Efficacy of ondansetron, metoclopramide, droperidol and dexametasone in preventing post-gynecological videolaparoscopy nausea and vomiting in outpatient setting. Comparative study

Abstracts

JUSTIFICATIVA E OBJETIVOS: Embora o ondansetron seja apontado como uma das drogas mais eficientes no controle das náuseas e vômitos pós-operatório (NVPO), seu alto custo o torna inviável para uso rotineiro. Este estudo teve como finalidade verificar entre o droperidol, a metoclopramida e a dexametasona qual se aproxima mais da eficácia do ondansetron na prevenção de NVPO em laparoscopias ginecológicas. MÉTODO: Participaram do estudo 100 pacientes submetidas à laparoscopia ginecológica sob anestesia geral venosa e inalatória, divididas aleatoriamente em cinco grupos de acordo com a medicação antiemética recebida. O grupo GO (n = 20) recebeu ondansetron (4 mg); o grupo GM (n = 20): metoclopramida (10 mg); grupo GD (n = 20): droperidol (1,25 mg), o grupo GX (n = 20): dexametasona (8 mg) e o grupo GC - grupo controle (n = 20) não recebeu medicação antiemética. Foram verificadas as incidências de náusea e/ou vômito no pós-operatório, os parâmetros hemodinâmicos, o tempo na sala de recuperação pós-anestésica (SRPA) e o tempo da anestesia. RESULTADOS: Não houve diferença estatística entre os grupos quanto aos dados antropométricos, hemodinâmicos, tempo de recuperação e tempo de anestesia. Houve diferença estatística entre os grupos quanto à incidência de náusea (GO < GD < GX < GM < GC) e de vômitos (GO < GD < GX < GM < GC). CONCLUSÕES: Neste estudo, o ondansetron foi o agente mais eficaz na profilaxia de náusea e vômito e o droperidol foi a droga que mais se aproximou da eficácia do ondansetron na prevenção de NVPO.

ANTIEMÉTICOS; ANTIEMÉTICOS; ANTIEMÉTICOS; ANTIEMÉTICOS; CIRURGIA, Ginecológica; COMPLICAÇÕES; COMPLICAÇÕES

SCIENTIFIC ARTICLE

Efficacy of ondansetron, metoclopramide, droperidol and dexametasone in preventing post-gynecological videolaparoscopy nausea and vomiting in outpatient setting. Comparative study^*

Eficacia de ondansetron, metoclopramida, droperidol y dexametasona en la prevención de nausea y vómito luego de laparoscopía ginecológica en régimen ambulatorial. Estudio comparativo

Múcio Paranhos de Abreu, TSA^I; João Lopes Vieira, TSA^II; Iara Ferreira da Silva^III; Luiz Eduardo Paula G Miziara^III; Renata Fófano^IV

^IInstrutor do CET/SBA do Instituto Penido Burnier e Centro Médico de Campinas

^IIProfessor Doutor Coordenador da Disciplina de Anestesiologia do CCMB da PUC-SP, Co-Responsável pelo CET/SBA do Instituto Penido Burnier e Centro Médico de Campinas

^IIIME₂ (2003) do CET/SBA

^IVME₂ (2002) do CET/SBA

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Although being considered one of the most effective drugs to control postoperative nausea and vomiting (PONV), ondansetron is unfeasible for routine use due to its high cost. This study aimed at comparing the efficacy of droperidol, metoclopramide, and dexametasone as compared to ondansetron in preventing PONV after gynecological laparoscopies.

METHODS: Participated in the study 100 patients submitted to gynecological laparoscopies under general intravenous and inhalational anesthesia, who were randomly distributed in five groups according to the antiemetic medication. Group GO (n = 20) received ondansetron (4 mg); Group GM (n = 20) received metoclopramide (10 mg); Group GD (n = 20) received droperidol (1.25 mg); Group GX (n = 20) received dexametasone (8 mg); and Group GC - control group (n = 20) was not medicated. The following events were recorded: incidence of postoperative nausea and/or vomiting, hemodynamic parameters, PACU stay and anesthetic length.

RESULTS: There were no statistically significant differences among groups in demographics, hemodynamic parameters, recovery and anesthetic length. There were statistical differences among groups in the incidence of nausea (GO < GD < GX < GM < GC) and vomiting (GO < GD < GX < GM < GC).

CONCLUSIONS: Ondansetron was the most effective agent in preventing nausea and vomiting, and droperidol was the closest drug to ondansetron in preventing PONV.

Key Words: ANTIEMETICS: dexametasone, droperidol, metoclopramide, ondansetron; COMPLICATIONS: nausea, vomiting; SURGERY: Gynecological: laparoscopic

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Aunque el ondansetron es considerado una de las drogas mas eficientes para control de nausea y vómito post-operatorio (NVPO), su alto costo torna inviable su uso en forma rutinaria. Este estudio tuvo como finalidad verificar entre droperidol, metoclopramida y dexametasona cual se aproxima más a la eficacia del ondansetron en la prevención de NVPO en laparoscopías ginecológicas.

