Case Reports
Continuous Droperidol Infusion for Management
of Agitated Delirium in an Intensive Care Unit
MARK A. FRYE, M.D., MICHAEL F. COUDREAUT, M.D.
SUSAN M. HAKEMAN, M.D., BHAVIK
THOMAS B. STROUSE, M.D., CHRISTINE E. SKOTZKO, M.D.
D roperidol is a high-potency butyrophenone
parenteral neuroleptic originally synthe-
sized in the early 19605 for treatment of mania
and control of agitation.1.2 Its pharmacological
profile differs from its butyrophenone relative
haloperidol. Specifically. droperidol possesses
greater potency. faster onset of action and meta-
bolic rate of elimination, and greater likelihood
of sedation. Most of the past American literature
has promoted the use of droperidol as a preanes-
thetic agent 3 and antiemetic. 4
Since the 1980s droperidol has returned to
the psychiatric milieu for treatment of agitation
in schizophrenia, mania. drug-induced psycho-
sis. and delirium. For management of acutely
agitated patients, droperidol has proved as effica-
cious. if not more so, than haloperidol in low-
dose intramuscular injection. s There is literature
to suggest that the rate of extrapyramidal symp-
toms (EPS) is less for droperidol than haloperi-
dol. 6 Furthermore, Szuba et al. 7 reported the
incidence of EPS was 9% for patients receiving
intramuscular droperidol (mean SO =7.0
2.8 mg) vs. 5% for patients receiving intravenous
droperidol (60 31.7 mg). This observation is
consistent with previous animal and clinical re-
ports that show less EPS generation when a
neuroleptic is given at high dose. 8.9 Additionally,
Menza et al. 1o showed, in a prospective study, less
EPS in a group of patients receiving intravenous
haloperidol vs. oral haloperidol. These studies
suggest that EPS occurs with decreasing order of
frequency in oral. intramuscular, and intravenous
preparation.
Originally promoted by Oencker in 1976,11
VOLUME 36 NUMBER 3. MAY - JUNE 1995
G. SHAH, M.D.
there is literature supporting the use of intrave-
nous haloperidol at high doses ( 100 mg/day) 12 for
control of agitation in a medical sening and one
case report of a 24-hour cumulative dose of 1,200
mg. D Tesar and Stern l4 have anecdotally ob-
served electrocardiographic Q-T interval prolon-
gation with this treatment, but two recent reports
associate the use of intravenous haloperidol with
Torsades de Pointes (TOP) arrhythmia. This ar-
rhythmia is heralded by QTc (the Q-T interval
corrected for heart rate) prolongation beyond
normal QTc values generally accepted to be be-
tween 390 and 440 ms. Episodes of TOP are
frequently unsustained and intermittent but may
progress to sustained lethal arrhythmias of ven-
tricular tachycardia and ventricular fibrillation. ls
Metzger and Friedman 16 reported a case se-
ries consisting of three male patients who de-
veloped TOP or Q-T interval prolongation with
intravenous haloperidol; all patients had pre-
viously documented histories of alcohol abuse
and dilated cardiomyopathy, which inde-
pendently have been associated with arrhythmo-
genesis. Wilt et al. 17 identified four acutely
medically iII female patients treated with intra-
venous haloperidol in an intensive care unit; the
Received June 21, 1994; revised August 18. 1994; ac-
cepted September 14. 1994. From the UCLA Neuropsychia-
tric Institute, Depanment of Psychiatry and Biobehavioral
Sciences, UCLA School of Medicine. Los Angeles. CA.
Address correspondence to Dr. Frye, Biological Psychiatry
Branch. National Institute of Mental Health. Building 10.
Room 3N212. 9000 Rockville Pike. Bethesda. MD 20892.
Copyright 1995 The Academy of Psychosomatic
Medicine.
301
Case Reports
majOrity of the patients had QTc intervals of
600 ms or greater prior to the development of
TOP.
We are unaware of any previous reports on
the safety of continuous intravenous droperidol
therapy for the treatment of delirium and agita-
tion. The following case vignettes exemplify our
clinical experience with intravenous droperidol
therapy and possible cardiac side effects.
Case Reports
Case I. A 34-year-old man with a past psychiatric
history of autism and atypical psychosis was elec-
tively admined for an aortic valve replacement.
