KARDİYOVASKÜLER CERRAHİDE REMİFENTANİL Doç.Dr.Tayfun Güler

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 36

DOZ İndüksiyon: 0.5-2 mcg/kg (>30-60 sn) İdame: 0.05-2 mcg/kg/dk 35

HEMODİNAMİK ETKİLERİ Anesth Analg 1995;80:990-993 34

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 33

KARDİYAK KATETERİZASYON Amaç: Hemodinamik stabilite Hızlı ve erken derlenme Yöntem: 30 pediyatrik hasta (1.5-20 ay) 0.6MAC sevofluran + Grup I : 0.2 mcg/kg/dk remifentanil Grup II: 0.3 mcg/kg/dk remifentanil Sonuç: İntübasyona hemodinamik yanıtta azalma Kalp hızı ve sistolik kan basıncında azalma Ekstübasyon süreleri Grup I: 7.3 dk Grup II: 6.6 dk Acta Anaesthesiol Scand 2002 Apr;46(4):355-60   Remifentanil infusion for cardiac catheterization in children with congenital heart disease. Foubert L, Reyntjens K, De Wolf D, Suys B, Moerman A, Mortier E. Department of Anesthesia, Division of Cardiac Anesthesia, Ghent University Hospital, Belgium. Luc.Foubert@rug.ac.be BACKGROUND: Cardiac catheterization of children with congenital heart disease is increasingly being performed under general anesthesia. Haemodynamic stability during anesthesia and fast and adequate recovery after the procedure is crucial in these patients. We performed a pilot study to evaluate hemodynamic stability when using remifentanil for anesthesia during cardiac catheterization. We also evaluated extubation times and recovery characteristics. METHODS: In a randomized, prospective, double-blind study 30 children (aged 1.5-20 months) received a continuous infusion of either 0.2 (group 0.2) or 0.3 microg/kg/min remifentanil (group 0.3) as part of a balanced anesthesia with 0.6 MAC sevoflurane. Heart rate, noninvasive arterial blood pressure, end tidal CO2 and pulse oxymetry were monitored throughout the procedure. Extubation times were noted, and recovery from anesthesia was evaluated using Aldrete scores. RESULTS: : Haemodynamic response to intubation was well blunted in both groups. No significant changes in hemodynamic variables were noted from induction of anesthesia until 10 min after intubation. From then on there was a decrease in HR and systolic arterial pressure, which remained significant throughout the procedure in both groups. Extubation times were similar in both groups: 7.3 min (2,1) in group 0.2 vs. 6.6 min (2,1) in group 0.3 (NS). The number of patients with an Aldrete score of nine or more was 14 (group 0.2) vs. 15 (group 0.3), 10 min after extubation (NS). CONCLUSION: Both dose regimens of remifentanil provided stable hemodynamic conditions during anesthesia for cardiac catheterization of children with congenital heart disease and allowed for rapid and adequate recovery. Acta Anaesthesiol Scand 2002;46:355-60 32

KARDİYAK KATETERİZASYON Yöntem: 55 pediyatrik hasta (2 ay-12 yıl) Premedikasyon: Midazolam (oral) Anestezi Remifentanil (0.1 mcg/kg/dk) Sonuç: 23 olguda başarılı sedasyon 32 olguda ek sedatif gereksinimi Stabil hemodinami Hızlı derlenme Minimal komplikasyon J lower than the scores recorded at baseline and 15 minutes. In 23 patients, the remifentanil infusion maintained a satisfactory level of sedation, but 32 patients required Cardiothorac Vasc Anesth 2001 Dec;15(6):736-9Related Articles, Links   One center's experience with remifentanil infusions for pediatric cardiac catheterization. Donmez A, Kizilkan A, Berksun H, Varan B, Tokel K. Department of Anesthesiology, University of Baskent, School of Medicine, Kavaklidere, 06690 Ankara, Turkey. aslidonmez@hotmail.com OBJECTIVE: To investigate the efficacy of a remifentanil infusion for pediatric cardiac catheterization. DESIGN: Prospective. SETTING: University hospital. PARTICIPANTS: Children undergoing cardiac catheterization (n = 55). INTERVENTIONS: All patients (age range, 2 months to 12 years) were premedicated with an oral mixture of hydroxyzine and midazolam 60 minutes before the procedure. A remifentanil infusion was initiated at 0.1 microg/kg/min before the start of cardiac catheterization. Noninvasive systolic blood pressure, heart rate, oxygen saturation (SpO(2)), respiratory rate, and sedation score were recorded before the remifentanil infusion and every 15 minutes thereafter throughout the procedure. Episodes of apnea, vomiting, pruritus, and muscle rigidity and recovery time were noted. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in systolic blood pressure, heart rate, SpO(2), or respiratory rate during the procedure. The sedation scale scores at 30, 45, 60, 75, and 90 minutes of remifentanil infusion were significantly additional drugs (18 received midazolam, and 14 received midazolam plus ketamine). Recovery was rapid after the remifentanil infusion was discontinued, with a mean time of 2.04 +/- 2.32 minutes to reach a recovery score of > or =5. Three patients experienced apnea after bolus doses of remifentanil, 1 patient vomited, and 1 patient complained of pruritus. CONCLUSION: In pediatric cases in which other intravenous analgesics and sedatives are contraindicated, remifentanil infusion appears to be a suitable alternative based on its associated rapid recovery and stable hemodynamics. Copyright 2001 by W.B. Saunders Company J Cardiothorac Vasc Anesth. 2001;15:736-9. 31

