Kein Opioidüberhang bei Patienten mit transdermalem Buprenorphin und Fast-Track-Anästhesie nach Eingriffen am offenen Herzen

Zusammenfassung

Ziel der Studie: Führt die Anwendung einer fentanylgestützten Narkose bei Patienten mit Buprenorphin transdermal zu protrahierten Aufwachzeiten, einer verlängerten Atemdepression oder einer Toleranzentwicklung mit Fentanylresistenz? Methodik: In einer offenen Studie wurden Patienten mit einem Buprenorphinpflaster (n = 22), die sich einer Operation am offenen Herzen unter einer fentanylgestützten Enflurannarkose unterziehen mussten einer randomisierten Kontrollgruppe (n = 21) mit ähnlichen operativen Eingriffen gegenübergestellt. Gemessen wurden die Zeit bis zur Extubation, die arteriellen Blutgase, der Aldrete Erholungsscore und PONV. Ergebnisse: Bei ähnlichen Operations- und Narkosezeiten waren der intraoperative Fentanylverbrauch (0,69 mg ± 0,23 versus 0,67 mg ± 0,16), die Zeiten bis zur Extubation (25,2 min ± 6.1 versus 33,3 min ± 5,0), der Aldrete Erholungsscore (0,69 ± 0,23 versus 0,67 ± 0,16) und die postoperativen arteriellen Blutgase unter Sauerstoffatmung (paO₂ 136 torr ± 48 versus 128 torr ± 35; paCO₂ 43,3 torr ± 3,3 versus 41,9 torr ± 1,2) signifikant nicht unterschiedlich. Nausea/Emesis war dagegen in der Kontrollgruppe signifikant (p < 0,01) häufiger. Schlussfolgerung: Wegen der vorangegangenen langfristigen Buprenorphinapplikation und den daraus resultierenden Adaptationsmechanismen ist bezüglich Atmung und Vigilanz keine Wirkungsverlängerung bis in die postoperative Phase zu erwarten. Die präoperative Gewöhnung an ein Opioid wie Buprenorphin führt auch zu geringeren PONV Raten.

Abstract

Objective: Simultaneous use of opioids with a different pharmacological profile may lead to unexpected prolongation of effects. In an open label study possible overhang in post-operative respiratory effects and vigilance was determined in a group of patients (n = 22) carrying a transdermal buprenorphine patch for at least 2 months for treatment of chronic pain, undergoing a fentanyl-based fast-track enflurane anesthetic technique for open-heart operation. Data was compared with another randomised group (n = 21) undergoing similar open-heart procedures with no other opioid than fentanyl on board. Methods and Results: Following induction with fentanyl and a barbiturate, depth of anesthesia with enflurane (Fi 0.5) was guided using the bispectral index (BIS). Additional doses of fentanyl were given when blood pressure and/or heart-rate increased 20 % above pre-induction levels. Early postoperative extubation was initiated once the cardiovascular system was stable and there were no signs of respiratory impairment. Following a similar time of operation and anesthesia and a similar total dose of fentanyl (0.69 mg ± 0.23 SD versus 0.67 mg ± 0.16 SD), postoperatively, there were no significant differences between the buprenorphine- and the control group regarding the time till extubation (25.2 min ± 6.1 versus 33.3 min ± 5.0) and the arterial blood gases under oxygen inhalation (paO₂ 136 torr ± 48 SD versus 128 torr ± 35 SD; paCO₂ 43.3 torr ± 3.3 SD versus 41.9 torr ± 1.2 SD and the post-anesthetic vigilance and recovery score (6.8 ± 1.0 versus 7.5 ± 0.8) 60 minutes after end of anesthesia. Contary to the control group, there was a lower and significant (p < 0.01) incidence of PONV in patients with transdermal buprenorphine.

Conclusion: Patients using a buprenorphine patch for the relief of chronic pain cannot be regarded as opioid naïve. Due to adaptive mechanisms and the development of tolerance, there is no prolongation of the respiratory depression induced by intraoperative fentanyl. Long-term use of transdermal buprenorphine does not lead to potentiation or prolongation of opioid effects in cardiac surgery patients.

Transdermales Buprenorphin - Fentanyl - Opioidnarkose - Adaptationsmechanismen - Kardiochirurgie

Transdermal buprenorphine - fentanyl - opioid anesthesia - additive effects - open-heart surgery

