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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.51 no.5 Campinas Sept./Oct. 2001
Efficacy of ondansetron and alizapride in preventing gynecological laparoscopy nausea and vomiting*
Eficacia del ondansetron y de la alizaprida en la prevención de náusea y vómito en laparoscópia ginecológica
Eliana M Ganem, TSA, M.D.I; Paula Fabris, M.D.II; Marlene Z Moro, M.D.II; Yara Marcondes Machado Castiglia, TSA, M.D.III
IProfessora Adjunta Livre-Docente do Departamento
de Anestesiologia da FMB - UNESP
IIME2 do CET/SBA da FMB - UNESP
IIIProfessora Titular do Departamento de Anestesiologia da FMB - UNESP
BACKGROUND AND OBJECTIVES: Gynecological
laparoscopy is a procedure with a high incidence of postoperative nausea and
vomiting (PONV). This study aimed at comparing the efficacy of ondansetron and
alizapride in preventing PONV in patients submitted to gynecological laparoscopy.
METHODS: Participated in this study 52 women physical status ASA I and II, aged 21 to 50 years, without previous gastric complaint, who were submitted to diagnostic or surgical laparoscopy. Patients were distributed in 2 groups: Group 1 - intravenous ondansetron (4 mg) and Group 2 - intravenous alizapride (50 mg), before anesthetic induction. All patients were premedicated with oral midazolam (7.5 mg), were induced with sufentanil (0,5 µg.kg-1) and propofol (2 mg.kg-1). Propofol (115 µg.kg-1) and N2O/O2 (FIO2 = 40%) were used for maintenance, and atracurium (0,5 mg.kg-1) was the neuromuscular blocker. Postoperative analgesia was achieved with cetoprofen (100 mg) and buscopam composto®.
RESULTS: Both groups were identical in demographics and surgery and anesthesia duration. One Group 1 patient referred nausea. One Group 2 patients referred nausea and 3 referred vomiting, but results were not statistically significant.
CONCLUSIONS: Ondansetron and alizapride were comparable in preventing PONV in patients submitted to gynecological laparoscopy.
Key words: ANTIEMETICS: alizapride, ondansetron; COMPLICATIONS: nausea, vomiting; SURGERY, Gynecological: laparoscopy
JUSTIFICATIVA Y OBJETIVOS: La
laparoscópia ginecológica es procedimiento que determina alta incidencia
de náusea y vómito en el pós-operatorio. Este estudio tuvo por
finalidad comparar la eficacia del ondansetron con la alizaprida, en la prevención
de náusea y vómito en pacientes sometidas a laparoscopia ginecológica.
MÉTODO: Participaran del estudio 52 pacientes, estado físico ASA I o II, con edades entre 21 y 50 años, sin quejas gástricas previas, sometidos a laparoscópia para diagnóstico o cirugía. Las pacientes fueron divididas en 2 grupos: el grupo 1 recibió ondansetron (4 mg) y el grupo 2 alizaprida (50 mg), por vía venosa, antes de la inducción de la anestesia. Todas las pacientes recibieron midazolam (7,5 mg) por vía oral como medicación pré-anestésica, sufentanil (0,5 µg.kg-1), propofol (2 mg.kg-1) para inducción, propofol (115 µg.kg-1) y N2O/O2 en fracción inspirada de O2 a 40% para manutención y atracúrio (0,5 mg.kg-1) como bloqueador neuromuscular. La analgesia pós-operatoria fue realizada con cetoprofeno (100 mg) y buscopan compuesto®.
RESULTADOS: Los dos grupos fueron idénticos cuanto a los datos antropométricos y la duración de la cirugía y de la anestesia. En el grupo 1 (n = 27) una paciente presentó náusea, en el grupo 2, una paciente presentó náusea y tres vomitaron, resultados estadísticamente no significativos.
CONCLUSIONES: El ondansetron y la alizaprida fueron similares en la prevención de náusea y vómito en pacientes sometidas a laparoscopia ginecológica.
Postoperative nausea and vomiting are common in laparoscopic procedures 1,2. A multifactorial etiology, such as surgical technique 3,4, gender, age and weight 1,5, anesthetic technique 6-8 and anesthetic drugs, contributes for their incidence 9.10. Young and healthy women submitted to gynecological laparoscopies are at increased risk for emetic symptoms11. Several antiemetic drugs have been studied aiming at preventing 11-14 and treating 15 nausea and vomiting after laparoscopic procedures. Ondasetron acts by competitive inhibition of central nervous system seratoninergic receptors, especially in the extreme area, the solitary tract nucleus and parasympathetic terminations of the GI tract 16. Alizapride acts by inhibiting dopaminergic receptors of the trigger's chemoreceptor zone, in the fourth ventricle floor and in peripheral afferent pathways 17.
This study aimed at evaluating the efficacy of ondasetron and alizapride in preventing nausea and vomiting in gynecological laparoscopy.
After the Clinical Research Ethics Committee approval and their written and informed consent, participated in this study 52 female patients, aged 21 to 50 years, physical status ASA I and II and body mass index below 30, to be submitted to diagnostic or surgical gynecological laparoscopy. Patients with current or previous gastric complaints, history of nausea and vomiting in previous anesthesias, with movement kinetosis, psychiatric diseases, menstruated and alcohol and drug abusers were excluded from the study. Patients were randomly distributed in two groups according to the antiemetic drug, that is, group 1, ondasetron (4 mg) and group 2 alizapride (50 mg).
