Comparison of Ondansetron and Granisetron for Prevention of

Nausea and Vomiting Following Day–Care Abdominal

Laparoscopies

Original Article

INTRODUCTION

The most distressing symptoms that follow anesthesiaand surgery are pain and vomiting. The syndrome of nausea,retching and vomiting is known as ‘sickness’ and each partof it can be distinguished as a separate entity. Sometimesnausea and vomiting may be so distressing that it can affectthe patient psychologically, physically and financially by adelay in hospital discharge. With the change in focus frominpatient to ambulatory anesthesia, there has been anincreased interest in the “Big Little Problem” of nausea andvomiting [1,2]. The etiology and pathophysiology of PONVare multifactorial with patient, medical and surgery relatedfactors [3,4]. Three patients related variables i.e. femalegender, smoking and age; 2 operative variables like durationof surgery, types of surgery (laparoscopic surgery, strabismussurgery) and 3 anesthesia related variables i.e. use of opioidsintraoperatively, N2O and intravenous anesthesia withPropofol. Various pharma-cologic agents are rapidly comingup with increasing efficacy to prevent and treat PONV. Thenewer classes of antiemetics are NK-1 (substance P) receptorantagonists and Serotonin (5-HT3) receptor antagonists (e.g.Ondansetron, Granisetron, Dolasetron, Tropisetron, etc.) havereplaced the older traditional antiemetics like Phenothiazines(promethazine), antihistamines (diphenhydramine),Butyrophenones (drop-eridol), steroids (dexamethasone) andBenzamides (metoclopramide) because of their side effectsand lesser efficacy [5].

COMPARISON OF ONDANSETRON AND GRANISETRON FORPREVENTION OF NAUSEA AND VOMITING FOLLOWING DAY–

CARE ABDOMINAL LAPAROSCOPIES

Ankur Parmar*, V Manjula** and JM Reddy****Registrar, Department of Anesthesiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India,

**Consultant, ***Senior Consultant, Department of anesthesiology, Apollo Health City,Jubilee Hills, Hyderabad 500 033, India.

Correspondence to: Dr Ankur Parmar, Registrar, Department of Anesthesiology, Indraprastha Apollo Hospitals,Sarita Vihar, New Delhi, 110 076, India.

The most common and distressing symptoms, which follow anaesthesia and surgery, are pain and emesis.The consequences of PONV are physical, surgical and anesthetic complications for patients as well asfinancial implications for the hospitals or institutions. Sometimes nausea and vomiting may be moredistressing especially after minor and ambulatory surgery, delaying the hospital discharge. Laparoscopicsurgery is one condition, where risk of PONV is particularly pronounced due to pneumo-peritoneum causingstimulation of mechanoreceptors in the gut. In spite of plenty of anti-emetic drugs available no single drug is100% effective in prevention of PNV and combination therapy has got a lot of side effects.

Key words: Ondansetron, Post-anesthesia Vomiting, Granisetron.

Laparoscopy is a technique of minimal invasivesurgery. The hallmark of laparoscopy is the creation of‘pneumoperi-toneum’ with pressurized CO2 which resultsin a high incidence of Post Operative Nausea andVomiting (PONV) (40-75% of patients) [6,7].

Laparoscopic procedures are regarded as standardoperations for the study of PONV. The present study wascarried out to examine the incidence of nausea andvomiting following – laparoscopic cholecystectomy andcompare the efficacy of granisetran Ondansetrom in itsmanagement [8-11].

The aim and objectives

To compare the anti-emetic and anti-nausea effect,incidence of PONV, duration of action and costeffectiveness of intravenous Granisetron (1 mg) andOndansetron (8 mg) in a randomized double blind studyfor prophylaxis of post operative nausea and vomiting(PONV) in ASA grade I and II adult patients undergoingabdominal laparoscopies under general anaesthesia.