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 30

VASKÜLER CERRAHİ Majör vasküler cerrahi: Karotid endarterektomi: Literatürde veri yok Karotid endarterektomi: Lokal anestezi Bölgesel anestezi Genel anestezi Rev Esp Anestesiol Reanim 2001 Dec;48(10):508-12   [Carotid endarterectomy under remifentanil 29

KAROTİD ENDARTEREKTOMİ Bölgesel veya lokal anestezi Ek analjezik gereksinimi Cerrahi sırasında başlarını hareket ettirememeleri Servikal omurgadan doğan ağrı Cerrahi manüplasyonun oluşturduğu ağrı Hemodinamik ve respiratuar instabilite Bölgesel veya lokal anestezi altında karotis endarterektomi uygulanan hastaların önemli bir kısmı ek analjezik gereksinimi duyar. Cerrahi sırasında başlarını hareket ettirememelerinden kaynaklanan rahatsızlık hissi, servikal omurgadan doğan ağrı karotid kılıfı ve mandibulanın altındaki cerrahi manüplasyonun oluşturduğu ağrı bir yandan hastayı rahatsız ederken diğer yandan da hemodinamik ve respiratuar instabilite nedeni olabilir. Bölgesel anestezi uygulanan hastalarda 3-6 mcg/kg/st remifentanil infüzyonunun yeterli analjezi/sedasyon sağladığı bildirilmiştir. Ancak solunum depresyonu ve bulantı riski, propofole göre daha yüksektir. Br J Anaesthesia, 2002, Vol. 89, No. 4 637-640 28

KAROTİD ENDARTEREKTOMİ Servikal pleksus bloğu + Remifentanil (3 mcg/kg/st) veya Propofol (1 mg/kg/st) Yeterli analjezi/sedasyon Solunum depresyonu ve bulantı riski, propofole göre daha yüksek Remifentanil or propofol for sedation during carotid endarterectomy under cervical plexus block. Krenn H, Deusch E, Jellinek H, Oczenski W, Fitzgerald RD. Department of Anaesthesia and Intensive Care, City of Vienna Hospital Lainz, A-1130 Vienna, Austria. BACKGROUND: During carotid endarterectomy under regional anaesthesia, patients often require medication to control haemodynamic instability and to provide sedation and analgesia. Propofol and remifentanil are used for this purpose. However, the benefits, side-effects, and optimal dose of these drugs in such patients are unclear. METHODS: Sixty patients were included in a prospective, randomized, single blinded study. All patients received a deep cervical plexus block with 30 ml ropivacaine 0.75% and were randomized to receive either remifentanil 3 micro g kg(-1) h(-1) or propofol 1 mg kg(-1) h(-1). The infusions were started after performing the regional block and were stopped at the end of surgery. Arterial pressure, ECG, ventilatory rate, and Pa(CO(2)) were measured continuously and recorded at predetermined times. Twenty-four hours after surgery, patient comfort, and satisfaction were also evaluated. RESULTS: In three patients, the infusion of remifentanil had to be stopped because of severe respiratory depression or bradycardia. No significant differences were found between the two groups in haemodynamic variables or sedative effects, but there was a significantly greater decrease in ventilatory frequency and increase in Pa(CO(2)) in the remifentanil group. The patient's subjective impressions and pain control were excellent in both groups. CONCLUSION: As a result of the higher incidence of adverse respiratory effects with remifentanil and similar sedative effects, propofol is preferable for sedation during cervical plexus block in elderly patients with comorbid disease at the dosage used. Br J Anaesth 2002;89:637-40 27

