Altuğ KOL, Sacit GÜLEÇ, Dilek CEYHAN, Ayten BİLİR

Flunarizin ön tedavisinin postoperatif morfin tüketimine etkisi

Amaç: Çalışmamız alt batın cerrahisi uygulanacak hastalara preoperatif dönemde oral yoldan verilecek 10 mg flunarizinin, toplam morfin tüketimi ve postoperatif analjezi kalitesi üzerine etkilerini araştırmak amacıyla planlandı. Gereç ve Yöntem: Yaşları 18-55 arasında değişen 30 hasta çalışmaya dahil edildi. Hastalar rastgele olarak iki gruba ayrılarak flunarizin grubunda bulunan hastalara 2 adet 5 mg flunarizin kapsül ve plasebo grubuna da 2 adet plasebo kapsül operasyondan 2 saat önce verildi. Ekstübasyondan hemen sonra ve 15. dakikada aldrete post-anestezi skoru ile derlenme durumları değerlendirildi. Postoperatif dönemde analjezi amacıyla intravenöz hasta kontrollü analjezi yöntemi ile morfin başlandı ve ilk analjezik ihtiyaç zamanları kaydedildi. Ekstübasyondan sonra Ramsay sedasyon skalası, vizüel analog skalası (VAS) skoru ve morfin tüketimleri belirlendi. Bulgular: Flunarizin grubunda 5. dakikadaki sistolik arteriyel basınç değerlerinin düşüklüğü plaseboya göre anlamlı bulundu. İntraoperatif 45. dakikadaki kalp atım hızı flunarizin grubunda plaseboya göre anlamlı düşüktü. Postoperatif 12. saatteki VAS değeri, flunarizin grubunda istatistiksel olarak anlamlı düşüktü. Postoperatif sedasyon skorları iki grup arasında fark göstermedi. Flunarizinin ilk analjezik ihtiyaç zamanını uzatmadığı ve benzer şekilde toplam morfin tüketimini azaltmadığı gözlendi. Sonuç: Preoperatif dönemde oral yoldan 10 mg tek doz şeklinde verilen flunarizinin klinik parametreler üzerine belirgin etkisinin olmadığı ve bu dozda analjezik etkisinin bulunmadığı ya da morfinin analjezik etkisini potansiyalize edici etki göstermediği sonucuna varıldı.

The effect of flunarizine pretreatment on postoperative morphine consumption

Objectives: This study was designed to document the effects 10 mg flunarizine, administrated in the preoperative period, on postoperative morphine requirement and analgesic quality, in abdominal surgery. Methods: Thirty patients, aged 18 to 55 years, were studied. Patients were randomly allocated to one of two equally sized groups, and received either 2 capsules of 5 mg flunarizine (Group I) or 2 placebo capsules (Group II) 2 hours before the operation, immediately after the extubation and at the 15th minute, Aldrete postanesthesia recovery scores were assessed. In the postoperative period, patients were connected to a patient-controlled analgesia device for intravenous morphine, and the first analgesic requirement time was recorded. Ramsay sedation scale, visual analogue pain scale and morphine consumption were assessed after the extubation. Results: Systolic arterial pressures at the 5th minute of the preoperative period were significantly lower in the flunarizine group than placebo group. Heart rates in the 45th minute were also lower in the flunarizine group. Flunarizine patients reported statistically lower visual analogue pain scale values in the postoperative 12th hour. There was no significant difference in postoperative sedation scores between the groups. Flunarizine did not lengthen the first analgesic requirement time and similarly did not lessen the morphine requirement. Conclusion: We conclude that 10 mg flunarizine administered in the preoperative period had no significant effects on clinical parameters, had no analgesic effect and did not augment the analgesic effects of morphine at this dose.

