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*Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City; and
Department of Anesthesiology, Toride Kyodo General Hospital, Toride City, Ibaraki, Japan
Address correspondence and reprint requests to Y. Fujii, Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, 2-1-1, Amakubo, Tsukuba City, Ibaraki 305, Japan.
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Abstract |
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Implications: We compared the efficacy of granisetron and perphenazine given orally for preventing postoperative vomiting after tonsillectomy with or without adenoidectomy in children. Preoperative oral granisetron was more effective than perphenazine.
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Introduction |
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Methods |
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Patients were randomly assigned to receive orally either granisetron 40 µg/kg or perphenazine 70 µg/kg (n = 50 each) 1 h before surgery. A randomization list was generated, and syrups with either granisetron or perphenazine were prepared by personnel not involved in the study, according to the list. The doses of graniserton or perphenazine chosen in this study were referred to in previous studies by us (7) and Naganuma (10).
Patients were not allowed to have solid food after midnight before surgery. Clear liquids were permitted up to 3 h before surgery. No preanesthetic medications were administered. Anesthesia was induced by increasing concentration of sevoflurane in 66% nitrous oxide (N2O) and oxygen (O2) via a mask. After an inhaled induction of anesthesia, atropine 0.01 mg/kg IV was administered, followed by fentanyl 1 µg/kg IV, and tracheal intubation was facilitated with vecuronium 0.1 mg/kg IV. After tracheal intubation, anesthesia was maintained with N2O/O2 (2:1) and sevoflurane 0.5%–3.0% (inspired concentration). Ventilation was controlled mechanically and was adjusted to maintain PETCO2 35–40 mmHg as measured by using an anesthetic/respiratory gas analyzer (UltimaTM; Datex, Helsinki, Finland). Muscle relaxation was achieved with vecuronium, and residual neuromuscular blockade was antagonized by a combination of atropine 0.02 mg/kg IV and neostigmine 0.04 mg/kg IV at the end of surgery. The trachea was extubated when the patient was awake. Rectal temperature was monitored and maintained at 37 ± 1°C throughout surgery. Postoperatively, all patients were admitted to the hospital and remained there for 2 days (i.e., 0–3 h in the postanesthesia care unit, 3–24 h in the postoperative ward, and 24–48 h in the general ward). Clear liquids were offered only if the patient requested them, and other oral intake was not allowed for 4 h after recovery from anesthesia. Postoperative analgesia was provided by acetaminophen 10–25 mg/kg rectally for mild pain and pentazocine 0.3 mg/kg IV for severe pain.
Postoperatively, all episodes of retching and vomiting during the first 24 h after anesthesia (i.e., 0–3 h in the postanesthesia care unit and 3–24 h in the ward) were recorded by nursing staff who did not know which treatment each patient had received. Vomiting was defined as the forceful expulsion of gastric contents from the mouth; retching was defined as the labored, spasmic, rhythmic contraction of the respiratory muscles, including the diaphragm, chest wall, and abdominal wall muscles, without the expulsion of gastric contents (2). Nausea was not assessed as a separate entity in this study because of the young age of the patients. A complete response—defined as no vomiting, no retching, and no need for rescue antiemetic medication—was recorded during the first 24 h after anesthesia. If two or more episodes of vomiting occurred during the first 24 h after anesthesia, another rescue antiemetic (e.g., domperidone rectally) was given. At the end of every observation period, the nurses asked the parents about their children's postanesthetic condition and problems (i.e., adverse events due to the study drugs). A trained research nurse evaluated sedation of the patients. The evaluations were performed with a linear numerical scale ranging from 0 (no sedation) to 10 (extreme sedation).
Statistical analyses of data between the groups were performed by using analysis of variance with Bonferroni's correction for multiple comparison, 
2 test, two-tailed Fisher's exact probability test, or the Mann-Whitney U-test, where appropriate. The number needed to treat (NTT), a useful estimate of clinical relevance of treatment effect, was also calculated (11). A P value of <0.05 was considered significant. All values are expressed as mean ± SD, n (%), or median (range). The primary end point of the study was a complete response to antiemetic therapy, defined as no emetic symptoms or no need for another rescue medication. Power analysis was used to determine the number of patients in the study based on the assumptions that (a) the incidence of emesis in patients receiving oral perphenazine would be 40% based on data from the use of IV perphenazine (12); (b) an improvement from 60% to 85% was considered of clinical importance; and (c) 
= 0.05 and a power (1-ß) = 0.8. Based on these assumption, 50 patients per group were required.
