A multi-center study of intrathecal neostigmine for analgesia following vaginal hysterectomy.
BACKGROUND
Intrathecal neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of neostigmine have come from one Brazilian university. This multicenter, placebo-controlled trial investigated the effects of 25-75 microg intrathecal neostigmine on analgesia and blood pressure in women undergoing vaginal hysterectomy.


METHODS
After institutional review board approval was obtained at the three university centers, and after patients gave informed consent, 92 women scheduled for vaginal hysterectomy were randomized to receive an intrathecal injection of 2 ml bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 microg neostigmine. Blood pressure, heart rate, pain and nausea (both assessed by visual analog scale), and intravenous morphine use were recorded during surgery and at specified intervals afterward.


RESULTS
Morphine use was reduced similarly by all doses of neostigmine. Only the 75-microg dose of neostigmine increased the nausea score in the recovery room. The incidence of treatment for nausea was greater in patients receiving neostigmine (61%) than in those receiving saline placebo (29%) and was unaffected by neostigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine.


CONCLUSIONS
These data in patients after vaginal hysterectomy suggest that analgesia from intrathecal neostigmine may occur at doses less than 50 microg. In these doses, neostigmine does not reduce spinal bupivacaine-induced hypotension but may increase the need for treatment of nausea.
Department of Surgery, Orthopedics and Traumatology, Faculty of Medicine of Ribeirăo Preto, University of Săo Paulo, Brazil. dhood@bgsm.edu
G R
GR
Lauretti
D D
DD
Hood
J C
JC
Eisenach
B L
BL
Pfeifer
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007045:Hysterectomy, Vaginal / Q000009:adverse effects*; D007278:Injections, Spinal; D008875:Middle Aged; D009388:Neostigmine / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D010919:Placebos
D000700:Analgesics; D002800:Cholinesterase Inhibitors; D010919:Placebos; D009388:Neostigmine