Literature DB >> 7856891

Phase I safety assessment of intrathecal neostigmine methylsulfate in humans.

D D Hood1, J C Eisenach, R Tuttle.   

Abstract

BACKGROUND: In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha 2-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 micrograms) 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 micrograms) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micrograms) caused mild nausea, and 500-750 micrograms caused severe nausea and vomiting. Neostigmine (150-750 micrograms) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micrograms dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100-200 micrograms) 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.

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Year:  1995        PMID: 7856891     DOI: 10.1097/00000542-199502000-00003

Source DB:  PubMed          Journal:  Anesthesiology        ISSN: 0003-3022            Impact factor:   7.892


  30 in total

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Review 2.  Anaesthetic agents for advanced regional anaesthesia: a North American perspective.

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Journal:  Drugs       Date:  2005       Impact factor: 9.546

3.  Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine, Morphine and Neostigmine.

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Review 4.  The spinal biology in humans and animals of pain states generated by persistent small afferent input.

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Review 5.  Use of neostigmine in the management of acute postoperative pain and labour pain: a review.

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Journal:  CNS Drugs       Date:  2006       Impact factor: 5.749

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Review 7.  Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis.

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Journal:  Pharmacol Ther       Date:  2009-04-23       Impact factor: 12.310

8.  Neostigmine decreases bupivacaine use by patient-controlled epidural analgesia during labor: a randomized controlled study.

Authors:  Vernon H Ross; Peter H Pan; Medge D Owen; Melvin H Seid; Lynne Harris; Brittany Clyne; Misa Voltaire; James C Eisenach
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9.  Preclinical toxicity screening of intrathecal oxytocin in rats and dogs.

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Review 10.  Neuraxial analgesia in neonates and infants: a review of clinical and preclinical strategies for the development of safety and efficacy data.

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Journal:  Anesth Analg       Date:  2012-07-13       Impact factor: 5.108

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