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Results |
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Discussion |
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Granisetron is effective for the treatment of vomiting in patients receiving cytotoxic drugs (13), and we recently demonstrated that it reduces the incidence of vomiting after tonsillectomy, with or without adenoidectomy, in children (6,7). The precise mechanism of granisetron for preventing postoperative vomiting is not known, but it may act on sites containing 5-HT3 receptors (14).
The fact that granisetron is much more expensive than other antiemetics for IV injection may delay its widespread use as an antiemetic medication. With oral administration, this difference in cost may be reduced (8). Our hospital pharmacy pays $12.60 for PO granisetron 1 mg, compared with $33.40 for IV granisetron 1 mg. We recently evaluated the efficacy of granisetron given orally for preventing postoperative vomiting after pediatric tonsillectomy with or without adenoidectomy and demonstrated that preoperative oral granisetron in a minimal dose of 40 µg/kg provides effective antiemetic prophylaxis (9). Therefore, the same dose (i.e., 40 µg/kg) of granisetron was chosen in this study.
Perphenazine is a phenothiazine with potent antiemetic effects. Its antiemetic action has been attributed to its ability to block receptors in the chemoreceptor trigger zone, specifically the dopaminergic receptors (2). Perphenazine 70 µg/kg IV reportedly reduces the incidence of postoperative vomiting in children undergoing tonsillectomy, with an antiemetic efficacy similar to that of ondansetron (12). The dose of oral perphenazine to be used in children is not well established but has been extrapolated from the dosage used in adult investigations. Pherphenazine 70 µg/kg given orally in this study is comparable to the recommended adult dosage of 2–8 mg (10). Further studies regarding dose-response curve available for the antiemetic effect of oral perphenazine are needed.
We could not find any report comparing the efficacy of the two oral antiemetics, granisetron and perphenazine, for preventing postoperative vomiting in children undergoing tonsillectomy with or without adenoidectomy. Our results demonstrated that a complete response (no emesis, no rescue) within the first 24-h period after anesthesia in patients who had received granisetron was greater than that in those who had received perphenazine as an oral antiemetic regimen (P < 0.05). This suggests that prophylactic oral antiemetic therapy with granisetron is more effective than perphenazine for preventing postoperative vomiting after tonsillectomy with or without adenoidectomy in children. However, this suggestion may be limited because there have been no reports that the doses of the two antiemetics, granisetron and perphenazine, given orally are equipotent.
Although the failure to include a control group receiving placebo may be considered a deficiency in our study design, we did not do so because we have already shown that granisetron given orally is a better antiemetic than placebo for preventing postoperative vomiting after pediatric tonsillectomy (9). Moreover, Aspinal and Goodman (15) have shown that there is a lack of reliable clinical information concerning placebo-controlled trials of another 5-HT3 receptor antagonist, ondansetron, for preventing postoperative nausea and vomiting.
The most commonly reported adverse event was headache, the incidence of which was not different between the treatment groups. Excessive sedation was also not observed in any of the groups. Thus, preoperative oral granisetron, as well as perphenazine, is considered to be relatively free of adverse effects for preventing postoperative vomiting in children.
The use of PO compared with IV granisetron reduces the price of antiemetic therapy. In Japan, however, oral granisetron ($12.60 for 1 mg) is still more expensive than oral perphenazine ($0.90 for 2 mg). Thus, using PO granisetron as an antiemetic may be criticized because of its high cost. In this study, a cost-effective analysis was not performed. However, oral granisetron was more effective than oral perphenazine in increasing a complete response. Therefore, the choice of antiemetics should be based on the calculation of costs, but also on the preference of patients.
In conclusion, the efficacy of preoperative oral granisetron 40 µg/kg is superior to oral perphenazine 70 µg/kg for preventing postoperative vomiting in children undergoing tonsillectomy with or without adenoidectomy.
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This article has been cited by other articles:
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  C. M. Bolton, P. S. Myles, T. Nolan, and J. A. Sterne Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a systematic review and meta-analysis Br. J. Anaesth., November 1, 2006; 97(5): 593 - 604. [Abstract] [Full Text] [PDF]
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 P. Kranke, C. C. Apfel, N. Roewer, and Y. Fujii Reported Data on Granisetron and Postoperative Nausea and Vomiting by Fujii et al. Are Incredibly Nice! • Response Anesth. Analg., April 1, 2000; 90(4): 1004 - 1007. [Full Text] [PDF]
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