MATERIALS & METHODS

The study was carried out at Apollo Health City,Hyderabad from May 2008–October 2009 after obtainingdue institutional approval and informed written consentfrom 60 patients.

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127 Apollo Medicine, Vol. 8, No. 2, June 2011

INCLUSION CRITERIA

(i) Patients of ASA Grade I & II,

(ii) Patients aged between 30-60yrs,

(iii) Patients belonging to either sex,

(iv) Patients weighing between 40-80kg,

(v) Patients scheduled for day care abdominallaparoscopic surgeries in the surgery department ofthe hospital.

EXCLUSION CRITERIA

(i) Patients with any known systemic, metabolic orendocrine disorder,

(ii) Patients with known allergy to the drugs under study,

(iii) Patients with history of PONV, Gastro esophagealreflux disease & motion sickness,

(iv) Patients with anticipated airway difficulty,

(v) Uneducated patients who were unable to cooperatewith the investigator.

STUDY TYPE: Prospective, randomized,comparative, double blinded study.

METHOD

The pre-anesthetic check of the patients was done aday before surgery. The patients were randomly dividedinto two groups using the coin flip method:

• Group A (n=30): IV injection Ondansetron 8mgdiluted in normal saline to a total volume of 5mLadministered 2 minutes before induction.

• Group B (n = 30): IV injection Granisetron diluted innormal saline to a total volume of 5mL administered2 minutes before induction.

PREOPERATIVE PREPARATION

All the patients were allowed to take light and non-residual diet in the evening of previous day of operation.All of them received tab. Alprazolam 0.5mg and tab.Ranitidine 150mg orally night before surgery. All thepatients were advised to remain nil per oral after midnight.

ANESTHETIC TECHNIQUE

Study medications were prepared and administeredjust 2 minutes before induction by anesthetist in identical5-mL syringes to ensure blinding.

General anesthesia was induced with inj. Propofol(1%) 2mg/kg IV, inj. Vecuronium 0.08mg/kg IV and inj.

Fentanyl 100 mcg IV. Endotracheal intubation was donewith appropriate sized cuffed ETT. A nasogastric tube wasplaced orally to promote baseline emptying of thestomach of air and gastric contents.

Maintenance of anesthesia was done with oxygen andnitrous oxide at the ratio of 1:2, sevoflurane 1% andintermittent positive pressure ventilation facilitated byintermittent doses of inj. Vecuronium 1mg IV. Theperitoneal cavity was insufflated with CO2 Pneumo-peritoneum was established, intraabdominal pressuremaintained around 10-15 mmHg. The IV fluid used duringsurgery was 0.9% saline. Pulse, blood pressure,electrocardiogram, oxygen saturation and end tidalcarbondioxide values were monitored throughoutanesthesia.

At the end of surgery the patients were extubated afterthe residual neuromuscular block was reversed with inj.Neostigmine 0.05mg/kg & inj. Glycopyrrolate 0.02mg /kgslow IV, and shifted to the recovery room.

OBSERVATIONS

The observations were recorded as per the followingprotocol:

1. Pulse rate, blood pressure (BP) and oxygensaturation (SPO2) were recorded prior to theinduction.

2. Intraoperative pulse, BP, SPO2 and end tidal carbondioxide (ETCO2) were recorded throughout thesurgery and the mean was calculated.

3. All the patients were asked for nausea and wereobserved for vomiting.

- Every 1 hourly for 2 hours (i.e. at 0, 1st and 2ndhours)

- Every 2 hourly till 6th hour (i.e. at 4th and 6thhour)

- At 12th hour then at 24hrs (through phone calls)

4. The incidence of postoperative nausea and vomitingwere scored as per the following scoring system asproposed by M. Dresner, et al [13].

Postoperative Nausea Score PostoperativeVomiting score

0–None 0–None1–Mild intermittent nausea 1–One vomit only2–Constant modulate nausea 2–Several vomits3–Severe nausea 3–Repeated retching/

vomiting

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Apollo Medicine, Vol. 8, No. 2, June 2011 128

5. Nausea and vomiting were evaluated by thefollowing variables: the incidence of nausea andvomiting, episodes of vomiting, rescue antiemetics,and complete responses. For the purpose of datacollection, retching (same as vomiting but withoutexpulsion of gastric content) was consideredvomiting. A vomiting episode was defined as theevents of vomiting that occurred in a rapid sequence(<1 min between events). If events of vomitingwere separated by >1 min, they were consideredseparate episodes.

6. The instruction was given that the patients with >2episodes of vomiting should receive Inj. Dexa-methasone (8mg) IV stat as rescue medication [14].

7. The complete response was defined as no nausea, novomiting, and no antiemetic medication during a 24-h postoperative period.

STATISTICAL ANALYSIS

Data was represented as mean ± standard deviationwherever applicable. The 2 groups were comparedcategorically for nausea and vomiting. A p-value <0.05 wastaken as statistically significant by student’s t-test. Thesoftware used in the study was WINDOSTAT version 8.6.

OBSERVATIONS

Table 1 shows the age, sex & body weight distributionin the 2 groups of patients. There was no significantdifference in age, sex and body weight distribution in thetwo groups.

Table 2 shows the preoperative pulse, blood pressure(Systolic & diastolic) and SPO2 in the 2 groups of patients.There was no statistically significant difference in thebaseline values of the patients in the 2 groups.

As per Table 3, none of the cases in the two groupsshowed any significant hemodynamic deviation from thepreoperative values in the intraoperative period.

There was statistically no significant difference in the2 groups in the Table 4, for the type of surgeries which thepatients underwent.

The duration of anesthesia of the patients wasobserved in both the groups and the mean value wascalculated for the comparison in each group. There was nosignificant difference in the mean duration of anesthesia inthe two groups in the Table 5 (P>0.1).

Figures 1 (a) & 1 (b) show that the patients in group Bdid not have nausea in the first 4 hours post operatively

Table 1. Patient demography

Group No. of cases Male(%) Female(%) Age Inyrs. ± Sd Weight in Kg ±Sd

A 30 6 (19.8%) 24 (80.2%) 46.4±9.06 53.0±8.28B 30 7 (23.3%) 23 (76.7%) 45.7±10.18 54.27±7.77

Table 2. Preoperative pulse, blood pressure & oxygen saturation

Group No. of Pulse Systolic blood Diastolic blood Oxygen saturationcases (B/M) ± SD pressure pressure SPO2 (%) ± SD

(mm Hg)± SD (mmHg)± SD

A 30 79.53±10.60 123.86±7.99 81.13±4.86 98.83±0.87B 30 78.86±10.94 121.93±7.94 80.60±5.15 99.23±0.77

Table 3. Intraoperative mean pulse, blood pressure & oxygen saturation

Group No. of Mean pulse Systolic blood Diastolic blood Oxygen saturationcases (B/M) ± SD pressure pressure SPO2 (%) ± SD

(mm Hg) ± SD (mmHg) ± SD

A 30 79.53±10.61 123.86±7.99 81.13±4.86 100B 30 78.86±10.94 121.93±7.94 80.60±5.15 100

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and the incidence of higher scores was also less after 4hour.

The nausea score in group A is higher in comparison togroup B. Statistical analysis by student’s t-test indicatessignificance at 1 (P=0.027*), 4 (P=0.013*), 6 (P=0.032*),and 12 hours (P=0.001*) whereas there was no significantdifference observed at 0,2 & 24 hours.

There was no vomiting in group A for first 2 hours andin group B for the first 12 hours. The vomiting scoresindicated significant statistical difference in vomiting at12 hours in Group A (P=0.039*).

