Paediatric Anaesthesia 1999 9: 527–530

Prevention of postoperative vomiting withgranisetron in paediatric patients with andwithout a history of motion sickness

YOSHITAKA FUJII md , YUHJI SAITOH md , HIROYOSHI

TANAKA md∗ AND HIDENORI TOYOOKA mdDepartment of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine,Tsukuba City, Ibaraki, Japan, ∗Department of Anaesthesiology, Toride Kyodo GeneralHospital, Toride City, Ibaraki, Japan

SummaryA history of motion sickness is one of the patient-related factors

associated with postoperative emesis. This prospective, randomized,

double-blind, placebo-controlled study was undertaken to assess the

efficacy of granisetron, a selective 5-hydroxytryptamine type 3

receptor antagonist, for preventing postoperative vomiting after

tonsillectomy in 120 children with (n=60) and without (n=60) a

history of motion sickness. Patients received a single dose of

granisetron (40 lg·kg−1) or placebo (saline) (n=30 of each)

intravenously after an inhalation induction of anaesthesia. A

complete response, defined as no vomiting, no retching and no need

for another rescue medication, during the first 24 h after anaesthesia

was 77% and 13% in patients with a history of motion sickness who

had received granisetron or placebo, respectively; the corresponding

incidence was 83% and 40% in those without it (P< 0.05; v2 test with

Yates’ continuity correction). No clinically serious adverse effects

due to the study drug were observed in any of the groups. In

conclusion, prophylactic antiemetic therapy with granisetron is

effective for preventing postoperative emesis in children with a

history of motion sickness as well as in those without it.

Keywords: vomiting: antiemetics; granisetron; motion sickness;

surgery: tonsillectomy

Introduction a variety of factors, including patient demographics,

types of surgery, anaesthetic technique andPostoperative vomiting is a common problem,

postoperative care (2). A history of motion sicknessparticularly in children (1). The aetiology of

is one of the patient-related factors associated withpostoperative emesis is complex and is dependent on

postoperative emesis (3). Granisetron as well as

ondansetron is a selective 5-HT3 receptor antagonist,

and has more potent and longer acting propertiesCorrespondence to: Yoshitaka Fujii, Department of Anaesthesiology,

against cisplatin-induced emesis than ondansetronUniversity of Tsukuba Institute of Clinical Medicine, 2–1–1,

Amakubo, Tsukuba City, Ibaraki 305–0005, Japan. (4). We have recently demonstrated that it reduces

527 1999 Blackwell Science Ltd

528 Y. FUJII ET AL.

the incidence of postoperative vomiting in children CO2 tension between 4.6 kPa and 5.2 kPa

(5,6). However, there has been no report to assess (35–40 mmHg) as measured by an anaesthetic/

the antiemetic effect of granisetron on the incidence respiratory gas analyser (UltimaTM, Datex, Helsinki,

of postoperative emesis in children with a history Finland). Opioid analgesics were not used

of motion sickness. This prospective, randomized, throughout surgery. Muscle relaxation was achieved

double-blind, placebo-controlled study was designed with vecuronium and was reversed be a combinationto compare the prophylactic use of granisetron with of atropine 0.02 mg·kg−1 i.v. and neostigmineplacebo for preventing postoperative emesis in 0.04 mg·kg−1 i.v. at the end of surgery. The tracheachildren with and without a history of motion was extubated when the patient was awake. Ansickness undergoing tonsillectomy. orogastric tube was not permitted. Rectal

temperature was monitored and maintained at 37°Cusing hot water pads throughout surgery.MethodsPostoperatively, all patients were admitted to the

After obtaining our institutional review board hospital. Clear liquids were offered only if the patientapproval and informed consent from each parent, requested. No patients were given other oral intake120 children with (n=60) and without (n=60) a for 4 h after recovery from anaesthesia. If two orhistory of motion sickness, ASA physical status I or more episodes of emetic symptoms occurred duringII, aged 4–10 years, scheduled for tonsillectomy with the first 24 h after anaesthesia, another rescueor without adenoidectomy were studied. A history antiemetic (e.g. domperidone 10–30 mg rectally) wasof motion sickness was collected as a part of the

given. After operation, analgesia was provided bydemographic information. The patient was regarded

acetaminophen 100–300 mg rectally for mild pain andto have motion sickness when he/she gave a recent

pentazocine 0.3 mg·kg−1 i.v. for severe pain.history of any of the three symptoms on preoperative

