Postoperatif Bulantı Kusma Profilaksisinde Kullanılan Ondansetron ve Metoklopramidin EKG’de QT Aralığına Etkileri

Year 2008, Volume: 25 Issue: 4, 117 - 124, 29.12.2009

Sezgin Bilgin F. Emre Üstün Ali Ekşi Elif BENGİ Şener İ. Serhat Kocamanoğlu Binnur Sarıhasan

Abstract

Bu çalışmada ondansetron ile metoklopramidin QT aralığına etkilerini karşılaştırmak amaçlanmıştır.
Çalışmaya 18–65 yaş arası, ASA I-II (American Society of Anesthesiologists) grubu 100 hasta alındı. Anestezi indüksiyonu propofol, remifentanil ve veküronyum ile sağlandıktan sonra idamede O2/kuru hava içinde %4–6 desfluran uygulandı. Entübasyondan sonra rasgele gruplardan birine ondansetron 4 mg/2ml (Grup-O), diğerine metoklopramid 10 mg/2ml (Grup-M) ve kontrol grubuna 2 ml serum fizyolojik (Grup-K) iv. verildi. Hastaların indüksiyon öncesi, entübasyon sonrası, ilaçlar uygulandıktan sonra operasyon süresince hemodinamik, solunumsal parametreleri ve ısı değerleri kaydedildi. Eş zamanlı EKG örnekleri alındı. EKG’de QT aralıkları ölçülüp, Bazzet formülüyle kalp hızına göre düzeltilmiş değerler (QTc) hesaplandı.
Hasta grupları arasında demografik özelliklerde, kaydedilen vital bulgularda ölçüm dönemlerinde anlamlı fark bulunmadı (p>0.05). İndüksiyon öncesi bazal QTc değerlerinde gruplar arasında farklılık saptanmadı (p>0.05). Entübasyon sonrası QTc değerleri gruplarda sırasıyla Grup-K’da 13,2±11, Grup-O’da 20,4±8 ve Grup-M’de 19,0±10 ms uzadı (p<0,001 grup içi karşılaştırmalarda entübasyon öncesi değerine göre). İntraoperatif ve postoperatif diğer tüm ölçüm dönemlerinde QT aralığı ondansetron grubunda diğer iki gruba göre anlamlı olarak uzundu. QTc değerleri kontrol grubunda intraoperatif 30., metoklopramid grubunda 15. dakikada indüksiyon öncesi değerlere ulaşırken, ondansetron grubunda intraoperatif tüm değerler, indüksiyon öncesine göre yüksekti.
Literatürde metoklopramidin sağlıklı gönüllülerde QTc mesafesini uzattığı rapor edilmişse de anestezide bu etkisini araştıran bir çalışma yoktur. Ondansetron alan hastalarda QTc değerlerinin metoklopramide göre daha yüksek olduğu ve daha uzun süre yüksek kaldığı, QT aralığı uzun olan riskli hastalarda, bulantı kusma profilaksisinde ondansetron yerine metoklopramidin tercih edilmesinin daha uygun olacağı kanısına varıldı.
Anahtar kelimeler: Ondansetron, metoklopramid, QT aralığı


The Effects of Ondansetron and Metoclopramide Used for Postoperative Nousea and Vomiting Prophylaxis on the QT Interval
The aim of this study is to compare the effects of ondansetron and metoclopramide on the QT interval.
100 patients between 18-65 age and with ASA physical status I-II were enrolled in this study. General Anesthesia was induced with 2–3 mg/kg propofol, 1 µg/kg remifentanil and 0,1 mg/kg vecuronium. Anesthesia was maintained with 4% inspired desflurane (in an air – oxygen mixture). The patients randomly divided into three groups. After intubation, the patients received one of the three study medications. The study medication consisted of either saline (Group-K) or 4 mg ondansetron (Group-O) or 10 mg metoclopramide. Hemodinamic parameters, oxygen saturation and body temperature values were recorded before induction, after intubation and during the surgery after delivering of the study drugs. Synhcronous ECG samples were recorded too. The QT intervals were measured and corrected for heart rate (QTc) according to the formula of Bazett.
The three study groups were similar with respect to their demographic characteristics, the type of surgery, hemodinamic parameters and body temperature. Basal QTc values were also similar in the groups. After intubation QTc prolongation values were 13.2±11 (Group-K), 20.4±8 (Group-O), 19.0±10 (Group-M) ms in groups respectively. After administration the study drugs at intraoperative and postoperative all measurement times, the QT interval was found more prolonged in ondansetron group then the other two groups. In the control group at 30. min, and in the metoclopramide group at 15. min the QTc values were the same as the values measured before induction. In the ondansetron group all the values measured intraoperatively were higher when compared with the baseline values.
Although it is reported that metoclopramide prolongs the QT interval in healthy volunteers, there is no study which investigates this effect during surgery. In the patient received ondansetron the QTc values are longer and this prolongation lasted more than in the patient received metoclopramide. These results suggest that, instead of using ondansetron, using metoclopramide for the PONV prophilaxis would be safer on the high risk patients whose QT interval is long.

