Nausea is the uncomfortable sensation of an impending episode
of vomiting. It is often associated with prodromal symptoms such
as salivation, swallowing, pallor and tachycardia {1}. Vomiting is
a complicated process, mediated by a central coordinating "vomiting
center", thought to reside in the brainstem (close to the Tractus
Solitarius). Called the Parvicellular Reticular Formation, or the
Emetic Center (EC) {4}, it receives inputs from the pharynx, GI
tract, mediastinum, higher cortical centers (e.g. the visual,
gustatory, olfactory & vestibular centers), and the Chemoreceptor
Trigger Zone (CTZ). The CTZ is located within the brainstem, in
the Area Postrema. Because the CTZ is not protected by the blood-brain barrier, it is exposed to blood borne substances ("toxins")
and relays this information to the EC. CTZ activity is modified by
a variety of receptors, including dopaminergic, histaminic,
muscarinic, and serotonergic. Most anti-emetic drugs have
antagonist activity at one or more of these receptors. The EC
receives this input, and initiates the vomiting sequence, in a
rather complex interplay of various systems (see references {1,4}
for further details).
DIAGRAM OF VOMITING MECHANISMS:
Receptor Activity--(+/-)-> ------ -------
Blood borne toxins--(+)--> | CTZ |----> | |
Vestibular input----(+)--> ------ (+) |Emetic |--> Vomiting
(+) |Center |--> Efferents
Cortex (vision, taste, smell, etc)------>| |
Pharynx |-----> -------
GI Tract, Mediastinum |(vagus)
Adapted from Watcha, et al. {1}
AGENTS ACTING ON RECEPTORS ON THE CTZ:
(-) Ondansetron :: Droperidol :: Atropine :: Promethazine
:: :: ::
(+) Serotonin :: Dopamine :: Muscarinic :: Histamine
Agents
Risks factors for PONV:{5}
Certain risk factors are unavoidable, such as those caused by
the procedure and those associated with a particular patient.
Since these cannot be modified, when they are present, diligent
prophylaxis should be pursued. The choice of anesthetic is one
factor that the anesthesiologist has control over.
Surgical Factors:
The following types of surgery have been found to correlate
with a higher incidence of PONV: Laparoscopic (especially
gynecological), strabismus, middle ear, orchiopexy, stomach,
duodenal, gall bladder and extracorporeal shock wave lithotripsy.
The length of surgery has also been correlated with PONV risk,
perhaps as a result of increased duration of anesthesia.
Patient factors:
AGE: peak between 11 & 14; GENDER: women > men (although this
is not true for preadolescents and patients older than 80--maybe a
gonadotrophic factor?); OBESITY; ANXIETY/STRESS; HISTORY of
motion sickness or N/V with previous anesthetics; GASTROPARESIS
(e.g. diabetes, chronic cholecystitis, some neuromuscular
disorders, bowel obstruction); FULL STOMACH
Post-operative factors:
PAIN (especially pelvic); DIZZINESS (dehydration,
hypotension); MOTION (sitting up too early); early ORAL INTAKE;
post-operative NARCOTICS
TREATMENT OPTIONS:
NOTE: The costs of each agent are presented for comparison
only. The following prices were obtained in New York, U.S.A.,
around 9/95. Small center prices are from a local distributor, and
the large hospital prices are from a pharmacy purchasing agent.
Prices may vary among institutions, distributors, states and
countries.
Ondansetron (Zofran) - Cerenex Pharm. (919) 248-2100
$23.00/4 mg dose (Small center price)
$17.00/4 mg dose (Large hospital price)
(no generic available)
MECHANISM: Serotonin (5HT3) receptor antagonist.
SIMILAR AGENTS: Granisetron, Tropisetron
Found to be effective in both prophylaxis against and treatment
of PONV. Some studies show the effects to last up to 24 hours
{16}. The optimal dose is 50 mcg/kg, or about 4 mg IV in the
average adult {17}. All 5HT3 antagonists act in a similar manner,
but their duration of action differs. Side effects are minimal,
but include headaches and constipation {18}. They usually do NOT
cause sedation. One study {19} shows that addition of 8 mg of
dexamethasone (decadron) decreased PONV significantly, compared to
ondansetron alone, but routine use of steroids needs careful
consideration.