Medications at admission included fluphenazine (20
mg po bid), trihexyphenidyl (2 mg po bid), car-
bamazepine (200 mg po tid), and hydralazine (25 mg
po bid) for hypertension. There was no history of
substance abuse, and all routine admission labs were
normal. His ECG showed normal sinus rhythm with
a OTc interval of 400 ms and left ventricular hyper-
trophy.
Initial mental status examination revealed a
young man with poor eye contact without psycho-
motor agitation or posturing. He was cooperative,
able to follow simple commands, euthymic, and did
not endorse paranoid delusions or hallucinations. All
orally administered medications were withheld the
day prior to surgery.
The patient's operation was without compli-
cation. Immediately postoperatively, there was ven-
tricular ectopy and a single episode of unsustained
supraventricular tachycardia that was treated with in-
travenous adenosine. Postoperatively the patient was
maintained on continuous infusions of nitroglycerin,
dobutamine, amrinone, lidocaine, and fentanyl.
Psychiatric consultation was requested emer-
gently when the patient became markedly agitated
anempting to pull out his endotracheal and bilateral
chest tubes. He had been treated over the previous
8 hours with a total of 30 mg iv morphine sulfate
and 8 mg iv lorazepam.
The patient's vital signs were normal with the
exception of sinus tachycardia (130 bpm). His post-
operative hematocrit, hemoglobin, electrolytes, arte-
rial blood gas, and urine output were normal. The
patient was found to have waxing and waning men-
tal status and was diagnosed with delirium compli-
cated by pain and emergence from anesthesia.
302
A 10-mg dose of intravenous droperidol was
briefly effective for management of his agitation.
A 20-mg intravenous droperidol bolus caused a de-
crease in blood pressure from 120/60 to 100/50 with
compensatory tachycardia Continuous droperidol in-
fusion was started at 5 mg/hour and was titrated up
to 8 mg/hour with a single dose of 6 mg vecuronium
to assist in controlling agitation. No further adjunc-
tive benzodiazepines or narcotics were given.
ECG evaluation during droperidol therapy
showed increased OTc intervals of 426 and 476 ms
with no development of arrhythmia.
On postoperative Day 3 the patient was extu-
bated and all drips, including droperidol, were dis-
continued. Previous psychotropic medications were
reinstituted without recurrence of agitation. The pa-
tient was discharged 1 week after his surgery.
Case 2. A 54-year-old man with a past psychiatric
history of schizoaffective disorder was admilled for
evaluation of unstable angina and hypertension.
Psychotropic medications at admission included
haloperidol (5 mg tid), lithium carbonate (300 mg
tid), and trihexyphenidyl (2 mg tid); cardiac medica-
tions included lovastatin (20 mg bid) and metoprolol
(50 mg po bid) for hypertension.
Initial cardiac evaluation included the follow-
ing: an ECG documenting first-degree heart block
and OTt interval of 437 ms, an elevated CPK at
219 (normal ~180) without an elevated MB frac-
tion, and eventual cardiac catheterization demon-
strating multiple vessel disease, including 90%
stenosis of the left anterior descending coronary
artery. Psychotropic medications were withheld pre-
operatively and the patient underwent four-vessel
coronary artery bypass surgery without complica-
tion. Postoperatively he was maintained on continu-
ous intravenous infusion of nitroglycerin, dopamine,
ranitidine, and nasogastric administration of haloperi-
dol, metoprolol, and aspirin.
Psychiatric consultation was requested on the
first postoperative day for life-threatening agitation
unresponsive to midazolam (8 mg), lorazepam
(3 mg), meperidine (Demerol; 25 mg), morphine
(14 mg), and haloperidol (8 mg), which had been
given over the preceding 10 hours. The patient's vi-
tal signs included sinus tachycardia (120 bpm),
blood pressure = 120nO, temperature of 39.50 Cel-
sius, and urine output of less than 50 cc/hour. The
patient was noted to have a left pleural effusion and
atelectasis on chest X ray. A blood gas examination
revealed a ph 7.35, P02 = 103, PC02 = 40 on 60% 02'
White blood cell count was elevated to 11.8.
PSYCHOSOMATICS

On examination. the patient was alert but dis-
oriented with unintelligible mumbling. He was
unable to follow simple commands and exhibited
marked psychomotor agitation. Postcardiotomy
delirium was diagnosed. complicated by possible
pulmonary infection.
Given the ineffectiveness of nasogastric tube
haloperidol. a 5-mg droperidol intravenous bolus
was given and was effective in controlling agitation.
