Postoperative pain can contribute to reduction in the patient's well-being and, if it is pronounced, delayed rehabilitation and an increase in the total cost for nursing and treatment.~Experimental studies has shown that infusion of remifentanil over some period of time, can result in acute opioid tolerance and hyperalgesia (1-2).~One clinical trial has shown that intraoperative infusion of remifentanil gives acute opioid tolerance with subsequent increased postoperative pain and increased opioid consume postoperative (3).~The development of opioid tolerance probably has several mechanisms. One topical mechanism is opioid induced influence of N-methyl-d-aspartate (NMDA)-receptor and its intracellular second-messenger-systems. This results in central sensitization to pain stimulus in the dorsal horn and the brain (4-5), with following development of hyperalgesia.~Several strategies can be successful to reduce or prevent opioid induced hyperalgesia, for example NMDA-receptor antagonists, alfa-2 agonists, opioid rotation or combination of opioids with different receptor selectivity (6-8).~The theoretical background for pre-treating the opioid receptor with an other opioid (fentanyl) that gives less tendency to hyperalgesia than remifentanil, is that it can reduce the development of tolerance and hyperalgesia of remifentanil.~The aim of this trial is to examine the possibility that i.v. administration of fentanyl 1,5 µgr/kg before start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given in the end of surgery (the traditional method).~This is to be measured by less pain postoperative (VAS, visual analog scale, and a five point verbal rating scale) and less fentanyl consumed (measured by using PCA).~Literature:~Vinik HR, Kissin I (1998) Rapid development of tolerance to analgesia during remifentanil infusion in human. Anesth Analg 86:1307-1311.~Angst MS, Koppert W, Pahl I, Clark JD, Schmelz M (2003) Short-term infusion of the µ-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 106:49-57.~Guignard et al. (2000) Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 93:409-417.~Larcher A, Laulin JP, Celerier E, Le Moal M, Simonnet G (1998) Acute tolerance associated with a single opioid administration: involvement of N-methyl-D-aspartate-dependent pain facilitatory systems. Neuroscience Vol 84:583-589.~Celerier E, Laulin J, Larcher A, Le Moal M, Simonnet G (1999) Evidence for opiate-activated NMDA processes masking opiate analgesia in rats. Brain Research 849:18-25.~Celerier E, Rivat C, Jun Y, Laulin JP, Larcher A, Reynier P, Simonnet G(2000) Long-lasting hyperalgesia induced by fentanyl in rats: preventive Effect of ketamin. Anesthesiology 92:465-472.~Bie B, Fields HL, Williams JT, Pan ZZ (2003) Roles of a alfa-1 and alfa-2-adrenoreceptors in the nucleus raphe magnus in opioid analgesia and opioid abstinence-induced hyperalgesia. Journal of Neuroscience 23:7950-7957.~Mao J, Prince DD, Caruso F, Mayer DJ (1996) Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats. Pain 67:361-368.
The aim of this trial is to examine the possibility that fentanyl 1,5 µgr/kg given intravenously (i.v.) before the start of remifentanil infusion for anesthesia gives less development of tolerance/hyperalgesia postoperative than fentanyl given at the end of surgery (the traditional method).