Study # pts. N/V-Placebo N/V-Ondansetron
----- ------ ----------- ---------------
{20} 77 49% 21%
{16} 544 54% 23%
{21} 120 45% 17%
Droperidol (Inapsine) - Janssen Pharm. (800) 526-7736
$5.10 for 5 mg (Small Center Pricing)
$4.42 for 5 mg (Large Hospital Pricing)
$1.24 for 5 mg (Generic, Large Hospital)
Dose may range from 0.25 mg to 5 mg IV (see below)
MECHANISM: Dopamine (DA) antagonist.
SIMILAR AGENT: prochloroperazine (compazine)
Droperidol is a highly effective antiemetic with a long
duration of action (8 hours or more). It is a butyrophenone with
some antagonist action at noradrenergic, serotonergic, and GABA
receptors, as well as its primary antagonism at dopaminergic
receptors {22}. Side effects include sedation (it is in the same
medication class as haloperidol (Haldol)), agitation (especially in
pediatric patients), dysphoria, and dyskinesias. Its use is
relatively contraindicated in patients with Parkinsonism or other
central dopamine depleting disease states. The usual dose is about
75 micrograms(mcg)/Kg(about 5 mg in a 70 KG adult). However, at
this level, side effects are more prevalent, and sedation may delay
emergence from anesthesia and/or RR discharge {1}. In an attempt
to minimize side effects, the lowest effective dose has been
examined in several controlled studies:
Study # pts. Dose in 70 KG N/V: Drop. vs. Plac.
----- ------ --------- -------- --------------------
{23) 150 5 mcg/Kg (0.3 mg) 10% vs. 41%
{24} 140 5 mcg/Kg (0.3 mg) 4% vs. 35%
10 mcg/Kg (0.63 mg) 4% vs. 35%
{23} 150 10 mcg/Kg (0.63 mg) 9% vs. 41%
{25} 185 20 mcg/Kg (1.25 mg) 17% vs. 40%
{26} 140 20 mcg/Kg (1.25 mg) 20% vs. 65%
It is difficult to compare data between studies, because risk
for PONV and response to therapy varies among age groups and
procedure types. Among the dose comparison studies, the consensus
seems to be that 5 mcg/kg can be effective, but may be unreliable,
especially in high risk patients/procedures (such as pediatric
strabismus surgery). 10 mcg/Kg seems to be more reliable, but
additional doses may be required in the recovery period {27}.
Where there is a greater risk for PONV, 20 mcg/kg seems to be the
optimum dose, with minimal sedation and agitation. However,
delayed agitation on the night after surgery has been reported with
doses as low as 1.25 mg {27}.
METOCLOPROMIDE:
$2.46/10 mg dose (small center)
$0.88/10 mg dose (Large hospital)
$0.25/10 mg dose (generic, large hospital)
MECHANISM:
central-dopamine antagonist;
peripheral-increases gastric motility.
SIMILAR AGENT: domperidone (motilium)
Some studies show this agent to be effective in PONV
prophylaxis, others do not demonstrate a statistically significant
difference from placebo. The usual dose is 10 mg IV, but better
results have been reported with doses of 15-20 mg IV.
Study Pts Surgery Dose N/V vs Plac. p
----- ---- ---------- ---------- ------------ -----
{28} 102 Peds T&A 0.15 mg/Kg 47% vs. 70% <0.03
{29} 110 Strabismus 0.25 mg/Kg 29% vs. 88% <0.01
{30} 48 Spinal MSO4 20 mg IM 17% vs. 58% <0.05
{31} 182 Adult Ortho 20 mg IV 58% vs. 83% <0.05
{25} 185 Adult Ortho 10 mg IV same as placebo
{26} 140 Laparoscopy 10 mg PO same as placebo
{32} 77 Spinal anes 10 mg IV same as placebo
{17} 60 Termin.Preg. 10 mg IV same as placebo
ALTERNATIVE TREATMENTS:
Since most antiemetics have undesirable side effects, or are
expensive, alternative treatments for PONV have been investigated.