KAROTİD ENDARTEREKTOMİ 48 hasta Anestezi indüksiyonu: Remifentanil: 0.75-1.0 mcg/kg (> 2 dk) Lidokain %5: Glottise lokal anestezi Endotrakeal intübasyon Anestezi idamesi Remifentanil: 1 mcg/kg/dk (0.35-1.5) Hasta kooperasyonu : + Bradikardi(28), hipotansiyon(25), hipertansiyon (3) RESULTS: The objective of anesthesia was reached in all the patients. The most common hemodynamic alterations were bradycardia (28), arterial hypotension (25), elevated blood pressure (3) and altered aortic output. All changes were corrected quickly with the treatment used, guided by the evolution of hemodynamic parameters. Postanesthetic recovery came in less than 4 min. The only episodes of hyper -and hypotension consisted of a few episodes of mild hyper- (12) and hypotension (1), which were soon corrected. No alterations attributable to hemodynamic instability occurred. During surgery, an intracarotid shunt was necessary in only one patient. Three suffered surgically-related neurological complications after the operations. No complications could be attributed to anesthesia. DISCUSSION: An advantage of this technique is that the duration of anesthesia is not limited, with adequate ventilation and maintenance of an adequate state of consciousness for clinical evaluation of the repercussions of carotid clamping. Hemodynamic monitoring detected the appearance of imbalances requiring therapeutic intervention. The procedure is interesting provided it is performed according to a strict protocol, with continuous clinical and instrumental monitoring of the patient's status. 26 Rev Esp Anestesiol Reanim 2001;48:508-12

KAROTİD ENDARTEREKTOMİ GENEL ANESTEZİ Diseksiyon, tromboz, hemoraji Erken derlenme ve nörolojik muayene Anestezi yöntemi Desfluran (%2) + remifentanil (0.1 mcg/kg/dk) Desfluran (%2) + fentanil ( 2 mcg/kg/dk) Remifentanil ile derlenme daha hızlı Genel anestezi altında gerçekleştirilen karotid endarterektomi operasyonlarında diseksiyon, tromboz ya da hemoraji gibi komplikasyonların erken postoperatif dönemde tanınabilmesi için hastanın hızla uyanması ve nörolojik muayeneye hazır hale gelmesi gereklidir. Bu hastalarda desfluran veya remifentanil zeminli anestezi teknikleri, fentanil anestezisine üstündür. Bu amaçla desfluran (%2) anestezi verilen hastalarda remifentanil ile indüksiyon (1 mcg/kg > 30 sn) ve 0.1 mcg/kg/dk infüzyon uygulaması ile klasik fentanil ile desteklenen anesteziye göre daha hızlı uyanma ve nörolojik muayeneye hazır hale gelme sağlanmıştır. Br J Anaesth 2001;86:44-9 25

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 24

KORONER ARTER CERRAHİSİ Anestezide amaçlar Bilinç kaybı Hemodinamik stabilite Nörohümoral stres yanıtın baskılanması Kardiyovasküler durum bozukluğu Miyokardın korunması Yüksek doz opioid Morbidite / mortalite :  Yoğun bakımda kalış süresi :  Kardiyak anestezide kardiyovasküler stabilite temel hemodinamik prensiptir. Kardiyovasküler işlevin bozuk olduğu bu hastalarda miyokardın korunması da önemlidir. Klasik olarak derin bir intraoperatif analjezi, hormonal ve metabolik stres yanıtların baskılanmasında gereklidir. Bu amaçla sık olarak yüksek doz opioidler kullanılmaktadır. Yüksek doz opioid anestezisi ile kardiyak cerrahi sonrası morbidite ve mortalite sonuçları önemli oranda düzelmiştir. Ancak yüksek doz opioid kullanımı postoperatif solunum depresyonu olasılığı ve yoğun bakımda kalış süresini uzatmaktadır. Br J Anaesth 2001; 87: 718-726 23

