Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period.
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.
Beilin
B
B
Department of Anesthesiology, Rabin Medical Center, Gold-Hasharon Campus, Petah-Tiqva, Israel. beilinb@clalit.org.il
Bessler
H
H
Papismedov
L
L
Weinstock
M
M
Shavit
Y
Y
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
D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D006993:Hypnotics and Sedatives; D007375:Interleukin-1; D015850:Interleukin-6; D009020:Morphine; D010830:Physostigmine