Acupuncture:
Acupressure/acupuncture is a therapeutic modality that has been
in use in China for thousands of years. The P6 (Neiguan)
acupuncture point is located 2 "Chinese inches" (the width of the
proximal interphalyngeal thumb joint) proximal to the distal wrist
crease, approximately 1 cm deep to the skin, between the tendons of
the flexor carpi radialis and the palmaris longus. Stimulation of
this point is reported to reduce nausea, and anti-sea sickness
elastic wrist bands with a sphere to apply pressure to this point
are sold commercially. Several investigators have examined the
efficacy in prevention of PONV in controlled studies:
1) Fossoullaki et al {33} examined transcutaneous electrical
nerve stimulation (TENS) at the P6 point in 103 females for
hysterectomy: Placebo N/V-43%, P6 TENS-23% (p < 0.001).
2) Yang, et al {34} examined P6 point injection with 0.2 cc of
50% glucose in water on 120 patients for GLP: P6 point injection
had significantly less N/V than placebo.
3) Dundee et al {35} examined pressure at P6 vs. simple
acupuncture at P6 vs. TENS at P6 vs. placebo: All P6 methods showed
statistically significant improvement in PONV vs. placebo during
the first 6 hours. Patients receiving TENS and acupuncture had
significantly less N/V after 6 hours as well.
4) Ho et al {36}, examined the difference between TENS and
electro-acupuncture at the P6 point vs. placebo and
prochlorperazine in 100 patients for GLP's: N/V in placebo-44%, P6
TENS- 36%, P6 electro-acupuncture-12%, prochlorperazine-12%
Ginger Root (Zingiber Officinale)
Herbal medicine has been practiced for thousands of years with
mixed results. Modern pharmacology has isolated and quantified the
active compounds permitting more precise dosing. Ginger root has
been examined for efficacy in PONV prophylaxis in 2 placebo
controlled, double-blinded studies:
1) Bone et al {37} studied 60 women for major gynecological
surgery: There was a statistically significant decrease in PONV vs.
placebo, and a response rate similar to metoclopromide. The dosage
was 0.5 mg of powdered ginger root, in a capsule.
2) Phillips et al {38} studied 120 women after GLP: There was a
statistically significant decrease in PONV vs. placebo, and
response rate similar to metoclopromide.
Positive Suggestion:
The human mind is a powerful tool, and positive suggestions are
used by many people to help them change undesirable behaviors or
reinforce desirable ones. Eastern "mystics" have demonstrated
conscious control over autonomic functions, such as heart rate and
metabolic rate. The power of positive suggestion to reduce PONV
was examined in 2 controlled studies:
1) In a double-blind study of 60 women for major Gyn surgery,
Williams et al {39} demonstrated significantly less N/V in patients
who had received suggestions.
2) In a prospective study of 266 patients, Lauder et al {40}
demonstrated that the positive suggestion group required 16.5% less
antiemetics than the control group.
ECONOMICS OF PONV:
INSTITUTIONAL COSTS:
PONV can delay recovery room (RR) discharge by 47-61 minutes
{3}. The time and resources required to treat PONV add to the
institutional costs of the procedure, and have 2 components:
1) Direct cost: (extra time x nurses hourly wage) +
(materials & medications)
2) Opportunity cost {3}: Income lost from procedures that could
have been performed, had the resources been available (assuming
that RR delays back up into the O.R.). Assume that 48 minutes RR
delay = 0.4 O.R. cases that have to be delayed or postponed. If 5
patients each day had PONV, then 5 x (0.4) = 2 more cases that
could have been performed, with associated income loss to the
facility. Annual opportunity costs can be estimated by the
following formula:
(typical # procedures/year) x (PONV incidence rate) x (revenue
from extra patients who could have been treated--per case of PONV).