After a 8-hour fast, patients were premedicated with 7.5 mg oral midazolam. In the operating room and after obtaining a venous access, lactated Ringer's was infused (10 ml.kg-1.h-1) and intravenous ondasetron (4 mg) or alizapride (50 mg) were administered to group 1 (G1) or group 2 (G2), respectively, immediately before anesthetic induction. Monitoring consisted of electrocardioscope in DII, sphygmomanometer and pulse oximetry. Anesthesia was induced with sufentanil (0.5 µg.kg-1) and propofol (2 mg.kg-1).To help intubation, atracurium (0.5 mg.kg-1) and manual ventilation with 100% oxygen (O2) were administered. During manual ventilation and pump controlled propofol continuous infusion (115 µg.kg-1), tracheal intubation, capnography installation and gastric probe for stomach air release were performed. Anesthesia without rebreathing and nitrous oxide in 40% oxygen inspired fraction was the technique of choice. Tidal volume was 10 ml.kg-1 and respiratory rate enough to maintain carbon dioxide expired pressure (PETCO2) around 30 mmHg.
At the end of the surgical procedure, always performed by the same team, intravenous buscopam composto® and ketoprofen (100 mg) had already been administered for postoperative analgesia.
After anesthesia and neuromuscular block recovery with intravenous atropine (1 mg) and neostigmine (1.5 mg), patients were extubated as soon as they returned to effective spontaneous ventilation and were taken to the post-anesthetic care unit (PACU). In PACU, patients were asked about nausea and vomiting at 10-minute intervals for one hour. Nausea was evaluated by a numeric scale from 0 to 100, being 0 lack of nausea and 100 the worst possible nausea. Nausea was defined as an uncomfortable feeling of wishing to vomit and vomit as the effort or the expelling of gastric contents. Intravenous ondasetron (4 mg) was administered in the presence of those signs and symptoms.
Twelve hours after PACU discharge, patients would receive in the ward a new visit of an anesthesiologist for nausea and vomiting revaluation.
Statistical methods used were Student's t test for demographic data and anesthesia and surgery duration, and Fisher Exact test for nausea and vomiting.
Groups were homogeneous as to age, weight, height and surgery and anesthesia duration (Table I).
From the 27 Group 1 patients, only one referred nausea. From the 25 Group 2 patients, 4 referred emetic symptoms - 1 nausea and 3 vomiting (Table II). All patients referred signs and symptoms in the ward, in a time interval varying fro 3 to 6 hours after PACU discharge. Both patients referring nausea scored their symptoms as 20. There were no statistically significant differences between groups.
Our results have shown that both drugs although with different action mechanisms, were equally effective in preventing nausea and vomiting in patients submitted to gynecological laparoscopy, both in PACU and in the ward.
Four neurotransmitters - dopamine, serotonine, histamine and acetylcholine - modulate the chemoreceptor trigger zone in the extreme area 1. There are no drugs available in the market that would block all four neurotransmitters 11 and drug associations to treat emesis has been avoided due to possible toxic additive effects on the central nervous system11. Some authors have observed that the association of ondansetron and droperidol has reduced nausea and vomiting after gynecological laparoscopic surgery 15. Our results, however, have shown that ondansetron as a single antiemetic drug was very effective in preventing emesis.
There are several studies on 4 mg ondansetron to prevent nausea and vomiting in gynecological laparoscopic procedures. A decrease in such events is observed when it is compared to placebo 18-20, being ondansetron as effective as droperidol 11 and more effective than 10 mg metoclopramide 19,21. However, when higher metoclopramide doses (4 mg.kg-1) were administered they have been shown to be as effective as ondansetron in preventing emesis 13.
Alizapride, a benzamine by-product structurally related to metoclopramide, has proven to be effective in preventing and treating postoperative nausea and vomiting 17,22.
Our results have shown no statistically significant differences between alizapride and ondansetron. Similar results were found in non laparoscopic gynecological surgeries were higher ondansetron (8 mg) and alizapride (100 mg) doses were used 23.
Alizapride (50 mg, 100 mg and 200 mg) was compared to placebo in preventing nausea and vomiting in ambulatory patients. The incidence of vomiting was twice as low in groups receiving the drug 22. These authors highlight that 100 mg and 200 mg intravenous doses were effective in preventing postoperative nausea and vomiting.
In a study where three 50 mg alizapride doses were administered in two subsequent 4-hour intervals before anesthetic induction, it was observed that 66% of patients did not refer vomiting during the first 12 postoperative hours 17. In our study, 50 mg was the single dose and 84% of patients were free of symptoms during the 12 observation hours.
Patients menstruated were excluded from the study because the incidence of emesis during the menstrual cycle is increased in up to four times 24 and antiemetic effects are decreased 25. The same study has observed that, as from the 8th menstrual day, there has been no increase in nausea and vomiting in a specific period 25.
From the five patients referring nausea and vomiting, three were between the 10th and the 13th menstrual cycle day, thus close to ovulation, and two in the 26th and 27th menstrual cycle day.
It is important to stress that the difference in the cost of the drugs used in our study is considerably high. An ondansetron vial (4 mg) costs R$23.22 and an alizapride vial (50 mg) costs R$3.82 and this is an important factor in cost reduction without impairing the quality of care.
Our conclusion was that ondansetron and alizapride were equally effective in preventing gynecological laparoscopic surgery nausea and vomiting.
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18, 2001 *
Received from CET/SBA do Departamento de Anestesiologia da Faculdade de Medicina
de Botucatu (FMB - UNESP), SP
Accepted for publication March 7, 2001
Submitted for publication January
* Received from CET/SBA do Departamento de Anestesiologia da Faculdade de Medicina de Botucatu (FMB - UNESP), SP