However. this was complicated with a subsequent
hypotensive episode to 105/60. Hypotension contin-
ued with repetitive 5-mg bolus therapy prompting
commencement of a continuous infusion drip at
10 mg/hour. Blood pressure returned to 130/60 with
this change and agitation diminished.
Over the next 7 hours droperidol infusion was
increased to 20 mg/hour. at nursing discretion. for
optimal management of agitation without altering
blood pressure. Antibiotics were started empirically
with defervescence of the patient's temperature.
While on continuous cardiac monitoring. the pa-
tient's QTc interval peaked at 560 ms (baseline 437
ms). but there was no development of arrhythmia.
Droperidol infusion was discontinued on post-
operative Day 3 without recurrence of agitation. Vi-
tal signs. mental status exam. chest X ray. and
laboratory values all improved. Lithium was restan-
ed postoperative Day 9. at a reduced dose. and the
patient was discharged from the hospital the follow-
ing day.
Case 3. A 43-year-old man with a past medical his-
tory of atherosclerotic coronary artery disease. mitral
valvular disease (normal ejection fraction), myocar-
dial infarction, insulin-dependent diabetes mellitus,
and diabetic nephropathy underwent elective
cadaveric renal transplant nephrectomy secondary to
chronic rejection. He had no past psychiatric history
or substance abuse. Postoperatively he was noted to
have intermittent atrial fibrillation and extended peri-
ods of hypotension as low as 70/40. Quinidine ther-
apy was initiated for the new-onset atrial fibrillation.
Other medications at the time of evaluation included
cyclosporin, prednisone, acyclovir, isosorbide dini-
trate. and diltiazem.
A psychiatry consult was requested for the pa-
tient's sudden refusal offunher medical interven-
tion. Vital signs revealed a blood pressure of70/50,
pulse rate of 100, respiratory rate of 18, and normal
temperature. His initial ECG revealed normal sinus
rhythm with a QTc of 360 ms. On examination, the
patient was comfortably sitting in a chair endorsing
frustration with lack of sleep over the prior 72 hours
VOLUME 36-NUMBER 3 -MAY -JUNE 1995
Case Reports
and his chronic medical condition. He was paranoid
and stated he distrusted the motives of the staff.
refusing to elaborate further. The patient was diag-
nosed with delirium secondary to ongoing hypoten-
sion, sleep deprivation, and drug effects of
cyclosporin, prednisone, acyclovir, and quinidine.
In the course of psychiatric consultation. the
patient agreed to routine cardiac monitoring, intra-
venous fluids, and medications. A continuous infu-
sion of droperidol (I mg/hour) was staned
overnight, with the patient awakening rested the next
moming. He was less paranoid and more coopera-
tive with medical treatment. His vital signs were nor-
mal with no evidence of Q-T interval prolongation
on ECG (longest QTc recorded was 420 ms). On
postoperative Day 4. the patient was discharged.
Discussion
These case vignettes demonstrate the safety and
efficacy of droperidol continuous infusion ther-
apy for the management of agitated delirium in
patients on an intensive care unit. Delirium,
whatever the etiology, compromises the medical
staff's ability to provide effective medical inter-
vention. Cases I and 2 demonstrate postoperative
agitated delirium initially treated with benzo-
diazepines and narcotics that was ultimately
effectively managed with droperidol. Case 3
demonstrates effective control of agitated delir-
ium with continuous infusion of droperidol,
which increased patient autonomy and coopera-
tion and decreased the need for constant supervi-
sion. Also, with intravenous drip preparations,
the disadvantages of painful, erratic intramuscu-
lar absorption and potential complications of in-
tramuscular injection related to coagulopathies
and or CPK elevation are avoided. Droperidol
was generally well tolerated other than hypoten-
sion associated with bolus dosing.
The hypotensive effects of droperidol are
mediated through <XI-adrenergic receptor antago-
nism. Of all traditional neuroleptics, including
haloperidol, droperidol is the most potent at this
receptor site. 18 In a previous clinical study of
droperidol as an antiemetic, Kelley et al. 19 found
toxic side effects of prolonged sinus tachycardia
and decreased mean arterial pressure at loading
doses greater than 10 mg and maintenance doses
303
Case Reports
greater than 4 mg. Szuba et al. 7 reported one
cardiac complication of sinus tachycardia, pre-
sumably from hypotension, with a high-dose
(50 mg) intravenous droperidol bolus in a 69-
year-old woman without prior cardiac history.