KORONER ARTER CERRAHİSİ Düşük doz opioid anestezisi Volatil anestezik + opioid anestezisi İntroperatif dönem: Analjezinin kontrolünde güçlük Hipertansiyon Taşikardi Postoperatif dönem: Miyokard enfarktüsü Pek çok cerrahi merkezde ekonomik nedenlerden ötürü ekstübasyon süresi, yoğun bakımda ve hastanede kalış süresini kısaltmak için düşük veya orta derece yüksek opioid anestezisine geçilmiştir. Bu anestezi teknikleri ile intraoperatif analjezi düzeyinin iyi kontrol edilmesi zorunludur. Aksi taktirde intraoperatif hipertansiyon ve taşikardi postoperatif miyokard infarktüsü olasılığını arttırabilir. 22

KORONER ARTER CERRAHİSİ Dünyada yılda 800.000 koroner cerrahisi A.B.D.’de kardiyak cerrahinin maliyeti: 27 milyar USD/yıl Maliyet azaltma çabası: Fast-track kardiyak cerrahi Minimal invaziv kardiyak cerrahi 21

FAST-TRACK KARDİYAK CERRAHİ Amaç: Erken derlenme Erken ekstübasyon:1-6 saat Anestezi yöntemi: Remifentanil/propofol Remifentanil/isofluran Remifentanil/desfluran 20

REMİFENTANİL Anestezi indüksiyonu: Anestezi yöntemi (propofol +) KORONER ARTER CERRAHİSİ Anestezi indüksiyonu: Propofol: 0.5 mg/kg Remifentanil : 1 mcg/kg/dk Anestezi yöntemi (propofol +) Grup I: Remifentanil (1.0 mcg/kg/dk) Grup II: Remifentanil (1.5 mcg/kg/dk) Grup III: Remifentanil (2.0 mcg/kg/dk) Sonuç: İyi bir indüksiyon ajanı değil Cerrahiye yanıtta iyi baskılanma 1.0 mcg/kg/dk’nın üzerine ek avantaj yok Efficacy and safety of remifentanil in coronary artery bypass graft surgery: a randomized, double-blind dose comparison study. Geisler FE, de Lange S, Royston D, Demeyere R, Duthie DJ, Lehot JJ, Adt M, Dupeyron JP, Mansfield M, Kirkham AJ. Department of Anaesthesiology, Ignatius Ziekenhuis Breda, Breda, The Netherlands. OBJECTIVES: To compare the efficacy and safety of 3 doses of remifentanil as part of a total intravenous anesthesia technique with low-dose propofol in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Multicenter, multinational, double-blind, randomized, dose comparison study. SETTING: Nine hospitals in 5 countries. PARTICIPANTS: One hundred forty-one patients undergoing first-time elective CABG surgery. INTERVENTIONS: Patients were premedicated with a short-acting oral benzodiazepine up to 2 h before surgery and randomized to receive continuous infusions of remifentanil 1.0 microg/kg/min (n = 45), 1.5 microg/kg/min (n = 44), or 2.0 microg/kg/min (n = 43), in combination with propofol 3 mg/kg/h. Nine patients received remifentanil 1.0 microg/kg/min on an open-label basis. Three different induction sequences (IS) were used. In IS 1 (n = 31), induction was started with remifentanil infusion followed 5 minutes later by propofol 0.5 mg/kg bolus and infusion at 3 mg/kg/h. Further bolus doses of propofol (10 mg) were given if loss of consciousness (LOC) was not attained after 5 minutes; pancuronium, 0.04 to 0.1 mg/kg, was administered at LOC. In IS 2 (n = 68), a priming dose of pancuronium, 0.015 mg/kg, was administered just before starting remifentanil. In IS 3 (n = 42), bolus doses of propofol, 10 mg every 10 seconds, were given until LOC, followed by pancuronium, 0.04 to 0.1 mg/kg, and the remifentanil and propofol infusions were started. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among the remifentanil dose groups with regard to the primary outcome measure, responses to sternotomy/sternal spread/maximal sternal spread. Responses to these stimuli were recorded in 11%, 11%, and 14% of patients in the remifentanil 1.0, 1.5, and 2.0 microg/kg/min dose groups, respectively. Similarly, there were no significant differences in the responses to other surgical stimuli. There was a high incidence of muscle rigidity when remifentanil was used to induce anesthesia. CONCLUSIONS: All 3 remifentanil dose regimens provided profound suppression of responses to surgical stimuli in the majority of patients. There was no apparent advantage in starting the remifentanil infusion rate above 1.0 microg/kg/min. Remifentanil is not suitable for use as a sole induction agent. Copyright 2003, Elsevier Science (USA). All rights reserved. Cardiothorac Vasc Anesth 2003;17:60-8 19

