J Ayub Med Coll Abbottabad 2005;17(4) COMPARISON OF METOCLOPRAMIDE, PROCHLORPERAZINE AND PLACEBO IN PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING (PONV) FOLLOWING TONSILLECTOMY IN YOUNG ADULTS Muhammad Jamil, Syed Mushtaq Gilani, Shamsher Ali Khan Department of Anaesthesiology, Ayub Medical College and Teaching Hospital, Abbottabad Background: Postoperative nausea and vomiting following anaesthesia and surgery are common and can create considerable problems regarding management of patients and outcome of the surgical procedure. Methods: This study evaluates and compares the efficacy and safety of the metochlopramide to that of prochlorperazine in the prevention of postoperative nausea and vomiting after tonsillectomy in young adult patients. 150 patients, of either sex, undergoing tonsillectomy under the same anaesthetic technique were studied in a randomized, double blind, placebo controlled manner. Either metoclopramide 0.1-0.2 mg kg-1, prochlorperazine 0.1-0.2 mg kg -1 or 5% Dextose and normal saline (5% D/N.S) (2ml) as placebo was injected intravenously 10 minutes before induction of general anaesthesia. Episodes of nausea, retching/ vomiting, adverse events, vital signs, the need for rescue antiemetic drug ( metoclopramide 0.1-0.2 mg kg–1 IV) were recorded until four hours from the end of the surgical procedure. Results: The overall frequency of PONV was 18%, 16%, and 24% in group A (metoclopramide), B (prochlorperazine) and C (placebo) respectively. The need for rescue antiemetic was 2%, 8% and 12% in Prochloperazine group, metoclopramide group and control group respectively. These differences did not reach statistical significance (P>0.05). During the study period 82%, 84% and 76% of patients in group A, B and C respectively were found free from postoperative nausea and vomiting, and no adverse events related to either of the test medication were noted in any patient. Conclusion: It is concluded that the differences in the results of occurrence of PONV in the experimental group and control group are not statistically significant. However either Prochloperazine 0.1 – 0.2 mg kg-1 or metoclopramide 0.1 – 0.2 mg kg-1 can be safely administered as Prophylactic antiemetic till the availability of more efficacious and safe antiemetic drugs. Keywords: Postoperative nausea and vomiting (PONV), metoclopramide, prochlorperazine, tonsillectomy. INTRODUCTION
elective operations is not indicated but it may be justified in patients, who are at the greater risk of
Nausea and vomiting being among the most common
postoperative complaints can occur after general,
regional or local anaesthesia.1 The aetiology of
acupressure and acupuncture for prevention of PNOV
postoperative nausea and vomiting (PONV) is
have been found ineffective.8 Prophylaxis and
multifactorial and includes factors like patients
treatment has been attempted with various drugs like
characteristic, type of surgery, anaesthetic techniques
benzodiazepines9, 5-hydroxytryptamine (5HT3,
serotonin) antagonists10, benzamides,11,12 butypro-
Although considered a minor postoperative
phenones,13 Phenothiazines,14 antihistamines,15 ginger
complication PONV can be the most distressing,
root16 and antichloinergics.17 High dose
resulting in bleeding, dehydration, electrolyte5 and
metoclopramide is also considered to be 5HT3
acid base imbalance. Persistent, retching and
antagonist but extrapyramidal side effects are
vomiting can impair the results of various surgical
procedures and increase the risk of pulmonary
aspiration of vomitus. It may prolong the stay in the
prevention of PONV with either metoclopramide or
post anaesthesia care unit, delay discharge1 and
Prochlorprazine, both administered intravenously ten
minutes before induction of anaesthesia in a double
result in dehiscence of abdominal wounds, rupture of
The objective was to evaluate efficacy of
esophagus, surgical emphysema and bilateral
each drug in the prevention of PONV and to compare
the frequency of PONV in the experimental groups to
The frequency of postoperative nausea and
vomiting can be reduced by refined anaesthesia technique and by avoiding the factors predisposing to
it. Although routine antiemetic prophylaxis in
J Ayub Med Coll Abbottabad 2005;17(4) MATERIAL AND METHODS
and auscultation of the chest for breath sounds. Arterial haemoglobin oxygen (Sao2) saturation and
This study was conducted in the operation theatre and
pulse rate were also continuously displayed by the
wards of ENT department of Post Graduate Medical
Institute, Govt. Lady Reading Hospital Peshawar. A
At the completion of surgery the anesthetics
total of 150 patients from the ENT wards were
were turned off and the patient extubated. They were
included in the study. All of them were admitted in
put on the lateral side with slight head down tilt to
the ENT wards a day before surgery through the out
avoid aspiration of secretion, blood, regurgitated or
patient department. They were suffering from chronic
vomited materials into the lungs during the early
tonsillitis and underwent tonsillectomy.