Postoperatively, all episodes of retching andquestionnaire (i.e. retching, vomiting and loss of

vomiting during the first 24 h after anaesthesia wereappetite provoked by the transport with car, train

recorded every 3 h by specially trained nurses whoor plane). Patients who had a history of previous

had no knowledge of which treatment each patientpostoperative emesis, those who had gastrointestinal

had received. Vomiting was defined as the forcefuldiseases and those who had received antiemetic

expulsion of gastric contents from the mouth, andwithin 24 h before surgery were excluded from the

retching was defined as the laboured, spasmodic,study. Patients were not allowed to have solid food

rhythmic contraction of the respiratory muscles (2).after midnight before surgery. Clear liquids were

Nausea was not assessed as a separate entity in thispermitted up to 3 h before surgery.

study because of the age of the patients. CompletePatients of either group were randomly assigned

response, defined as no vomiting, no retching, andto receive either granisetron 40 lg·kg−1 or placebono need for another rescue antiemetic, was recorded(saline) i.v. (n=30 of each) after inhalationalwithin the first 24-h postanaesthetic period. Theinduction of anaesthesia. The dose of granisetrondetails of adverse events due to the study drug werechosen in this study has already been reported to berecorded. The level of sedation was also graded oneffective for preventing postoperative emesis (5,6).3-point scale and was assessed as 0=awake, 1=A randomization list was generated, and identicaldrowsy, and 2=asleep/excessive sedation.syringes containing each drug were prepared by

Statistical analysis was performed by ANOVA withpersonnel blinded to the study, according to the list.Bonferroni’s correction for multiple comparison, Chi-No preoperative medications were administered.square test with Yates’ continuity correction andAnaesthesia was induced using sevoflurane in 66%Kruskal–Wallis rank test, where appropriate. A P-nitrous oxide (N2O) and oxygen (O2) via face mask.value of < 0.05 was considered significant. Values areTracheal intubation was facilitated with vecuronium

mean SD, median (range) or numbers (%). Based on0.1 mg·kg−1 i.v. After tracheal intubation, anaesthesia

our previous studies (5,6), it was calculated that 30was maintained with N2O/O2 (2 1): and sevoflurane

patients per group would be required to demonstrate0.5%-3.0% (inspired concentration). Ventilation was

controlled and was adjusted to maintain an endtidal a 20% difference in values for a complete abolition

1999 Blackwell Science Ltd, Paediatric Anaesthesia, 9, 527–530

PREVENTION OF POSTOPERATIVE VOMITING WITH GRANISETRON 529

Table 1Patient details

Motion sickness (+) Motion sickness (−)

Granisetron Placebo Granisetron Placebo(n=30) (n=30) (n=30) (n=30)

Age (years) (ranges) 6.4±2.3 (4–10) 6.3±2.2 (4–10) 6.6±2.2 (4–10) 6.3±2.1 (4–10)

Sex (male/female) 16/14 15/15 16/14 16/14

Height (cm) 118.0±10.9 120.6±13.0 119.4±10.0 117.8±10.9

Weight (kg) 22.7±5.5 24.6±6.2 23.4±4.9 23.7±6.9

Duration of operation (min) 39±17 41±18 42±15 41±19

Duration of anaesthesia (min) 59±18 62±19 63±16 61±22

Analgesics used postoperatively (n)

Acetaminophen 25 24 25 25

Pentazocine 4 4 4 4

Types of surgery (n)

Tonsillectomy 20 21 21 20

Tonsillectomy with adenoidectomy 10 9 9 10

Values are mean ± SD or number.

Table 2Patients having complete response (no emesis, no rescue) vomiting, retching, or requiring another rescue antiemetic medication, and

sedation assessed by nurses during the first 24 h after anaesthesia

Motion sickness (+) Motion sickness (−)

Granisetron Placebo Granisetron Placebo(n=30) (n=30) P (n=30) (n=30) P

Complete response (no emesis, no rescue) 23 (77%) 4 (13%) 0.001 25 (83%) 12 (40%) 0.001

Vomiting 5 (17%) 22 (73%) 0.001 3 (10%) 14 (47%) 0.004

Retching 2 (7%) 6 (20%) 0.255 3 (10%) 5 (17%) 0.704

Rescue medication 2 (7%) 16 (60%) 0.001 0 (0%) 11 (37%) 0.001

Sedation (2/1/0) asssessed by nurses 0/2/28 0/2/28 1.0 0/1/29 0/1/29 1.0

Values are number (%).

in the incidence of adverse effects among the groups.of vomiting (which was regarded as the primaryIn addition, the levels of sedation were not differentendpoint) at P=0.05 with a power (1 –b)=0.8.among the groups (Table 3).