Incidence of postoperative nausea & vomiting

In group A patients nausea was observed in 13 patients(43.33%), vomiting in 12 patients (40%), both nausea &vomiting in 13 patients (43.33%) & no sickness in 17patients (56.67%) whereas in group B nausea wasobserved in 5 patients(16.67%), vomiting in 2 (6.67%)cases, both nausea & vomiting in 5 patients (16.67%) & nosickness in 25 patients (83.33%). Incidence of nausea wasmore in group A compared to group B. Incidence ofvomiting was also more in group A. Incidence of sicknesswas significantly high in group A. Incidence of nosickness was significantly more in group B which washigher than group A (P-value <0.05). It was also observed

that in spite of treatment though incidence of vomiting wasreduced, but nausea was not totally abolished in both thegroups as evident (Figs. 1-6).

DISCUSSION

Postoperative nausea and vomiting are observed aftergeneral, regional and local anesthesia. Reported incidenceof postoperative nausea and vomiting (PONV) afterabdominal laparoscopic surgeries ranges from 40-70%[6].

The effect of PONV ranges from transient discomfortto even catastrophic complications like rupture ofesophagus. Other effects are dehydration, electrolytedisturbances, poor surgical outcome in ophthalmic, head& neck surgery and abdominal wounds. It limits thebenefit of laparoscopy by delaying hospital discharge andat times results in an unanticipated overnight admission inhospital [6].

From the observations of table-1 it was found thatthere was no significant difference in age, sex and bodyweight (P value >0.1).

In Table 2 and 3, pre-operative and intraoperativepulse, BP and oxygen saturation of the 2 groups werestudied. The sudden hypotension or hypoxia, which arepositive factor of PONV were not observed. The durationof anesthesia or the type of surgery done did not show anymarked difference (Table 4 & 5) between the two groups.The anesthesia time was defined as the time fromanesthetic induction until the patient was shifted to post-anesthesia care unit.

From observation of the Figure 1 (a) & 1 (b), in Group-B (Granisetron 1mg) the postoperative nausea score

Table 4. Type of surgery

Group Laparoscopic Laparoscopic Laparoscopic Laparoscopiccholecystectomy inguinal hernioplasty appendicectomy ventral hernioplasty

Group A 14(40.67%) 7(2.33%) 7(2.33%) 2(0.67%)Group B 15(50%) 5(1.67%) 8(2.67%) 2(0.67%)

Table 5. Duration of anesthesia

Group No of Mean duration ofcases anesthesia (min.) ± SD

A 30 78.13 ± 12.11B 30 77.80 ± 11.24

Table 6. Incidence of postoperative nausea & vomiting

Group No. of cases Nausea Vomiting Total No sickness

A 30 13 (43.33%) 12 (40%) 13 (43.33%) 17 (56.67%)B 30 5 (16.67%) 2 (6.67%) 5 (16.67%) 25 (83.33%)

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Apollo Medicine, Vol. 8, No. 2, June 2011 130

(a)

(b)

Fig 1. (a) Post operative nausea score – Group A; (b) Postoperative nausea score – Group B

Fig 2. Mean post operative nausea score

(PONS) was significantly lower at 1, 4, 6 and 12 hoursafter completion of anesthesia. Post operative vomitingscore (POVS) in Table 6 showed no incidence of vomitingin patient under Group-B until 12 hours, whereasvomiting was reported around 4, 6, 12 and 24 hours afteranesthesia in Group A. There was a significant statisticaldifference in POVS at 12 hours, P value = 0.034. It showsthat the severity of both nausea and vomiting in theGranisetron group was significantly less than that in theOndansetron group.

From observation in Table 7, response to prophylacticmedication in Group-A and Group-B have shown that 17(56.67%) and 25 (83.33%) cases remained free fromnausea and vomiting, respectively. The number of caseswho vomited in group B were 2 (6.67%), but it was 12(40%) case in Group-A. The incidence of nausea in group-A and B were 13 (43.33%) and 5 (16.67%) casesrespectively. The overall incidence of PONV in Group Aand B were 43.33% and 16.67% respectively. Anotherimportant factor in post-op nausea & vomiting is IVadministration of antibiotics which was not taken intoaccount in our study.