MÉTODO: Participaron del estudio 100 pacientes sometidas a laparoscopía ginecológica con anestesia general intravenosa e inhalatoria, divididas aleatoriamente en cinco grupos de acuerdo con la medicación antiemética recibida. El grupo GO (n = 20) recibió ondansetron (4 mg); el grupo GM (n = 20): metoclopramida (10 mg); el grupo GD (n = 20): droperidol (1,25 mg), el grupo GX (n = 20): dexametasona (8 mg) y el grupo GC - grupo control (n = 20) no recibió medicación antiemética. Fueron verificadas la incidencia de nausea y/o vómito en el post-operatorio, los parámetros hemodinámicos, el tiempo en la sala de recuperación post-anestésica (SRPA) y el tiempo de la anestesia.

RESULTADOS: No hubo diferencia estadística entre los grupos en los registros antropométricos, hemodinámicos, tiempo de recuperación y de anestesia. Hubo diferencia estadística entre los grupos en la incidencia de nausea (GO < GD < GX < GM < GC) y vómito (GO < GD < GX < GM < GC).

CONCLUSIONES: En este estudio, el ondansetron fue el agente más eficaz para la prevención de nausea y vómito. El droperidol fue la droga que más se aproximó de la eficacia del ondansetron para prevenir NVPO.

INTRODUCTION

Postoperative nausea and vomiting (PONV) are the most common adverse effects after anesthetic-surgical procedures, especially gynecological laparoscopies^1-5. Although its etiology is not fully defined, it is known that PONV is a multifactorial event⁴. Factors increasing the incidence of PONV are patient-related, such as gender, age, weight, anxiety and previous PONV history, among others; and procedure-related, such as surgery site and length, ventilation under mask and potentially emetogenic drugs. Young patients submitted to diagnostic or surgical gynecological laparoscopy are at high risk for developing PONV^6,7.

Some studies have proven the efficacy of ondansetron in preventing and treating PONV^8,9, however its high cost prevents its routine use. Other studies have shown that low droperidol doses (0.625 to 1.25 mg) have satisfactory, although limited antiemetic effect in highly emetogenic procedures¹⁰. Literature is inconclusive as to the optimal droperidol dose, but 1.25 mg has been considered satisfactory.

Metoclopramide, widely used to prevent dopaminergic receptors stimulation and to speed gastric emptying, is not very effective in preventing PONV after laparoscopic procedures.

Dexametasone and other glucocorticoids seem to have antiemetic effects, improving the efficacy of antiemetic therapies.

Videolaparoscopic gynecological procedures have a high incidence of postoperative vomiting and prevention is needed for patients with associated risk factors for PONV.

This study aimed at evaluating which of the following drugs: droperidol, dexametasone and metoclopramide, was closest to ondansetron in preventing and treating PONV after gynecological laparoscopy.

METHODS

After the institution’s Ethic Committee approval and their formal consent, participated in this study 100 patients aged 22 to 62 years, physical status ASA I and II, submitted to diagnostic or surgical gynecological laparoscopy under general intravenous and inhalational anesthesia. Exclusion criteria were patients with previous history of postoperative nausea and vomiting and those with gastric disorders. Patients were randomly distributed in five groups according to the antiemetic drug, administered immediately after anesthetic induction: group GO: ondansetron (4 mg); group GM: metoclopramide (10 mg); group GD: droperidol (1.25 mg); group GX: dexametasone (8 mg) and group GC (control) not medicated.

After minimum 8-hour fast, patients were referred to the operating room, intravenous 20G catheter was inserted in left arm and lactated Ringer’s solution was started (10 mL.kg^-1.h^-1).

Monitoring consisted of cardioscope at D_II lead, noninvasive blood pressure, pulse oximeter, capnography and expired gases analysis. Anesthesia was induced with midazolam (0.05 mg.kg^-1), fentanyl (3 µg.kg^-1), 2% lidocaine (1 mg.kg^-1), propofol (1.5 mg.kg^-1) and atracurium (0.5 mg.kg^-1) for all patients. After manual ventilation with 100% oxygen patients were intubated and anesthesia was maintained with N₂O:O₂ 1:1 and isoflurane (1 MAC), under mechanical ventilation with carbon dioxide reabsorption.

Respiratory rate was adjusted to maintain P_ETCO₂ in approximately 37 mmHg. Whenever necessary, 50 µg fentanyl was administered. Postoperative analgesia was achieved with ketoprofen (100 mg). At surgery completion patients were extubated after effective spontaneous ventilation recovery and were referred to the post-anesthetic recovery unit (PACU). No patient needed neuromuscular reversal. Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were recorded for statistical analysis in the following moments:

M1 = Before induction;

M2 = After tracheal intubation;

M3 = Before peritoneal inflation;

M4 = 10 minutes after inflation;

M5 = 20 minutes after inflation;

M6 = End of anesthesia;

M7 = PACU discharge.

