Acta Anaesthesiol Scand 2008; 52: 280–284
Printed in Singapore. All rights reserved
Low-dose haloperidol prevents post-operative nausea and
vomiting after ambulatory laparoscopic surgery
T. F. WANG1,2, Y. H. LIU3, C. C. CHU1, J. P. SHIEH1, J. I. TZENG1 and J. J. WANG1
1
Department of Anaesthesiology, Chi-Mei Medical Centre, Tainan, Taiwan, 2Department of Gastroenterology, Song-Shan Armed Forces
General Hospital, Taipei, Taiwan and 3Department of Anaesthesiology, Cathay Medical Centre, Taipei, Taiwan
Background: We evaluated the prophylactic effect of low-dose
haloperidol (1 mg) on post-operative nausea and vomiting
(PONV) in women undergoing ambulatory laparoscopic sur-
gery. Droperidol (0.625 mg) and saline were controls.
Methods: One hundred and fifty women undergoing
ambulatory laparoscopic surgery under general anaesthe-
sia were enrolled in this randomized, double-blind, and
placebo-controlled study. After tracheal intubation, the
haloperidol group (n 5 50) received intravenous haloper-
idol (1 mg), the droperidol group (n 5 50) received intra-
venous droperidol (0.625 mg), and the saline group (n 5 50)
received intravenous saline.
Results: Haloperidol- and droperidol-group patients
reported a lower incidence of PONV [24% and 23% vs.
49% (saline group); Po0.05] and requested fewer doses of
rescue antiemetics [13% and 16% vs. 38% (saline group);
Po0.05] during the first four post-operative hours. During
P OST-OPERATIVE nausea and vomiting (PONV) is
one of the most common complications asso-
ciated with general anaesthesia (1–3). Droperidol, a
major tranquilizer with dopamine 2 (D2) receptor
antagonist effect, was one of the most commonly
used antiemetics for PONV (4, 5). However, in
December 2001, the FDA issued a ‘black-box’
warning for droperidol due to its potential QT
prolongation-related cardiac side effect (6). Despite
the arguments from many clinicians that this warn-
ing was inappropriate, announcement led to a
marked withdrawal of droperidol from the market
and to a search for a substitute.
Haloperidol, a major tranquilizer with a chemical
structure similar to that of droperidol, was consid-
ered a possible substitute for droperidol (7, 8).
Haloperidol also has a D2-receptor antagonist effect
and has been used in palliative care as an antie-
metic for nausea and vomiting (9). Some studies
This work was done in Chi-Mei Medical Centre
280
r 2007 The Authors
Journal compilation r 2007 The Acta Anaesthesiologica Scandinavica Foundation
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2007.01525.x
the 24-h post-operative period, haloperidol- and droper-
idol-group patients also reported a lower incidence of
PONV [31% and 32% vs. 62% (saline group); Po0.01]. No
differences were found between the haloperidol and dro-
peridol groups.
Conclusion: Like droperidol (0.625 mg), prophylactic in-
travenous haloperidol (1 mg) significantly reduced the
incidence of PONV in women undergoing ambulatory
laparoscopic surgery.
Accepted for publication 12 September 2007
Key words: Antiemetics; droperidol; haloperidol; laparo-
scopic surgery; post-operative nausea and vomiting.
r 2007 The Authors
Journal compilation r 2007 The Acta Anaesthesiologica Scandinavica Foundation
also suggested that haloperidol has an antiemetic
effect on PONV (8, 10–12). However, for this claim,
only a few double-blind, randomized, and placebo-
controlled studies have been conducted (8). Also,
no published study has evaluated the prophylactic
effect of low-dose haloperidol on PONV in patients
undergoing ambulatory surgery.
In women undergoing ambulatory laparoscopic
surgery, the incidence of PONV is high (450%)
(13–15). A prophylactic antiemetic may be helpful
for these patients. In the present study, we per-
formed a double-blind, randomized, and placebo-
controlled trial to evaluate the prophylactic antie-
metic effect of low-dose haloperidol on PONV in
women undergoing ambulatory laparoscopic sur-
gery. Droperidol and saline were controls.
Materials and methods
After obtaining Institutional Review Board ap-
proval and written informed consent from the