Using this formula, the "average" day-surgery center in the U.S.A.
loses from $253,000 - $1,520,000/year in revenue due to time lost
treating PONV {3}. Clearly, PONV has a significant impact on
revenues, and a cost-effective method of addressing the problem
needs to be found.
COST-EFFECTIVENESS OF PROPHYLAXIS:
When discussing cost-effectiveness, the important factors to be
considered include the cost of preventing a case of PONV (treated),
the resource cost when PONV occurs (untreated), and
the actual incidence of PONV (how many truly require treatment).
If [(cost of treatment) x (total # patients)] is greater than
[(cost of not treating) x (actual # cases PONV)], then routine
prophylaxis of all patients would not be cost-effective. For
example, in a study by Watcha & Smith {41}, it was determined that
for ondansetron to be cost effective for routine prophylaxis, the
incidence of PONV would need to be greater than 33%. For routine
droperidol prophylaxis to be cost-effective, the incidence of PONV
would need to be at least than 10%.
Several studies have shown that a low dose of droperidol (0.25
or 0.5 mg IV) was just as effective as the usual doses (e.g. 1.25
or 2.5 mg IV) in prophylactic treatment of PONV, without the
undesirable side effects usually noted at higher levels. A 10 cc
multi-dose vial of droperidol (2.5 mg/cc) would contain 50-100
doses at a cost of about $10.00, and thus routine prophylaxis would
cost just 10 to 20 cents per patient.
DISCUSSION:
PONV is costly, inconvenient, and uncomfortable. Routine
prophylaxis may be expensive or have undesirable side effects. Of
the studies reviewed, droperidol and ondansetron seem to be the
most consistently reliable agents for PONV prophylaxis. Higher
doses of droperidol (2.5 mg or more) may be more dependable, but
sedation and agitation are more prevalent. Routine prophylaxis at
this dose would subject too many patients to the risk of unpleasant
side effects. Routine prophylaxis with ondansetron would give
fewer side effects, but would be expensive (about $20.00 per
patient).
One Cost Effective Strategy:
A reasonable strategy may be to use low dose droperidol (10-20
mcg/Kg) as routine prophylaxis in all patients. At this dose, side
effects are negligible and the overall incidence of PONV is
reduced. A larger dose of droperidol (25-50 mcg/Kg) can be used
for high risk procedures or patients, with an expectation of
minimal side effects. For those few remaining patients that break
through prophylaxis, ondansetron may be used to reduce the duration
of the PONV episode--to speed up RR discharge (freeing up
resources)--and could give the patient relief that could last up to
24 hrs {16}. Another rationale for this approach is that
droperidol and ondansetron act a different receptors, and should be
expected to act in synergy.
Studies that compare agents:
{29} - Metoclopromide (0.15 or 0.25 mg/Kg) vs. droperidol (0.075
mg/Kg) vs. placebo in 110 cases of pediatric strabismus surgery:
N/V - Placebo 88%, Meto. 0.15 mg/Kg 68% (not sig.), Meto. 0.25
mg/Kg 29% (sig.), Drop. 33% (sig.)
{21} - Ondansetron (4 mg IV) vs. droperidol (1.25 mg IV) vs.
placebo in 120 adult orthopedic cases, double blinded: N/V -
placebo 45%, ondan. 17%, drop. 18%, both sig. vs. placebo, but not
sig. different
{42} - Ondansetron (0.15 mg/kg) vs. droperidol (0.075 mg/Kg) in 57
cases of pediatric strabismus surgery, double blinded: Emesis free
- ondan. 94%, drop. 81% (no sig. difference)
Studies that combine agents:
{43} - Combining agents with actions at different receptor sites,
in sub-therapeutic doses (to minimize side effects) was shown
statistically to be as effective as a therapeutic dose of
droperidol by Michaloudis, et al. in 71 GLP's - droperidol 0.5 mg +
metoclopromide 5 mg + hyoscine 0.1 mg vs. droperidol 1.25 mg.