postoperative period. Their airways were kept cleared
Three independent samples each of size 50
of clots or secretions. Oxygen was provided via
randomly selected from normally distributed
facemask 4 – 6 L/min till full recovery of the patients
population of young adults of either sex with the
in the recovery room. Radial pulse for the rate,
same variance were named as group A, B and C
rhythm and volume, systolic and diastolic blood
according to prophylactic antiemetic they received.
pressure, respiratory rate and temperature were
All patients included were adults (16–30
years), American Society of Anesthesiologists (ASA)
Physical status class I of both sexes being selected
maintenance fluid till the patients were allowed orally
randomly. Patients suffering from preoperative
for fluid intake. A trained nurse unaware of the
emesis, taking anxiolytic or Sedatives, having history
nature of the study drugs observed and nursed the
of drug allergy, clotting disorders, vertigo or ear
patients in the recovery room and wards. She
disease, airway difficulty or pregnancy were
assessed the patients for the frequency of the nausea,
excluded from the study. These patients were kept
retching, vomiting or any side effects of drugs for 4
nothing per oral for 6 hours preoperatively. An
hours in the postoperative period. A rescue
Intravenous line was secured with an 18-gauge
antiemetic (metoclopramide 0.1 – 0.2 mg kg-1 IV)
cannula on the dorsum of the hand in all patients. The
was administered either on the demand of the patient
patients randomly received in a double blind fashion
or at the discretion of the observing nurse. A
either metoclopramide 0.1 – 0.2 mg kg-1 (2ml),
Performa designed for the recording of the
prochlorperazine 0.1 – 0.2 mg kg–1 (2ml) or 5%
demographic data, the type of the prophylactic
Dextose in Normal Saline (2ml) intravenously in the
antiemetic drug given, the rescue antiemetic used if
preparation room, 10 minutes before induction of
indicated and the record of postoperative emetic
anaesthesia. The same anaesthetic technique was
sequelae, was attached with the chart of the patient.
used for all patients. On entry into the operation
theatre, replacement of the fluid deficit was started
with Ringer lactate & Dextose 5% (Ringolact D).
Category 1: Patients experienced no nausea, retching
Morphine 0.05 mg kg-1 and atropine 0.01 mg kg-1
were administered intravenously to each patient just
before induction of general anaesthesia.
Category 3: Patients suffered from retching /
The patients were preoxygenated with 100%
oxygen via facemask for three to five minutes.