patients, 150 women who were ASA physical
status I or II and scheduled for gynaecologic
laparoscopic surgery in an ambulatory setting
were enrolled in this double-blind, randomized,
and placebo-controlled study. Patients who were
breast-feeding, weighed 490 kg, were taking any
medication other than an oral contraceptive pill, or
had received an antiemetic within 24 h before
surgery were excluded. Before surgery, their
phases of menstrual cycle were collected and di-
vided into (1) pre-menstrum–menstrum phase
(days 25–, 1–6), (2) early follicular phase (days 7–
12), (3) ovulatory phase (days 13–15), and (4) luteal
phase (days 16–24).
Upon arrival in the operating room, the patients
were randomly assigned to one of three groups
(n 5 50 each) using a computer-generated random-
number table. Fifteen minutes after the induction
of anaesthesia, the haloperidol group received in-
travenous haloperidol (1 mg), the droperidol group
received intravenous droperidol (0.625 mg) (4), and
the saline group received intravenous saline. Study
medications in identical 2 ml syringes were pre-
pared by a nurse anaesthetist to ensure that the
anaesthesiologists were blinded to their contents.
The patients and the investigators who collected
the post-operative data were blinded to the rando-
mization.
The anaesthetic regimen and surgical procedure
were standardized for all patients. Anaesthesia was
induced with intravenous fentanyl (2 mg/kg) and
propofol (2 mg/kg). Tracheal intubation was facili-
tated with intravenous rocuronium (1 mg/kg).
Anaesthesia was maintained with 8–12% (inspired
concentration) desflurane in oxygen. Ventilation
was controlled mechanically and adjusted to main-
tain an end-tidal partial pressure of CO2 between
30 and 40 mmHg. Additional rocuronium was
administered as required.
During anaesthesia, a standard lead II electro-
cardiogram was recorded at a paper speed of
25 mm/s and an amplification of 0.1 mV/mm at
the time of drug injection as well as every 1 min for
10 min after the injection. The QT intervals were
measured manually from the onset of the QRS
complexes until the end of the T wave and cor-
rected for the patient’s heart rate using a previously
published formula (16). A corrected QT interval
(QTc) was then obtained.
Laparoscopic surgery was conducted under vi-
deo guidance and involved 2 or 3 punctures of the
abdomen. During surgery, the patients were placed
in a Trendelenburg position and the abdomen was
Haloperidol reduced PONV
insufflated with CO2 with an intra-abdominal pres-
sure of 10–12 mmHg. Post-surgery, the residual
neuromuscular blockade was reversed using intra-
venous neostigmine (0.04 mg/kg) mixed with in-
travenous atropine (0.02 mg/kg), and the trachea
was extubated after the recovery of spontaneous
respiration and consciousness.
After surgery, patients were transported to the
post-anaesthetic care unit (PACU). During their
stay in the PACU (4 h), their blood pressure, heart
rate, and respiratory rate were monitored every
15 min. Oxygen saturation (SaO2; using pulse oxi-
metry) was monitored continuously. Intravenous
ketorolac (30 mg) was given routinely for the pre-
vention of post-operative pain. The intensity of
post-operative pain was assessed using a 10 cm
visual analogue scale score (0 5 no pain to
10 5 most severe pain). This was evaluated before
their discharge from the PACU. Because pain after
laparoscopic surgery is relatively minor, the pa-
tients did not receive further analgesic treatment
after discharge.
Nausea and vomiting were assessed immedi-
ately after surgery and at 1-h intervals in the
PACU for 4 h. In addition, nausea and vomiting
were assessed by telephone 24 h after surgery, on a
three-point ordinal scale (0 5 none, 1 5 nausea, and
2 5 vomiting). In the present study, no distinction
was made between vomiting and retching (i.e., a
retching event was considered a vomiting event).
In PACU, ondansetron (4 mg) was given intrave-
nously when vomiting occurred or on patient
request. No nausea, no vomiting, and no rescue
antiemetic medication during a 24-h post-operative
period was defined as successful protection.
The level of sedation was evaluated 30 min after
each patient arrived in the PACU. It was classified
as 1 5 awake; 2 5 drowsy, responds to verbal com-
mands; 3 5 asleep, responds to touch or pain sti-
muli; and 4 5 no response. Post-operative
extrapyramidal side effects (EPS: motor restless-
ness, acute dystonia, or tardive dyskinesia) were
also noted. Patients were discharged from hospital
after a 4-h stay in PACU. Twenty hours after
discharge, occurrences of PONV and EPS were
assessed using telephone interviews.
Sample size was pre-determined using a power
analysis based on the following assumptions: (1)
the incidence of PONV without antiemetic prophy-
laxis was 60% (13, 14), (2) a 30% reduction in the
total incidence PONV (from 60% to 30%) would be
clinically relevant, and a 5 0.05 (two-sided) and
b 5 0.2 (power 5 80%). An analysis showed that
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T. F. Wang et al.

