title: Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration.
abstract: Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 microg, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine.
authors.affiliation: Department of Anesthesia, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Gurun
authors.forename: R
authors.initials: R
authors.lastname: Leinbach
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: M D
authors.initials: MD
authors.lastname: Owen
authors.forename: J C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D015360:Analgesia, Epidural / Q000295:instrumentation; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis; D005947:Glucose / Q000008:administration & dosage*; D007278:Injections, Spinal / Q000295:instrumentation; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced; D009187:Myelitis / Q000209:etiology; D009388:Neostigmine / Q000008:administration & dosage / Q000627:therapeutic use*; D009619:Nociceptors / Q000187:drug effects; D010226:Parabens / Q000008:administration & dosage*; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012449:Safety; D012472:Salivation / Q000187:drug effects; D012756:Sheep; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D014202:Tremor / Q000139:chemically induced
chemical_list: D000700:Analgesics; D002800:Cholinesterase Inhibitors; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D009388:Neostigmine; C015358:methylparaben; D005947:Glucose; C006068:propylparaben