At the completion of study the patients were
Thiopentone sodium 4 – 5 mg kg-1 IV was given
divided into three groups according to the
followed by suxamethonium 1 – 1.5 mg kg-1 IV to
Group A: Patients received metoclopramide, 0.1 –
Anaesthesia was maintained with halothane
0.5% - 2% and nitrous oxide 60% in oxygen (40%),
Group B: Patients received Prochlorperazine, 0.1 –
via a Bain circuit. The patients were provided
assisted ventilation manually till resumption of
Group C: Patients received placebo 5% Dextose with
spontaneous respiration. Ringolact D was infused
intravenously for replacement of deficit and
A fixed effect model was used for analysis
maintenance fluids. The patient’s radial pulse was
of variance (ANOVA) in order to test for the equality
monitored by regular palpation for rate, rhythm and
of means. Chi square test was used for analysis of the
volume. The arterial blood pressure (systolic and
frequency of postoperative nausea, vomiting, overall
diastolic) was monitored every ten minutes. Standard
frequency of PONV and the need for rescue
lead 11 was used for continuous ECG display. The
antiemetic drug. The exact value for probability was
respiration of the patient was monitored clinically by
obtained when our null hypothesis was true a value of
observation of the respiratory rate, chest expansion
the test statistic as extreme or more extreme in the
J Ayub Med Coll Abbottabad 2005;17(4)
appropriate direction than the one actually computed
Table-4: Overall frequency of PONV
was quoted as p-value where ever appropriate.
Groups Number patients
P<0.05 was considered as significant. The results were shown in the form of tables.
Patients in all the three groups were similar with no
statistically significant difference regarding age
metoclopramide as a rescue antiemetic to control
(P=0.192), weight (P=0.4803). There was also
PONV. In group C, 12% received metoclopramide
similarity amongst the groups with respect to ASA
while in group B, 2% of patients needed it to alleviate
physical status, the history of previous anaesthetic
PONV during the 4 hours follow up period (Table-5).
exposure, history of motion sickness, type and duration of surgical procedure. (Table-1)
Table-5: The need for rescue antiemetic (metoclopramide 0.1-0.2 mg kg –1 I.V) Table-1: Demographic data of the patients. Groups Number patients % C A (n=50)
These differences were not statistically significant
DISCUSSION
Nausea and vomiting are unpleasant sequelae of
anaesthesia and surgery. It is distressing to the patient
Nausea was experienced by 4% of patients
and potentially detrimental to the postoperative
in group A, 12% in group B and 14% in group C
during the study period. The frequency of nausea was
It may arise after regional anaesthesia,
less in group A when compared with group C and B,
particularly if hypotension occurs but are more
but the difference did not reach statistical
common after general anaesthesia. The overall
incidence of emesis was a high as 75 – 80% when
Table-2:Number of Patients experiencing nausea
ether and cyclopropane were in routine use. This fell to 20% - 30% with the advent of halothane in the mid
Groups Number patients
1950’s. There is now evidence that the use of
propofol is associated with an incidence of less than
10%. Addition of nitrous oxide to general
anaesthesia, use of opioids as anaesthesia supplement
and as analgesic, reversal of residual effects of non-
depolarizing muscle relaxant at the end of surgery
and 10% in groups A, B and C respectively. It was
with neostigmine and operation like strabismus
considerably less in group B than in group A and C.
surgery, laparatomy and throat surgery are associated
with higher incidence of PONV. The routine
Table-3:Number of Patients experiencing
prophylactic use of antiemetics to prevent PONV is
vomiting
hard to justify. However it is lucid to give a prophylactic antiemetics drug to patients, high risk
Groups Number patients
for emesis and aspiration.1 Much information has
been published on the efficacy and side effects of
various antiemetic drugs. However there is a
continued search for an ideal antiemetic that is
effective, safe, cheaper and easily available. This
study was designed as a part of these efforts to search
and 24% in group A, B and C respectively.
out a solution for minimizing the occurrence of
comparable in group A and B and higher in group C
The frequency of PONV in groups A, B and
as compared to the other two groups (Table-4).