ResultsDiscussion

Except for a history of motion sickness, patient

demographics and types of operation were not The aetiology of postoperative emesis in paediatric

patients undergoing tonsillectomy with or withoutdifferent among the groups (Table 1).

A complete response (no emesis, no rescue) during adenoidectomy is multifactorial in origin (2). Age,

sex, obesity, a history of previous postoperativethe first 24 h after anaesthesia was greater in patients

with and without a history of motion sickness who vomiting, surgical procedure, anaesthetic technique

and postoperative pain are considered to increasehad received granisetron than in those who had

received placebo (P< 0.05) (Table 2). The incidence in the incidence of postoperative emesis. In this study,

however, there were no differences among the groupspatients with a history of motion sickness who had

received placebo were different from that in those with respect to patients demographics, types of

operation, anaesthetic administered, and analgesicswithout it (P=0.041).

The most frequently reported adverse events were used postoperatively, except for a history of motion

sickness. Children with a history of previousheadache and constipation. There was no difference

1999 Blackwell Science Ltd, Paediatric Anaesthesia, 9, 527–530

530 Y. FUJII ET AL.

Table 3Adverse events

Motion sickness (+) Motion sickness (−)

Granisetron Placebo Granisetron Placebo(n=30) (n=30) (n=30) (n=30)

Headache 3 (10%) 3 (10%) 2 (7%) 2 (7%)

Constipation 2 (7%) 2 (7%) 2 (7%) 2 (7%)

Values are number (%).

postoperative vomiting were excluded from the 5-HT3 receptor antagonists (e.g. droperidol andstudy. Therefore, the difference in a complete metoclopramide) (2). In this study, there were noresponse (no emesis, no rescue) between patients differences in the incidence of headache andwho had received granisetron and those who had constipation among the groups. Furthermore, excessivereceived placebo can be attributed to the difference sedation was not observed in any of the groups.in the study drugs administered. We also showed in In Japan, granisetron (US$ 102.00 for 3 mg) as wellthis study that the incidence of postoperative emesis as ondansetron (US$ 103.00 for 3 mg) is much moreduring the first 24 h after anaesthesia was higher in expensive than other antiemetics, droperidol (US$ 1.80patients with a history of motion sickness who had for 1.25 mg) and metoclopramide (US$ 0.60 for 10 mg).received placebo than in those without it. However, the use of these two antiemetics is limited

Granisetron has been proved to be effective for because of their undesirable adverse effects, such aspreventing emesis induced by cancer chemotherapy excessive sedation and extrapyramidal symptoms.(7). We have recently demonstrated that it reduces In conclusion, prophylactic antiemetic therapythe incidence of vomiting after paediatric with granisetron 40 lg·kg−1 is effective for preventingtonsillectomy (5,6). The exact mechanism of its action postoperative emesis in both paediatric patients within the prevention of postoperative emesis is not and without a history of motion sickness.known, but it is likely to be related to its action of 5-HT3 receptors (8). In this clinical trial of 120 paediatricpatients with and without a history of motion Referencessickness, a complete response was greater in patients

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with a history of motion sickness are more susceptible and emesis. Br J Anaesth 1990; 64: 728–730.4 Andrews PLR, Bhandari P, Davey PT et al. Are all 5–HT3 receptorto postoperative emesis than those without it (2,3).

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granisetron for preventing postoperative emesis in after strabismus surgery and tonsillectomy in children. Can JAnaesth 1996; 43: 35–38.paediatric patients with and without a history of

6 Fujii Y, Tanaka H, Toyooka H. Effective dose of granisetron formotion sickness. Our results demonstrated thatpreventing postoperative emesis in children. Can J Anaesth 1996;

granisetron-treated patients experienced less emetic 43: 660–664.7 Bermudez J, Boyle EA, Minter WD et al. The anti-emetic potentialsymptoms than placebo-treated patients, regardless

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prophylactic use of granisetron would be effective 8 Carmichael J, Cantwell BMJ, Edwards CM et al. Afor the control of postoperative emesis in paediatic pharmacokinetic study of granisetron (BRL 43694), a selective

5–HT3 receptor antagonist: correlation with anti-emeticchildren with a history of motion sickness as well asresponse. Cancer Chemother Pharmacol 1989; 24: 45–49.

in those without it.Granisetron lacks the sedative, dysphoric and

extrapyramidal symptoms associated with other non Accepted 22 February 1999

1999 Blackwell Science Ltd, Paediatric Anaesthesia, 9, 527–530