Introduction:-

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

Source: http://ayubmed.edu.pk/JAMC/PAST/17-4/11jamil.pdf