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Prevention of Postoperative Nausea and Vomiting With Antiemetics in Patients Undergoing Middle Ear Surgery
Comparison of a Small Dose of Propofol With Droperidol or Metoclopramide
Yoshitaka Fujii, MD;
Hiroyoshi Tanaka, MD;
Noriaki Kobayashi, MD
Arch Otolaryngol Head Neck Surg. 2001;127:25-28.
ABSTRACT
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Objective To compare the efficacy and safety of a small dose of propofol with
other commonly used antiemetics, droperidol and metoclopramide, for the prevention
of postoperative nausea and vomiting in patients undergoing middle ear surgery.
Design Prospective, randomized, double-blind study.
Setting University-affiliated teaching hospital.
Patients Ninety patients (48 females, 42 males) scheduled for middle ear surgery.
Intervention Patients received propofol, 0.5 mg/kg, droperidol, 20 µg/kg, or
metoclopramide hydrochloride, 0.2 mg/kg, intravenously at the end of the surgical
procedure. A standardized general anesthetic technique was employed throughout
the surgical procedure.
Main Outcome Measure Emetic episodes and safety assessment were performed during 2 periods—0
to 3 hours in the postanesthetic care unit and 3 to 24 hours in the ward—after
receiving anesthesia.
Results The incidence of patients who were emesis free during the 0- to 3-hour
period after receiving anesthesia was 93% for those who received propofol,
73% for those who received droperidol, and 70% for those who received metoclopramide,
respectively; the respective corresponding incidence during the 3- to 24-hour
period after receiving anesthesia was 90%, 67%, and 60% (P<.05,
overall Fisher exact probability test). No clinically adverse events were
observed in any of the groups.
Conclusion A small dose of propofol is a better antiemetic than droperidol or metoclopramide
for the prevention of postoperative nausea and vomiting after middle ear surgery.
INTRODUCTION
POSTOPERATIVE nausea and vomiting after (PONV) surgery are distressing
and there are frequent adverse events after receiving general anesthesia during
surgery,1 with a high incidence in patients
undergoing middle ear surgery.2, 3
Most of the antiemetics used—antihistamines (eg, hydroxyzine), butyrophenones
(eg, droperidol), and dopamine receptor antagonists (eg, metoclopramide)—prevent
PONV, but have undesirable adverse effects, such as excessive sedation, hypotension,
dry mouth, dysphoria, restlessness, and extrapyramidal symptoms.1
The selective antagonists of serotonin3-receptors (eg, ondansetron
or granisetron) are effective for the prevention of PONV.4, 5
However, several investigators6, 7
have criticized serotonin3-receptor antagonists because of their
high cost. Propofol given at a small dose possesses direct antiemetic properties.8 A recent report by Honkavaara and Saarnivaara9 has compared the efficacy of subhypnotic doses of
thiopental sodium (1.0 mg/kg) and propofol (0.5 mg/kg) for the prevention
of PONV after middle ear surgery, and also has demonstrated that propofol
provides prophylaxis against emesis. However, to our knowledge, there have
been no studies comparing the efficacy of propofol administration with the
commonly used and well-established antiemetics droperidol and metoclopramide
hydrochloride in the prevention of PONV after middle ear surgery. We conducted
a prospective, randomized, double-blind study to evaluate the efficacy and
safety of a small dose of propofol with droperidol or metoclopramide for preventing
PONV in patients undergoing middle ear surgery.
PATIENTS AND METHODS
Approval of our institutional review board and written informed consent
from patients were obtained. Ninety patients (48 females, 42 males) with American
Society of Anesthesiologists physical status 1 (ie, no organic, physiological,
biochemical, or psychiatric disturbance), aged 25 to 68 years, and scheduled
for middle ear surgery (tympanoplasty or mastoidectomy) were enrolled in the
study. Patients who had gastrointestinal tract diseases, those who were pregnant
or menstruating, and those who had taken antiemetics within 24 hours before
surgery were excluded from the study.