REMİFENTANİL vs FENTANİL KORONER ARTER CERRAHİSİ Anestezi indüksiyonu: Propofol: 0.5 mg/kg Remifentanil : 1 mcg/kg/dk Anestezi yöntemi: (isofluran %0.5 +) Grup I: Remifentanil (1 mcg/kg/dk) Grup II: Fentanil Sonuç: Sternotomiye hemodinamik yanıt, fentanil ile  Ekstübasyon ve yoğun bakımda kalış süreleri aynı Anesth Analg 2001;92:1084 –1093 19

REMİFENTANİL vs SUFENTANİL KORONER ARTER CERRAHİSİ Anestezi indüksiyonu: (Etomidat +) Grup I: Sufentanil (0.5 mcg/kg) Grup II: Remifentanil (0.15-0.3 mcg/kg) Anestezi idamesi: (Propofol +) Grup I: Sufentanil (0.5-1. mcg/kg/st) Grup II: Remifentanil (0.15-0.3 mcg/kg/dk) Sonuç: Somatik ve hemodinamik yanıt: Benzer Katekolamin düzeyi: Remifentanil ile  Derlenme: Remifentanil ile daha hızlı Journal of Cardiothoracic and Vascular Anesthesia Volume 16, Issue 6, December 2002, Pages 703-708 This Document Abstract Actions Cited By Save as Citation Alert E-mail Article Export Citation DOI: 10.1053/jcan.2002.128415 PII: S1053-0770(02)00126-X   Copyright © 2002 Elsevier Science (USA). All rights reserved. Original Articles Remifentanil-clonidine-propofol versus sufentanil-propofol anesthesia for coronary artery bypass surgery*1 K. Gerlach MD, Th. Uhlig MD, DEAA, M. Hüppe MD, E. Kraatz MD, L. Saager MD, A. Schmitz MD, V. Dörges MD and P. Schmucker MD From the Departments of Anesthesiology and Cardiothoracic Surgery, University Lübeck, Lübeck, Germany. Available online 19 December 2002. Abstract Objective: To compare a remifentanil-clonidine-propofol regimen with conventional sufentanil-propofol anesthesia. Design: Randomized, nonblinded trial. Setting: A single university hospital. Participants: Male patients scheduled for coronary artery bypass graft (CABG) surgery. Interventions: In the control group, anesthesia was induced with 0.5 g/kg of sufentanil and 0.2 to 0.3 mg/kg of etomidate after preoxygenation. Propofol (50 to 100 g/kg/min) and sufentanil (0.5 to 1.0 g/kg/h) were started after endotracheal intubation. Sufentanil was stopped after aortic decannulation. In the remifentanil-clonidine group, anesthesia was started with remifentanil (0.15 to 0.3 g/kg/min), followed by etomidate (0.2 to 0.3 mg/kg). Propofol was started at 50 to 100 g/kg/min, and after endotracheal intubation, clonidine infusion was started (6 to 20 g/h). Patients received piritramide (0.15 mg/kg) and metamizole (20 mg/kg) for transitional analgesia. In both groups, propofol infusion was reduced to 30 to 60 g/kg/min at skin closure and stopped when assisted spontaneous breathing led to adequate gas exchange. Measurements and Main Results: The main outcomes were recovery times; somatic variables; plasma catecholamine levels; and self-recorded pain, nausea, and vomiting. Patients in the remifentanil-clonidine group were extubated earlier and had lower plasma epinephrine and norepinephrine levels. After transitional analgesia, the remifentanil-clonidine patients had similar postoperative analgesic use and self-reported pain and side-effect scores. Conclusion: Compared with a sufentanil-propofol regimen, an anesthetic regimen for CABG surgery that combines remifentanil, clonidine, and propofol provides similar hemodynamics. The remifentanil-clonidine regimen reduces catecholamine levels and hastens recovery from anesthesia. J Cardiothorac Vasc Anesth 2002;16:703-708 17

MİNİMAL İNVAZİV CABG Amaç: Anestezi yöntemi: Erken ekstübasyon: İlk 1-6 saat Operasyon odasında operasyon bitiminde Anestezi yöntemi: Remifentanil, alfentanil Sevofluran, desfluran 16

