labs/etc. allowing an earlier psychiatric disposition to be made as
medical etiologies are ruled out in parallel.
2) If psychiatry is unavailable or it's unsafe then consider giving something
else that has less back side down time but can achieve a similar up front clinical
effect: adequate onset time/calming-sedating enough to allow restraints/seclusion/redirection
and at least 1-2 hours for lab-imaging acquisition/results, is safe (and titratable
if more is needed), and allows a potentially earlier metabolic window for
mental clarity/off set that is amenable to a formal psychiatric interview. This is in my mind, preferably midazolam (or
diazepam if no midazolam) with an IV onset less than 5min, can be quickly/safely
titrated to effect, and can also be given IM.
Granted bezodiazepines can potentially worsen delirium but generally if they’re
shorter acting and less likely to be hanging around this makes this less likely
to persist. I agree benzos do not directly
address their psychosis like the anti-psychotics but my counter-argument would
be that these could be administered later if still needed. Don’t get me wrong, I have no problem with
5/2 but I like it best after a disposition is made (and it also carries the added
advantage of making the nurses happier in regards to behavior management and
puts people out of their misery while waiting forever for a bed). However, I will think twice now after Dr.
Miller’s analysis and consider more second generation use if using
antipsychotics for acute agitation management.
Submitted by Christopher Miller, PGY-2
Edited by Louis Jamtgaard, PGY-3 @Lgaard
Faculty Reviewed by Chris Holthaus
Submitted by Christopher Miller, PGY-2
Edited by Louis Jamtgaard, PGY-3 @Lgaard
Faculty Reviewed by Chris Holthaus
References:
1) http://www.currentpsychiatry.com/specialty-focus/schizophrenia-other-psychotic-disorders/article/haloperidol-clearly-is-neurotoxic-should-it-be-banned/194f71df8139c102e153b6839a066424.html
2) Wright P, Birkett M, David SR, et al. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry. 2001;158:1149-1151.
2) Wright P, Birkett M, David SR, et al. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry. 2001;158:1149-1151.
3) Wilson et al. The psychopharmacology of agitation: consensus
statement of the american association for emergency psychiatry project Beta
psychopharmacology workgroup. West J Emerg Med. 2012, 13(1), 26-34.
Additional References:
Additional References:
Currier et al. J Clin Psychiatry. 2004, 65(3), 386-94.
Wilson et al. Despite
expert recommendations, second-generation antipsychotics are not often
prescribed in the emergency department.
J Emerg Med. 2014, 46(6), 808-13.