Efficacy of ondansetron and alizapride in preventing gynecological laparoscopy nausea and vomiting

Abstracts

JUSTIFICATIVA E OBJETIVOS: A laparoscopia ginecológica é procedimento que determina alta incidência de náusea e vômito no pós-operatório. Este estudo teve por finalidade comparar a eficácia do ondansetron e da alizaprida na prevenção de náusea e vômito em pacientes submetidas à laparoscopia ginecológica. MÉTODO: Participaram do estudo 52 pacientes, estado físico ASA I ou II, com idades entre 21 e 50 anos, sem queixas gástricas prévias, submetidas à laparoscopia para diagnóstico ou cirurgia. As pacientes foram divididas em 2 grupos: o grupo 1 recebeu ondansetron (4 mg) e o grupo 2, alizaprida (50 mg), por via venosa, antes da indução da anestesia. Todas as pacientes receberam midazolam (7,5 mg) por via oral como medicação pré-anestésica, sufentanil (0,5 µg.kg-1) e propofol (2 mg.kg-1) para indução, propofol (115 µg.kg-1) e N2O/O2 em fração inspirada de O2 a 40% para manutenção e atracúrio (0,5 mg.kg-1) como bloqueador neuromuscular. A analgesia pós-operatória foi realizada com cetoprofeno (100 mg) e buscopam composto®. RESULTADOS: Ambos os grupos foram idênticos quanto aos dados antropométricos e à duração da cirurgia e da anestesia. No grupo 1 (n=27) uma paciente apresentou náusea, No grupo 2, uma paciente apresentou náusea e três vomitaram, resultados estatisticamente não significativos. CONCLUSÕES: O ondansetron e a alizaprida foram similares na prevenção de náusea e vômito em pacientes submetidas à laparoscopia ginecológica.

ANTIEMÉTICOS; ANTIEMÉTICOS; CIRURGIA, Ginecológica; COMPLICAÇÕES; COMPLICAÇÕES

SCIENTIFIC ARTICLE

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

Correspondence

SUMMARY

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 (F_IO₂ = 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

RESUMEN

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.

INTRODUCTION

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.

METHODS

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 D_II, 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 (P_ETCO₂) 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.

RESULTS

Groups were homogeneous as to age, weight, height and surgery and anesthesia duration (Table I).

Brazilian Journal of Anesthesiology, 2001; 51: 5: 401-406

Efficacy of ondansetron and alizapride in preventing gynecological laparoscopy nausea and vomiting

Eliana M Ganem; Paula Fabris; Marlene Z Moro; Yara Marcondes Machado Castiglia

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.

Brazilian Journal of Anesthesiology, 2001; 51: 5: 401-406

Efficacy of ondansetron and alizapride in preventing gynecological laparoscopy nausea and vomiting

Eliana M Ganem; Paula Fabris; Marlene Z Moro; Yara Marcondes Machado Castiglia

DISCUSSION

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 8^th 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 10^th and the 13^th menstrual cycle day, thus close to ovulation, and two in the 26^th and 27^th 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.

REFERENCES

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Endereço para correspondência:

Dra. Eliana Marisa Ganem

Deptº de Anestesiologia da FMB - UNESP

Distrito de Rubião Júnior

18618-970 - Botucatu, SP

*

Recebido do CET/SBA do Departamento de Anestesiologia da Faculdade de Medicina de Botucatu (FMB - UNESP), SP

Publication Dates

• Publication in this collection
  14 Mar 2011
• Date of issue
  Oct 2001

History

• Reviewed
  07 Mar 2001
• Received
  18 Jan 2001