C was 18%, 16% and 24% respectively. The
J Ayub Med Coll Abbottabad 2005;17(4)
frequency of PONV in group B (16%) is less as
also received pethidine IM 6 hourly for analgesia and
compared to group A (18%) and group C (24%), but
they were followed up for 24 hours postoperatively.
the difference did not reach statistical significance
(P>0.05). The frequency of PONV in the group C is
ondansetron 0.06 mg kg-1 IV and Prochlorperazine
similar to 24% reported by Khan et al.18 The
0.2 mg kg –1 IM and Prochlorperazine 0.1 mg kg–1 IV,
frequency of vomiting in groups A and C was 14%
given during induction of general anaesthesia to
and 10% respectively, which is comparable to each
patients undergoing adenotonsillectomy. Nausea
other. It was 4% in groups B which is less as
perse occurred with similar frequency in-between 6%
compared to the other groups, but the difference did
and 11% of patients in each test drug group.
not reach statistical significance (P>0.05).
Vomiting perse without accompanying complaints of
Mckenzie et al19 reported vomiting 54% in
nausea also occurred with similar frequency in
placebo group. They studied woman undergoing
between 11% and 19% of patients in each group. The
laparoscopic gynaecological surgery under local and
incidences of the dual complaints of nausea and
general anesthesia, their result is much higher than
vomiting were also similar in those given placebo
my result. The frequency of nausea in my study in
and prochlorperazine IV 29% and 21% respectively,
but greatly reduced to 3% and 2% respectively in
respectively. This difference did not reach statistical
those given prochlorperazine IM and on dansetron
IV. The frequency of nausea and vomiting in my
Bone et al16 and Raphael and Norton20 have
study is comparable to that of Vanden Berg study.
reported the incidence of nausea as 28% and 53%
But the frequency of vomiting in group B
respectively in their patients who received a similar
(Prochlorperazine) in my study is lower 4%, than that
dose of metoclopramide (0.1 – 0.2 mg kg-1 ) as in my
reported by Vanden Berg. This may be due to the
study. The result of my study is much lower than
following reason that many young children were
their results. This is because they have performed
adenoidectomy in addition to tonsillectomy was
gynaecological surgery and followed up their patients
performed on these children, they received
postoperatively for 12 hours. Similarly Bone et al16
nondepolarizing muscle relaxants that needed
had reported the incidence of emetic sequelae as 70%
reversal with neostigmine at the end of surgery, they
in the placebo group and 45% and 50% in the ginger
also received Parenteral opioids for analgesia
root and metoclopramide groups respectively. These
postoperatively and the the observation time was
results are also higher than those of my study.
Norton20 have reported the incidence of vomiting in
CONCLUSION
This study has demonstrated that the occurrence of
PONV is comparable in metoclopramide group
respectively. They received metoclopramide as a
(18%) and prochlorperazine group (16%). While the
occurrence of PONV is higher in the control group.
But these differences are not statistically significant
incidence of nausea in the placebo group as 30% and
(P>0.05). The need for rescue antiemetic was least in
in the metoclopramide group as 20%. The incidence
the prochlorperazine group (2%) as compared to the
of nausea in their patients is also higher than in my
metoclopramide group (8%) and control group
patients. The incidence of vomiting in placebo and
(12%). These differences also did not reach statistical
respectively. Their studies were performed on women
undergoing minor gynaecological procedures and
metoclopramide can be safely administered as
prophylactic antiemetic till the availability of more
The study of Rudra21 shows the incidence of
efficacious and safe antiemetic drug. Their does of
0.1-0.2mg kg–1 are also effective for the prophylaxis
metoclopramide group and 85% in the placebo group.
of postoperative nausea and vomiting. More
experimental work is required to explore the various
metoclopramide group needed rescue antiemetic.
aspects of the problem of PONV. This may include
Thus the incidence and severity of PONV in the
the proper patient preparation, anaesthetic techniques,
study of A Rudra is considerably higher than that of
doses of drugs and comparative studies regarding
my study. This is due to the fact that Rudra
efficacy, safety and cost benefit ratio of various
performed study on female patients who underwent
upper abdominal surgery (Cholecystectomy), they
J Ayub Med Coll Abbottabad 2005;17(4) REFERENCES
12. Tramer M, Moore A, McQuay H. Prevention of
vomiting after paediatirc strabismus surgery, a
Watch MF, White PF. Postoperative nausea and
systematic review using review using the numbers
vomiting, its etology, treatment and prevention
needed to treat method. Br J Anaesth 1995;75:556-61.