During PACU stay, the presence of nausea and/or vomiting was periodically evaluated and recorded by an anesthesiologist. After PACU discharge, patients were referred to the outpatient setting where they remained for approximately four hours until hospital discharge. Longer outpatient setting stay due to nausea and vomiting was observed. Anesthetic length, hemodynamic parameters and PACU stay were also observed. During outpatient setting stay, patients were asked about the presence of nausea and/or vomiting and results were recorded. Student’s t test was used to compare weight, height and age, and non-parametric Kruskal-Wallis test for independent samples was used to compare the incidence of nausea and vomiting, considering significant p < 0.05.

Hemodynamic parameters (blood pressure and heart rate) were coded, digitized and analyzed with the World Health Organization (WHO) statistical software Epi-Info, release 6.04.

RESULTS

Groups were homogeneous in demographics data and physical status (ASA) (Table I).

There were no statistically significant differences among groups in hemodynamic parameters (Table II and Table III) and intravenous drug doses (Table IV).

There were no statistical differences among groups in anesthetic length and PACU stay (Table V).

There was statistical difference among groups in the incidence of postoperative nausea: GO < GD < GX < GM < GC (Figure 1).

There was statistical difference among groups in the incidence of postoperative vomiting: GO < GD < GX < GM < GC (Figure 2).

DISCUSSION

The high incidence of vomiting after videolaparoscopic gynecological procedures was evident also in this study where control group patients had 26.09% vomiting. However, after postoperative vomiting treatment with metoclopramide, there has been no additional PACU or hospital stay, that is, there was no significant difference in PACU stay, corresponding to general anesthesia recovery stage II. Patients were referred to outpatient setting recovery (recovery-2) where they remained until hospital discharge (general anesthesia recovery stage III)^11,12, when they no longer presented nausea and/or vomiting. Group’s uniformity with regard to PACU discharge has also shown no influence of antiemetic drugs, especially droperidol in the dose used, in PACU stay. Hospital discharge within the estimated period of four hours after PACU discharge was achieved in all groups, also showing the efficacy of the anesthetic technique.

Ondansetron was the most effective drug in preventing postoperative nausea (4.55%) and vomiting (5.26%), which is in line with other authors^8-10,13-15. From all drugs studied, droperidol was the closest to ondansetron in preventing nausea (5.27%) and vomiting (9.09%) after videolaparoscopic gynecological procedures, in the conditions of this study.

Metoclopramide and dexametasone were, in this order, the less effective drugs. Alone, they have not promoted satisfactory results since none of them was able to significantly decrease the incidence of vomiting as compared to the control group. It is known that nausea and vomiting have a multifactorial etiology^2,7 related to four types of neurotransmitters modulating the triggering chemoreceptor zone located in the postreme area: dopamine, serotonin, histamine and acetylcholine⁹.

Antiemetic drugs are classified according to their action on pharmacological receptors and, in general, single therapy may not be enough to control PONV. Some authors suggest the association of two or more antiemetic agents to achieve better results^16-18. A study has shown that prophylactic intravenous granisetron (3 mg) associated to dexametasone (8 mg), were more effective than granisetron alone to decrease PONV in patients submitted to Cesarean section under spinal anesthesia¹⁶. The same authors have concluded, in a different study, that prophylactic therapy with granisetron and dexametasone was more effective than each antiemetic drug alone to prevent post-pediatric procedures vomiting¹⁷.

Other authors have shown that the association of intravenous droperidol (1.25 mg) and ondansetron (4 mg) was significantly better than droperidol alone to control PONV in women submitted to laparoscopic gynecological procedures¹⁸. Our study has not combined antiemetic drugs since our aim was to study them separately.

So, in the conditions of our study where single antiemetic drugs were used, ondansetron was the most effective agent to prevent nausea and vomiting, and droperidol was the closest drug to ondansetron, representing an acceptable option to prevent nausea and vomiting after outpatient videolaparoscopic gynecological procedures.

REFERENCES

Submitted for publication June 27, 2005

Accepted for publication November 22, 2005

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• 13. Malins AF, Field JM, Nesling PM et al - Nausea and vomiting after gynaecological laparoscopy: comparison of premedication with oral ondansetron, metoclopramide and placebo. Br J Anaesth, 1994;72:231-233.
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• 17. Fujii, Saitoh, Tanaka H et al - Prophylactic therapy with combined granisetron and dexametasone for the prevention of post-operative vomiting in children. Eur J Anaesthesiol, 1999;16:376-379.
• 18. Mckenzie R, Uy NT, Riley TJ et al - Droperidol/ondansetron combinations controls nausea and vomiting after tubal banding. Anesth Analg, 1996;83:1218-1222.

*

Received from Hospital Centro Médico de Campinas e Instituto Penido Burnier, Campinas, SP

Publication Dates

• Publication in this collection
  22 Mar 2006
• Date of issue
  Feb 2006

History

• Accepted
  22 Nov 2005
• Received
  27 June 2005