In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha2 -adrenergic agonists. This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers.Methods
After institutional review board approval and informed consent, 28 healthy volunteers were studied. The first 14 volunteers received neostigmine (50–750 micro gram) through a #19.5 spinal needle followed by insertion of a spinal catheter. The remaining 14 volunteers received neostigmine through a #25 or #27 spinal needle without a catheter. Safety measurements included blood pressure, heart rate, oxyhemoglobin saturation, end-tidal carbon dioxide, neurologic evaluation, and computer tests of vigilance and memory. Analgesia in response to ice water immersion was measured.Results
Neostigmine (50 micro gram) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micro gram) caused mild nausea, and 500–750 micro gram caused severe nausea and vomiting. Neostigmine (150–750 micro gram) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micro gram dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100–200 micro gram) in saline, injected through a #25 or #27 needle, caused protracted, severe nausea, and vomiting. This did not occur when dextrose was added to neostigmine. Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water.Conclusions
The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose, method of administration, and baricity of solution. These effects in humans are consistent with studies in animals. Because no unexpected or dangerous side effects occurred, cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted.