Paediatric Anaesthesia 1998 8: 241–244

Comparison of granisetron and droperidol in theprevention of vomiting after strabismus surgeryor tonsillectomy in children

YOSHITAKA FUJII MD∗ , YUHJI SAITOH MD†,HIROYOSHI TANAKA MD‡ AND HIDENORI TOYOOKA MD∗∗Department of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine,Tsukuba City, Ibaraki, Japan† Department of Anaesthesiology and Critical Care Medicine, Tokyo Medical and DentalUniversity School of Medicine, Bunkyo-ku, Tokyo, Japan‡ Department of Anaesthesiology, Toride Kyodo General Hospital, Toride City, Ibaraki, Japan

SummaryThis prospective, randomized, double-blinded study evaluated theantiemetic efficacy of granisetron and droperidol in 80 ASA physicalstatus I children, aged 4–10 years, undergoing strabismus surgery ortonsillectomy with or without adenoidectomy. After anaestheticinduction, the patients received either granisetron (40lg·kg−1, n=40)or droperidol (50lg·kg−1, n=40) intravenously. The incidence ofvomiting during the first 24h after anaesthesia was 15% and 38%after administering granisetron and droperidol, respectively(P=0.02). The requirement for rescue antiemetic therapy for thetreatment of two or more episodes of vomiting was 0% withgranisetron and 18% with droperidol (P=0.001). In conclusion,granisetron was superior to droperidol in reducing the incidenceand frequency of postoperative vomiting in paediatric patients.

Keywords: strabismus; tonsillectomy; complications: vomiting;antiemetics; droperidol, granisetron

Introduction antiemetic in prevention of vomiting after strabismussurgery and tonsillectomy in children (5,6). Recently,

The incidence of vomiting in children undergoingit has been reported that another 5-HT3 receptor

strabismus repair or tonsillectomy is high when noantagonist, granisetron, has a more potent and longer

prophylactic antiemetic is provided (1,2).activity against vomiting associated with

Antiemetics, such as droperidol, have been evaluatedchemotherapy than ondansetron (7), and it has been

for management of postoperative emesis in paediatricdemonstrated that this agent is effective in the

patients (1,3), but efficacy is still debated (4).prevention of paediatric postoperative emesis (8).

Ondansetron, a selective 5-hydroxytryptamine typeWe performed a prospective, randomized, double-

3 (5-HT3) receptor antagonist, is a prophylacticblinded trial to evaluate the efficacy of granisetronand droperidol for preventing vomiting afterstrabismus repair or tonsillectomy with or withoutCorrespondence to: Dr Y. Fujii, Department of Anaesthesiology,

University of Tsukuba Institute of Clinical Medicine, 2-1-1, adenoidectomy in children.Amakubo, Tsukuba City, Ibaraki 305, Japan.

241 1998 Blackwell Science Ltd

242 Y. FUJII ET AL .

Methods 10–15mg·kg−1 acetaminophen p.r. for mild pain and0.3mg·kg−1 pentazocine i.v. for severe pain.

The study was approved by our institutional ethics Postoperatively, all episodes of retching andvomiting during the first 24h after recovery fromcommittee, and informed consent was obtained fromanaesthesia were recorded by nursing staff who didthe parents of 80 children, ASA physical status I,not know which antiemetics the patients hadbetween the age of four and ten years, undergoingreceived. Since we could not assess nausea in youngstrabismus repair or tonsillectomy with or withoutchildren, data for only retching and vomiting wereadenoidectomy. Patients who had a history of motionanalysed. Retching was defined as the process ofsickness and/or previous postoperative vomiting,straining to expel the stomach contents withoutand those who had received antiemetics within 24hbringing out anything. Vomiting was defined as anbefore surgery were excluded from the study. Theact of expelling the stomach contents by an activepatients enrolled in the study were not allowed toprocess. For the purpose of analysis in this study,have solid food after midnight and clear liquids werethe act of retching was considered to be the same aspermitted up to three h prior to surgery.vomiting. The details of any adverse effectNo preoperative medications were administered.throughout the study (0–24h after anaesthesia) wereAnaesthesia was induced by increasing concentrationalso recorded by a designated follow-up nurse whoof sevoflurane in 66% nitrous oxide (N2O) and oxygenspecifically inquired for restlessness and(O2) via mask. Tracheal intubation was facilitatedextrapyramidal signs.with 0.1mg·kg−1 vecuronium i.v. After tracheal

Statistical analysis was performed with one-wayintubation, anaesthesia was maintained with N2O/analysis of variance (ANOVA) with BonferroniO2 (2:1) and sevoflurane 0.5%–3.0% (inspiredcorrection for multiple comparison, Chi-squared testconcentration). Ventilation was controlledwith a Yates’ continuity correction, or Fisher’s exactmechanically and was adjusted to keep PETCO2 probability test, as appropriate. A P value <0.05 wasbetween 4.6kPa and 5.2kPa (34–38mmHg) asconsidered significant. All values were expressed as

measured by an anaesthetic/respiratory gas analysermean±SD, median (range) or number (%). We set

(Capnomac Ultima, Datex, Finland). The patientsa=0.05 and b=0.8, and used a large magnitude to

received, in a randomized double-blinded manner, aeffect (effective size 0.8) to estimate a sufficient

single dose of either granisetron (40lg·kg−1, n=40) sample size. The analysis showed that the 40 patientsor droperidol (50lg·kg−1, n=40) intravenously (i.v.) per group would be sufficient.over 2–5 min after the induction of anaesthesia andprior to surgery. Identical syringes containing either

Results40lg·kg−1 granisetron or 50lg·kg−1 droperidol, wereprepared by personnel not involved in the study. Patient demographics, surgical procedures,Additional neuromuscular blocking drugs were used anaesthetic and postoperative management wereas required. At the end of the surgical procedure, summarized in Table 1. There were no differencesantagonism of muscle relaxation was achieved with between the treatment groups. During the first 24h0.02mg·kg−1, atropine and 0.04mg·kg−1 neostigmine after anaesthesia, the incidence of postoperativei.v., and the trachea was extubated. Orogastric tubes vomiting in patients who had received granisetronwere not used. Rectal temperature was monitored was lower than those who had received droperidoland maintained at 37±1°C using a hot water pad (15% vs 38%, P=0.02) (Table 2).throughout surgery. Postoperatively, all patients were Seven of 40 children (18%) who had receivedadmitted to the hospital. Clear liquids were offered droperidol needed another rescue antiemetic for theonly if the child requested, and other oral intake was treatment of two or more episodes of vomiting,not allowed for 4h after recovery from anaesthesia. whereas none (0%) who had received granisetronEach patient who had two or more episodes of required this (P=0.001) (Table 2).vomiting within 24h after anaesthesia was given The most frequently reported adverse events werea standard rescue antiemetic (e.g., domperidone). headache and drowsiness, which were relatively

mild. There were no differences in the incidence ofPostoperative analgesia was provided by

1998 Blackwell Science Ltd, Paediatric Anaesthesia, 8, 241–244

GRANISETRON AND DROPERIDOL IN STRABISMUS SURGERY 243

Table 1 Granisetron has already been shown to be effectivePatient demographics and surgical procedures

in the treatment of vomiting in patients receivingcytotoxic drugs (9). It has also been demonstratedGranisetron Droperidol

Group (n=40) (n=40) that this antiemetic reduces the incidence of vomitingfollowing strabismus surgery or tonsillectomy withAge (yr) 6.7±2.2 6.5±2.2or without adenoidectomy in paediatric patients (8).Height (cm) 120.2±11.0 119.7±11.1

Weight (kg) 24.2±6.0 24.5±7.2 The incidence of postoperative vomiting during theSex (male/female) (n) 22/18 21/19 first 24h after anaesthesia in patients who hadDuration of operation (min) 60 (11–116) 55 (15–98)

received granisetron was relatively low in this study.Duration of anaesthesia (min) 81 (30–150) 77 (30–120)Postoperative analgesic administered This was in accordance with our previous study (8).

Acetaminophen (mg) 238±54 245±71 Although the exact mechanism of granisetron forPentazocine (mg) 1.4±3.2 1.6±3.2

preventing postoperative vomiting remains unclear,Types of operation performed (n)Strabismus repair 10 10 it has been suggested that this drug may act onTonsillectomy 13 14 sites containing 5-HT3 receptors with demonstratedTonsillectomy with adenoidectomy 17 16

antiemetic effects (10).Values are mean±SD, median (range) or number. There were no It is well-known that 40–80lg·kg−1 granisetron issignificant differences between the treatment groups. effective for the treatment of cancer therapy-induced

vomiting (11). It has been recently demonstrated that40lg·kg−1 granisetron is as effective as 60lg·kg−1

granisetron and both reduce the incidence ofadverse events between the treatment groupspostoperative vomiting when compared to 20lg·kg−1

(granisetron; 18%, droperidol; 20%). Nogranisetron or placebo (12). Consequently, 40lg·kg−1

extrapyramidal symptom was observed in eithergranisetron is the minimum effective dose forgroup.preventing vomiting after strabismus surgery ortonsillectomy with or without adenoidectomy in

Discussion children (12). Therefore, this dose of granisetron wasadministered in this study.The aetiology of vomiting after strabismus repair and

Droperidol is a major tranquillizing drug thattonsillectomy with or without adenoidectomy is notpossesses antiemetic activity as a result of itsprecisely known, but a number of factors, includingantagonistic property at dopamine receptor, and isage, sex, obesity, operative procedure, anaestheticrecommended for preventing postoperative vomitingtechnique and postoperative pain are considered toin children undergoing strabismus surgery orincrease the incidence of postoperative vomiting (4).tonsillectomy with or without adenoidectomy (1,However, in this study, the treatment groups were3). It is documented that droperidol 50–75lg·kg−1similar for patient demographics, surgical procedure,reduces the incidence of postoperative vomiting,anaesthetic administered and postoperativewhereas this drug in lower doses (<50lg·kg−1) doesanalgesics used. Therefore, the differences in thenot attenuate the incidence of vomiting afterincidence of vomiting after surgery between thestrabismus surgery in children (1,3,13). In this study,groups can be attributed to the differences in the

antiemetic agents administered. therefore, droperidol was used in this dose.

Table 2Incidence and frequency ofvomiting during the first 24hafter anaesthesia

Granisetron DroperidolGroup (n=40) (n=40) P values

No. (%) of patients experienced vomiting 6 (15%) 15 (38%) 0.02once 6 (15%) 8 (20%) 0.385twice or more 0 (0%) 7 (18%) 0.001

P values: granisetron vs droperidol.

1998 Blackwell Science Ltd, Paediatric Anaesthesia, 8, 241–244

244 Y. FUJII ET AL .

For the prevention of postoperative vomiting in Referenceschildren, granisetron and droperidol have been used

1 Abramowitz MD, Oh TH, Epstein BS et al. The antiemetic(1,3,8,12). We could find no report comparing the effect of droperidol following outpatient strabismus surgeryefficacy of these antiemetics for preventing vomiting in children. Anesthesiology 1983; 97: 579–583.

2 Carithers JS, Gebhart DE, Williams JA. Postoperative risks ofafter strabismus surgery or tonsillectomy with orpediatric tonsilloadenoidectomy. Laryngoscope 1987; 97:

without adenoidectomy. In this study, the incidence 422–429.of vomiting in patients who had received granisetron 3 Grunwarld Z, Schreiner MS, Parness J et al. Droperidol

decreases the incidence and the severity of vomiting afterwas lower than those who had received droperidoltonsillectomy and adenoidectomy in children. Paediatr Anaesth(P=0.02). This suggests that granisetron is more 1994; 4: 163–167.

effective than droperidol in reducing the incidence 4 Watcha MF, White PF. Postoperative nausea and vomiting. Itsetiology, treatment, and prevention. Anesthesiology 1992; 77:of vomiting after strabismus repair or tonsillectomy162–184.with or without adenoidectomy in children.

5 Litman RS, Wu CL, Catanzaro FA. Ondansetron decreasesThis study also demonstrated that 18% of children emesis after tonsillectomy in children. Anesth Analges 1994; 78:

478–481.who had received droperiodol needed a rescue6 Rose JB, Martin TM, Corddry DH et al. Ondansetron reducesantiemetic (e.g. domperidone) for the treatment of

the incidence and severity of poststrabismus repair vomitingtwo or more episodes of vomiting, whereas none in children. Anesth Analges 1994; 79: 486–489.

7 Andrews PLR, Bhandari P, Davey PT et al. Are all 5-HT3who had received granisetron required this agentreceptor antagonists the same? Europ J Cancer 1992; 28A: S2–S6.(P=0.001). Thus, it is suggested that granisetron

8 Fujii Y, Tanaka H, Toyooka H. Granisetron reduces vomitingreduces the frequency of postoperative vomiting after after strabismus surgery and tonsillectomy in children. Can Jstrabismus surgery and tonsillectomy with or without Anaesth 1996; 43: 35–38.

9 Bermudez J, Boyle EA, Miner WD et al. The anti-emetic potentialadenoidectomy in children.of the 5-hydroxytryptamine3 receptor antagonist BRL 43694.In this study, the incidence of adverse events was Br J Cancer 1988; 58: 644–650.

comparable among the treatment groups. Extra- 10 Carmichael J, Cantwell BMJ, Edwards CM et al. Apharmacokinetic study of granisetron (BRL 43694A), a selectivepyramidal symptoms were not observed in any5-HT3 receptor antagonist: correlation with antiemeticgroup, but the use of droperidol has been describedresponse. Cancer Chemotherapy Pharmacol 1989; 24: 45–49.

to be associated with these symptoms (13,14). It has 11 Furue H, Ohta K, Taguchi T et al. Clinical evaluation ofgranisetron against nausea and vomiting induced anticancerbeen reported that granisetron lacks the sedative,drugs. Optimal dose-finding study. J Clin Ther Med 1990; 6:dystonic and extrapyramidal side effects (15). Thus,49–61 (Japanese).

unlike droperidol, granisetron is considered to be 12 Fujii Y, Toyooka H, Tanaka H. Effective dose of granisetron forpreventing postoperative emesis in children. Can J Anaesthrelatively free of adverse effects. This was in1996; 43: 660–644.agreement with our previous studies (8,12).

13 Christensen S, Farrow-Gillespie A, Lerman J. Incidence ofThe cost of granisetron ($102 for 3mg) is greater emesis and postanesthetic recovery after strabismus surgery

in children: a comparison of droperidol and lidocaine.than droperidol ($1.8 for 1.25mg). Thus, the useAnesthesiology 1989; 70: 251–254.of granisetron may be limited because of its cost.

14 Dupre LJ, Steiglitz P. Extrapyramidal syndromes afterHowever, the decision on antiemetics should not premedication with droperidol in children. Br J Anaesth 1980;necessarily be limited to these costs but also should 52: 831–833.

15 Falkson G, vanZyl AJ. A phase I study of new 5HT3-receptortake into consideration the preferences of the patients.antagonist, BRL43694A, an agent for the prevention ofIn conclusion, preoperative administration of chemotherapy-induced nausea and vomiting. Cancer

granisetron is superior to droperidol in reducing the Chemotherapy and Pharmacol 1989; 24: 193–196.incidence and frequency of vomiting after strabismussurgery or tonsillectomy with or without adenoid-ectomy in children. Accepted 4 September 1997

1998 Blackwell Science Ltd, Paediatric Anaesthesia, 8, 241–244