Neostigmine-Induced Muscle Twitches and Fasciculations

Mechanism and Clinical Context

Neostigmine inhibits acetylcholinesterase, causing accumulation of acetylcholine in the synaptic cleft, which can lead to excessive stimulation of nicotinic receptors and result in fasciculations (muscle twitches) 1, 2
The American Society of Anesthesiologists recommends that neostigmine should be administered with caution, as it can cause muscle twitches and fasciculations, particularly when administered inappropriately or in excessive doses 1, 2

The Anaesthesia society recommends that neostigmine should only be administered when there are at least 4 responses to TOF stimulation (corresponding to TOF ratio ≥0.2) 5, 4
The Anaesthesia society recommends using 40-50 mcg/kg of neostigmine based on ideal body weight 5, 3, 4
The Anaesthesia society recommends never administering neostigmine when TOF ratio is already ≥0.9 3, 4
The Anaesthesia society recommends always co-administering neostigmine with anticholinergic agents (atropine 0.02 mg/kg or glycopyrrolate) to prevent cholinergic side effects 4

Administering neostigmine when the train-of-four (TOF) ratio is already ≥0.9 can paradoxically impair neuromuscular transmission and cause muscle weakness rather than typical fasciculations 3, 4
Neostigmine 40 mcg/kg given when TOF ratio >0.9 may decrease the TOF ratio and impair neuromuscular function for 17-52 minutes 3