Premedication consisted of orally administered diazepam, 5 mg. Anesthesia
was induced with intravenous (IV) administration of a combination of thiopental
sodium, 5 mg/kg, and fentanyl citrate, 2 µg/kg, and vecuronium bromide,
0.2 mg/kg, was used to facilitate tracheal intubation. After tracheal intubation,
anesthesia was maintained with 1.0% to 3.0% (inspired concentration) of sevoflurane
and 66% of nitrous oxide (which was replaced by air before closure of the
middle ear cavity) in oxygen. Additional analgesia during surgical procedure
was achieved with fentanyl citrate, 50 µg IV. Ventilation was mechanically
controlled and was adjusted to keep an end-tidal PCO2 at 35 to
40 mm Hg throughout the surgical procedure as measured by an anesthetic–respiratory
gas analyzer (Ultima; Datex-Omeda Division, Instrumentarium Corp, Helsinki,
Finland). Muscle relaxation was maintained with vecuronium as required. At
the end of surgery, in a randomized, double-blind manner, patients IV received
propofol, 0.5 mg/kg, droperidol, 20 µg/kg, or metoclopramide hydrochloride,
0.2 mg/kg. For reversal of muscle relaxation, a combination of atropine sulfate,
0.02 mg/kg, and neostigmine methylsulfate, 0.04 mg/kg, was administered IV,
and then the trachea was extubated when the patient was awake. No patient
had a nasogastric or an orogastric tube placed during surgery. Rectal temperature
was monitored and maintained at 37°C ± 1°C (mean ± SD)
using a warming pad. Postoperatively, patients received rectally indomethacin
sodium, 50 mg, when they reported pain. The use of oral narcotic analgesics
was not permitted in any of the 3 groups.
All episodes of PONV (nausea, retching, or vomiting) were recorded by
the nursing staff without knowledge of which antiemetic the patients had received
during the 2 periods, ie, within the first 24 hours after receiving anesthesia
or 0 to 3 hours in the postanesthetic care unit and 3 to 24 hours in the ward.
Nausea was defined as the subjectively unpleasant sensation associated with
awareness of the urge to vomit; retching was defined as the labored, spasmodic,
rhythmic contraction of the respiratory muscles without the expulsion of gastric
contents; and vomiting was defined as the forceful expulsion of gastric contents
from the mouth.1 These nurses asked the patients
if retching or vomiting had occurred and if they felt nauseous, with only
2 possible answers (yes/no). If 2 or more episodes of PONV occurred during
the first 24 hours after receiving anesthesia, another rescue antiemetic (domperidone)
was given rectally. The details of any adverse effects throughout the study
were recorded by the nursing staff.
Patient demographic data were analyzed by analysis of variance with
Bonferroni correction for multiple comparison and  2 test.
The number of patients experiencing emetic episodes and requiring rescue medication,
and the incidence of adverse events were compared with Fisher exact probability
test. P <.05 was considered statistically significant.
All values were expressed as mean ± SD or number (percentage). Based
on previous studies by Honkavaara et al2, 4
and us,5 it was calculated that 30 patients
per group would be required to demonstrate a 30% difference in values for
PONV (which was regarded as the primary end point) at  = .05 with a
power (1 - ß) = .8.
RESULTS
Patient profile and information on surgery and anesthesia are summarized
in Table 1. The treatment groups
were comparable for demographics of patients and types of operation.
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Table 1. Patient Demographics*
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There were no differences among the groups for the number of patients
who experienced only nausea, retching, or vomiting, or who required rescue
medication. The only difference was found in the incidence of emesis-free
patients during the 0- to 3-hour period after receiving anesthesia, which
occurred in 93%, 73%, and 70% of patients who had received IV infusion of
propofol, droperidol, and metoclopramide, respectively. The corresponding
incidence during the 3- to 24-hour period after anesthesia was 10%, 30%, and
30%, respectively (Table 2). Thus,
the efficacy of propofol therapy is superior to droperidol or metoclopramide
therapy for increasing an emesis-free episode during the 2 test periods for
patients undergoing middle ear surgery (P<.05).
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Table 2. Number of Patients in Each Group Having Each Emetic Symptom
During Both Study Periods*
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The most common untoward adverse events were headache and dizziness,
which were not serious. No difference in the incidence of adverse effects
was observed among the groups (Table 3).