{44} - Mathia, et al. found combining droperidol and metoclopromide
did not decrease the incidence of N/V over droperidol alone.
Other agents (not discussed):
{45} - Ephedrine (0.5 or 1 mg/Kg) vs. metoclopromide (0.15 mg/Kg)
vs. droperidol (0.05 mg/Kg) in 100 cases of pediatric hernioplasty:
ephedrine no different than placebo (either dose), meto. & drop.
sig. less N/V than placebo but no sig. difference between them.
{31} - Alizapride (100 or 200 mg) vs. metoclopromide (20 mg) vs.
droperidol (1.25 mg) vs. placebo: N/V - placebo 83%, aliz. 100 mg
46% (p<0.01), aliz. 200 mg 33%(p<0.05), drop. 35% (p<0.001), meto.
not sig. different than placebo.
{25} - Domperidone (5 or 10 mg) vs. droperidol (1.25 mg) vs.
metoclopromide (10 mg) in 185 orthopedic cases: Vomiting - placebo
40%, dom. 42% (not sig.), drop. 17% (sig.), meto 37% (not sig.).
{46} - Transdermal scopolamine patch (140 mcg initially, then 5
mcg/hr thereafter) vs. droperidol (1.25 mg) vs. placebo in 96
females for same day surgery: Nausea - placebo 25%, patch 20 %,
drop. 15% (p<0.05); vomiting - no difference among groups.
{47} - Dixyrazine (0.25 mg/Kg) vs. droperidol (0.075 mg/Kg) vs.
placebo in 61 cases for pediatric strabismus surgery: N/V - placebo
65%, dix. 25% (sig. vs. placebo & with less sedation than drop.),
drop. 48% (sig.).
CITED REFERENCES:
1 - Watcha-MF, White-PF. "Postoperative nausea and vomiting. Its
etiology, treatment and prevention". Anesthesiology.
77:162-84. 1992
2 - Carroll NV, Miederhoff P, Cox FM, Hirsch JD. "Post operative
nausea and vomiting from outpatient surgery centers". Anesth
Analg. 80:903-9. 1995
3 - Hirsch-J. "Impact of postoperative nausea and vomiting in the
surgical setting". Anaesthesia. 49(Suppl):30-1. 1994
4 - Andrews-PL. "Physiology of nausea and vomiting". Br J
Anaesth. 69(Suppl):2S-19S. 1992
5 - Kenny GN. "Risk factors for postoperative nausea and
vomiting". Anaesthesia. 49(suppl):6-10. 1994
6 - Borgeat A, Wilder Smith OH, Sutter PK. "The non-hypnotic
therapeutic applications of propofol". Anesthesiology.
80:642-56. 1994
7 - Reimer EJ, Montgomery CJ, Bevan JC, et.al. "Propofol
anesthesia reduces early postoperative emesis after pediatric
strabismus surgery". Can J Anaesth. 40:927-33. 1993
8 - Jellish WS, Leonetti JP, Murdoch JR, Fowles S. "Propofol
based anesthesia as compared with standard techniques for
middle ear surgery". Otolatyngol Head Neck Surg. 112:262-7.
1995
9 - Ranta P, Nuutinen L, Laitinen J. "The role of nitrous oxide
in postoperative nausea and recovery in patients undergoing
upper abdominal surgery". Acta Anesthesiol Scand. 35:339-41.
1991
10 - Muir JJ, Warner MA, Offord KP, et.al. "Role of nitrous oxide
and other factors in postoperative nausea and vomiting: a
randomized and blinded prospective study". Anesthesiology.
66:513-8. 1987
11 - Sengupta P, Plantevin OM. "Nitrous oxide and day-case
laparoscopy: effects on nausea and return to normal activity".