These reports resemble Cases I and 2 and their
drug-induced hypotensive episodes. The com-
mencement ofcontinuous intravenous infusion in
our patients avoided further blood pressure diffi-
culties. Hypotension is also associated with in-
travascular volume depletion; this is particularly
prevalent in postoperative patients and may con-
tribute to the development of hypotension and
increased heart rate. Of note, Case 3 did not have
exacerbation of previous hypotension with drop-
eridol infusion. Q-T intervals and prolongation
are presented in Table I.
Q-T interval prolongation above accepted
normal ranges was noted in Cases I and 2 without
associated progression to arrhythmia, particu-
larly TOP. As noted. the mean QT. prolongation
was 17.3%. Similar observation has been docu-
mented previously by Guy et al,20 who showed an
average 40-ms QT. prolongation in 70% of pa-
tients selected for general anesthesia who were
given 0.25 mg/kg intravenous droperidoI. The
progression of Q-T interval prolongation to TOP
can be potentiated by congenital, nonpharmaco-
logic, and pharmacologic agents that include psy-
chotropic medications such as phenothiazines
and heterocyclic agents. 15
Metzger and Friedman '6 noted a mean 27%
increase in the QT. interval after haloperidol intra-
venous therapy in their three patients with comor-
bid cardiomyopathy and history of alcohol abuse.
Two patients developed TOP with preceding max-
imum QT. intervals of 457 and 538 ms, respec-
tively, with the final patient expiring of a cardiac
arrest and possible terminal arrhythmia. We an-
TABLE l. Baseline QT. interval and peak
prolongation
QT. Baseline, QT. Peak, Increase,
ms ms %
Case 1 400 476 16
Case 2 437 560 22
Case 3 360 420 14
Mean 399 485.3 17.3
304
ticipated, but did not find, this cardiac complica-
tion with droperidol therapy. These studies sug-
gest, however. that precautions should be taken
to minimize potential complications during use
of continuous intravenous droperidol therapy.
We suggest continuous cardiac monitoring
to evaluate changing ECG intervals and to imme-
diately recognize the development of arrhythmia
in patients receiving continuous droperidol infu-
sion. Previous existing medical and psychiatric
conditions should be evaluated for relative con-
traindications for droperidol therapy as a treat-
ment intervention for agitation. Explicitly, this
should be thought of as "compound liability" for
Q-T interval prolongation and possible TOP ar-
rhythmogenesis. Examples would include ad-
junctive use or overdose of heterocyclic
antidepressants. delirium associated with endo-
crine or electrolyte disturbances, vascular acci-
dent. cardiac arrhythmia, current antiarrhythmic
therapy, or gender as a recent review reported that
70% of all cases of TOP related to cardiovascular
drugs were in women. 21 Again, these would be
judged as relative contraindications; severe. life-
threatening agitation for which psychiatric con-
sultation is requested may necessitate institution
of continuous droperidol infusion with moni-
toring in an intensive care unit. Case 3, as an
example, did have "compound liability" with
quinidine therapy for atrial fibrillation and hypo-
tension; droperidol infusion for treatment of agi-
tated delirium did not produce an abnormal
prolongation of QT.
This case series is methodologically limited
by the lack of formal prospective rating scale
measurement but is reflective of our clinical ex-
perience with this treatment. It promotes the
safety (particularly with hypotension and ar-
rhythmogenesis) and efficacy of continuous in-
travenous droperidol infusion therapy as a
method of treating delirium and concomitant
agitation in patients on an intensive care unit.
References
I. Janssen P. Niemegeers C. Schellekens K. et al: The phar-
macology of dehydrobenzperidol and short-acting
neuroleptic agent chemically related 10 haloperdiol. Ar-
PSYCHOSOMATICS

znemittelforschung 1963; 13;205
2. Bobon J. Breulet M. Colinet M. et al: Present treatment
of manic states. Acta Psychiatr Belg 1972; 72:617~32
3. Morrison JO: Orugs used in neuroleptanalgesia. Interna-
tional Anesthesiology Clinic 1969; 7:141-157
4. Laszlo J: Treatment of nausea and vomiting caused by
cancer chemotherapy. Cancer Treat Rev 1982; 9:~9
5. Resnick M. Bunon BT: Oroperidol vs. haloperidol in the
initial management of acutely agitated patients. J Clin
Psychiatry 1984; 45:298-299
6. Ayd FJ: Parenteral droperidol for acutely disturbed be-
havior in psychotic and nonpsychotic individuals. Inter-
national Drug Therapy Newsletter 1980; 15:13-16
7. Szuba MP. Bergman KS. Baxter LR Jr. et al: Safety and
efficacy of high-dose droperidol in agitated patients. J
Clin Psychopharmacology 1992; 12: 144-145
8. Rifkin A. Quitlin F. Carillo C. et al: Very high dosage
fluphenazine for nonchronic treatment refractory patients.
