Download Psychosis - treatment

http://www.bestbets.org/cgi-bin/bets.pl?record=00060
Is haloperidol or a benzodiazepine the safest treatment for acute psychosis in the critically ill
patient?
Norman Khasati and Jacqueline Thompson - Report by:
Search checked by: Joel Dunning - RCS Research Fellow
Institution:
Department of Cardiac Surgery, Wythenshawe Hospital
Date submitted:
18th February 2004
Date completed:
1st June 2004
Last modified:
1st June 2004
Status:
Green (complete)
Three part question
In [patients in a high dependency setting] is [haloperidol or benzodiazepines] the safest treatment in [treating
acute psychosis]?
Clinical scenario
Its 1am and you are the registrar on call. You are asked to see a 70 year old lady 3 days post aortic valve
replacement. She is confused and agitated and is trying to pull out her central line. She has already removed
her arterial line and is on the side of the bed demanding to see her husband and wanting to get her clothes
to go home. Her pulse is 160 and she is in AF, her BP is 100/55 and her oxygen saturation is 92%. She has
no past psychiatric history and the nurses are very keen to see her sedated as it is currently taking 3 people
to keep her under control. You want to control her agitation but you are anxious that you may oversedate her
or cause cardiac side-effects as a result of additional drug administration. You wonder what is the optimal
policy for sedation of this agitated lady.
Search strategy
Medline 1966-Nov 2003 using the OVID interface [exp haloperidol OR haloperidol.mp OR
benzodiazepine.mp OR exp lorazepam OR lorazepam.mp or exp diazepam OR diazepam.mp ] AND [exp
Critical Care OR exp Critical Illness/ OR critically ill patient.mp. OR exp Intensive Care Units/ OR coronary
care unit.mp OR cardiac surg$ unit.mp OR High dependency.mp]
Search outcome
294 papers were found of which 5 papers were clinically relevant. One of these papers summarised several
case reports that were also found. In addition 4 more papers were found on checking reference lists. All
these papers are presented in the table
Relevant paper(s)
Author,
date and
country
Patient group
Study type
(level of
evidence)
36 patients attending for
endoscopy received
intravenous diazepam.
Respiratory and
cardiopulmonary
Rao S et al, function was measured
Cohort
1973,
using indicator-dilution
study (2b)
Canada
technique with CVP and
invasive BP monitoring
18 patients has
moderate to severe
obstructive lung disease
Outcomes
Cardiac parameters
post diazepam in
normal patients (Pts
with abnormal lung
function had similar
or less marked
findings)
Respiratory
parameters after
diazepam
Key results
Study weaknesses
Heart rate mean inc
13.4%. Blood pressure
mean drop 12.5%. Stroke
volume mean drop of
Non post operative,
31.5% at 15 mins. Cardiac
non cardiac patients
output mean dec. 14%
High doses of
pCO2 mean 8% increase. diazepam
SaO2 normal pts no
change, lung pts mean
drop 92%-88%
received mean 34mg
diazepam
18 patients with normal
lung function received
mean 58mg
Enough diazepam was
used to allow
endoscopy
Mean dose of 100mg per
day to control agitation.
Patient 1 had 140mg on
day 1 then 7.5mg per 4
hours maintenance.
Dose of haloperidol
Patient 2 had 20mg per 4
Small case series
hours and 270mg in one
day. Patient 3 had 485mg
over 8 hours. Patient 4 had
up to 530mg per day
No complications reported
Complications
in these 4 patients
Patient suffered a cardiac
arrest immediately after
haloperidol administration.
Single case report
Complication
A second cardiac arrest
Case report
occurred 2 hours later
(5)
Not a patient post
immediately after a second
cardiac surgery
7.5mg dose of haloperidol
Case report of 4 cardiac
patients in the Coronary
Care Unit requiring high
TesarGE et dose Haloperidol for
Case
al,
control of agitation.
Series
1985,
(5)
USA
Initial starting dose of
5mg but rapidly
increased to single
doses of 30-75mg
Case report of a single
patient on an intensive
Huyse F &
care unit for legionella
van
pnumoniae pneumonia
Schijndel
receiving haloperidol
RS,
1988,
7.5mg of iv haloperidol
Holland
administered for
agitation while weaning
Retrospective cohort of
2,000 medically ill
patients with cancer
Adams F,
1988,
Canada
Protocol used :
5mg of haloperidol and
Cohort
0.5mg of lorazepam
study
and hydromorphone.
