Neostigmine Overdose and Expected Clinical Presentation

Mechanism of Action and Expected Effects

Fasciculations would be expected as part of the excessive nicotinic receptor stimulation, characterized by increasing muscle weakness that can progress through involvement of respiratory muscles, according to the American College of Medical Toxicology 1

The expected clinical presentation of neostigmine overdose includes muscarinic symptoms such as nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, and bradycardia, as well as cholinergic crisis characterized by increasing muscle weakness, as described by the FDA label and supported by evidence from Critical Care Medicine 1

Neostigmine inhibits acetylcholinesterase, causing accumulation of acetylcholine in the synaptic cleft, which leads to excessive stimulation of nicotinic receptors and results in fasciculations (muscle twitches) 2

Standard therapeutic intravenous doses of neostigmine range from 40-50 mcg/kg (0.04-0.05 mg/kg) of ideal body weight, with a 70 kg person requiring approximately 2.8-3.5 mg intravenously 3, 4, 5, 6
The American Society of Anesthesiologists recommends intravenous doses in the range of 40-50 mcg/kg for therapeutic use, which for a 70 kg person translates to approximately 2.8-3.5 mg 3

The initial depolarization from acetylcholine excess is clinically manifested as fasciculations before progressing to paralysis in overdose situations, according to the American College of Critical Care Medicine 7
Organophosphate compounds that permanently inhibit acetylcholinesterase produce weakness, fasciculations, and paralysis through the same unopposed acetylcholine action at nicotinic receptors, as reported by the American College of Critical Care Medicine 7