MİNİMAL İNVAZİV CABG Anestezi indüksiyonu (propofol +) Remifentanil: 2 mcg/kg Alfentanil: 40 mcg/kg Anestezi idamesi (propofol +) Remifentanil: 0.25 - 0.5 mcg/kg/dk Alfentanil: 0.5 - 1 mcg/kg/dk Uyanma ve ekstübasyon süreleri remifentanil gurubunda çok daha kısa A comparison of remifentanil and alfentanil for use with propofol in patients undergoing minimally invasive coronary artery bypass surgery. Ahonen J, Olkkola KT, Verkkala K, Heikkinen L, Jarvinen A, Salmenpera M. Department of Anesthesia, University Central Hospital and University of Helsinki, Helsinki, Finland. jouni.ahonen@pp.inet.fi Most patients undergoing minimally invasive direct coronary artery bypass surgery can be awakened and tracheally extubated in the operating room. We have compared two techniques of total IV anesthesia in this patient population: 30 patients (aged 44 to 74 yr; 24 male) premedicated with temazepam were randomly assigned to receive either remifentanil-propofol or alfentanil-propofol. Anesthesia was induced with remifentanil 2 microg/kg or with alfentanil 40 microg/kg, with propofol, and maintained with remifentanil at 0.25 or 0.5 microg x kg(-1) x min(-1) or alfentanil at 0.5 or 1 microg x kg(-1) x min(-1). The stable maintenance infusion rate of propofol was adjusted for age. Times to awakening and tracheal extubation were recorded. Postoperatively, IV morphine provided by patient-controlled analgesia was used for 48 h. Times to awakening and tracheal extubation (mean +/- SD) were shorter (P < 0. 01) in patients receiving remifentanil, and interpatient variations in times to awakening and tracheal extubation smaller (awakening 25 +/- 7 vs 74 +/- 32 min, and extubation 27 +/- 7 vs 77 +/- 32 min). Analysis of variance revealed that postoperative consumption of morphine was dependent on both the intraoperative opioid and the time elapsed after surgery (P < 0.05): patient-controlled analgesia morphine use during the first 3 h after awakening was more in patients receiving remifentanil (P < 0.01). Implications: Recovery of patients undergoing Minimally Invasive Direct Coronary Artery Bypass Surgery is significantly shorter and more predictable after total IV anesthesia with remifentanil-propofol than with alfentanil-propofol, which may be important if the goal is that patients will be awakened and tracheally extubated in the operating room. 15 Anesth Analg 2000;90:1269-74

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 14

PEDİYATRİK KARDİYAK ANESTEZİ Fast-track kardiyak cerrahi: Propofol Midazolam Remifentanil Sevofluran Desfluran 13

PEDİYATRİK KARDİYAK ANESTEZİ 50 ASD + VSD Anestezi yöntemi: İndüksiyon : Sevofluran İdame: Grup I: Remifentanil Grup II: Fentanil Kan basıncında azalma aynı Kalp hızında azalma remifentanil ile daha fazla Ekstübasyon süreleri aynı Postoperatif analjezik gereksinimleri aynı                    A comparison of remifentanil and fentanyl for fast track paediatric cardiac anaesthesia. Friesen RH, Veit AS, Archibald DJ, Campanini RS. Department of Anesthesiology, The Children's Hospital, University of Colorado School of Medicine, Denver, Colorado, USA. Background: Fast track anaesthetic protocols for cardiac surgical patients have been developed to facilitate early tracheal extubation. We compared anaesthetics based on either remifentanil or fentanyl for fast track paediatric cardiac anaesthesia. Methods: Fifty patients with atrial septal defect or simple ventricular septal defect who were deemed suitable for fast track anaesthetic management were randomly assigned to group R (remifentanil) or group F (fentanyl). After sevoflurane induction, patients received either R infusion or F bolus. Following intubation, isoflurane 0.5 MAC was administered to all patients. Blood pressure (BP) and heart rate (HR) were recorded at baseline and pre- and postinduction, intubation, skin incision and sternotomy. Other parameters measured included time to extubation, reintubation rate and requirements for postoperative analgesia, ondansetron, and nitroprusside in the paediatric intensive care unit. Results: BP decreased similarly from baseline in both groups. Decreases in HR over time were significantly greater in group R. Haemodynamic response to incision/sternotomy was low and similar in both groups. There were no significant differences in extubation time, reintubation incidence, postoperative narcotic requirements, postoperative hypertension or postoperative nausea/vomiting. Conclusions: The remifentanil based anaesthetic was associated with a significantly slower HR than the fentanyl based anaesthetic. The clinical implications of the slower HR during remifentanil anaesthesia could be important and should be investigated. Paediatr Anaesth 2003;13:122-5 12