Br J Anaesth. 60:570-3, April, 1988
12 - Sukhani R, Lurie J, Jabamoni R. "Propofol for ambulatory
gynecological laparoscopy: does omission of nitrous oxide
alter postoperative emetic sequelae and recovery?" Anesth
Analg. 78:831-5. 1994
13 - Felts JA, Poler SM, Spitznagel EL. "Nitrous oxide, nausea and
vomiting after outpatient gynecological surgery". Can J
Anaesth. 2:168-71. 1990
14 - Lonie DS, Harper NJ. "Nitrous oxide anesthesia and vomiting".
Anaesthesia. 41:703-7, July, 1986
15 - Honkavaara P, Lehtinen AM, Hovorka J, Korttila K. "Nausea and
vomiting after gynecological laparoscopy depends upon the
phase of the menstrual cycle". Can J Anaesth. 38:876-9.
1991
16 - McKenzie R, Kovac A, O'Connor T, et.al. "Comparison of
ondansetron versus placebo to prevent nausea and vomiting in
women undergoing ambulatory gynecologic surgery".
Anesthesiology. 78:21-8. 1993
17 - Watcha MF, Bras PJ, Cieslak GD, Pennant JH. "The dose-response relationship of ondansetron in preventing
postoperative emesis on pediatric patients undergoing
ambulatory surgery". Anesthesiology. 82:47-52. 1995
18 - Currow DC, Noble PD, Stuart-Harris RC. "The clinical use of
ondansetron". Med J Aust. 162:145-9, February 6, 1995
19 - McKenzie R, Tantisira B, Karambelkar DJ, et.al. "Comparison
of ondansetron with ondansetron plus dexamethasone in the
prevention of postoperative nausea and vomiting". Anesth
Analg. 79:961-4. 1994
20 - Rodrigo MR, Campbell RC, Chow J, et.al. "Ondansetron for
prevention of postoperative nausea and vomiting following
minor oral surgery: a double-blind randomized study". Anaesth
Intensive Care. 22:576-9. 1994
21 - Gan TJ, Collis R, Hetreed M. "Double-blind comparison of
ondansetron, droperidol and saline in prevention of
postoperative nausea and vomiting". Br J Anaesth. 72:544-7.
1994
22 - Simpson PJ. "Special techniques" in Nummo WS, Smith G eds.
Anaesthesia, Vol. 1 Oxford:Blackwell Scientific Publications.
P.840 1989
23 - Millar JM, Hall PJ. "Nausea and vomiting after prostaglandins
in day-case termination of pregnancy. The efficacy of low
dose droperidol". Anaesthesia. 42:613-8. 1987
24 - O'Donovan N, Shaw J. "Nausea and vomiting in day-case dental
anaesthesia. The use of low dose droperidol". Anaesthesia.
39:1172-6. 1984
25 - Kortilla K, Kauste A, Auvinen J. "Comparison of domperidone,
droperidol, and metoclopromide in the prevention and treatment
of nausea and vomiting after balanced general anesthesia".
Anesth Analg. 58:396-400. 1979
26 - Pandit SK, Kothary SP, Pandit UA, et.al. "Dose-response study
of droperidol and metoclopromide as antiemetics for outpatient
anesthesia". Anesth Analg. 69:798-802. 1989
27 - Melnick B, Sawyer R, Karambelkar D, et.al. "Delayed side
effects of droperidol after ambulatory general anesthesia".
Anesth Analg. 69:748-51. 1989
28 - Ferrari LR, Donlon JV. "Metoclopromide reduces the incidence
of vomiting after tonsillectomy in children". Anesthesia and
Analgesia. 75:351-4. 1992
29 - Lin DM, Furst SR, Rodarte A. "A double-blinded comparison of
metoclopromide and droperidol for prevention of emesis
following strabismus surgery". Anesthesiology. 76:357-61.
1992
30 - Knudsen K, Lisander B. "Metoclopromide decreases emesis after
spinal anesthesia supplemented with subarachnoid morphine".