Keywords

-

References

• Booker PD, Whyte SD, Ladusans EJ. Long QT syndrome and anaesthesia. Br J Anaesth 2003; 90: 349–366.
• Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350: 1013–1022.
• Charbit B, Albaladejo P, Funck-Brentano C, et al. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 2005; 102: 1094–1100.
• Chan MT, Choi KC, Gin T, et al. The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting. Anesth Analg. 2006; 103: 1155–1162.
• Baguley WA, Hay WT, Mackie KP, et al. Cardiac dysrhythmias associated with the intravenous administration of ondansetron and metoclopramide. Anesth Analg 1997; 84: 1380–1381.
• Kasinath NS, Malak O, Tetzlaff J: Atrial fibrillation after ondansetron for the prevention and treatment of postoperative nausea and vomiting: A case report. Can J Anaesth 2003; 50: 229–231.
• Gan TJ, Meyer T, Apfel CC et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003; 97: 62–71.
• Bentsen G, Stubhaug A. Cardiac arrest after intravenous metoclopramide – a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest. Acta Anaesth Scand. 2002; 46: 908.
• Ellidokuz E, Kaya D. The effect of metoclopramide on QT dynamicity: double-blind, placebo-controlled, cross-over study in healthy male volunteers. Aliment Pharmacol Ther. 2003; 181: 151–155.
• Fleming GF, Vokes EE, McEvilly JM, et al. Double-blind, randomized crossover study of metoclopramide and batanopride for prevention of cisplatin-induced emesis. Cancer Chemother Pharmacol. 1991; 28: 226–227.
• Bazette HC. An analysis of the time-relations of electrocardiograms. Heart 1920; 7: 353–370.
• Wisely NA, Shipton EA. Long QT syndrome and anaesthesia. Eur J Anaesthesiol 2002; 19: 853–859.
• Boike SC, Ilson B, Zariffa N et al. Cardiovascular effects of i.v. granisetron at two administration rates and of ondansetron in healthy adults. Am J Health Syst Pharm 1997; 54: 1172–1176.
• Keefe DL. The Cardiotoxic Potential of the 5-HT3 Receptor Antagonist Antiemetics: Is There Cause for Concern? Oncologist 2002; 7; 65–72.
• Zhang Y, Luo Z, White PF, et al. A Model for Evaluating Droperidol’s Effect on the Median QTc Interval. Anesth Analg 2004; 98: 1330–1335.
• Lischke V, Behne M, Doelken P, et al. Droperidol causes a dose-dependent prolongation of the QT interval. Anesth Analg 1994; 79: 983–986.
• Gan TJ. “Black Box” Warning on Droperidol: A Report of the FDA Convened Expert Panel. Anesth Analg 2004; 98: 1809–1818.
• White PF, Song D, Abrao J, et al. Effect of Low-dose Droperidol on the QT Interval during and after General Anesthesia. Anesthesiology 2005; 102: 1101–1105.
• Navari RM, Koeller JM. Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists. Ann Pharmacother. 2003; 37: 1918–1919.
• Hesketh P, Navari R, Grote T et al. Double-bind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. J Clin Oncol 1996; 14: 2242–2249.
• Gin T, Chan MT. QTc Changes after Ondnasetron and Droperidol for the Prevention of Postoperative Nausea and Vomiting. ASA Abstracts 2006; October 14–18. Chicago IL.
• Shah, Rashmi R. Drugs, QTc Interval Prolongation and Final ICH E14 Guideline: An Important Milestone with Challenges Ahead. Drug Safety. 2005;28: 1009–1028.
• Saarnivaara L, Lindgren L. Prolongation of QT interval during induction of anaesthesia. Acta Anaesthesiol Scand 1983; 27: 126–130.
• Korpinen R, Saarnivaara L, Siren K. QT interval of the ECG, heart rate and arterial pressure during anaesthetic induction: comparative effects of alfentanil and esmolol. Acta Anaesthesiol Scand 1995; 39: 809–813.
• Saarnivaara L, Simola M. Effects of four anticholinesterase-anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure. Acta Anaesthesiol Scand 1998; 42: 460–463.