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 11

CPB ve FARMAKOKİNETİK Hemodilüsyon Bölgesel kan akımlarının değişmesi Hipotermi Proteine bağlanmada değişme, Heparin kullanımı Baypas donanımının ilaçları absorbsiyonu Akciğerlerin dolaşımdan ayırılması Kardiyak cerrahide CPB’ın ilaç farmakokinetiği üzerine önemli etkileri vardır: gibi nedenler 10

CPB ve FARMAKOKİNETİK Remifentanil: 68 CABG hastası Yüksek klirens hızı Hızlı doku dağılımı 68 CABG hastası Dağılım volümü:  (%86) Klirens hızı:  (%6.3 / 10C) Remifentanilin yüksek klirens hızı ve hızlı doku dağılımı, CPB’ın farmakoniteğini etkilemesine neden olabilir. CPB’ın başlaması ile birlikte dağılım volümünün artmasına bağlı olarak remifentanil kan konsantrasyonu azalır Buna karşılık hipotermi ile birlikte remifentanil eliminasyon hızı azalır. Bu nedenle infüzyon hızı değiştirilmezse hipotermi, remifentanilin kan konsantrasyonunun artmasına neden olur. Önerilen, her 5 derecelik azalma için remifentanil infüzyon hızının %30 kadar azaltılmasıdır. Anesth Analg 2001;93:1100 –5 9

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 8

MALİYET 90 hasta Kardiyak cerrahi Anesth Analg 2001;93:859-64. 7 Mekanik ventilasyon süresi, hastanede kalış süresi ve hastane maliyeti aynı The purpose of this study was to compare the effects of three different opioid techniques for cardiac surgery on postoperative pain, time to extubation, time to intensive care unit discharge, time to hospital discharge, and cost. Ninety adult patients undergoing cardiac surgery were randomized to a fentanyl-based, sufentanil-based, or remifentanil-based anesthetic. Postoperative pain was measured at 30 min after extubation and at 6:30 AM on the first postoperative day. Pain scores at both times were similar in all three groups (P > 0.05). Median ventilator times of 167, 285, and 234 min (P > 0.05), intensive care unit stays of 18.8, 19.8, and 21.5 h (P > 0.05), and hospital stays of 5, 5, and 5 days (P > 0.05) for the Fentanyl, Sufentanil, and Remifentanil groups did not differ. Three patients needed to be tracheally reintubated: two in the Sufentanil group and one in the Fentanyl group. Median anesthetic costs were largest in the Remifentanil group ($140.54 [$113.54-$179.29]) and smallest in the Fentanyl group ($43.33 [$39.36-$56.48]) (P < or = 0.01), but hospital costs were similar in the three groups: $7841 (Fentanyl), $5943 (Sufentanil), and $6286 (Remifentanil) (P > 0.05). We conclude that the more expensive but shorter-acting opioids, sufentanil and remifentanil, produced equally rapid extubation, similar stays, and similar costs to fentanyl, indicating that any of these opioids can be recommended for fast-track cardiac surgery. IMPLICATIONS: To conserve resources for cardiac surgery, fentanyl-, sufentanil-, and remifentanil-based anesthetics were compared for duration of mechanical ventilation, intensive care unit length of stay, hospital length of stay, and cost. The shorter-acting anesthetics, sufentanil and remifentanil, produced equally rapid extubation, similar stays, and similar costs to fentanyl; thus, any of these opioids can be recommended for fast-track cardiac surgery. Anesth Analg 2001;93:859-64. 7

REMİFENTANİL Hemodinamik etkileri Kardiyak kateterizasyon Vasküler cerrahi Kardiyak cerrahi Koroner arter cerrahisi Pediyatrik kardiyak cerrahi CPB ve farmakokinetik Maliyet Postoperatif analjezi 6

POSTOPERATİF ANALJEZİ Endikasyon: Postoperatif derlenme odası Yoğun bakım ünitesi Analjezi kalitesi Yeterli 5

POSTOPERATİF ANALJEZİ Doz 0.1-0.15 mcg/kg/dk Doz artırımı 0.025 mcg/kg/dk Ek sedatif gereksinimi 0.2 mcg/kg/dk (maksimum doz) Lisanslı doz aralığı 0.006-0.74 mcg/kg/dk Prescribing and monitoring • The dose of remifentanil used in intensive care is initially 0.1–0.15 g/kg/minute. The dose can then be increased at increments of 0.025g/kg/minute to achieve the desired level of sedation and analgesia. If the infusion rate reaches 0.2 g/kg/minute and the desired level of sedation is not reached, then a sedative agent such as propofol should be added. The licensed dose range is 0.006–0.74 g/kg/minute. • 4 Crit Care Med 2002; 30:119-141