43 patients per group would be sufficient. A series droperidol groups reported a lower incidence of
of one-way analyses of variance were conducted to PONV than those in the saline group (Po0.05,
examine differences in parametric variables be- Table 2). In addition, fewer patients in the haloper-
tween the three groups. If a significant difference idol and droperidol groups requested a rescue
was found, the Bonferroni t-test was used to detect antiemetic (ondansetron 4 mg) than those in the
the intergroup differences. The Kruskal–Wallis test saline group (Po0.05 and 0.01). During the total
was used to evaluate differences in nonparametric observation period (0–24 h), patients in the halo-
variables between the three groups, and then the peridol and droperidol groups reported a lower
Mann–Whitney rank sum test was used for inter- incidence of PONV and a higher percentage of
group differences. Categorical variables were ana- successful protection than those in the saline group
lysed using a series of 3  2 w2 tests to determine (Po0.01, for each comparison, Table 2). No differ-
differences between the three groups, and then
using 2  2 w2 tests or Fisher’s exact tests, as
appropriate, for intergroup differences. All fol- Table 2
low-up analyses were corrected for the number of Incidence of post-operative nausea and vomiting and uses of
simultaneous contrasts using Bonferroni’s adjust- rescue antiemetics.
ments. A P-value of o0.05 was considered to be Group Haloperidol Droperidol Saline
significant. (1 mg) (0.625 mg)
n 45 44 47
In the PACU (0–4 h post-operatively)
Nausea 7 (16%) 6 (14%) 12 (26%)
Results Vomiting 4 (9%) 4 (9%) 11 (23%)
Total 11 (24%)* 10 (23%)* 23 (49%)
Of the 150 patients enrolled in this study, 14 Rescue antiemetic 6 (13%)+ 7 (16%)* 18 (38%)
patients were withdrawn due to surgical reasons After discharge (4–24 h post-operatively)
(n 5 6) or incomplete data collection after they had Nausea 5 (11%) 6 (14%) 12 (26%)
Vomiting 0 (0%) 0 (0%) 2 (4%)
been discharged from the hospital (n 5 8). The data Total 5 (11%)* 6 (14%) 14 (30%)
from the remaining 136 patients were analysed. No From 0–24 h post-operatively
differences were found between the three groups in Nausea 10 (22%) 10 (23%) 17 (36%)
patient characteristics and anaesthesia (Table 1). In Vomiting 4 (9%) 4 (9%) 12 (26%)
+
Total 14 (31%) 14 (32%)+ 29 (62%)
the PACU, vital signs were stable and not different Successful protection 31 (69%)+ 30 (68%)+ 18 (38%)
between the three groups. No patient had a SaO2
Data are number of patients (%).
below 90%. *Po0.05.
During their stay in the PACU (0–4 h post-opera- +
Po0.01, compared with the saline group.
tively), patients in both the haloperidol and the PACU, post-anaesthetic care unit.

Table 1
Patient characteristics.
Group Haloperidol (1 mg) Droperidol (0.625 mg) Saline
n 45 44 47
Age (y/o) 33.5  5.2 34.2  6.1 32.3  5.6
Weight (kg) 55.4  9.1 57.2  9.8 56.5  9.1
Height (cm) 155.7  5.2 156.2  4.1 156.3  3.3
Motion sickness 10 (22%) 11 (25%) 8 (17%)
Previous PONV 5 (11%) 6 (14%) 5 (11%)
Types of surgery
Tubal ligation 22 (49%) 20 (45%) 24 (51%)
Ovarian cystectomy 12 (27%) 8 (18%) 11 (23%)
Myomectomy 11 (24%) 16 (36%) 12 (26%)
Phases of menstrual cycle (days)
Pre-menstrum–menstrum (25–, 1–6) 5 (18%) 6 (14%) 4 (9%)
Early follicular (7–12) 14 (31%) 12 (27%) 15 (32%)
Ovulatory (13–15) 12 (27%) 11 (25%) 12 (26%)
Luteal (16–24) 19 (42%) 15 (34%) 20 (43%)
Duration of surgery (min) 36.1  11.3 36.7  10.3 37.3  8.6
Duration of anaesthesia (min) 48.2  12.4 52.1  12.5 50.6  12.4

Data are means  standard deviation or number (%) of patients.