It has been observed in various studies that antiemetictherapy is often very effective in reducing incidence ofvomiting or retching, but less so for nausea [17-21].

From the observations in the Table 6, on comparingthe total nausea scores at the end of surgery between groupA and group B it was evident that the duration ofantinausea effect after a single dose of Ondansetron 8mgwas significantly less than that of single dose ofGranisetron 1mg. The nausea score in the Group B waszero till the end of 4 hours. There was a statisticallysignificant difference at the end of 1st, 4th, 6th and 12thhours, with the P values as 0.027, 0.013, 0.032 and 0.001respectively. Similarly, there were no reported cases ofvomiting in the Granisetron group till the end of 12 hourswhich was statistically significant (P = 0.039) whencompared to the vomiting score in the Ondansetron group.Also, as evident by the higher total scores of nausea andvomiting in group A, Granisetron 1mg reduces theseverity of nausea and vomiting better than Ondansetron8mg, the P = 0.003 for total nausea score and P = 0.019 for

Table 7. Total nausea & vomiting score

Group Total nausea score Total vomiting score(Mean ± SD) (Mean ± SD)

Group A 1.93 ± 2.74 0.40 ± 0.49Group B 0.33 ± 0.92 0.13 ± 0.34P value 0.003 0.019

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131 Apollo Medicine, Vol. 8, No. 2, June 2011

(a) (b)

Fig 3. (a) Post operative vomiting score – Group A; (b) Post operative vomiting score – Group B

Fig 4. Mean post operative vomiting score

Fig 5. PONV incidence in Group A Fig 6. PONV incidence in Group B

total vomiting score comparing both the groups. Thisshows that there was a significantly prolonged antinauseaand antiemetic effect with intravenous administration ofGranisetron in the patients undergoing day care abdominallaparoscopies although there was not a need to administerthe rescue antiemetic or a need of readmission in both thegroups. This implies that the requirement of Granisetron1mg is twice daily as compared to thrice daily requirementof Ondansetron 8mg.

Cost is an ever-increasing concern in today’s healthcare system. Prophylactic antiemetic with Granisetron isrelatively inexpensive. On comparing the cost of one doseof inj. Ondansetron 8mg, MRP Rs. 42.00, with one dose ofinj. Granisetron 1mg, MRP Rs. 18.95, it is clearly evidentthat the therapy of PONV with Granisetron per dose is

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approximately 2.21 times cheaper than the treatment withOndansetron.

PONV can lead to a number of unwanted side effectsincluding fluid and electrolyte imbalance, wounddehiscence, delayed discharge of day care patients, unanti-cipated hospitalization of day care patients with extracosts to the patient and the hospital. Increasingly there is atrend towards day care surgery therefore these last twofactors have become important considerations. PONV canlead to a lot of stress for the patient, their relatives andhealth workers and create major negative impact onpatient satisfaction and overall surgical experience.

CONCLUSION

From the present study, it was concluded that-

• There was no significant hemodynamic difference inthe patients receiving Ondansetron or Granisetron.

• The patients who received Granisetron had signi-ficantly less severe Post Operative Nausea comparedto the group that received Ondansetron.

• There was a decrease in the incidence of postoperative nausea in the patients receivingGranisetron as compared to Ondansetron.

• The incidence of post operative vomiting wassignificantly less with Granisetron than withOndansetron.

• The duration of action of Granisetron was longerthan Ondansetron even when administered at thestart of anesthesia, as evident by the post operativenausea and vomiting scores.

• The cost effectiveness of the therapy of PONV wassignificantly more with Granisetron than withOndansetron.

Hence, Granisetron can be used as an antiemetic agentin abdominal laparoscopic surgeries to reduce theincidence of postoperative nausea & vomiting.

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