POSTOPERATİF ANALJEZİ Maliyet 3

POSTOPERATİF ANALJEZİ Pediyatrik kardiyak cerrahi 18 olgu Remifentanil (0,1 mcg/kg/dk) veya Morfin : 1 mg/kg Yetersiz analjezi / titrasyon güçlüğü Bell, G.T., Dickson, U., Arana, A., Marshall, C., Robinson, D. & Morton, N.S. Remifentanil vs fentanyl/morphine for pain control during paediatric cardiac surgery. Paediatric Anaesthesia 12 (9), 817-817 Remifentanil vs fentanyl/morphine for pain control during paediatric cardiac surgery. Bell GT, Dickson U, Arana A, Marshall C, Robinson D, Morton NS. The Royal Hospital for Sick Children, Yorkhill, Glasgow, G3 8SJ. INTRODUCTION: Remifentanil is a potent synthetic opioid that does not accumulate after infusion or repeated bolus doses. It may be rapidly titrated to the requirements of individual patients. Remifentanil has potential advantages for paediatric cardiac surgery in being able to provide potent analgesia required to blunt the stress response in theatre and a lack of prolonged sedative affects that may delay progress in intensive care. METHODS: After approval by the local ethics committee, 18 patients were randomised to receive a titrated infusion of remifentanil (0-1 mcg.kg.min-1) or a standard dose of fentanyl (30 mcg.kg-1) pre-bypass with morphine (1 mg.kg-1) on rewarming. The anaesthetic technique aside from analgesia was that normally used by the consultant anaesthetist responsible for the case. Blood samples for glucose and cortisol were taken at regular intervals from induction through bypass and into the first 24 hours of postoperative intensive care. Urine samples taken over the same period were analysed for 3 methythistidine:creatinine ratios. In addition to biochemical indicators of the stress response we recorded baseline haemodynamic parameters and any acute physiological events. RESULTS: Statistical analysis is not yet complete - initial analysis shows that both techniques obtunded the stress response to a very similar extent. Ten patients were randomised to receive morphine and eight to receive remifentanil (there were late cancellations in the remifentanil group). One patient was withdrawn from the remifentanil group for a protocol violation. There were two incidences of inadequate analgesia in the remifentanil group one related to rapid haemodilution going onto cardiopulmonary bypass and a second as a consequence of an infusion line kinking. DISCUSSION AND CONCLUSIONS: Although it was our original intention to continue remifentanil up to 24 hours postoperatively, this was only achieved in four out of the seven remifentanil patients due either to discharge to the ward or to difficulty in titration of an appropriate dose for spontaneously breathing patients in intensive care. In our unit it became appropriate to start a morphine infusion to replace remifentanil within the first few hours of PICU admission. The episode of inadequate analgesia going on to bypass occurred when remifentanil was infusing at 1 mcg.kg.min-1 which illustrates high inter-individual variation. The other episode when a peripheral line kinked emphasises the importance of line patency and we would recommend that infusions are given centrally to help ensure adequate delivery. Paediatric Anaesthesia 2002;12: 817 2

POSTOPERATİF ANALJEZİ Yan etkiler: Hipotansiyon Kas rijiditesi Bradikardi Solunum depresyonu Sürekli infüzyon 50 mcg/ml (dekstroz ya da SF içinde) 3 günden daha fazla kullanımına ilişkin veri yok Side effects include hypotension, muscle rigidity, including chest wall rigidity, bradycardia. Like all opiates, it can cause respiratory depression. However, the short duration of action means any side effects are short lived. • Remifentanil is not a controlled drug. • Remifentanil should be given as a continuous infusion. The recommended dilution is 50mcg/ml, diluted in sodium chloride 0.9% or glucose 5%.Remifentanil has only been used in studies in intensive care patients for up to 3 days, and there is no safety or efficacy data for longer than 3 days. 1

REMİFENTANİL Avantajlar: Dezavantajlar: Geniş doz aralığı Stres yanıtta azalma Derin intraoperatif analjezi Erken derlenme Dezavantajlar: Kan basıncında azalma Kalp hızında azalma