Reg Anesth. 19:390-4. 1994
31 - Kauste A, Tuominen M, Heikkinen H, et al. "Droperidol,
alizapride and metoclopromide in the prevention and treatment
of postoperative emetic sequelae". Eur J Anaesthesiol. 3:1-9. 1986
32 - Spelina KR, Gerber HR, Pagels IL. "Nausea and vomiting during
spinal anesthesia. Effect of metoclopromide and domperidone:
a double-blind trial". Anaesthesia. 39:132-7. 1984
33 - Fassoulaki A, Papilas K, Sarantopoulos C, Zotou M. "TENS
reduces the incidence of vomiting after hysterectomy". Anesth
Analg. 76:1012-4. 1993
34 - Yang LC, Jawan B, Chen CN, et al. "Comparison of P6 acupoint
injection with 50% glucose in water and intravenous droperidol
for prevention of vomiting after GLP". Acta Anesthesiol
Scand. 37:192-4. 1993
35 - Dundee JW, Ghaly RG, Chestnutt WN, et al. "Effect of
stimulation of the P6 antiemetic point on PONV". Br J
Anaesth. 63:612-8. 1989
36 - Ho RT, Jawan B, Fung St, et al. "Electro acupuncture and
postoperative emesis". Anaesthesia. 45:327-9. 1990
37 - Bone ME, Wilkinson DJ, Young JR, et al. "Ginger root -- a new
anti-emetic. The effect of ginger root on PONV after major
gynecological surgery". Anaesthesia. 45:669-71. 1990
38 - Phillips S, Ruggier R, Hutchinson SE. "Zingiber officinale
(ginger)--an antiemetic for day case surgery". Anaesthesia.
48:715-7. 1993
39 - Williams AR, Hind M, Sweeney BP, Fisher R. "The incidence and
severity of PONV in patients exposed to positive suggestions".
Anaesthesia. 49:340-2. 1994
40 - Lauder GR, McQuillan PJ, Pichering RM. "Psychological adjunct
to perioperative emesis". Br J Anaesth. 74:266-70. 1995
41 - Watcha-MF, Smith I. "Cost-effectiveness analysis of
antiemetic therapy for ambulatory surgery". J Clin Anesth.
6:370-7. 1994
42 - Litman RS, Wu CL, Lee A, et al. "Prevention of emesis after
strabismus surgery repair in children: a prospective, double-blinded, randomized comparison of droperidol vs. ondansetron".
J Clin Anesth. 7:58-62. 1995
43 - Michaloudis D, O'Keefe N, O'Sullivan K, Healy TE. "PONV: a
comparison of anti-emetic drugs used alone or in combination".
J R Soc Med. 86:137-8. 1993
44 - Mathia WJ, Bell SK, Leak WD. "Effects of preoperative
metoclopromide and droperidol on PONV in ambulatory surgery
patients". AANA Journal. 56:325-33. 1988
45 - Liu YC, Kang HM, Liou CM, Tao HS. "Comparison of the emetic
effect among ephedrine, droperidol and metoclopromide in
pediatric inguinal hernioplasty". Ma Tsui Hsueh Tsa Chi.
30:37-41. 1992
46 - Tigerstadt I, Salmela L, Aromaa U. "Double-blind comparison
of transdermal scopolamine, droperidol and placebo against
PONV". Acta Anesthesiol Scand. 32:454-7. 1988
47 - Larsson S, Jonmarker C. "Postoperative emesis after pediatric
strabismus surgery: the effect of dixyrazine to droperidol".
Acta Anesthesiol Scand. 34:227-30. 1990
48 - Lim-KS, Lim-BL, Tee-CS, Vengadasalam-D. "Nausea and vomiting
after termination of pregnancy as day surgery cases:
comparison of 3 different doses of droperidol and
metoclopromide as anti-emetic prophylaxis". Singapore Med J.
32:342-3. 1991
49 - Carroll-NV, Miederhoff-P, Cox-PM, Hirsch-JD. "Postoperative
nausea and vomiting after discharge from outpatient surgery
centers". Anesth Analg. 80:903-9, May, 1995