13. Buther M, Walder B, Elm Fvetal. Is lower dose
Beattie WS, Lindblad T, Buckley DN, Forrest JB.
haloperidol a useful antiemetic. A Meta-analysis of
Mensturation increases the risk of nausea and vomiting
published and unpublished Randomized trials.
after laparoscopy, a prospective randomized study
14. Van den Berg AA. Comparison of ondansetron and
Lerman J. Surgical and patient factor involved
prochloperazine for the prevention of nausea and
postoperative nausea and vomiting Br J Anaesth
vomiting after adenotosillectiomy. Canjanaesth
Kamath B, Curran J, Hawkey C. Anaesthesia,
15. Knapp MR, Beecher HK. Postanaesthetic nausea,
movement and emesis. Br J Anaesth 1990; 64; 728-30.
vomiting and retching. JAMA 1956;160;376-85.
Andrews PLR. Physiology of nausea and vomiting Br J
16. Bone Me, Wilkinson DJ, Young JR, McNeil J,
Charltron S. Ginger root a new antiemetic. The effect of
ginger root on postoperative nausea and vomiting after
emphysema Pneumomediastinum and bilateral
major Gyneacological surgery. Anaesthesia
pneumothoraces after postoperative vomiting Br J
17. Honkavaara P. Effect of transdermal hyoscine on
Capouet V, De Pauw C, Vernet B. Single dose i, v
nausea and vomiting during and after ear surgery under
tropisetron in the prevention of postoperative nausea
local anesthesia. Br J Anaesth 1996;76:49-53.
and vomiting after gynecological surgery, Br J Anaesth
18. Khan FA. Soomro NA, Kamal RS. A review of 6978
consecutive admission to the recovery room at a
Shenkman Ze’ EV, Holzman RS, Kim E. Acupressure-
university hospital J Pak Med Assoc 1991;41:2-6
Acupuncture Antiemetic prophylaxes in children under
19. Mckenzie R, Kovac A, Connor TO. Comparison of
going Toxsillectomy Anesthesiology 1999; 90; 1311-6.
ondansetron versus placebo to prevent postoperative
Florio TD. The use of midazolam for persistent
nausea and vomiting in woman undergoing ambulatory
postoperative nausea and vomiting Anaesth Intensive
gynaecologic surgery. Anesthesiology 1993;78:21-8.
20. Raphael JH, Norton AC. Antiemetic efficacy of
10. Bowhayar, Mayha, Rudnicka AR. A randomized
prophylactic ondansetron in laparoscopic surgery.
controlled trail of the antiemetic effect of three doses of
Randomized, double-blind comparison with
ondansetron after strabismus surgery in children. Paed
metoclopramide. Br J Anaesth 1993;71:845-8.
21. Rudra A. Comparison of ondansetron, metoclopramide
11. Madej TH, Simpson KH. Comparison of the use of
and placebo in the prevention of emetic episodes
domperidone, droperidol and metoclopramide in the
following Cholecystectomy. Anesthesiology 1993;
prevention of nausea and vomiting following major
metoclopramide surgery. Br J Anaesth 1986;58;884-7.
________________________________________________________________________________________________________________ Address For Correspondence: Dr Muhammad Jamil, Department of Anaesthesia, Ayub Medical College & teaching Hospital, Abbottabad Tel: 0300-9114624
SON LAS INHALOCÁMARAS VALVULADAS UNA MEJOR OPCIÓN FRENTE A LOS ESPACIADORES A LA HORA DE FORMULAR INHALADORES DE DOSIS MEDIDA? Fabio Bolívar MD1, Elvira Aguilera MD2, Isabel C. Bolívar MD3 1. Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander (UIS). Bucaramanga, Colombia. 2. Subgerente Mediplast Ltda. Bucaramanga, Colombia. 3. Comité Cie