(4)
20 mins later if no
response 10mg
haloperidol and 0.52mg lorazepam. Repeat
this at 30 min intervals
until agitation controlled
Review of the literature
and presentation of a
protocol for
tranquilisation of
Agitated ICU patients
Protocol :
Tesar GE &
0.5-2.0mg mild agitation
Stern TA,
Review
5.0-10mg moderate
1988,
(5)
agitation
USA
10mg or more severe
agitation
Allow 20 mins before
repeat dose
If agitation persists
double dose and repeat
Development of
practise parameters on
Shapiro AJ behalf of the American
Systematic
et al,
College of Critical Care
Review
1995,
Medicine
(3a)
USA
Task force of 40 experts
from the society
Outcome
Patient discharged home
Protocol has been safely
Clinical experience in
used in 2 cancer centers
2000 patients
for 8 years
No clinical data or
follow up data given
about these 2000
patients
No demographics or
patient selection given
Safety seems to be
decided according to
authors clinical memory
Not cardiac patients
Onset of action 10-30mins
but is very safe.
Haloperidol use and
Haloperidol produces
complications
trivial effects on
haemodynamic function
Additional use of
lorazepam
Lorazepam has fewer
cardiovascular
complications than other
benzodiazepines. In
severe agitation lorazepam
2-10mg may also be given
Presented as level 1
evidence. Usual dose 510mg. Onset of action 3060 min after IV
administration
Benzodiazepines not Stated that
recommended for
benzodiazepines may
acute delirium
cause a paradoxical
Haloperidol is the
preferred treatment
for delirium in the
critically ill patient
Review is essentially
expert opinion rather
than systematic review
of the literature
Not specifically
constructed for patients
post cardiac surgery
Quoted papers in
support of
recommendations are
case series? and
convened to construct
these guidelines in
conjunction with full
literature review over
the course of 1 year
Lorazepam is
preferred agent for
prolonged treatment
of anxiety in the
critically ill patient
Nondelirious, medically
Improvement in
hospitalized AIDS
delirium score at 24
patients were
hours (mean initial
prospectively entered
score was 20)
into the study.
Randomization to
Breitbart W
treatment was
Double
et al,
performed if patient
Blind PRCT
1996,
subsequently met DSM- (2b)
USA
IIIR criteria for delirium
Adverse effects
Treatment:
haloperidol (N = 11),
chlorpromazine (N =
13), lorazepam (N = 6).
30 critically ill patients
who received
intravenous haloperidol
for delusional agitation
Tisdale JE
et al,
6 patients known to get
2001,
torsades de pointes
USA
after haloperidol
therapy
QT interval in study
pts
Casecontrol
study
(3b)
QT interval in control
pts
Odds of developing
torsades
24 control patients
Review of papers
Dose required to
documenting torsades
Hassaballa
cause torsades de
de pointes after iv
HA & Balk
Review of pointes
haloperidol
RA,
case series
2003,
(5)
Outcome of torsades
19 individual cases of
USA
de pointed in these
torsades de pointes
patients
found in the literature
worsening of symptoms. reviews and not well
No mention made of
conducted clinical trials,
cardiovascular effects
calling level of
Presented as level 2
recommendation into
evidence. Lorazepam
question
causes less hypotension
than other
benzodiazepines
Haloperidol: 8 point
improvement,
Not post operative or
chlorpromazine:8 point
cardiac surgical
improvement, lorazepam:
patients
1.5 point improvement.