282
 Haloperidol reduced PONV

450 treating delirium, hallucinations, and other psy-

Haloperidol 1 mg
Droperidol 0.625 mg
chomotor-related illnesses (8, 10–12). It has also
Saline been suggested that haloperidol has a potent antie-
440 metic effect on PONV (5); however, more evidence
is needed to confirm this claim. In this double-
QTc (ms)

blind, randomized, and placebo-controlled study,

we found that haloperidol (1 mg) had a significant
430
prophylactic antiemetic effect on PONV in women
undergoing ambulatory laparoscopic surgery. This
effect was similar to that of droperidol (0.625 mg).
420 PONV is one of the most common and annoying
side effects in women undergoing ambulatory
0 1 2 3 4 5 6 7 8 9 10 laparoscopic surgery (13–15). The risk factors of
Time (min) being female, the use of laparoscopic technique,
Fig. 1. Mean QTc intervals ( standard deviation; ms) vs. time desflurane and fentanyl, and the duration of anaes-
(min). We found no differences between groups. thesia may contribute to this episode (17, 18). In our
study design, we controlled for all these factors. All
the female patients received similar surgical pro-
Table 3 cedures performed by the same team of anaesthe-
Post-operative sedation, pain, and side effects. siologists and surgeons. As predicted, the use of
anaesthetic drugs (e.g., desflurane and fentanyl)
Group Haloperidol Droperidol Saline
(1 mg) (0.625 mg) and the duration of anaesthesia and surgery were
n 45 44 47
similar between groups. The incidences of motion
Level of sedation (1–4) 1 (1–2) 1 (1–2) 1 (1–2) sickness and previous PONV were also similar
Intensity of pain 2 (1–3) 2 (1–3) 2 (1–3) between groups. Therefore, differences in the oc-
(using VAS; 1–10) currence of PONV between groups can be attrib-
Extrapyramidal side 0 (0%) 0 (0%) 0 (0%)
effects (EPS) uted to the differences in the experimental
medications used.
Data are number (%) or median (range). Previous studies demonstrated that female pa-
VAS, visual analogue scale score.
tients have a two to three times greater incidence of
PONV than males (19, 20). Vomiting increases as
ences were found between the haloperidol and girls approach menarche and the incidence in post-
droperidol groups. menopausal females is similar to that of men,
During anaesthesia, no differences were found suggesting a major hormonal influence (20–23).
between the QTc intervals after and before injec- The plasma levels of gonadotropin, oestrogen,
tions of drugs (haloperidol and droperidol). No and progesterone may be the confounding factors,
differences were also found between the three but the detailed relationships between hormones
groups during a 10-min observation period and PONV are still unknown (19, 23). In our study,
(Fig. 1). The level of sedation, which was evaluated we considered the influence of menstrual cycle on
30 min after each patient’s arrival in the PACU, was PONV (19, 23) and the phases of menstrual cycle of
low in all three groups, and no differences were the patients were collected (Table 1). However, no
found between groups (Table 3). The intensity of differences were found between groups, which
post-operative pain, which was evaluated 4-h post- excluded the influence of menstrual cycle on our
operatively, was minor in all three groups and no study result.
differences were found between the three groups Although high-dose haloperidol is suspected to
(Table 3). No EPS were found in the three groups produce some side effects, e.g., QT prolongation,
during a 24-h post-operative observation period. sedation, and EPS (8, 9), we found that low-dose
haloperidol (1 mg) did not produce significant
prolongation of QTc intervals nor any significant
sedative effect or EPS. These findings might be due
Discussion
to the size of the dose of haloperidol. Doses of
Haloperidol, the first butyrophenone in a series of haloperidol from 1 to 5 mg have been suggested as
major tranquilizers, is an effective neuroleptic for being effective in treating PONV (8). In the present