COMMENT
The reported incidence of PONV after middle ear surgery (tympanoplasty
or mastoidectomy) is 62% to 80% when no prophylactic antiemetic is given.2, 3 The cause of PONV after middle ear
surgery remains unclear, but probably is multifactorial.1
A number of factors, including age, sex, obesity, a history of motion sickness,
and/or previous PONV, menstrual cycle, operative procedure, anesthetic technique,
and postoperative pain, are considered to affect the incidence of PONV.1 Surgical factors also include an increased middle
ear pressure caused by nitrous oxide.3 In this
study, however, these factors were well balanced among the groups, and no
pressure was generated in the middle ear from diffusion of nitrous oxide,
which was replaced by air before closing the tympanic membrane. Therefore,
the difference in the incidence of PONV among the groups can be attributed
to the drugs studied.
Propofol possesses direct antiemetic properties,8
and this effect is not due to the lipid emulsion (Intralipid) in the formulation
of propofol.10 The exact mechanism by which
propofol acts as an antiemetic is unknown, but propofol is not considered
to have vagolytic properties.8 Hammas et al11 have recently evaluated the effects of propofol on
nausea and vomiting induced by ipecacuanha which is known to release serotonin
and have demonstrated that propofol reduces the intensity of retching after
ipecacuanha administration. These findings suggest that propofol may have
a weak serotonin3-antagonistic effect.
Propofol at a subhypnotic dose (0.5 mg/kg) given at the end of surgery
provides prophylaxis against PONV.9 The same
dose of propofol was used in this clinical trial. The doses of other antiemetics,
droperidol and metoclopramide, were chosen from the results of several studies
regarding the prevention of PONV.12, 13
More conventional doses of these antiemetics, droperidol, 20 µg/kg,
and metoclopramide hydrochloride, 0.2 mg/kg, have been used for the prevention
of PONV12, 13 and have not been
associated with adverse effects, such as excessive sedation and extrapyramidal
symptoms.1 In our study, therefore, droperidol,
20g/kg, or metoclopramide hydrochloride, 0.2 mg/kg, was administered by IV.
For the prevention of PONV, droperidol and metoclopramide have been
used often, but there are contradictory findings in reports concerning the
effectiveness of these 2 antiemetics.1 We could
not find any report to compare the efficacy of a small dose of propofol with
droperidol or metoclopramide for preventing PONV after middle ear surgery.
Our results demonstrated that the incidence of patients experiencing an emesis-free
episode during the 2 study periods—0 to 3 hours and 3 to 24 hours after
receiving anesthesia—was less in patients who had received propofol
therapy than in those who had received either droperidol or metoclopramide
therapy (P<.05). This suggests that a small dose
of propofol given at the end of the surgical procedure is more effective than
droperidol or metoclopramide for increasing an emesis-free episode in patients
undergoing middle ear surgery.
The major deficiency in our study was the failure to include a control
group receiving placebo. However, we have already shown a high incidence of
PONV after middle ear surgery in patients who had received placebo.5 Moreover, Aspinall and Goodman14
have shown that there is a lack of reliable clinical information concerning
placebo-controlled trials of the serotonin3-receptor antagonist
ondansetron for the prevention of PONV. Therefore, the control group receiving
placebo was excluded from this clinical trial.
Adverse events observed in this study were not serious, and there were
no differences in the incidence of headache and dizziness among the groups.
Excessive sedation and extrapyramidal symptoms were not observed in any of
the groups.
In conclusion, we have shown that a small dose (0.5 mg/kg) of propofol
administered IV at the completion of surgery is a better antiemetic than either
droperidol, 20 µg/kg, or metoclopramide hydrochloride, 0.2 mg/kg, for
preventing PONV in patients undergoing middle ear surgery. Further studies
are needed to compare the efficacy of propofol at small doses with a serotonin3-receptor antagonist (eg, ondansetron or granisetron) for reducing
the incidence of PONV after middle ear surgery.
AUTHOR INFORMATION
Accepted for publication June 16, 2000.
From the Department of Anesthesiology (Drs Fujii and Tanaka) and Otolaryngology
(Dr Kobayashi), Toride Kyodo General Hospital, Toride City, Japan.
Corresponding author: Yoshitaka Fujii, MD, Department of Anesthesiology,
University of Tsukuba Institute of Clinical Medicine, 2-1-1 Amakubo, Tsukuba
City, Ibaraki 305, Japan.
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