p<0.001 neuroleptics vs
5 patients died within 8
lorazepam
days of initiation of
Extra-pyramidal side
treatment
effects were low with
haloperidol and
Low doses of all drugs
chlorpromazine, but ALL
used, haloperidol mean
patients with lorazepam
2.8mg, chlorpromazime
had treatment limiting side
50.0mg, Lorazepam
effects including
3.0mg in 1st 24 hours
oversedation, disinhibition,
ataxia, and increased
Small numbers
confusion, causing study
to be stopped early
Prior to haloperidol 501 +/44 ms. After haloperidol
606 +/- 61 ms vs. p =
Note a 3 page erratum
0.007
section appears in a
Prior to haloperidol 466 +/- subsequent issue of J
44ms. After haloperidol
Clin Pharmacol, with
507 +/- 60 ms vs. p = 0.01 several significant
changes, compared to
12 fold increased risk in
the original article
those with QT interval >
521 msec
Mean dose 507mg. Lowest
Selected collection of
dose single dose of 10mg.
individual cases from
Highest dose 1,000mg in
the literature
30 mins
None of these patients
died as a result of the
episode
Search strategy for
finding papers not
given
Comment(s)
The American College of Critical Care Medicine has provided the highest quality review in this area. They
conclude that the first line drug for acute agitation in the critical care environment is haloperidol and that
cardiovascular side effects are rare. In addition they state that benzodiazepines may in fact exacerbate
symptoms, although lorazepam is a safer second line drug than other benzodiazepines such as diazepam.
However this guideline is mainly based on expert consensus in conjunction with case reports. Rao et al
demonstrate the unacceptable cardiovascular side-effects with diazepam with an average 14% drop in
cardiac output. Breitbart et al in a well conducted randomized controlled trial compared lorazepam and
haloperidol in medically unwell AIDS patients. They found that haloperidol produced significantly better
resolution of delirium and lorazepam invariably produced treatment limiting side-effects including increased
confusion , disinhibition and ataxia. We could find no other papers that documented a poorer performance of
lorazepam compared to haloperidol either in terms of side effects or resolution of delirium, and in fact Adams
et al described the safe use of a combined policy of both drugs given together. This utilises the fact that the
onset of action for lorazepam is faster and allows a lower dose of haloperidol to be used. Tesar et al reported
the safe use of haloperidol in doses of 100mg per day or more in agitated patients post cardiac surgery and
presents a protocol for its safe use, but the complication of Torsades de pointes is well documented.
Hassaballa reported 19 cases of Torsades after haloperidol and Huyse reported a case of cardiac arrest
after 7.5mg of haloperidol. Tisdale performed an interesting study that demonstrated that haloperidol always
causes a prolonged QT interval and advocates cardiac monitoring and extra caution with a QT interval over
521 msec.
Clinical bottom line
Haloperidol should be considered the first line drug for agitated patients post cardiac surgery, however
lorazepam either alone or in conjunction with haloperidol is an acceptable alternative.
References
1. Rao S, Sherbaniuk RW, Prasad K, Lee SJ, Sproule BJ. Cardiopulmonary effects of diazepam. Clin
Pharmacol Ther 1973;14(2):182-189.
2. Tesar GE, Murray GB, Cassem NH. Use of high-dose intravenous haloperidol in the treatment of
agitated cardiac patients. J Clin Psychopharmacol 1985;5(6):344-347.
3. Huyse F, van Schijndel RS. Haloperidol and cardiac arrest. Lancet 1988;2(8610):568-569.
4. Adams F. Emergency intravenous sedation of the delirious, medically ill patient. J Clin Psychiat
1988;49:(12 SUPPL. DEC);p 22-27.
5. Tesar GE, Stern TA. Rapid Tranquilization of the Agitated Intensive Care Unit Patient. J Intensive
Care Med 1988;3(4):195-201.
6. Shapiro BA, Warren J, Egol AB et al. Practice parameters for intravenous analgesia and sedation for
adult patients in the intensive care unit: an executive summary. Society of Critical Care
Medicine.[comment]. Crit Care Med 1995;23(9):1596-1600.
7. Breitbart W, Marotta R, Platt MM,et al. A double-blind trial of haloperidol, chlorpromazine, and
lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiat
1996;153(2):231-237.
8. Tisdale JE, Rasty S, Padhi ID, et al. The effect of intravenous haloperidol on QT interval dispersion
in critically ill patients: comparison with QT interval prolongation for assessment of risk of Torsades
de Pointes. J Clin Pharmacol 2001;41(12):1310-1318.
9. Hassaballa HA, Balk RA. Torsade de pointes associated with the administration of intravenous
haloperidol. Am J Ther 2003;10(1):58-60.