title: Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period.
abstract: BACKGROUND
  Recently, new drugs and techniques for the treatment of postoperative pain were introduced, with the goal of enhancing opiates' analgesia while minimizing their side-effects. Cholinergic agents play an antinociceptive role, but their clinical use is quite limited, due to side-effects. Physostigmine is a cholinesterase inhibitor, which crosses the blood-brain barrier and elevates brain acetylcholine level. Physostigmine can produce analgesia by itself, and enhance opiate analgesia; but these effects are of short duration following bolus administration.
  
  
  METHODS
  We compared pain intensity and morphine consumption in two postoperative treatment groups: One group received continuous physostigmine infusion combined with morphine-based patient-controlled analgesia (PCA), and the other received PCA alone. Cholinergic anti-inflammatory pathways have recently been described. We therefore also compared changes in proinflammatory cytokine production in the two pain management groups.
  
  
  RESULTS
  Continuous infusion of physostigmine combined with morphine-based PCA in the postoperative period significantly reduced opiate consumption, and enhanced the analgesic response. Patients in the physostigmine group also exhibited reduced ex-vivo production of the proinflammatory cytokine, IL-1beta. At the same time, physostigmine increased nausea and vomiting, mostly in the first 2 h of the postoperative period.
  
  
  CONCLUSIONS
  Physostigmine combined with morphine in the postoperative period reduced morphine consumption, enhanced analgesia, and attenuated production of the proinflammatory cytokine, IL-1beta. This latter finding may account for the decreased pain observed in this group; this cytokine is known to mediate basal pain sensitivity and induce hyperalgesia in inflammatory conditions. Taking into account the other potential beneficial effects of physostigmine, we suggest that a continuous infusion of physostigmine should be considered as a useful component in multimodal postoperative analgesia.
authors.affiliation: Department of Anesthesiology, Rabin Medical Center, Gold-Hasharon Campus, Petah-Tiqva, Israel. beilinb@clalit.org.il
authors.forename: B
authors.initials: B
authors.lastname: Beilin
authors.forename: H
authors.initials: H
authors.lastname: Bessler
authors.forename: L
authors.initials: L
authors.lastname: Papismedov
authors.forename: M
authors.initials: M
authors.lastname: Weinstock
authors.forename: Y
authors.initials: Y
authors.lastname: Shavit
mesh_terms: D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D007118:Immunoassay; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism; D010830:Physostigmine / Q000627:therapeutic use*; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology
chemical_list: D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D006993:Hypnotics and Sedatives; D007375:Interleukin-1; D015850:Interleukin-6; D009020:Morphine; D010830:Physostigmine