283
T. F. Wang et al.
study, we used the lowest suggested dose. We also
found that droperidol (0.625 mg) did not produce
significant side effects. These results might also be
explained by the size of the dose (4).
Cost is an ever-increasing concern in today’s
health care systems, and it is generally accepted
that the first-line antiemetic should be cost-effec-
tive. In Taiwan, 1 mg of haloperidol costs US$0.30
and 0.625 mg of droperidol costs US$0.27. Both
antiemetics are remarkably less expensive than
the 4 mg minimum effective dose of the rescue
antiemetic ondansetron, which costs US$7.47.
In conclusion, the prophylactic use of haloper-
idol (1 mg) effectively reduced the incidence of
PONV with minimum side effects in women un-
dergoing ambulatory laparoscopic surgery. No dif-
ferences were found between haloperidol (1 mg)
and droperidol (0.625 mg) on PONV. Haloperidol
(1 mg) is a suitable alternative for droperidol
(0.625 mg) on PONV in women undergoing ambu-
latory laparoscopic surgery.
References
1. Apfel CC, Roewer N, Korttila K. How to study postopera-
tive nausea and vomiting. Acta Anaesthesiol Scand 2002; 46:
921–8.
2. Raeder J. How do we move further in research on post-
operative nausea and vomiting? Acta Anaesthesiol Scand
2005; 49: 1403–4.
3. Myles PS, Williams DL, Hendrata M et al. Patient satisfac-
tion after anaesthesia and surgery: results of prospective
survey of 10811 patients. Br J Anaesth 2000; 84: 6–10.
4. McKeage K, Simpson D, Wagstaff AJ. Intravenous droper-
idol: a review of its use in the management of postoperative
nausea and vomiting. Drugs 2006; 66: 2123–47.
5. Shende D, Bharti N, Kathirvel S et al. Combination of
droperidol and ondansetron reduces PONV after pediatric
strabismus surgery more than single drug therapy. Acta
Anaesthesiol Scand 2001; 45: 756–60.
6. Gan TJ, White PF, Scuderi PE et al. FDA ‘‘black box’’
warning regarding use of droperidol for postoperative
nausea and vomiting: is it justified? Anesthesiology 2002;
97: 287.
7. Ayd FJ Jr. Haloperidol: twenty years’ clinical experience. J
Clin Psychiatry 1978; 39: 807–14.
8. Buttner M, Walder B, von Elm E et al. Is low-dose haloper-
idol a useful antiemetic? A meta-analysis of published and
unpublished randomized trials. Anesthesiology 2004; 101:
1454–63.
9. Critchley P, Plach N, Grantham M et al. Efficacy of halo-
peridol in the treatment of nausea and vomiting in the
palliative patient: a systematic review. J Pain Symptom
Manage 2001; 22: 631–4.
284
10. Aouad MT, Siddik-Sayyid SM, Taha SK et al. Haloperidol
vs. ondansetron for the prevention of postoperative nausea
and vomiting following gynaecological surgery. Eur J
Anaesthesiol 2007; 24: 171–8.
11. Parlow JL, Costache I, Avery N et al. Single-dose haloper-
idol for the prophylaxis of postoperative nausea and
vomiting after intrathecal morphine. Anesth Analg 2004;
98: 1072–6.
12. Dyrberg V. Haloperidol (Serenase) in the prevention of
postoperative nausea and vomiting. Acta Anaesthesiol Scand
1962; 6: 37–47.
13. Wang JJ, Ho ST, Liu HS et al. Prophylactic antiemetic effect
of dexamethasone in women undergoing ambulatory
laparoscopic surgery. Br J Anaesth 2000; 84: 459–62.
14. Huang JC, Shieh JP, Tang CS et al. Low-dose dexametha-
sone effectively prevents postoperative nausea and vomit-
ing after ambulatory laparoscopic surgery. Can J Anesth
2001; 48: 973–7.
15. Sniadach MS, Alberts MS. A comparison of the prophylac-
tic antiemetic effect of ondansetron and droperidol on
patients undergoing gynecologic laparoscopy. Anesth Analg
1997; 85: 797–800.
16. Wisely NA, Shipton EA. Long QT syndrome and anaes-
thesia. Eur J Anaesthesiol 2002; 19: 853–9.
17. Gan TJ. Risk factors for postoperative nausea and vomiting.
Anesth Analg 2006; 102: 1884–98.
18. Rüsch D, Eberhart L, Biedler A et al. Prospective
application of a simplified risk score to prevent post-
operative nausea and vomiting. Can J Anesth 2005; 52:
478–84.
19. Beattie WS, Lindblad T, Buckley DN et al. The incidence of
postoperative nausea and vomiting in women undergoing
laparoscopy is influenced by the day of menstrual cycle.
Can J Anaesth 1991; 38: 298–302.
20. Palazzo MGA, Strunin L. Anaesthesia and emesis. II:
prevention and management. Can Anaesth Soc J 1984; 31:
407–15.
21. Rita L, Goodarzi M, Seleny F. Effect of low dose droperidol
on postoperative vomiting in children. Can Anaesth Soc J
1981; 28: 259–62.
22. Forrest JB, Cahalan MK, Rehder K et al. Multicenter study
of general anesthesia. II. Results. Anesthesiology 1990; 72:
262–8.
23. Honkavaara P, Lehtinen AM, Hovorka J et al. Nausea and
vomiting after gynaecological laparoscopy depends upon
the phase of the menstrual cycle. Can J Anaesth 1991; 38:
876–9.
Address:
Jhi-Joung Wang
Department of Anaesthesiology
Chi-Mei Medical Centre
No. 901, Chung-Hwa Rd
Yung-Kang City
Tainan Hsien
Taiwan
e-mail: 400002@mail.chimei.org.tw