Arch Gen Psychiatry 1971; 25:398-403
9. Torum M. Takashima M: Haloperidol in large doses
reduces the cataleptic response and increases norad-
renaline metabolism in the brain of the rat. Psychophar-
macology 1985; 24:231-236
10. Menza MA. Murray GB. Holmes VF. et al: Decreased
extrapyramidal symptoms with intravenous haloperidol.
J Clin Psychiatry 1987; 48:278-280
II. Dencker SJ: High-dose treatment with neuroleptics in the
acute phase of mental disease. Proc R Soc Med 1976;
69(suppl I): 32-34
12. Tesar GE. Murray GB. Cassem NH: Use of high-dose
intravenous haloperidol in the treatment of agitated car-
Countertransference Issues in Tennination
of Life Support in Acute Quadriplegia
CARLA RODGERS, M.D., HOWARO L. FIELD, M.D.
ELISABETH J. SHAKIN KUNKEL, M.D.
W ith improved medical technology, victims
of trauma, particularly from motor vehicle
accidents, who might otherwise have died soon
after reaching the hospital, are now being kept
alive and conscious. I According to the Supreme
Court, patients in this situation have the right,
under the Due Process clause of the Constitution,
to refuse treatment, even if that refusal results in
VOLUME 36 NUMBER 3 MAY - JUNE 1995
Case Reports
diac patients. J Clin Psychopharmacol 1985; 5:344-347
13. Sanders KM. Murray GB. Cassem NH: High-dose intra-
venous haloperidol for agitated delirium in a cardiac
patient on intra-aonic balloon pump. J Clin Psychophar-
macoll99l; 11:146-147
14. Tesar GE. Stern TA: Rapid tranquilization of the agitated
intensive care unit patient. Journal of Intensive Care
Medicine 1988; 3:195--201
15. Braunwald E (ed): Hean Disease: A Textbook of Cardio-
vascular Medicine. Philadelphia. WB Saunders. 1992
16. Metzger E. Friedman R: Prolongation of the corrected QT
and Torsades de Pointes cardiac arrhythmia associaled
with inlravenous haloperidol in the medically ill. J Clin
Psychopharmacol 1993; 13: 128-132
17. Wilt JL. Minnema AM. Johnson RF. et al: Torsades de
Pointes associated with the use of intravenous haloperi-
dol. Ann Intern Med 1993; 119:391-394
18. Peroutka SJ. Snyder SH: Relationship of neuroleptic drug
effects al brain dopamine. serotonin. alpha adrenergic.
and histamine receptors to clinical potency. Am J Psychia-
try 1980; 137:1518-1522
19. SL Kelley. Braun TJ. Meyer TJ. et al: Trial of droperidol
as an antiemetic in cisplatin chemotherapy. Cancer Treal-
ment Repons 1986: 70;469-472
20. Guy JM. Andre-Fouet X, Pone J. el al: Torsades de
Pointes and prolongation of the duration of QT interval
after injection of droperidol. Annales de Cardiologie et
O'Angiologie 1991; 40:541-545
21. Makkar RR. Fromm BS. Steinman RT. et al: Female
gender as a risk factor for Torsades de Pointes associated
with cardiovascular drugs. JAMA 1993; 270:2590-2597
Received August 17. 1993; revised April 29. 1994;
accepted May 12. 1994. From the Depanment of Psychiatry
and Human Behavior. Jefferson Medical College. Philadel-
phia. PA. Address correspondence to Dr. Rodgers. Depart-
ment of Psychiatry and Human Behavior. Jefferson Medical
College. 1020 Sansom Street. Thompson Building. Suite
1652, Philadelphia. PA 19107-5004.
Copyright 1995 The Academy of Psychosomatic
Medicine.
305