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1. Pasternak GW. Pharmacological mechanisms of opioid analgesics. Clin Neuropharmacol 1993;16(1):1-18.
2. Del Pozo E, Caro G, Baeyens JM. Analgesic effects of several calcium channel blockers in mice. Eur J Pharmacol 1987;137(2-3):155-60.
3. Contreras E, Tamayo L, Amigo M. Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance. Eur J Pharmacol 1988;148(3):463-6.
4. Miranda HF, Pelissier T, Sierralta F. Analgesic effects of intracerebroventricular administration of calcium channel blockers in mice. Gen Pharmacol 1993;24(1):201-4.
5. Weizman R, Pankova IA, Schreiber S, Pick CG. Flunarizine analgesia is mediated by μ-opioid receptors. Physiol Behav 1997; 62:1193-5.
6. Ries CR, Azmudéh A, Franciosi LG, Schwarz SK, MacLeod BA. Cost comparison of sevoflurane with isoflurane anesthesia in arthroscopic menisectomy surgery. Can J Anaesth 1999;46(11):1008-13.
7. Werz MA, Macdonald RL. Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials. J Pharmacol Exp Ther 1983;227(2):394-402.
8. North RA, Williams JT. Opiate activation of potassium conductance inhibits calcium action potentials in rat locus coeruleus neurones. Br J Pharmacol 1983;80(2):225-8.
9. Kavaliers M. Stimulatory influences of calcium channel antagonists on stress-induced opioid analgesia and locomotor activity. Brain Res 1987;408(1-2):403-7.
10. Prado WA. Involvement of calcium in pain and antinociception. Braz J Med Biol Res 2001;34(4):449-61.
11. Del Pozo E, Ruiz-García C, Baeyens JM. Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test. Gen Pharmacol 1990;21(5):681-5.
12. Miranda HF, Bustamante D, Kramer V, Pelissier T, Saavedra H, Paeile C, et al. Antinociceptive effects of Ca2+ channel blockers. Eur J Pharmacol 1992;217(2-3):137-41.
13. Kumar R, Mehra R, Ray SB. L-type calcium channel blockers, morphine and pain: Newer insights. Indian J Anaesth 2010;54(2):127-31.
14. Doğrul A, Yeşilyurt Ö, Işımer A, Güzeldemir ME. L-type and T-type calcium channel blockade potentiate the analgesic effects of morphine and selective μ opioid agonist, but not to selective δ and κ agonist at the level of the spinal cord in mice. Pain 2001;93:61-8.
15. Pereira IT, Prado WA, Dos Reis MP. Enhancement of the epidural morphine-induced analgesia by systemic nifedipine. Pain 1993;53(3):341-5.
16. Zarauza R, Sáez-Fernández AN, Iribarren MJ, Carrascosa F, Adame M, Fidalgo I, et al. A comparative study with oral nifedipine, intravenous nimodipine, and magnesium sulfate in postoperative analgesia. Anesth Analg 2000;91(4):938-43.
17. Nitahara K, Matsunaga M, Katori K, Yotsui H, Higuchi H, Higa K. Effect of continuous low-dose intravenous diltiazem on epidural fentanyl analgesia after lower abdominal surgery. Br J Anaesth 2003;90(4):507-9.
18. Weizman R, Getslev V, Pankova IA, Schrieber S, Pick CG. Pharmacological interaction of the calcium channel blockers verapamil and flunarizine with the opioid system. Brain Res 1999;818(2):187-95.
19. Holmes B, Brogden RN, Heel RC, Speight TM, Avery GS. Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs. 1984;27(1):6-44.
20. Diener HC. Flunarizine for migraine prophylaxis. In: Diener HC, editor. Drug treatment of migraine and other headaches. Basel: Karger; 2000. p. 269-78.
21. Billman GE. The calcium channel antagonist, flunarizine, protects against ventricular fibrillation. Eur J Pharmacol 1992;212(2-3):231-5.
22. Pfaffenrath V, Oestreich W, Haase W. Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study. Cephalalgia 1990;10(2):77-81.
23. Balkan S, Aktekin B, Önal Z. Efficacy of flunarizine in the prophylactic treatment of migraine. Gazi Med Jour 1994;5:81-4.
24. Yücel A. Hasta kontrollü analjezi (PCA). In: Erdine S, editör. Ağrı. 2. Baskı, İstanbul: Nobel Tıp Kitabevi; 2002. p. 144-53.
25. Choe H, Kim JS, Ko SH, Kim DC, Han YJ, Song HS. Epidural verapamil reduces analgesic consumption after lower abdominal surgery. Anesth Analg 1998;86(4):786-90.
26. Fassoulaki A, Zotou M, Sarantopoulos C. Effect of nimodipine on regression of spinal analgesia. Br J Anaesth 1998;81(3):358-60.
27. Gupta H, Verma D, Ahuja RK, Srivastava DN, Wadhwa S, Ray SB. Intrathecal co-administration of morphine and nimodipine produces higher antinociceptive effect by synergistic interaction as evident by injecting different doses of each drug in rats. Eur J Pharmacol 2007;561(1-3):46-53.