Literatur

• 1 Rapp S E, Ready L B, Nessly M L. Acute pain managment in patients with prior opioid consumption: a case-controlled restrospective review.  Pain. 1995;  61 195-201
• 2 De Castro J, Andrieu S, Boogaerts J. Buprenorphine. A review of its pharmacological properties and therapeutical uses. In: De Castro J (ed) New Drug Series, Vol. 1. Antwerpen; Kluwer 1982: NVM & ISA pp 180
• 3 Lehmann K A, Weski C, Hunger L, Heinrich C, Daub D. Biotransformation von Fentanyl. II. Akute Arzneimittelinteraktion - Untersuchungen bei Ratte und Mensch.  Anaesthesist. 1982;  31 221-227
• 4 Aldrete J A, Kroulik D. A postanesthetic recovery score.  Anesth Analg. 1970;  49 924-928
• 5 Freye E. Opioide in der Medizin, 6. Auflage. Berlin, Heidelberg, New York; Springer 2004: 469
• 6 Hambrook J, Rance M J. The interaction of buprenorphine with the opiate receptor: lipophilicity as a determinig factor in drug-receptor kinetics. In: Kosterlitz H (ed) Opiates and endogenous peptides. Amsterdam; North-Holland 1976: 295-301
• 7 Sadee W, Rosenbaum J S, Herz A. Buprenorphine: Differential interaction with opiate receptors subtypes in vivo.  J Pharmacol Exp Ther. 1982;  223 157-162
• 8 Tyers M B. A classification of opiate receptors that mediate antinociception in animals.  Br J Pharmacol. 1980;  69 503-512
• 9 Akram A, Thangam J, Kanti B. Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery.  Indian J Physiol Pharmacol. 1997;  41 361-368
• 10 Tufano R, Leone D, di Napoli E, de Negri P. Anesthesia with buprenorphine in open heart surgery. In: VII European Congress of Anaesthesiology Vienna; 1986
• 11 Boas R A, Villiger J W. Clinical action of fentanyl and buprenorphine: The significance of receptor binding.  Br J Anaesth. 1985;  57 192-196
• 12 Schmidt W K, Tam S W, Shotzberger G S, Smith D H, Clark R, Vernier V G. Nalbuphine.  Drug Alcohol Depend. 1985;  14 339-362
• 13 Magnan J, Paterson S J, Tavani A, Kosterlitz H W. The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties.  Naunyn-Schmiedebergs Arch Pharmacol. 1982;  319 197-205
• 14 Yassen A, Olofsen E, Dahan A, Danhof M. Pharmacokinetic-phaemacodynamic modeling of the antinociceptive effect of buprenorphine and fentanyl in rats: role of receptor equilibration kinetics.  J Pharmacol Exp Ther. 2005;  313 1136-1149
• 15 Chen Z R, Irvine R J, Somogyi A A, Bochner F. Mu receptor binding in commonly used opioids and their metabolites.  Life Sci. 1991;  48 2165-2171
• 16 Portenoy R K. Constipation in the cancer patients: Causes and management.  Med Clin North Am. 1987;  71 303-311
• 17 Kreek M J. Medical safety and side effects of methadone in tolerant individuals.  JAMA. 1973;  233 665-668
• 18 Taub A. Opioid analgesics in the treatment of chronic intractable pain of non-neoplastic origin. In: Kitahata LM, Collins JG (eds) Narcotic Analgesics in Anesthesiology. Baltimore; Williams and Wilkins 1982: 199-208
• 19 Bruera W, MacMillan K, Hanson J, MacDonalds R N. The cognitive effects of the administration of narcotic analgesics in patients with cancer pain.  Pain. 1989;  39 13-16
• 20 Meert T F. Pharmacotherapy of opioids: present and future developments.  Pharm World Sci. 1996;  18 1-15
• 21 Lewis J W. Buprenorphine.  Drug Alcohol Depend. 1985;  14 363-372
• 22 De Castro J, Parmentier P. Antimorphinques et anesthesie analgesique sequentielle. III: Pharmacodynamie des principaux antidotes de la morphine. Bruxelles; Academia S.A. 1975: 47-49
• 23 Walker E A, Zerni G, Woods J H. Buprenorphine antagonism of mu opiods in the rhesus monkey tail-withdrawal procedure.  J Pharmacol Expt Ther. 1995;  273 1345-1352
• 24 Bullingham R ES, McQuay H J, Bennett M RD. Buprenorphine kinetics.  Clin Pharmacol Ther. 1980;  28 667-672
• 25 Walsh S L, Eisenberg T. The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic.  Drug Alcohol Depend. 2003;  70 S13-S27
• 26 Manner T, Kanto J, Salonen M. Use of a simple test to determine the residual effects of the analgesic component of balanced anaesthesia.  Br J Anaesth. 1987;  59 978-982
• 27 Okutani R, Kono K, Kinoshita O, Nakamura H, Isshida H, Philbin D M. Variations in hemodynamic and stress hormonal response in open heart surgery with buprenorphine/diazepam anesthesia.  J Cardiothorac Anesth. 1989;  3 401-406
• 28 Khan F A, Zaidi A, Kamal R S. Comparison of nalbuphine and buprenorphine in total intravenous anaesthesia.  Anaesthesia. 1997;  52 1095-1101
• 29 Beltrutti D, Niv D. Pain relief after simultaneous administration of intravenous buprenorphine and intrathecal morphine in terminally ill patients; A report of two cases.  Pain Clin. 2000;  12 121-123
• 30 Young A M, Kapitsopoulos G, Makhay M M. Tolerance to morphine-like stimulus effects of mu opioid agonists.  J Pharmacol Exp Ther. 1991;  257 795-805
• 31 Morgan D, Cook C D, Smith M A, Picker M J. An examination of the interaction between the antinociceptive effects of morphine and various µ-opioids: the role of intrinsic efficacy and stimulus intensity.  Anesth Analg. 1999;  88 407-413